Melanoma of the nipple and areola.

Fourteen primary melanomas arising in the nipple and areola of the breast were treated by mastectomy and axillary dissection. Four patients had axillary lymph node metastases and all were dead within 3 years of their operation, while the 10 patients with no axillary node involvement were free from recurrent disease 5 years after their operation. On the basis of clinical and anatomical studies, it is suggested that a wide local excision without mastectomy is adequate for the treatment of nipple and areola melanomas.


Sclerotherapy for hydrocoele and epididymal cysts.

A prospective study was carried out on the efficacy of sclerotherapy for the treatment of hydrocoeles and epididymal cysts. Thirty-six hydrocoeles and 13 epididymal cysts were treated and followed up for between 1 and 2 years. Thirty-four hydrocoeles were cured, 1 failed to respond to treatment and 1 recurred after treatment. All 13 epididymal cysts were cured.


Late infection of a total hip prosthesis presenting as an ischiorectal abscess.

Late infection of a total hip arthroplasty recently presented as an ischiorectal abscess. A likely pathogenesis is suggested and the literature on late infection in prosthetic joints is reviewed.


Congenital heart block and maternal systemic lupus erythematosus.

The association between infants with congenital heart block (CHB) and the presence or later development of maternal systemic lupus erythematosus or other connective-tissue disease (CTD) was reviewed in 67 cases. In 24 cases CHB was diagnosed at or before birth. Of nine necropsies on affected infants, seven showed endomyocardial fibrosis. The results suggest that one in three mothers who deliver babies with CHB have or will develop CTD. The association is probably explained by placental transfer of a maternal antibody. Awareness of the association may lead to prevention of the birth of children with CHB and better neonatal care of affected children.


Extradural haematoma: effect of delayed treatment.

The case records of patients with extradural haematomas treated in the Lothian region during 1951-60 and 1968-77 were analysed to assess the effect of delay in treatment on morbidity and mortality. Delay was defined as the time from deterioration in level of consciousness to surgical evacuation of clot. There were 83 supratentorial extradural haematomas unassociated with intradural clot or contusion. The mean delay in patients who died was 15.7 hours, while in good-quality survivors the mean delay was 1.9 hours. Mortality decreased from 33.3% during 1951-60 to 8.9% during 1968-77. In addition, good recovery without morbidity occurred in 40.7% of patients in the earlier period and 67.9% in the later period. Mean delays from deterioration in level of consciousness to operation were 9.8 and 2.4 hours in the earlier and later periods respectively. The results emphasise the need for immediate operation in patients deteriorating with extradural haematomas. Direct admission of all head-injured patients to a head and spinal injuries unit staffed by neurosurgeons resulted in minimal delay times as well as a reduction in morbidity and mortality.


Hyponatraemia and severity and outcome of myocardial infarction.

A total of 235 consecutive patients admitted to a coronary care unit were investigated for serum electrolyte and urea concentrations; activities of aspartate amino-transferase, lactate dehydrogenase, and lactate dehydrogenase isoenzymes; electrocardiographic changes; clinical state; and outcome. Hyponatraemia, hypochloraemia, and uraemia were common in patients with confirmed myocardial infarctions, the degree of infarction correlating well with all the above indices of severity. The day-to-day variability of plasma sodium, chloride, and potassium concentrations was often increased above normal. Disturbances were greater in patients given diuretics. It is concluded that plasma sodium concentration fall after infarction and that the extent and duration of the fall are indices of the severity of the infarction.


Reports by anaesthetists to procurators-fiscal: analysis of "anaesthetic deaths" over 10 years in four Scottish teaching hospitals.

Review of 489 "anaesthetic deaths" reported to procurators-fiscal over 10 years disclosed only 30 that were thought to justify such reporting. Most of the remainder occurred in patients so desperately ill at the time of operation that death was expected. Postmortem examinations ordered by the Crown authorities in nearly all cases were probably largely unrewarding and mostly unnecessary. The results suggest that the present regulation on reporting should be revised to focus more attention on the few deaths that occur in patients who have no apparent contraindication to anaesthesia or operation.


Prospective study of genetic counselling.

A prospective study was carried out on 200 consecutive subjects seen for counselling (consultands) for serious genetic disorders. Educational and social background of consultands and their knowledge and understanding of their particular problem were assessed before counselling, and their response was determined immediately afterwards and three months and two years later by an independent observer not concerned in the genetic counselling. The husband's educational background was particularly important in influencing a couple's comprehension of counselling. X-linked recessive and chromosomal disorders presented the most difficulties in comprehension. The counsellors' assessment of comprehension was a good guide to the consultands' comprehension as assessed at subsequent follow-up. The proportion deterred from having children increased with time and over a third had been sterilised within two years of counselling. It is suggested that follow-up after counselling should be routine, especially when the counsellor suspects that comprehension has not been good, in X-linked recessive and chromosomal disorders, and when the risks of having an affected child are considered to be high.


Pinealoblastoma with retinoblastomatous differentiation.

A case of primitive neuroectodermal tumour originating from pineal parenchymal cells in a 2 1/2-year-old boy is described. The tumour exhibited divergent lines of differentiation including neuroblastic and photoreceptor differentiation, thus aligning it with neuroblastomas and with retinoblastomas. The tumour recalls the function of the pineal as a photoreceptor organ at an earlier stage of its phylogenesis.


An analysis of factors influencing measurements of dopamine, noradrenaline, glutamate decarboxylase and choline acetylase in human post-mortem brain tissue.

Measurements have been made of dopamine, noradrenaline, glutamate decarboxylase (GAD) and choline acetylase (CAT) in a variety of regions from human post-mortem brain tissue, and the results analysed as a function of ante-mortem and post-mortem factors which may influence such measurements. The agonal status of the patient emerged as a major influence on the post-mortem measurement of GAD activity, without significantly affecting the other biochemical parameters. Of the other ante-mortem factors investigated, there appeared to be no differences between male and female, no circadian fluctuations, and few significant age-related changes, in any of the biochemical parameters measured in different brain regions. Moreover, the results indicated that the enzymes GAD and CAT are remarkably stable in human brain during routine post-mortem handling. Similar findings were made for dopamine and noradrenaline, although a substantial loss of both catecholamines probably occurs in the first few hours after death.


Increased dopamine concentration in limbic areas of brain from patients dying with schizophrenia.

Dopamine, noradrenaline, glutamate decarboxylase (GAD) and choline acetyl-transferase (CAT) were measured in post-mortem brain samples from more than 50 patients dying with a hospital diagnosis of schizophrenia and an equal number of controls. GAD was measured in 14 different brain regions, and was significantly lower in both control and schizophrenia patients who died following a protracted illness. If GAD values from patients who died suddenly were compared, no significant differences were observed between the control and schizophrenia groups. There was also no differences between the CAT values measured in 13 different brain regions in the two groups. Noradrenaline values were not different in the two groups in most limbic areas or in the caudate nucleus, but were elevated in the schizophrenic group in nucleus accumbens and in anterior perforated substance. These differences were not, however, statistically significant. On the other hand dopamine concentrations in nucleus accumbens and in anterior perforated substance were significantly elevated (by 34 and 95 per cent, respectively) in the schizophrenia group as compared with controls, although dopamine values were not different in caudate nucleus, putamen, septal nuclei or amygdala. The finding of elevated concentrations of dopamine in certain areas of the limbic forebrain in schizophrenia is discussed in relation to current hypotheses of the involvement of dopamine in this illness, and the difficulties of determining whether the observed changes are related to chronic treatment with antischizophrenic drugs.


Pontine and extrapontine myelinolysis.

No coherent theory has been advanced to explain either the particular localization of the myelinolytic lesions of central pontine myelinolysis or their pathogenesis. However, several lines of evidence support the generalization that the centre of the basis pontis has a special susceptibility to a metabolic fault. The constancy of localization of the lesion and its bilateral symmetry are the very attributes that characterize other metabolic (nutritional) disorders, such as the assymmetrical degeneragion of the papillomacular bundles within the optic nerves and tracts in deficiency amblyopia and the specific affection of the paraventricular regions in the Wernicke-Korsakoff syndrome. And clinically, the frequent occurrence of central pontine myelinolysis in a setting of severe metabolic derangement, particularly of the serum sodium, points in the same direction.


Control of the saccadic and smooth pursuit systems after cerebral hemidecortication.

Saccadic and smooth pursuit eye movements were analysed in 5 patients eight to twelve years after cerebral hemidecortication. Saccadic peak velocities were mildly reduced and saccadic durations were prolonged in both horizontal directions. Slowing of saccades may signify a loss of cerebral modulation of the discharge frequency and duration of brain-stem burst units or a less specific susceptibility of the hemidecorticate brain to fatigue. Symmetrical latencies of saccades to 20- and 40-degree target steps into the hemianopic and intact visual fields provided evidence for brain-stem processing of retinal signals from the hemianopic field. Latencies of saccades to 5-degree target steps into the blind hemifield were significantly longer than to 5-degree steps into the intact field. Disparity between saccadic latencies to parafoveal (5 degrees) and peripheral (20- and 40-degrees) targets indicated that such visual capacity in the hemianopic field is dependent upon target eccentricity.


Different types of disturbed motor control in gait of hemiparetic patients.

The pattern of muscle activation in walking was studied in a group of 26 hemiparetic patients. Electromyograms were taken with surface electrodes from 6 muscle groups of the paretic leg and analysed after rectification and time averaging. The sagittal rotations in hip, knee and ankle joint were determined with intermittent light photography. The muscle activation pattern of each patient was compared to that in healthy subjects as well as to the movements performed by the patient and to the normal movement pattern. The normal patterns of movement and muscle activation were assessed from compiled data from 10 healthy female volunteers and average values of angular displacements and amplitude of intergrated EMG were determined at each 5 per cent of the gait cycle. Change of muscle length was determined with a length recording transducer. Gait capacity varied highly in the group of patients studied and the movement pattern also varied markedly. Three types of abnormal muscle activation pattern were disclosed in the patients. In 9 patients, the calf muscles were prematurely activated in the stance phase, probably due to enhanced stretch reflexes (Type I). In another 9 patients, EMG activity was abolished or extremely low in 2 or more of the muscles examined (Type II). In 4 patients, there was a pathological coactivation of several or all of the muscles during part of the gait-cycle, thus disrupting the normal sequential shift of activity in antagonistic muscles (Type III). In the remaining 4 patients, the muscle activation pattern was more complex and no common pattern was discerned.


Peripheral auditory input to the midbrain limbic area and related structures.

The effect of peripherally applied auditory stimulation on unit activity in midbrain limbic and related regions was investigated in the freely behaving rat. Two pure tones (1 and 10 kHz) and a noise generated by the discharge of a solenoid were used as stimuli presented randomly with 1 min mean interval between presentations. Computer-aided analysis of unit activity indicated that (1) a high proportion of neurons in the limbic midbrain region give excitatory responses to the three stimuli; (2) a majority of the responses have short latencies, especially in the dorsal raphe nucleus; (3) frequency and physical properties of the stimuli seemed not crucial for eliciting responsiveness; (4) habituation to repeated presentation of stimuli was not characteristic of the excitatory responses in the limbic midbrain region. These results are discussed in the light of possible functions of this region.


Amino acids in rat neostriatum: alteration by kainic acid lesion.

Unilateral stereotaxic injection of 10 nmol of the glutamomimetic substance, kainic acid, into the rat striatum caused permanent, significant decreases in the levels of glutamate (40--50%), aspartate (35--40%), taurine (20--30%) and GABA (60--70%). There were initial, transient decreases in serine, glycine and alanine which returned to normal values within 16--32 days after injection. Glutamine levels were not altered in lesioned striatum. This coincided with a 55% increase in glutamine synthetase activity in the lesioned striatum compared either to the non-injected striatum or controls injected with saline. The high affinity uptake of choline by synaptosomal preparations of lesioned striatum was decreased by 70% compared to controls whereas that of glutamate/aspartate was either unchanged or somewhat on a per mg protein basis. This latter point may be illusory in that, because of widespread neuronal destruction, the total 'synaptosomal' protein obtained from the lesioned striata was only about 50% that from control tissue. The biochemical data are consistent with the histological and behavioral effects of kainic acid administration. The unchaning glutamine levels and increase in glutamine synthetase activity are consistent with the widespread gliosis and the lack of change in glutamate/aspartate high affinity uptake is consistent with a sparing of afferent terminals. The large decrease in glutamate and aspartate is consistent with hypotheses concerning the intraneuronal localization of a major pool of these amino acids, especially in GABAergic neurons. The decrease in taurine suggests that a portion of this amino acid in striatum is probably associated with neurons destroyed by kainic acid. The bulk of the taurine, however, is therefore associated either with glial cells or the afferents to the striatum.


Conditioning compensates the neglect due to unilateral 6-OHDA lesions of substantia nigra in rats.

The degree of the contralateral sensory neglect in rats with unilateral 6-OHDA lesions of substantia nigra was assessed by a conditioning procedure, employing lateralized CS. In the first experiment visual neglect (revealed by failure of the visually elicited placing reaction contralateral to the lesion) was shown to be accompanied by slower acquisition of a brightness discrimination task. The impairment was due to ipsilateral turning tendency rather then to visual deficit, however, since monocular relearning yielded equal savings with the ipsilateral and contralateral eyes. The second experiment showed that rats anesthetized with urethane reacted to noxious skin stimulation contralateral to the lesion with shorter-lasting EEG arousal than to ipsilateral stimulation of the same intensity. The electrophysiological asymmetry could be compensated by classical conditioning, i.e. by pairing habituated tactile stimuli with noxious tail shock. The conditioned arousal reaction could be elicited with the same efficiency from the neglected and intact body surface. It is concluded that neglect is due neither to a sensory nor to a motor failure, but that 6-OHDA lesions of substantia nigra in one hemisphere reduce the arousing efficiency of unconditioned stimuli and interfere with sensorimotor integrating mechanisms on the side contralateral to the lesion. Compensation of the neglect by conditioning indicates that the role of the nigrostriatal system can be partly substituted by other circuits.


The development of function of horizontal semicircular canal primary neurons in the rat.

The activity of primary horizontal semicircular canal neurons in newborn rats was compared to similar cells in adults. All animals were anesthetized with ether. Neurons were categorized as regular or irregular on the basis of their spontaneous activity. Horizontal semicircular canal neurons can respond to angular acceleration stimulation at birth. In newborn rats no regularly firing cells could be found, but the percentage of these cells and their average resting rate increased during growth. Neurons in newborn rats differ from those in the adult by having a lower average resting rate, a lower sensitivity to long-duration angular acceleration and taking longer to reach peak increase in firing during the stimulus. Sensitivity reaches adult values by about 4 days although the canal dimensions continue to increase until about 20 days.


Sununit structure of synaptosomal tubulin.

The subunit structure of rat brain synaptosomal tubulin was examined by high resolution two-dimensional gel fractionation. Whole brain cytoplasmic tubulin consists of two groups of alpha subunits (alpha1 and alpha2), and a minimum of two beta subunits (beta1 and beta2). Both alpha subunits consist of a major relatively acidic form and minor relatively basic forms. In contrast, tubulin purified from synaptoplasm contains an additional subunit, alpha3, which has the same isoelectric point but slightly faster electrophoretic mobility than alpha1 and alpha2. All synaptosomal alpha subunits are the relatively acidic forms and the minor basic forms are absent. The synaptosomal beta subunits have electrophoretic properties similar to the corresponding cytoplasmic forms. The alpha3 synaptosomal tubulin subunit has affinity for colchicine, has a tryptic peptide map similar to whole brain cytoplasmic alpha tubulin, and can be purified by a standard tubulin purification method.


Efferent projections of the parabigeminal nucleus in rats: a horseradish peroxidase (HRP) study.

The parabigeminal nucleus of the rat was made up of the dorsal, middle and ventral subgroups. When HRP was introduced into the superficial layer of the superior colliculus, labeled neurons were observed in the ipsilateral dorsal and ventral subgroups and in the contralateral middle subgroup. It was demonstrated that neurons of the dorsal and ventral subgroups sent fibers to the ipsilateral superior colliculus, and that those of the middle subgroup sent them to the anterior half of the contralateral colliculus, these fibers being arranged in 'anteroposterior' direction. HRP injections into the pretectal area, lateral geniculate body, suprachiasmatic nucleus and lateral hypothalamic area resulted in the labeling of neurons in the middle subgroup only when the supraoptic commissure and optic tract were injured by a pipette used in injections. Electrolytic lesions of the supraoptic commissure combined with collicular HRP injections resulted in no labeling of cells of the middle subgroup. From these findings, it could be concluded that neurons of the dorsal and ventral subgroups sent axons to the ipsilateral superior colliculus, and that fibers of neurons of the middle subgroup coursed through the supraoptic commissure to the contralateral superior colliculus.


Decentralization of the superior cervical ganglion in neonates impairs the development of the innervation of the iris. A quantitative ultrastructural study.

The superior cervical sympathetic ganglion was decentralized unilaterally by section of the preganglionic chain in 2- or 4-day-old rats. Twenty-one days post-operatively the dilator muscle of the iris was examined electron microscopically. Quantitative estimates demonstrated that there was a reduction both in the numbers of axon bundles and of individual axons in the iris innervated by the deafferented ganglion as compared with its fellow of the contralateral control side.


Protein and glycoprotein composition of synaptic junctions prepared from discrete synaptic regions and different species.

Synaptic junction (SJ) were isolated by subcellular fractionation from different areas of the steer brain and from the brains of different species (steer, rat, chicken and human) for the purpose of comparing their protein and glycoprotein composition. The synaptic junction fractions from different brain regions and species were of comparable morphological purity. Analysis of the polypeptide composition of isolated synaptic junction fractions via SDS polyacrylamide gel electrophoresis showed that the major polypeptides were represented in all junctional fractions independent of their source. Tubulin, actin, the major 52,000 Mr postsynaptic density protein and a group of proteins with a molecular weight of 200-250,000 Mr were all similarly represented. Most other components were also similar but quantitative differences were found for a few polypeptides. Interspecies differences were more prevalent than those between different brain areas of the same species. The protein compositions of different brain areas were similar even when an area consisting of primarily one neuronal type was compared to areas containing a mixture of neuronal types. However, two-dimensional gel electrophoresis revealed distinct (but usually minor) polypeptides in enriched quantities in one or more brain areas. Tryptic peptide maps were carried out on the major postsynaptic density protein of different species. These maps showed a high degree of conservation in this protein's primary structure among all species studied. The glycoproteins of isolated synaptic junctions which bind the plant lectin concanavalin A (Con A) were also examined. To identify individual Con A binding components, SJ fractions were solubilized and constituent glycoproteins were separated by SDS gel electrophoresis. Gels were then incubated in 125I-Con A. The glycoproteins which bound Con A in gels were few in number and were not the major Coomassie blue staining bands. The great majority of the Con A binding glycoproteins were similar between species and among brain areas of the same species.


Postnatal dendritic development in the rabbit visual cortex.

Golgi preparations of rabbit visual cortex aged 1-25 days, as well as similar tissues from adults, were examined for the growth of the dendritic arbor, and in particular the development of dendritic spines. The layer 5 pyramidal neurons and layer 4 stellate neuron were chosen as representatives of larger classes of neurons in the visual cortex. It was determined that the growth of the dendritic arbor, determined by counts of total number of dendritic and total dendritic length, is quite similar for pyramidal and stellate neurons. Dendritic spine development, however, is more rapid in pyramidal neurons than in stellate. This disparity in the rate of dendritic spine development is discussed in the light of physiologic studies on the development of receptive field properties in the rabbit visual cortex.


Effects of intranasal irrigation with mitotic inhibitors on olfactory behavior and biochemistry in mice.

Mice were trained to find buried food pellets or amyl acetate-scented sugar cubes. After training, the mice were intranasally irrigated with saline or one of several mitotic inhibitors--hydroxyurea (10 mM), ethidium bromide (2 mM), cytosine arabinoside (10 mM), or colchicine (0.25 mM). The behavioral testing was continued daily. By day 6 the colchicine animals had completely lost their ability to find sugar cubes. By day 8 all the ethidium bromide animals had lost their ability to find food pellets although 20% could still find the sugar cubes. The hydroxyurea animals exhibited a less dramatic and temporary deficit in olfactory capabilities which peaked near day 8. Cytosine arabinoside had no effect on olfactory-mediated behavior. The testing was terminated at 21 days. Two days later the animals were killed, olfactory tissue removed and assayed for thymidine incorporation into macromolecules, and the chemoreceptor marker, carnosine synthetase. All groups had a reduction in thymidine incorporation (33-25%). The ethidium bromide and colchicine groups exhibited a dramatic decrease in carnosine synthetase activity (ethidium bromide--olfactory bulb = 8% control, epithelium = 2%; colchicine--olfactory bulb = 10%, epithelium, 108%). These data are consistent with the notion that a functional mitotic process is necessary for continued olfactory capabilities and that in interruption in the normal mitotic process results in a decrease in olfactory chemoreceptor neurons and a loss in function.


Description of an indolaminergic cell component in the cat locus coeruleus: a fluorescence histochemical and radioautographic study.

Using Falck-Hillarp fluorescence histochemical and radioautographic techniques, it has been found that, in addition to the well-known catecholaminergic cells, the locus coeruleus (LC) of the cat contains a sizeable component of indolaminergic neurons. Indolaminergic cell bodies occur in all subdivisions of the LC complex. They are most numerous in the LC proper and subcoeruleus area, but are also present in the medial and lateral parabrachial, and Kölliker-Fuse nuclei. In all, the indolaminergic cells are estimated to make up 7-10% of the monoaminergic neuronal population of the LC complex. With the exception of the Kölliker-Fuse nucleus, where somewhat larger cells occur, the indolaminergic cell bodies in different parts of the LC complex share a common fluorescence histochemical appearance. They display round to fusiform shapes and measure 30 x 18 micron on the average, which makes them cytoarchitectonically similar to the small type of noradrenergic cells in the LC. The formaldehyde-induced fluorescence of the indolaminergic cells in the LC complex was analyzed microspectrofluorometrically and the recorded excitation and emission spectra (maxima at 370 and 530 nm, respectively) were found to be identical with those recorded from midline raphe neurons. No evidence of noradrenaline content was found in the indolaminergic cells of the LC. Radioautographic experiments after intratissular injections of tritiated serotonin showed that the indolaminergic cells of the LC complex possess uptake mechanisms for serotonin. Taken together these results provide strong evidence for serotonin being the transmitter of the indolaminergic neurons discovered in the LC of the cat.


Central locomotor programming in the rabbit.

In decorticate, unanaesthetized and curarized rabbit preparations, with both hindlimbs deafferented, locomotor-like discharges were recorded from nerves to flexors and extensors and their time patterns were compared. The bursts of rhythmic activities recorded from nerves to several flexor muscles acting at either joint were shown to be synchronous, with no differences in their time of onset. The same was true for the extensors. Nerves to bifunctional muscles (biceps posterior, semi-tendinosus and tenuissimus) acting on two consecutive joints (knee flexors, hip extensors) could display two consecutive bursts in each locomotor cycle, one being pure flexor and the other an extensor discharge. It is shown here that this functional bivalence is programmed centrally and can be modulated, i.e. the relative importance of the flexor and the extensor bursts can be changed in a predictable way through afferent (proprioceptive or cutaneous) influences, or through activation of the descending monoaminergic pathways. In extreme cases, complete functional reversal was observed in these bifunctional muscle nerves.


Neurochemical and morphological consequences of axon terminal degeneration in cerebellar deep nuclei of mice with inherited Purkinje cell degeneration.

The concentrations of free amino acids and the activities of transmitter-related enzymes, glutamic acid decarboxylase (GAD), choline acetylase (ChAC) and GABA-transaminase (GABA-t) were measured in cerebellar cortex and deep cerebellar nuclei from the mouse mutant Purkinje cell degeneration (pcd) at various times before and after Purkinje cell loss. Axosomatic synapses on target cells in pcd deep nuclei were quantified by electron microscopy during and after degeneration. The concentration of GABA (nmol/mg wet weight), the Purkinje cell transmitter, was normal in pcd cerebellar cortex and deep nuclei before onset of Purkinje cell degeneration on postnatal day 15. Just after the major period of Purkinje cell loss in cerebellar cortex, GABA concentration was unchanged in the cortical layers but fell to 50% of normal values in the deep nuclei of pcd animals killed either by decapitation or by microwave irradiation. No other measured free amino acid decreased. There were no long-term increases following Purkinje cell degeneration in the concentration of any transmitter amino acids or related enzymes, GAD, ChAC or GABA-t, and thus no indication of axonal sprouting reactions. Progressive losses occurred in wet weight and protein and in activity of GABA-t in both the cerebellar cortex and the deep nuclei of pcd animals. Electron microscopic analysis indicated that Purkinje cell axon terminals contact 30% or more of the somatic surface of principal neurons of the lateral nucleus of the normal cerebellum, but only about 2% of the corresponding sites in the pcd cerebellum. Glial leaflets, rather than other synaptic terminals take their place. Axon terminals may degenerate earlier than Purkinje somata in the pcd disease.


Neuroleptic and dopamine receptors: autoradiographic localization of [3H]spiperone in rat brain.

Rats were administered [3H]spiperone (SP: spiroperidol) by tail vein injection and 2 h later the brain was processed for light microscopic autoradiography. High densities of autoradiographic grains were found in all areas known to have a dopaminergic innervation, including the olfactory tubercles, nucleus accumbens, nucleus caudate-putamen, lateral septum, zona incerta, nucleus subthalamicus, arcuate nucleus, nucleus of the central amygdala, areas in the ventral tegmentum and the claustrum. There were also increased autoradiographic grain densities in other areas such as the midbrain and the frontal cortex indicating that binding occurred to other neurotransmitter receptors besides dopamine receptors. These studies delineate with a high resolution at an anatomical level the major binding sites for neuroleptic drugs in the forebrain. They suggest which areas of the brain are the most involved in neuroleptic drug action and they add further evidence that important regions are those receiving a dense dopaminergic innervation.


Dissociation of spontaneous and mating induced ovulation by frontal hypothalamic deafferentations in the rat.

Different types of anterior hypothalamic deafferentations have been used to investigate the nervous pathways involved in spontaneous and mating-induced ovulation in the rat. Knife cuts which circumscribed the suprachiasmatic nuclei on all but their ventral surface and either their rostral or caudal poles prevented spontaneous ovulation, but the rats were sexually receptive (copulation plugs and sperm in the smear), and mating induced ovulation. Similar types of cut extended dorsally so as to sever the continuity between the preoptic area and the mediobasal hypothalamus also prevented spontaneous ovulation, and although these rats were also receptive, mating did not induce ovulation. Two possible explanations are considered: either (i) that difference between the effects of the two types of cut is a direct function of the differing proportions of gonadotrophic hormone-containing axons severed, or (ii) cuts in the region of the suprachiasmatic nuclei specifically impair a mechanism for the maintenance of diurnal rhythms, to which the abnormality in gonadotrophin control is secondary.


Activity of dentate granule cells during learning: differentiation of perforant path input.

Experiments were conducted which extended previous findings regarding the activity of the perforant path and its synaptic relationship to the granule cells of the dentate gyrus during conditioning. A differential conditioning paradigm was utilized in which rats were trained to respond to one of two different tone frequencies. Results demonstrated that (1) tone elicited averaged evoked potentials recorded from the perforant path terminal zone in the outer molecular layer of the dentate gyrus were similar for both the positive and negative tones regardless of frequency or reversal of the reinforcement condition; (2) extracellular unit discharge patterns of dentate granule cells were differentially associated with the positive and negative tones as demonstrated by post stimulus histograms (PSHs); (3) this differential pattern of unit discharges could be reversed following establishment of criterion differential behavioral responding after reversal of the reinforcement contingency between the two tone stimuli and (4) the differential unit discharge pattern was not present when behavioral responding was not differentiated to the two tone stimuli, e.g., immediately following reversal of the reinforcement contingency. The results are discussed within the context of other anatomically defined functional circuits within the hippocampus which could serve as the basis for alteration of the non differentiated excitatory perforant path input into a differential dentate granule cell discharge pattern for behaviorally relevant sensory stimuli.


Effect of TEA on light emission from aequorin-injected aplysia central neurons.

Aplysia central neurons were injected with the calcium-sensitive photoprotein aequorin and stimulated with trains of identical depolarizing voltage-clamp pulses. The light emissions grew and the outward currents declined in successive pulses. Tetraethylammonium (TEA) enhanced the light emissions to single depolarizing pulses and suppressed the outward current. The remaining net inward current is carried primarily by calcium ions and does not facilitate. The aequorin emissions were larger at all amplitudes of depolarizing pulses that elicited emissions, and the facilitation of emissions in a train of pulses was reduced. The effect of TEA on outward current was nearly maximal when sodium ions were partially replaced with 0.1 M TEA, while the aequorin emissions were further enhanced by increasing the TEA concentration to 0.459 M. TEA enhanced the aequorin emissions at all voltages. These observations suggest that the action of TEA on aequorin emissions is not strictly a consequence of its better known outward current blocking action. The effects of TEA could be partly due to the lowered sodium concentration of these solutions. Replacement of sodium by Tris, sucrose or mannose, however, all produced no enhancement of emissions. Tetramethylammonium (TMA) replacement of sodium had effects similar to those of TEA. Thus TEA and TMA appear to have a specific effect. Part of the enhancement of light emissions by TEA is due to the removal of a series resistance error in the voltage clamp, and this may also account partly for the reduced facilitation of aequorin emissions in TEA. The remainder of the action of TEA on aequorin emissions evidently reflects a specific but previously unrecognized action on the cellular metabolism of calcium ions or on the voltage-dependent calcium channels.


The toxic effects of saline drinking water on young turkey poults.

Turkey poults were offered ad libitum a diet containing 2.5 g salt/kg and tap water containing, 0, 90 or 105 mn NaCl to drink from 1 to 12 d of age. 2. High mortality with oedbema and ascites occurred mainly from 5 to 8 d in poults given the saline solutions. Mortality seemed to be related to salt and water intakes. 3. Plasma and body composition indicated abnormal retention of salt and water in poults younger than 12 d of age offered hypotonic saline. 4. In a second experiment using the same diet poults were offered hypotonic saline (105 mn NaCl in tap water) from 5, 9 or 13 d of age. High mortality with oedema and ascites was only observed when saline was given from 5 or 9 d. 5. The results suggest that from about 5 to 10 d of age there is a relative functional renal insufficiency which causes susceptibility to the toxic effects of saline water.


Reproductive performance of turkey hens as influenced by hormone implants.

Large White turkey hens were implanted with silicone capsules containing either cholesterol (control), progesterone, 17-beta oestradiol (E2), oestrone (E1) or a combination of progesterone and E2. Egg production and fertility were measured. Blood samples were collected weekly for measurement of progesterone by radioimmunoassay. 2. Progesterone alone caused a several-fold increase in serum progesterone concentrations initially and significantly depressed egg production. Simultaneous administration of E2 significantly decreased progesterone concentration, but did not ameliorate the decrease in egg production. 3. There were significant positive correlations between serum progesterone concentration and egg production in control birds and those receiving E2 and E1. There was no significant correlation between progesterone concentration and fertility. 4. The results indicated that, within the physiological range, higher progesterone concentrations are associated with higher egg production. However, maintenance of constant progesterone concentrations throughout the reproductive season by means of implants was not achieved. Implants of E1 and E2 did not affect fecundity.


The tryptophan requirement of broiler chicks.

The "available" tryptophan requirements of male and female broiler chicks were determined at 7-d intervals from 0 to 56 d, using a diet-dilution technique. Availability of tryptophan in the diets was estimated by growth assay with chicks. 2. The tryptophan requirements were 2.4 (males) and 2.2 g/kg of diet (female) from 0-7 d, and 1.7 g/kg (males and females) from 7-35 and 35-56 d. The absolute requirement of the chick for tryptophan increased with age and was significantly different for male and female birds. 3. A highly significantly predictive equation relating tryptophan requirement to mean body weight and gain was established.


Isolation and identification of avian mycoplasmas in Singapore.

Two hundred and forty batches of chickens with chronic respiratory syndrome were tested for mycoplasmas. One hundred and five batches (43.8%) were found to have mycoplasmosis. A total of 110 isolates of mycoplasma was cultured, of which nine isolates were identified as Mycoplasma gallisepticum, 48 avian sero-group D, 45 M. gallinarum, one M. iners and seven unclassified. 2. Identification of the mycoplasmas isolated was carried out by biochemical and serological tests (disc growth inhibition and agar gel diffusion tests). A modified agar gel diffusion test using solubilised antigens with sodium deoxycholate-glucose solution was developed for serotying of mycoplasmas.


Growth hormone and prolactin secretion in growing domestic fowl: influence of sex and breed.

Plasma growth hormone (GH) and prolactin concentrations were measured between 1 and 24 weeks of age in both sexes of a laying strain of chickens and from 1 to 9 weeks of age in broiler cockerels. 2. GH and prolactin concentrations were highest in young birds and higher in males than in females. 3. In both sexes GH and prolactin concentrations were correlated inversely with age and body weight and positively with relative weight gain. 4. Differences in growth rate between broilers and layers were related to differences in blood GH concentrations. 5. Water deprivation for periods of 6, 12, 18 or 24 h increases plasma prolactin markedly but did not affect GH secretion significantly.


Stereospecific analysis of triacylglycerols via racemic phosphatidylcholines and phospholipase C.

A method of simultaneous determination of stereospecific distribution and molecular association of acyl groups in triacylglycerols has been developed. The analysis is based on a random generation of rac-1,2-diacylglycerols by Grignard degradation, synthesis of rac-phosphatidylcholines, and a stereospecific stepwise release of 1,2-sn- and 2,3-sn-diacylglycerols by phospholipase C. The exact structure of the original triacylglycerols is reconstituted on the basis of complete analysis of the molecular species of the 1,2-sn- and 2,3-sn-diacylglycerols as the tertiary-butyldimethylsilyl ethers by gas chromatography with mass spectrometry. The validity of the method is demonstrated by analyses of synthetic triacylglycerols of known structure. A practical application is illustrated by determination of the fatty acid distribution in lard.


Purification and some properties of five endo-1,4-beta-D-xylanases and a beta-D-xylosidase produced by a strain of Aspergillus niger.

Five different xylanases and a beta-D-xylosidase in the culture medium of Aspergillus niger have been purified to homogeneity from 13- to 52-fold by a procedure of gel and hydroxylapatite chromatography. The strain was isolated from soil of the African equatorial forest. Gel chromatography of the purified enzymes indicated that three of the xylanases have molecular weights of 31,000 and the other two xylanases have molecular weights of 50,000. beta-D-Xylosidase has a molecular weight of 78,000. The pH curves of the xylanases were quite diverse and showed pH optima ranging from 4.0 to 6.5. Characteristic action patterns were obtained for each of the purified xylanases by gel chromatography of the xylan digests on Bio-Gel P-2. The enzymes degraded arabinoxylan by an endomechanism, producing L-arabinose, D-xylose, xylobiose, and a mixture of branched arabinose-xylose and D-xylose oligosaccharides. All xylanases seemed to be capable of liberating L-arabinose from either arabinoxylan or the arabinose-xylose oligosaccharides. Branched arabinose-containing D-xylose oligosaccharides were slowly hydrolyzed, so that these sugars accumulate in the digest. Two xylanases showed relatively broad substrate specificity and were able to degrade also crystalline cellulose. beta-D-Xylosidase showed optimal activity at pH 6.7 to 7.0 and at 42 degrees C. The Km for o-nitrophenyl-beta-D-xylopyranoside was 0.22 mM and xylotriose was hydrolyzed more rapidly than xylobiose.


The localization of honey bee thorax trehalase.

Differential and sucrose gradient centrifugation of honey bee thoraces, disrupted by gentle methods and using mannitol-triethanolamine-EDTA buffer at pH 6.5, showed that in the honey bee thorax 92-94.8% of the trehalase was mitochondrial. Since only 92-95% of the cytochrome c oxidase, a known mitochondrial enzyme, was found in the mitochondrial fraction by these methods, it was concluded that honey bee trehalase is totally mitochondrial. Significant amounts of 'microsomal' or 'soluble' trehalase were formed only by harsh methods of thorax disruption and similar 'microsomal' or 'soluble' trehalases were also formed by harsh treatment of purified whole mitochondria. They thus seem to be artifacts of the isolation procedure. Studies (using marker enzymes) with purified intact mitochondria which were dispersed by various chemical, enzymatic, and physical methods showed that the trehalase in the mitochondria was membrane bound and that it was bound to either the outside of the inner membrane or to one of the sides of the outer membrane.


Changes in the net charge and subunit properties of ribulose bisphosphate carboxylase--oxygenase during cold hardening of Puma rye.

Ribulose bisphosphate carboxylase--oxygenase (RUBPCase) from leaves of cold-hardened and unhardened Puma rye was purified by gel filtration and ion exchange chromatography. The specific activity of the hardened form was twice that of the unhardened form. A difference in charge between the two forms of this  enzyme was proved by gel electrofocussing. The estimated isoelectric point (pI) values were 6.4 and 6.3 for the enzyme from the hardened and unhardened source respectively. The large subunit (55,000 molecular weight) of the enzyme from only the unhardened source formed at apparent dimer during sodium dodecyl sulfate (SDS) gel electrophoresis. At pH 6,8 it was also the source of an anomalous polypeptide with an apparent molecular weight of 47,000. This anomalous polypeptide appeared in both hardened and unhardened preparations after irreversible inactivation of RUBPCase activity by NaCl. It also appeared after preparation of the purified enzymes for SDS--PAGE in the absence of beta-mercaptoethanol, but this was reversible. The enzyme from the hardened source was less affected in the absence of reducing agent. Structural evidence was obtained for the previously reported cold hardening of the enzyme against freeze inactivation. A freeze-thaw cycle applied to the enzyme in vitro caused some polymerization of the large subunit and its anomalous polypeptide, in the absence of reducing agent, especially in the unhardened case. This increased with repeated cycles until the fifth cycle when the large subunit monomer and its satellite were abolished only in preparations from the unhardened source. These data indicate that the large subunit is a probable site of change that occurred in this enzyme during cold hardening.


Purification of dihydropterin reductase using immobilized Cibacron Blue.

Chromatography on columns of immobilized Cibacron Blue (Blue Dextran--agarose) can be used as a major step in the purification of quinonoid dihydropterin reductase. The reductase has been isolated from fractions of beef kidney by selective binding to the immobilized Cibacron in the presence of tetrahydropterin. The binding of the reductase to Blue Dextran and its specific elution from columns of Blue Dextran--agarose indicate that the reductase possesses the dinucleotide (NAD+) binding domain. The results of kinetic experiments give validity to both our affinity chromatography of the reductase and to an ordered mechanism for the formation of tetrahydropterin. Chromatography on Blue Dextran--agarose has been used to show that folate or amethopterin can compete with Cibacron Blue for the dinucleotide domain of the reductase. The p-aminobenzoyl-glutamate moiety of the folates competes with Cibacron Blue for the NADH site of the reductase. A stable binary complex of dihydropterin reductase with NADH has been detected by gel electrophoresis.


Distribution of the multiple molecular forms of glucose-6-phosphate dehydrogenase in different physiological states.

The distribution of the multiple molecular forms of rat liver and mammary gland glucose-6-phosphate dehydrogenase was determined by electrophoresis on 5% polyacrylamide gels. In both of these organs, changes in the distribution of enzyme activity among the several forms was slight even when approximately 20- to 40-fold changes in enzyme specific activity were achieved by fasting-refeeding experiments (for liver) or during pregnancy and lactation (for mammary gland). It was concluded that the induction of glucose-6-phosphate dehydrogenase in these two organs occurs without any major redistribution among the multiple molecular forms of this enzyme.


Phospholipids of the differentiating bacterium Caulobacter crescentus.

The phospholipid composition of the stalked and swarmer cell types of the differentiating, Gram-negative bacterium Caulobacter crescentus was determined. The phospholipid composition of the stalked cell type was 86.5% phosphatidylglycerol, 10.4% lysylphosphatidylglycerol, and 3.0% cardiolipin; that of the swarmer cell type was 84.1, 11.4, and 4.4% respectively. Phosphatidylethanolamine, which is a major phospholipid component of most Gram-negative bacteria, was totally absent.


Effects of ribosomal wash factors and spermidine on endogenous and exogenous mRNA stimulated protein synthesis in the wheat germ cell-free system.

Differential effects of Mg2+, spermidine, and reticulocyte ribosomal wash factors on the translation of endogenous, myeloma, and globin mRNA's have been observed in studies with the wheat germ cell-free protein synthesizing system. Spermidine stimulated globin mRNA translation but not the translation of endogenous wheat germ messages, and the polyamine actually inhibited the translation of myeloma mRNA. Ribosomal wash factors, on the other hand, stimulated endogenous and myeloma mRNA dependent protein synthesis in an Mg2+-dependent fashion but inhibited globin mRNA translation. The combination of ribosomal wash factors and spermidine was either stimulatory or inhibitory depending on the Mg2+ concentration and the message. It was further observed that translation of exogenous myeloma mRNA proceeded for only 60 min at 25 degrees C under all conditions tested in this study, while translation of endogenous wheat germ messages continued for longer periods of time. No differential effects of spermidine on the synthesis of high molecular weight myeloma proteins were observed.


Eccentric serous choroidopathy: a case report.

A patient presented with a serous detachment of the retina outside the macular region in one eye and three years later a similar detachment in the fellow eye. The clinical findings were otherwise identical to those seen in patients with idiopathic central serous choroidopathy. Idiopathic eccentric serous choroidopathy is probably a variant of idiopathic central serous choroidopathy. Its occurrence may be implications in understanding the pathogenesis of the latter condition.


Congenital abnormalities of lacrimal drainage: management of difficult cases.

Various congenital anomalies of the lacrimal drainage system are described against the background of normal development and their effective management is outlined.


The surgical management of macular pucker.

Contractions of collagenous membranes in the posterior cortical vitreous may produce macular pucker and loss of central vision. It is possible to separate these membranes from the retina, and if one succeeds in doing so there is reasonable improvement in central visison. Between December 1976 and September 1978, six patients with macular pucker were operated upon. The clinical details and results are described. The technique used was that of Machemer with the modifications demanded by use of the Klöti vitreous stipper. Several different instruments were used for dissection, the most useful being the joint knife used in stapedectomy.


Does the number of cells in the cornea decrease with age? A biochemical study.

We used biochemical techniques to investigate whether the cornea becomes more acellular with age. Guinea pigs of different body weights (age) were killed. From each cornea, a central full-thickness button (4 mm in diameter) was punched out. The DNA content of the corneal buttons was determined. Using spleen cells, the DNA content per diploid cell of guinea pig was also estimated. It was found that as the body weights of the animals increased, the amount of DNA per corneal disc decreased. This indicated that as the animal grows older the total cellular content of the cornea is reduced.


Epithelial downgrowth following cataract extraction.

This case of epithelial downgrowth following cataract extraction shows the typical sequence of a noneventful cataract extraction with satisfactory recovery but after a time, the appearance of conjunctival injection, iritis and attacks of elevated ocular pressure. A minimal membrane on the posterior surface of the cornea could be seen but the diagnosis rested on the sequence of events and was confirmed by the pathologic investigation. The apithelial cells grow freely on the iris, but extend onto the cornea and posteriorly apparently without hindrance. The epithelial cells form a basement membrane next to the iris, much as they do on the surface of the cornea next to Bowman's membrane. The source of the cells in this case was not identified; they presumably came from conjunctiva although no track through the sclera was found and the cells themselves did not show goblet cells.


Malignant melanoma of the conjunctiva after 11 years.

A 76-year-old lady presented with a conjunctival malignant melanoma, which had been incompletely excised 10 years earlier. After rapid and massive growth of the tumor, which was later removed along with the globe, there was no evidence of local or systemic recurrence during 22 months of observation until the patient died of unknown causes. Pathological examination of the ocular tissues obtained at operation showed intraocular extension of tumor into Schlemm's canal and the presence of tumor cells in vascular channels in the limbal region.


The nasal step in normal and glaucomatous visual fields.

We used an original method of kinetic and static analysis to examine the nasal visual field. When the nasal step is less than 4 degrees wide and its depth is less than 0.5 log units it may be merely a physiological sign of the anatomic and functional asymmetry of the retina. Sometimes it is an artifact. The nasal step can also be a glaucomatous defect. In this case it is often an early sign and it is wider than 4 degrees and its depth is greater than 0.5 log units. Because of its typical shape and invariable location it is easy to discover by kinetic perimetry and easy to check by static perimetry. If it is an early glaucomatous defect, it can be reversed. In practice the nasal step is an early and characteristic glaucomatous field defect like the isolated scotomas in the Bjerrum area, and it is easily detected and can be used as a sensitive marker in the follow up of glaucomatous damage.


Total transient visual loss and orbital foreign bodies.

Two children recovered vision after penetrating injury of the orbit by wood had produced sudden blindness. Absent light perception demands urgent action as early visual loss does not necessarily indicate a poor prognosis. The depth and direction of penetration and size of wooden fragments is difficult to assess clinically and radiologically. Immediate and delayed neurological complications should always be anticipated. Removal of all fragments of wood is of paramount importance in restoring visual acuity. Prolonged visual loss with symptoms and signs of retained foreign body demands vigorous management.


Unit activity in the superior colliculus of the cat following passive eye movements.

Unit response in the superior colliculus and underlying structures has been examined in the choralose-anaesthetized cat following passive movement of an occluded eye. One group of units was sensitive to small saccadic movements, responded regardless of the initial postion of the eye, and in most instances responded to movements in opposit directions. A second numerically smaller group also responded when they eye was moved at saccadic velocity but only when the eye passed a fixed point. Such units with fixed positional thresholds were found following movements in both nasal and temporal directions as well as to both upward and downward movement. Both types of unit response were found after transection of the optic nerve and were also recorded when individual extraocular muscles were subjected to controlled stretch. It is assumed that most unit activity seen after passive movement of the occluded eye is due to activity in extraocular muscle receptors. In the deep layers of the superior colliculus responses to small eye movements were found to be due to the activation of very low threshold receptors sensitive to vibration in the facial area.


Receptors for bradykinin and kallidin.

In order to establish if bradykinin (BK) and Lys-bradykinin (Lys-BK), alias kallidin, act on the same or on different receptors, experiments were performed on strips of cat terminal ileum and of rabbit aorta. The first preparation contains receptor B2 and the second has the newly identified receptor B1. The criterion used for establishing the identity of receptors for BK and Lys-BK in the cat ileum (receptor B2) was desensitization, while for the rabbit aorta (receptor B1) we measured the apparent affinity (pA2 value) of a competitive and specific inhibitor of BK, [Leu-OMe3,des-Arg9]-BK. Since cat ileum desensitized with BK or Lys-BK shows a significant decrease or a complete disappearance of the response to the other agent, while maintaining full sensitivity for histamine, and since the pA2 values of [Leu-OMe8,des-Arg9]-BK against BK and Lys-BK are identical in the rabbit aorta, we conclude that the two kinins act on the same types of receptors.


Blood dopamine beta-hydroxylase activity and noradrenaline levels in the developing white rat.

Dopamine beta-hydroxylase (DBH) (3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating) (EC 1.14.17.1) activity in serum of blood obtained by decapitation of white rats at 19, 20, and 21 days in utero, immediately after birth, and postnatally to 70 days, was measured. Noradrenaline (NA) and DBH in plasma from undisturbed, cannulated, postweaning rats were also assayed. During the last few days in utero and the first 2 postnatal days serum DBH activity tripled and then remained elevated during the suckling period. Upon weaning, serum DBH activity declined at first precipitously and then more slowly, until the adult level was reached around 70 days of age. This postweaning decrease in DBH activity was also observed with the cannulated animals. In contrast, plasma NA levels remained low and constant throughout the postweaning period. In suckling rats treated with 6-hydroxydopamine from 2 to 12 days of age, serum DBH activity decreased to less than half its initial value by day 8. It is suggested that the observed changes in serum DBH activity in fetal and postnatal rats reflect ontogenetic changes in sympathetic nerve terminals and that they are probably not correlated with release of NA.


The time course of brain and blood catecholamines, catechol O-methyltransferase, and amino acids in rats convulsed by oxygen at high pressure.

The time course of changes in blood and brain catecholamines, catechol O-methyltransferase (COMT), ammonia, and amino acids leading to convulsion by high pressure oxygen breathing (OHP) in rats has been investigated. Brain catecholamines were suppressed by OHP. They changed in phase with brain COMT concentration and consequently were not due to the action of this degrading enzyme. Convulsive actions seem not to be influenced by brain catecholamine concentration. Blood adrenaline concentrations are, however, significantly elevated both prior to and during convulsions. In both brain and blood, ammonia concentration increases, glutamate decreases, and glutamine-aspargine increases. It is proposed that the efficacy of the glutamate-glutamine ammonia buffering system in blood and brain is important in the prevention of the onset of convulsions but that when brain gamma-aminobutyric acid is depressed to critical levels, convulsions result.


[The effect of estradiol benzoate on liver function, cholesterol metabolism and bile acids in the quail].

Immature female quails were treated for 6 days with estradiol benzoate at daily 0.01-, 0.02-, 0.01-, and 1-mg dosages. At the end of treatment, bile outflow, biliary cholesterol (CST), and bile acid (BA) secretory rates and liver, bile, and serum CST and BA levels were determined. Some quails were used to measure the ratio (R) of the rates of intravenously injected [2-14C]acetate radioactivity incorporation in cholic (C) and chenodeoxycholic (CDC) acids excreted in bile. The oestrogenic treatments at doses greater than 0.01 mg/day caused a marked disturbance in hepatic function and in CST and BA metabolism: they induced an increase in relative liver weight, liver CST stores, serum CST, C, CDC, and SGOT levels and in choleresis (respectively up to 56, 57, 650, 6000, 700, 42, and 235% increase at the daily 0.1-mg dosage) and they decreased bile total BA and CDC levels, bile and serum CDC to C level ratios, and R ratio (by 71, 82, 69, 84, and 58%, respectively). An increase in the bile salts independent fraction of bile was responsible for hypercholeresis, whether alone at low dosage or in conjunction with other factors at higher dosage. These results are compared with those obtained in mammals, particularly in the rat.


The effects of muscarinic receptor blockers on the turnover rate of acetylcholine in various regions of the rat brain.

The actions of antimuscarinic agents (benztropine, trihexyphenidyl, and scopolamine) on the dynamics of acetylcholine (ACh) in central cholinergic neurons were examined in various rat brain areas. It was found that the pattern of changes in ACh turnover (TRACh) elicited by these drugs exhibited marked regional variations. After administration of the anticholinergic drugs, the TRACh in hippocampus and thalamus was increased, in cortex it was decreased, and in striatum it was unchanged. ACh concentration in the cortex and striatum was decreased while in hippocampus and thalamus ACh levels were unaltered. Further analysis of the cholinergic septo-hippocampal pathway using lesions of the fimbria-fornix and local drug injections into the septum argue against an in vivo action of these drugs on presynaptic or cell body muscarinic autoreceptors. Moreover, the data suggest that muscarinic receptor blockers cause an increased TRACh only in those areas where a feedback loop is operative, possibly by inhibiting a neuronal feedback loop involving at least one noncholinergic interneuron.


Serum MSH levels and pituitary MSH content: their fluctuation during pregnancy in the rat.

MSH was measured by a biological assay in the pituitary and serum of the rat during the whole term of pregnancy. The peptide showed changes in early pregnancy in serum, during the middle of pregnancy values of serum MSH became negative, and in late pregnancy it was possible to find high values during days 18 and 19 before delivery. Comparison between the amount of pituitary MSH and that in serum seems to show that between days 10 and 15 there is practically no, or just a litte, MSH synthesis, since the MSH values in serum are negative although the content of pituitary MSH is also low. A relation between the results found by other authors and that found by us was analyzed.


Pharmacological evidence for catecholamine-independent contractile effects of X-537A on the isolated working rat heart preparation.

The ionophore X-537A increased heart rate and contractility of the isolated, working rat heart preparation. The increased heart rate appeared to be caused solely by release of catecholamines as the response was completely eliminated by reserpine pretreatment or addition of propranolol to the perfusate. The inotropic response, however, had an apparent catecholamine-independent component as neither propranolol, nor propranol in combination with phentolamine, completely eliminated the inotropic response to X-537A. On the other hand, reserpine pretreatment did abolish the inotropic effect of the ionophore but this action appeared to be a nonspecific one as the responses to norepinephrine and to CaCl2 were substantially diminished.


Interaction of antidepressants with clonidine on rat brain total 3-methoxy-4-hydroxyphenylglycol.

The effects of some antidepressants on brain total 3-methoxy-4-hydroxyphenylglycol (MHPG) were studied in the rat. Desipramine decreased and mianserine increased the brain total MHPG concentration while the other antidepressants had no effect. They were also the only antidepressants that attenuated the lowering action of clonidine on brain total MHPG, but possibly through different mechanisms. Two tertiary amine tricyclic antidepressants, amitriptyline and imipramine, appeared to enhance the lowering action of clonidine on brain total MHPG. The results suggest that antidepressants are heterogeneous in their action on brain noradrenergic mechanisms in the rat.


Norepinephrine concentration in kidneys of normotensive Wistar-Kyoto and spontaneously hypertensive rats.

Renal norepinephrine (NE) concentration was measured in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) at 7, 9, 11, and 13 weeks of age. Although the weight of kidneys was similar in the two strains of rats, renal NE concentration was significantly lower in SHR at all ages (147 +/- 9 to 175 +/- 13 ng/g for SHR, and 216 +/- 8 to 262 +/- 17 ng/g for WKY rats). The difference in renal NE concentration during this time of rapidly increasing arterial pressure in the SHR suggests that renal NE may in some way be related to the development of hypertension.


Isolation of a non-tumor-inducing mutant of the Ti plasmid of Agrobacterium tumefaciens strain B6.

A nonpathogenic mutant of Agrobacterium tumefaciens strain B6 was isolated and its properties compared with the parental strain in an effort to localize the mutation. Both B6 and its mutant (B6-95) had similar colony color and morphology, were ketolactose positive, utilized octopine, and contained plasmid DNA. Kinetic analysis of DNA reannealing showed that total DNA homology and plasmid DNA homology between B6 and B6-95 was at least 90%. The length of both plasmids was found to be 58 micrometer. Plasmid DNA from both B6 and the mutant was digested with endonucleases and the fragments separated by agarose gel electrophoresis. In all cases the pattern for B6 was identical with that of B6(-95). The Ti plasmid from B6 and the mutant was transferred to an avirulent, plasmidless strain of A. tumefaciens by in vitro conjugation and transformation. All of the B6 transconjugants and transformants were virulent, whereas all of the mutant transconjugants and transformants were avirulent. Electrophoretic patterns of endonuclease-digested plasmid DNA from transformants were identical to those of plasmid DNA from B6. Therefore, we conclude that the virulence mutation lies on the Ti plasmid.


Phenotypic reversion of nitrogenase in pleiotropic mutants of Rhizobium meliloti.

In two out of three pleiotropic mutants of Rhizobium meliloti, defective in nitrate reductase induced by amino acid utilization in vegetative bacteria and in symbiotic nitrogen fixation, nitrogenase activity could be restored completely by purines and partially by the amino acids L-glutamate, L-aspartate, L-glutamine, and L-asparagine. The compounds restoring effectiveness in nitrogen fixation did not restore nitrate reductase activity in vegetative bacteria. The restoration of effectiveness supports our earlier conclusion that the mutation is not in the structural gene for a suggested common subunit of nitrogenase and nitrate reductase.


Plasmid-determined 2-hydroxypyridine utilization by Arthrobacter crystallopoietes.

Arthrobacter crystallopoietes has the ability to utilize 2-hydroxypyridine (2-HP) as a source of carbon and nitrogen and forms a blue extracellular pigment when grown in the presence of 2-HP. Ultracentrifugal analyses of pigment producing (Pig+) and pigment nonproducing (Pig-) strains of A. crystallopoietes revealed the presence of plasmid material in both strains. Recovery of plasmid DNA from Pig+ strains is two or three times greater than from Pig- strains. The molecular weight of plasmid DNA recovered from Pig+ strains (62 Mdaltons) is slightly higher than the molecular weight of plasmid DNA from Pig- strains. Consistent with the characterization of plasmid DNA from the two strains is that Pig+ strains contain a 63-Mdalton plasmid encoding 2-HP utilization as well as a cryptic plasmid of very nearly equal molecular weight. Pig- strains contain only the cryptic plasmid.


Nitrogen fixation by Rhizobium sp. 32H1. A morphological and ultrastructural comparison of asymbiotic and symbiotic nitrogen-fixing forms.

The induction of nitrogenase (C2H2) activity in asymbiotically cultured Rhizobium sp. 32H1 was found to be associated with morphological changes in the cells which were more pronounced than those seen in bacteroids. Polyphosphate granules were found in both bacteroids and cultured cells, but poly-beta-hydroxybutyrate vesicles were almost absent in bacteroids but were present in cultured cells. Freeze-etching techniques revealed no differences between the asymbiotically cultured nitrogen-fixing forms and bacteroids in that both the cell wall and cytoplasmic membrane cleavage planes were normal for gram-negative bacteria.


The effects of temperature, incubation atmosphere, and medium composition on arthrospore formation in the fungus Trichophyton mentagrophytes.

Several growth conditions were found to allow abundant arthrospore formation in T. mentagrophytes. These included growth at 32--37 degrees C on Sabouraud's medium (1% neopeptone, 4% glucose) and growth at temperatures below 32 degrees C solely on neopeptone or other complex peptide sources without the addition of glucose, a supplementary carbon source. Sabouraud's medium did not allow arthropsore formation at 30 degrees C under normal atmospheric conditions. However, if oxygen tension were reduced by partial replacement of air with either N2 or CO2 arthrosporulation did occur on Sabouraud's medium at 30 degrees C. The rate of germ tube elongation was lower under those conditions which supported arthrospore formation, suggesting a correlation between decreased rate of hyphal extension and arthrospore formation. Stimulation of arthrospore formation by sublethal concentrations of several antifungal agents tends to support this hypothesis.


Bacteriocins of phytopathogenic Corynebacterium species.

The majority (85% of all strains tested) of 12 phytopathogenic Corynebacterium species produced bacteriocin(s) on nutrient broth--yeast extract (NBY) medium. All C. nebraskense, C. michiganense, C. insidiosum, C. oortii, and C. iranicum strains produced bacteriocin(s). The optimal conditions for production of 23 distinct bacteriocins by eight species of Corynebacterium generally were 20 degrees C and 4 days of incubation on NBY or on modified Burkholder's agar that lacked peptone (MBAL). Production in liquid was marginal and not augmented by adding mitomycin C. Bacteriocins generally had little effect on other strains within a species but were inhibitory to other species. Most bacteriocins appeared to be bactericidal proteins resistant to heat (75 to 80 degrees C, 30 min) but sensitive to proteolytic enzymes. Some strains of C. nebraskense, C. michiganense, C. insidiosum, and C. flaccumfaciens produced two bacteriocins which were clearly differentiated by varying or testing one or more of the following: conditions for production, the indicator, heat stability, and susceptibility to proteolysis. Within certain limitations, a convenient and reproducible typing scheme was devised for strain and species differentiation of most phytopathogenic corynebacteria.


Polyadenylate-containing RNA in dormant and germinating Botryodiplodia theobromae pycnidiospores.

Hybridization of [3H]polyuridylic acid to RNA isolated from Botryodiplodia theobromae pycnidiospores yielded an estimate of about 6.25 x 10(5) polyadenylate-containing RNA (poly A(+) RNA) molecules per dormant spore. The number increased about fourfold by the time of germ tube emergence at 3 h. The average size of this presumed mRNA was about 4.1 x 10(5) daltons (1275 nucleotides), with an average polyadenylate segment length of 26 nucleotides. Neither of these values changed significantly during germination. The earliest detectable (first 30 min of germination) de novo synthesized mRNA's were rapidly incorporated into polyribosomes. This newly synthesized, presumably functional, mRNA was composed of both poly A(+) RNA and polyadenylate-lacking RNA. The average sizes of the two polyribosomal mRNA subpopulations and the total poly A(+) RNA population were identical.


In vitro attachment of Treponema hyodysenteriae to mammalian epithelial cells.

The interaction between Treponema hyodysenteriae and isolated swine intestinal epithelial cells or mouse adrenal cells in culture was examined. Studies were performed in which treponemes were incubated with each type of anomal cell in an atmosphere of 5% CO2 in air. Coincubation was terminated at various time intervals, and the percentage of treponemal attachment evaluated by light microscopy. The extent of attachment was dependent on both incubation time and temperature. The mechanism of attachment to the animal cell surface was examined by scanning electron microscopy. Interaction of the parasite with the host cell did not appear to alter cellular morphology or result in changes of the cell surface at the site of attachment. Preference for a cellular site of attachment was not found.


[Antibacterial activity of zearalenone].

Zearalenone, a mycotoxin secreted by Fusarium sp. and Gibberella zeae, shows a narrow range of antibacterial activity limited to some Gram-positive aerobic spore-forming bacteria. In Bacillus thuringiensis (Berliner), a highly sensitive species, this activity is characterized by a decrease of cellular division and induction of atypical cells. These effects resemble those obtained with two other mycotoxins which possess a lactone structure: aflatoxin B1 and patulin.


Heparin via the lung.

Only recently has it been realized that heparin is absorbed when administered into the lung. Im mice, rats, dogs and humans a large dose of intrapulmonary heparin has been shown to cause a moderate degree of hypocoagulability lasting from 48 hours to 14 days depending on the species. This study is part of an ongoing program investigating the effects of the intrapulmonary administration of heparin. Heparin, 1500 units/kg body weight was instilled into the lung in a group of 12 dogs and an equal volume of saline was given in a control group of 10 dogs. Various hemodynamic and metabolic measurements were made at intervals. As expected there was a prolonged moderate increase in clotting time, but no significant effects from intrapulmonary administration of heparin were demonstrated by any of the other measurements. Much work has yet to be done before intrapulmonary heparin can be used clinically but it has potential importance in the management of thromboembolic disease.


Cerebral surveillance during cardiac surgery.

There is at present no ideal method for determining the adequacy of cerebral blood flow during nonpulsatile cardiopulmonary bypass procedures. Clinical evaluation of cerebral function while the patient is under general anesthesia may be misleading and unsuspected cerebral damage could result if perfusion of the cerebrovascular bed is inadequate. Electroencephalography appears to be the only reliable noninvasive means of cerebral surveillance during the critical periods of nonpulsatile perfusion.


Exercise electrocardiography and myocardial perfusion imaging in the diagnosis of coronary artery disease: preliminary report.

Exercise electrocardiography and rest/exercise myocardial perfusion imaging with thallium-201 were performed in 43 patients with typical angina or atypical chest pain; the results were correlated with those of coronary arteriography. Exercise electrocardiography sensitivity was 65%, specificity was 78%, predictive value for a positive result was 73% and for a negative result was 93%. The low sensitivity of the exercise electrocardiogram was mainly due to the number (13 of 43, 30%) of inconclusive results (no ST-segment change on the electrocardiogram, but failure to attain the target rate), most of which were in the group with typical angina. The predictive value of exercise electrocardiography for both a positive and negative result was excellent in typical angina. In patients with atypical chest pain, the negative predictive value was high (90%) but the positive predictive value was very low (50%). The sensitivity of myocardial perfusion imaging was 71%, specificity was 59%, positive predictive value was 52% and negative predictive value 89%. The low specificity of this test is related to the number of false-positive results obtained, most of which occurred in the group with atypical pain. When the results of exercise electrocardiography and myocardial perfusion imaging are combined, the sensitivity is increased but specificity is unacceptably low. However, myocardial perfusion imaging in patients with an inconclusive result from exercise electrocardiography (most of them in the group with typical angina) showed a sensitivity of 80%, specificity of 88%, positive predictive value of 80% and negative predictive value of 100%.


CAGS lecture. Scientific salients in surgery.

Surgery, as a field of clinical skill and scientific knowledge, advances by Discovery, Development and Delivery. While the basic biosciences have been more productive in Discovery than have the clinical fields, surgery has participated in several important areas of Discovery. Developmental science is often called biomedical engineering. In this activity, surgery has been pre-eminent, while it is the study and perfection of Delivery that holds such promise for the future of surgery. Distribution and regionalization of operations, bidirectional referral flow, manpower norms and analysis of adverse outcomes are important horizons for study in surgical care delivery.


Ski fractures above or below the boot top.

In a group of 643 skiers with fractures of the tibial shaft there were 161 ski boot fractures. The authors identified and classified these fractures according to the amount of instability, comminution, angulation, displacement, rotational deformity and ankle joint involvement. The majority of less severe fractures occurred in children and adolescents while the number of more severe fractures increased in proportion to the skier's age. Seventy-two skiers were included in the follow-up examination. Closed management of ski boot fractures offered satisfactory results. Type 3 and 4 fractures (unstable, comminuted, with angulation greater than 15 degrees, displacement and rotational deformity) sometimes resulted in osteoarthritis of the ankle joint. The authors present a biomechanical explanation of deformity through a quasistatic force analysis of the observed fracture level.


Cholecystectomy with and without drainage.

The authors studied the effect of intraoperative drainage, presence of postoperative pyrexia, influence of appendectomy, chest complications and wound infection in 200 patients who had undergone routine uncomplicated cholecystectomy. One hundred patients in whom no drain was inserted were matched with 100 patients whose cholecystectomies, performed during the same period, included placement of a drain. There were 10 males and 90 females in each group; the mean age was 40.5 years in the undrained group and 40.4 years in the drained group. There was a significantly (P less than 0.05) higher frequency of chest complications, longer hospital stay and pronounced postoperative pyrexia (P less than 0.003) in the group with drainage. The rate of wound infection was substantially increased in both groups by adding appendectomy to the procedure, particularly if drains were not used. It is evident that the routine placement of a drain in an uncomplicated cholecystectomy is unnecessary and may even be harmful.


Severe coagulopathy following insertion of the LeVeen shunt: a potentially fatal complication.

Four patients who underwent insertion of the LeVeen shunt for treatment of medically intractable hepatic ascites had coagulation changes. Peritoneo-venous shunting was associated with a mild coagulopathy in two patients, simulating disseminated intravascular coagulation or primary fibrinolysis. The coagulopathy was severe in two patients and life-threatening in one of these. Postoperative coagulopathy may be detected by careful monitoring of coagulation indices and the risk of its development parallels the severity of liver disease.


Thrombosis and free fatty acids in patients subjected to total hip arthroplasty.

The plasma concentrations of free fatty acids were estimated at intervals before, during and after total hip arthroplasty in seven patients. Each patient underwent examination for deep vein thrombosis with iodine-125 leg scanning, impedance plethysmography and contrast venography. Substantially higher concentrations of free fatty acids were found in the plasma of patients shown to have thrombosis than in those without thrombosis.


Bacteriologic monitoring in abdominal aortic surgery.

In patients who undergo abdominal aortic operations, cultures have been recommended perioperatively to identify potential sources of graft infection. Bacteriologic monitoring was done in a group of patients receiving antibiotics prophylactically. Of 197 bowel bag cultures, 28 (14.2%) demonsrated small numbers of bacteria, usually Staphylococcus epidermidis, while of 31 aneurysm wall cultures, 7 (22.6%) grew bacteria. Four (6.6%) of 60 urine cultures done preoperatively indicated a significant bacteriuria, necessitating postponement of elective operations. Twenty-eight (46%) of 61 wounds revealed organisms of low pathogenicity, none of which caused overt infection. While the majority of 63 nasal cultures grew bacteria, this result did not influence the management of any patient. Eleven graft infections occurred in 517 abdominal aortic grafts inserted between 1967 and 1977. In three patients, infection was already present at the time of emergency operation while in another three, infections occurred subsequently, due to paraprosthetic-enteric fistulas in two and septicemia secondary to an operation on the genitourinary tract in the third. In the remaining five patients, no cause for infection was identified. Thus, no bowel bag culture and only one aneurysm wall culture was useful. This study has failed to demonstrate the value of routine cultures perioperatively in patients who undergo abdominal aortic operations.


Diagnostic ultrasonography in acute cholecystitis.

In a 12-month period 100 patients with clinical evidence of acute disease of the gallbladder were studied in hospital by grey-scale ultrasonography. During the same hospital admission it was possible to correlate results of ultrasonography with operative findings in 66 patients. In 52 patients the ultrasonographic diagnosis of gallstones was proved to be correct. There were no false-positive results. In seven patients the ultrasonographic report of a normal gallbladder without stones was also confirmed. In two patients, the report of a normal gallbladder without stones was erroneous. In two more patients the scan was indeterminate and stones were found at operation. In the remaining three patients echogenic material was reported and at operation minute stones and "sludge" were found. No complications resulted from the ultrasonography. The study showed that grey-scale ultrasonography is a reliable, rapid and safe technique for detecting gallstones in patients with a clinical diagnosis of acute cholecystitis.


Re-evaluation of thrombectomy in the management of iliofemoral venous thrombosis.

The authors studied 15 patients with iliofemoral venous thrombosis up to 8 years after the diagnosis was made, to determine whether there was late deterioration in venous function following thrombectomy. Twelve patients were treated by venous thrombectomy and anticoagulants and 3 by anticoagulants alone. Eight of the 12 patients subjected to thrombectomy had an excellent result with limbs that were considered normal. This did not confirm earlier reports which indicated that good early results were not maintained. In 4 of the 12 surgically treated patients minor symptoms of leg pain and swelling were present which also did not progress with time. In all patients treated by anticoagulants alone major symptoms of leg pain and severe swelling persisted. Three of the four patients with persistent minor symptoms after venous thrombectomy were found at operation to have left iliac vein compression syndrome. Only one of eight patients having an excellent clinical result had this syndrome.


Effect of cimetidine on chronic gastric ulcers produced experimentally in rats.

The authors have studied the effects of cimetidine on the healing of chronic gastric ulcers induced in rats. Gastric ulcers were produced by topical application of 60% acetic acid to the serosal surface of the lesser curvature of the stomach. Oral administration of cimetidine, 150 mg/kg daily, in two divided doses for a maximum of 14 days failed to produce any significant acceleration of healing.


Diarrhea and medullary carcinoma of the thyroid.

The authors present the case of a 34-year-old woman with disseminated medullary carcinoma of the thyroid to emphasize the value of calcitonin assay in the diagnosis of this condition despite the absence of a thyroid mass and negative scans. An increased concentration of serum carcino-embryonic antigen was confirmed. The diarrhea associated with the disease did not respond to indomethacin in this patient suggesting that in some cases of medullary carcinoma diarrhea is not due to excessive production of prostaglandins.


Antidepressants in the general hospital.

An approach to the use of antidepressant medication in the general hospital is presented. The type of depression most likely to respond to chemotherapy is described, categories of available antidepressant agents are discussed, and relevant pharmacologic aspects are outlined. This paper suggests clinical guidelines for the use of these drugs, particularly in medical and surgical patients.


Management of colonic and rectal injuries.

In managing a colonic or rectal injury the surgeon must decide whether it is acceptable to have feces passing over a suture line or anastomosis. If it is, resection and anastomosis or simple oversewing of the bowel can be done. If it is not, there are four choices: (a) closure of the wound, drainage and proximal diversion; (b) primary closure or resection and anastomosis of the wound with exteriorization; (c) formation of a double-barrelled colostomy; and (d) resection of the injured colon with formation of an end-colostomy and a mucosal fistula or a Hartmann procedure. The surgeon's choice should be dictated by the severity of the injury, the degree of fecal contamination and the general condition of the patient.


Adult-onset Still's disease.

Four adults with an illness similar to the systemic variant of juvenile rheumatoid arthritis seen in children (Still's disease) are described. All four had fever, an erythematous maculopapular rash, splenomegaly and arthritis. The arthritis was asymmetric and involved only a few joints simultaneously. Erosive arthritis developed in one patient. Three patients had a sore throat, two had pleurisy and pericarditis, and one had transient abnormalities of liver function. The laboratory features included anemia, leukocytosis and high leukocyte counts in the synovial fluid. High titres of rubella hemagglutination-inhibiting antibody were detected in two patients, one of whom was found to have rubella virus in the urine. Only one patient responded well to therapy with acetylsalicylic acid; the other three were given prednisone therapy, and two continue to require it.


Cancer of the bladder in Alberta: a urologic audit review.

A review was conducted of 660 cases of cancer of the bladder diagnosed in two periods, 1960--62 and 1968--70. A significant increase in the incidence of bladder cancer in both sexes, paralleling the trends in other parts of North America, was found. During the second period the disease was diagnosed earlier and, once diagnosed, was apparently treated more successfully. Overall 5-year survival rates increased from 57% to 70% for patients with stage O or A  disease, but were relatively constant, at about 36%, for patients with stage B1 or B2 disease. The survival rate for patients with stage O or A disease appeared to improve without clearly defined changes in treatment. Prospective randomized treatment trials are needed to properly assess the value of definitive and adjunctive methods of treatment.


Pulmonary veno-occlusive disease: antemortem diagnosis from roentgenographic and hemodynamic findings.

A 17-year-old boy with pulmonary veno-occlusive disease underwent Swan--Ganz catheterization. A normal pulmonary capillary wedge pressure was recorded in the presence of severe pulmonary arterial hypertension and roentgenographic evidence of pulmonary venous congestion. This triad of findings permitted an unequivocal diagnosis of pulmonary veno-occlusive disease, which was later confirmed at autopsy. The hemodynamics of this condition and of others included in the differential diagnosis are presented schematically.


Campylobacter enteritis.

Campylobacter jejuni/coli has recently become recognized as a common bacterial cause of diarrhea. Infection can occur at any age. The usual incubation period of campylobacter enteritis is 2 to 5 days. Fever, diarrhea and abdominal pain are the most common clinical features. The stools frequently contain mucus and, a few days after the onset of symptoms, frank blood. Significant vomiting and dehydration are uncommon. A rapid presumptive laboratory diagnosis may be made during the acute phase of the illness by direct phase-contrast microscopy of stools. Isolation of the organism from stools requires culture in a selective medium containing antibiotics and incubation under reduced oxygen tension at 42 degrees C. The organism persists in the stools of untreated patients for up to 7 weeks following the onset of symptoms. Erythromycin may produce a rapid clinical and bacteriologic cure, and should be used to treat moderately to severely ill patients as well as patients with compromised host defences. The emergence of erythromycin-resistant strains requires close monitoring. The epidemiologic aspects of campylobacter enteritis will be fully understood only when methods become available for differentiating strains of C. jejuni/coli. The historical background and current knowledge of campylobacter enteritis are reviewed in this paper.


Continuous intravenous arabinosyl cytosine infusions delivered by a new portable infusion system.

Eighty-six patients with acute leukemia were given 116 continuous intravenous arabinosyl cytosine (Ara-C) infusions (for 24 to 432 hours) with a new portable infusion device. The infusor is powered by interchangeable elastomeric 25 ml balloon reservoirs loaded from standard syringes. The reservoir contents are discharged at nearly constant pressure through an adjustable resistance element, thereby providing flow rates from 0.4 to 2.0 ml/hour. Serum levels of labeled Ara-C delivered by the infusor were found to achieve steady-state therapeutic levels within 24 hours. The average-flow-rate-to-indicator-setting ratio determined for each infusion via scalp vein needles was 0.9 +/- 0.2. Delivery through catheters was more reliable and an average-flow-rate-to-indicator-setting ratio of 0.1 +/- 0.1 was observed. The therapeutic effectiveness of Ara-C in combination with other agents was not compromised by this delivery system. Eleven of 14 patients who received all their induction Ara-C through the infusor achieved complete remission.


Factors that affect response to chemotherapy and survival of patients with advanced head and neck cancer.

A review of 164 patients with far advanced head and neck cancer, treated by a cytotoxic chemotherapy over a ten year period, at WAyne State University, Detroit, Michigan, was done in an attempt to determine factors that may influence the response to chemotherapy and subsequent survival. Response rate to methotrexate was 28%, 5-FU 31%, and porfiromycin 13%. Improved responses were noted with combination chemotherapy. Patients who failed to first line therapy rarely responded to other single agent or combination chemotherapy. Those who did not have prior surgery and/or radiotherapy had better results from drug therapy. Patients with good performance status at the time of initial chemotherapy, had better response to treatment (32% vs. 13% PR & CR) and longer survival (28 weeks vs. 9 weeks, p = 0.01) when compared to those with poor status. Patients who responded to chemotherapy have better survival compared to nonresponders (29 weeks vs. 16 weeks, p = 0.002). This information may prove helpful in future planning of multidisciplinary approach in the treatment of patients with head and neck cancer.


Thyroid neoplasia following irradiation for medulloblastoma: report of two cases.

Thyroid neoplasms occurred in two patients 14 and 18 years after treatment with radiation for medulloblastoma. One patient has a papillary cancer and the other patient had multiple adenomas and a Hurthle cell adenoma. In addition, the latter case had foci of hyperplasia plus a microfollicular transformation, which has not been described in association with prior thyroid irradiation. The radiation doses delivered to the thyroid through posterior cervical spinal ports (2000--3000 roentgens) fall within the upper range of radiation dosage associated with induction of neoplastic changes within the thyroid.


Central nervous system changes complicating the use of radiotherapy for the treatment of a nasopharyngeal neoplasm in a diabetic patient.

A case is reported of a diabetic patient with a nasopharyngeal neoplasm who developed radiation induced brainstem damage even though irradiated at a conventional time-dose-volume relationship. The clinical course was correlated with autopsy findings which revealed radiation changes in the brainstem consisting primarily of vascular hyalinization with foci of infarction, edema, and demyelination. Atherosclerotic changes were conspicuously absent and therefore not the case of the alterations. The changes occurred three months after completion of therapy, which was more rapid than expected for radiation injury. It is hypothesized that diabetes may have predisposed the patient to this severe complication of standard therapy. More needs to be learned concerning the relationship between diabetes mellitus and radiation complications. Perhaps a modified time-dose relationship should be considered.


Opium: a potential urinary bladder carcinogen in man.

Evidence is presented that opium addition is a risk factor for cancer of the bladder. A case-control study of 99 bladder cancer patients admitted to Nemazee Hospital in Shiraz, Iran was evaluated. Cancer patients and controls, matched by age and sex, were analyzed as to their opium and/or cigarette smoking habits. A high correlation between opium addiction and bladder cancer has been observed. This evidence significantly exceeded the one observed in relation to cigarette smoking only. The sex ratio for this cancer site, from hospitalized cases in Southern Iran, is estimated to be about nine male cases per one female case. This high male to female ratio was attributed to the greater addiction of males to opium. It was concluded that opium and, more likely, its pyrolysis derived fractions may represent potential bladder carcinogens in man.


Cellular angiomas of infancy: an ultrastructural study of two cases.

Vascular tumors in infants may be clinically disfiguring, requiring surgical intervention. Some of these lesions are histopathologically worrisome, due to increased cellularity and mitotic activity. The interpretation of these lesions is hampered by a surfeit of terminology, although, regardless of the diagnostic name, they are clinically benign. Two such cellular angiomas are reported, one typical and one unusual case. Electron microscopy of both cases demonstrated a heterogeneous cellular composition, primarily endothelial cells and pericytes. In those light microscopic areas of diffuse growth, primitive vascular structures were resolved. Electron microscopy may be diagnostically useful in supporting the light microscopic impression of a vascular tumor.


Undifferentiated intratubular germ cell tumor of the testis: light and electron microscopic study of a unique case.

A 34-year-old white man was found to have a nodule on the surface of right testis which turned out to be metastatic embryonal carcinoma within the tunica albuginea. Examination of the orchiectomy specimen revealed extensive undifferentiated intratubular germ cell tumor (carcinoma in situ) with foci of intratubular embryonal carcinoma and seminoma. Ultrastructure of the cells comprising the carcinoma in situ was similar to that of undifferentiated germ cells. The development of intratubular embryonal carcinoma and seminoma in a testis with extensive carcinoma in situ lends further support to the concept that carcinoma in situ or the testis represents an undifferentiated germ cell tumor from which other types of germ cell tumors of the testis may evolve.


Solitary plasmacytoma. I: Extramedullary soft tissue plasmacytoma.

The details of 16 patients with extramedullary plasmacytoma are presented. All but one presented with localized disease, and all were treated successfully by radiotherapy. Only one patient developed local recurrence and only one has developed disseminated disease. Radiotherapy is recommended as the primary treatment of choice for these localized radiosensitive tumors. It is suggested that the good prognosis of plasmacytomas of the head and neck, in contrast to plasmacytomas arising at other sites, is related to the observation that a high proportion of these tumors are localized at the time of diagnosis and that very large primary tumors are uncommon.