Speech patterning in recently admitted and chronic long-stay schizophrenic patients.

Several writers have suggested that schizophrenic patients show unusual formal, or non-content, patterns of speech. For reasons of methodology, none of their findings is easy to interpret, and important questions remain unanswered. In particular, we do not know how schizophrenic patients behave in free conversion, how their behaviour with another patient may differ from their behaviour with a psychiatrically normal partner, whether they show consistency across encounters, nor whether patients recently admitted to hospital differ from chronic long-stay patients. The first study was designed to examine the first three questions, by observing recently admitted schizophrenic patients in two free dyadic conversations, one with a schizophrenic partner and one with a psychiatrically normal partner, and comparing them with three control groups; depressive patients; patients suffering from neurotic or personality disorders; and psychiatrically normal chest patients. Consistently across their two encounters, schizophrenic subjects were found to behave similarly for the most part to all three control groups. The second study went on to examine the fourth question, by comparing recently admitted and chronic long-stay schizophrenic patients, and revealed no differences between the two groups. The investigation is discussed in the light of previous research, and it is suggested that a critical variable may be the setting and nature of the encounter in which the schizophrenic patient takes part.


The place of impulsiveness in a dimensional system of personality description.

Three questionnaire studies are reported in which sets of items traditionally used to measure impulsiveness were intercorrelated were correlated with measures of the major personality dimensions E (extraversion), N (neuroticism) and P (psychoticism), and also with the L (lie; dissimulation) scale. It It was found that impulsiveness in the broad sense (ImpB) breaks down into four factors (narrow impusliveness or ImpN, risk-taking, non-planning and liveliness) which are replicable from sample to sample and from males to females. These factors are positively correlated with each other and also with sociability to varying degrees. ImpB correlates quite well with extraversion, but even better with psychoticism; ImpN correlates positively with N and P, suggesting that this trait is somewhat pathological. It is suggested that the distinction between ImpB and ImpN is crucial for the discussion of the nature and measurement of extraversion and also for future experimental work on the causal background and experimental testing of impulsive behaviour patterns.


The Credit-Incentive system: motivating the participation of patients in a day hospital.

The Credit-Incentive System, a modified token economy, is a means of motivating the participation of day hospital patients in therapeutic activities through the use of contingent rewards. Credits are earned by patients for engaging in a wide variety of prosocial tasks and activities and can be spent for coffee, a free lunch, special time with professional staff, recreational events, and time off from the treatment centre. The receipt of credits is accompanied by social approval and recognition from the staff and other patients. Evaluations have shown that the credit system doubles the participation rate of patients in a partial hospitalization programme. The system also enhanced group cohesiveness, provides practice and feedback for cognitive re-integration, and offers opportunities of learning self-management. The results of two experiments suggest that the symbolic and social rewards mediated by the credits are the most important components of their effectiveness.


Preventing venous thromboembolism in elderly patients with hip fractures: studies of low-dose heparin, dipyridamole, aspirin, and flurbiprofen.

Low-dose heparin, dipyridamole (alone and in combination with aspirin), and flurbiprofen were evaluated as potential prophylactic agents against deep venous thrombosis in elderly patients with hip fractures. None of the agents that modify platelet behaviour could reduct the frequency of isotopically diagnosed venous thrombosis. Low-dose heparin reduced the overall frequency of venous thrombosis and its extent as judged by the frequency of bilaterally abnormal scans, but this reduction did not achieve statistical significance.


Microsomal enzymes in malnutrition as determined by plasma half life of antipyrine.

Nutritional-pharmacological interactions were studied in a group of malnourished subjects. Antipyrine was used to evaluate mixed-function oxidase in man. The results indicated that the rate of disappearance of antipyrine from plasma was strongly influenced by the nutritional status of the individual. The half life of antipyrine was modified in undernourished subjects and those with nutritional oedema. This finding indicates that drug regimens may have to be adjusted in patients who have antipyrine half lives that are shorter or longer than normal. Otherwise drug treatment may be inadequate or, in patients with impaired microsomal enzyme activity, potentially dangerous.


Acquired myopia in 11-year-old children.

Children who had acquired myopia by the age of 11 years were identified from a nationally representative sample. There were no overall sex differences in its occurrence but myopia was more common in children from non-manual families than in those from manual families. Short-sighted children were more likely to come from small families and to be of higher birth order than children with normal vision, and these associations held within each social class. At 11 years myopic children showed striking advantages in educational performance over their normal-sighted peers, as judged by tests of reading, arithmetic, and general ability. After adjustments had been made for social background, this age gain still amounted to over one year. Findings obtained at 7 years of age showed that superior educational attainments were already apparent before the onset of myopia. Children with myopia read in their leisure time more often than normally sighted children, but despite the visual impairment, they participated in outdoor sports as often as other children.


Patients in acute surgical wards: a survey in Glasgow.

A survey was made of all patients in general surgical, urological, and orthopaedic and accident wards in Glasgow on one day in June 1975. Its purpose was to define features of acute surgical practice of relevance to the future planning of resources, particularly bed numbers. Over 40% of the patients in both surgical and orthopaedic wards were over 65 years. Most patients had serious conditions and could not have been treated other than by admission to an acute surgical ward. But a substantial minority no longer needed such facilities and could have been transferred to second-line beds, although many still required skilled nursing care. Delay in the discharge of elderly patients from acute surgical wards as a consequence of non-surgical (often medical or social) problems results in a proportion of acute surgical beds fulfilling a second-line function. Unless arrangements for the earlier discharge of these patients are made any reduction in acute surgical beds is likely to restrict elective surgery, especially in orthopaedics.


Twelve months of deputising: 100 000 patient contacts with eighteen services.

An analysis of a 1-in-5 sample of nearly 500 000 patients contacts with 18 deputising services showed considerable variation in the way cells were handled. Telephonists, usually work on shifts including at least one operator who was a trained nurse handled, without sending a deputy, between 3% of new calls at one service and 19% at another. In one service, 19% of visits were made by deputies who were general practitioners; in another, 78%. At least 42% of patients visited by one service were apparently seen within one hour; 74% by another service. The proportions referred to hospital varied from 9% to 16%. The use of deputising services continues to grow; there is as yet no substantiated evidence of shortcomings in the care they provide. The possibility of reviewing the activity of the services, with the use of such indices as those described, might enable present limitations on their use to be lifted.


Presentation, management, complications, and outcome of acute renal failure in childhood: five years' experience.

During 1971-5, 72 episodes of acute renal failure were treated in 70 children aged up to 16 years. The commonest causes were renal hypoperfusion (31 cases), haemolytic-uraemic syndrome (12), glomerulonephritis (9), septicaemia (5), and congenital abnormalities (6). Though referral from other hospitals was generally prompt, 10 out of 51 patients had been observed for up to seven days before transfer. Dailysis was used in 44 cases, the most common complications of which were peritonitis in those treated with peritoneal dialysis and acute changes in fluid balance in those treated with haemodialysis. Altogether 37 patients fully recovered, 10 were discharged with chronically impaired renal function, 17 died, and six entered the dialysis and transplantation programme. The mortality fell from 33% in 1972 to 20% in later years, which was due solely to maintenance dialysis being available. Though all patients with irrevocable kidney failure who were suitable entered the dialysis and transplantation programme, with current financial restrictions we doubt whether we shall be able to find places for all such patients in the future.


Frequency of HLA antigen in asbestos workers with and without pulmonary fibrosis.

HLA antigens were determined in 37 patients with asbestosis and 37 matched controls with equivalent asbestos exposure but no pulmonary fibrosis. All had worked in the same textile factory. No significant differences in the prevalence of antigens were found between the two groups or between either group and controls who had not been exposed to asbestos. When the data were combined with findings from other pilot studies the previously suggested association between asbestosis and HLA-B27 was not confirmed. Subjects who were positive for HLA-B12 tended also to have advanced radiographic fibrosis. Asbestos workers without pulmonary fibrosis had an unexpectedly high frequency of HLA-BW5, which might indicate that this antigen protects against the development of pulmonary fibrosis.


Quinine-induced agranulocytosis: toxic effect of quinine bisulphate on bone marrow cultures in vitro.

In a case of quinine-induced agranulocytosis marrow culture studies confirmed the inhibitory effect on the patient's cells of equivalent therapeutic plasma concentrations of quinine. Similar concentrations had no effect on normal marrow cells. Quinidine, the stereoisomer of quinine, had no effect on either cells from the patient or normal cells. The results encourage the use of in-vitro bone marrow cultures for identifying drugs responsible for agranulocytosis.


Antiribonucleoprotein antibodies in connective tissue diseases: estimation by counterimmunoelectrophoresis.

One hundred and seventy-two patients with various connective tissue diseases were investigated for the presence of serum antibodies to extractable nuclear antigen (ENA) and its major components, ribonucleo-protein (RNP) and Sm antigen. The counter-immunoelectrophoresis assay allowed independent detection and measurement of antibodies to the different components. All 13 patients with mixed connective tissue disease (MCTD) had anti-RNP antibody in high titres, 16% of patients with systemic lupus erythematosus (SLE) had low titres, and none of the patients with scleroderma had anti-RNP antibody. MCTD seems to be more benign than either SLE or scleroderma. The counterimmunoelectrophoresis assay is a simple and sensitive technique for confirming the diagnosis.


Survey of gastroenteritis in children admitted to hospital in Newcastle upon Tyne in 1971-5.

In a survey of 674 children admitted to the main gastroenteritis unit in Newcastle upon Tyne from 1971 to 1975 there was a noticeable reduction in the incidence of severe dehydration and hypernatraemia, though there was no appreciable change in many characteristics of the patients. This period coincided locally (and nationally) with a determined effort on the part of health visitors and doctors to encourage mothers to breast-feed and to advise them to avoid giving concentrated milk feeds and ensure an adequate water intake during febrile illnesses. This may have contributed towards a reduction in the severity of the illness in children with gastroenteritis admitted to hospital. The overall mortality and the incidence of neurological complications in cases of hypernatraemia are low compared with previous reports.


Psychiatric training: the consultants' view.

All consultants in general psychiatry appointed between 1 October 1972 and 30 September 1975 were sent a questionnaire asking about their training experience in various aspects of psychiatric practice. The results showed that the standards of training in 13 areas of psychiatry were generally poor, although psychiatrists who had trained at the Maudsley Hospital had generally had better training than those who had worked in psychiatric hospitals. Perhaps the most alarming feature was the general lack of improvement over the past nine years. It will be several years before the effects of the visist of approval made by the Royal College of Psychiatrists can be seen and assessed. Meanwhile, the demands for a fairer share of experience for all trainees can perhaps be met by introducing rotational programmes that include both teaching and psychiatric hospitals.


Survey of safety and health care in British medical laboratories.

A retrospective postal survey of 24 000 medical laboratory workers in England, Wales, and Scotland showed highly variable standards of safety and health care. Pre-employment health screening was offered to two-thirds of employees, the physicians being the least likely to be examined (15%). Scottish laboratories provided better safety control than English and Welsh laboratories, while Public Health Service Laboratories had a better record than National Health Service establishments. Mouth pipetting is still practised in 65% of English and Welsh laboratories, and the use of protective clothing is rarely compulsory. The servicing of safety cabinets is often inadequate. Known and suspected carcinogens are still apparently used in a few laboratories (2-10%). In view of the wide variation in standards among laboratories, urgent consideration should be given to establishing regulations for codes of safe practice rather than relying merely on recommendations as at present.


Prevalence of intestinal parasitic infestation, salmonellosis, brucellosis, tuberculosis, and hepatitis B among immigrant children in Glasgow.

Two hundred Asian and 100 each of African, Chinese, and Scottish children were screened for intestinal parasitic infestations, salmonellosis, brucellosis, hepatitis B antigen (HBsAg), and tuberculosis. There was a fairly high incidence of Giardia lamblia among Asian and Scottish children and of Trichuris trichiura among the Chinese. Hookworm ova were seen only in Africa children. There were no chronic carriers of Salmonella or Brucella, and no one was suffering from salmonellosis or brucellosis. Tuberculin sensitivity was found in only 4% of immigrant and 1% of Scottish children: the difference was small and neither figure suggests a continuing high incidence of tuberculosis in Glasgow. Only seven immigrant children were found to be HBsAg carriers. Among the families of these carriers there was a high incidence (84%) of HBsAg or antibody (HBsAb). The survey shows that immigrant children in Glasgow do not constitute a health hazard to the indigenous population. Moreover, severe overcrowding is not a prominent feature among the immigrant families in Glasgow but is greatest among the local Scots.


Somatomedin in growth disorders and chronic renal insufficiency in children.

Somatomedin activity was measured using an embryonic chick cartilage assay in 33 normal and short normal children, 23 children with pituitary growth hormone (GH) deficiency, 14 children with sexual precocity, and 13 children with chronic renal insufficiency. In normal children somatomedin activity correlated well with chronological age: low valles in early childhood rose to higher than adult levels at puberty. Children with GH deficiency had significantly lower activities and those with sexual precocity significantly higher activities than normal children. In all three groups somatomedin activity correlated well with bone age. In children with chornic renal insufficiency there was a significant correlation between decreasing somatomedin activity and  both a reduced growth velocity and a falling glomerular filtration rate. Somatomedin activity and growth velocity were within normal limits in children with glomerular filtration rates above 30 ml/min/1-73 m2.


Newer fashions in illegitimacy.

In 1968 Illsley and Gill examined the rise in illegitimacy in the decade 1955-65 and showed that this rise, unlike rises in the first and second world wars, had not been accompanied by a fall in prenuptial conceptions but by a rise. Statistics from 1970 to 1975 have been examined and a third parameter, legal abortion, added. After a period characterised by an apparent rise in the total of extramarital conceptions there has since 1972 been a decline; and in the age group 20-24 this fall dates from 1971. Improved contraceptive practice is probably the reason.


Extensive condyloma lata.

A rare case of extensive lesions of secondary syphilis of varied morphology is presented. The predominant lesions were of conyloma lata, which were present on neck, axillae, inguinal folds, and inner thighs.


Pneumonia in mice produced by Neisseria gonorrhoeae.

Gonococci of colony type 1 were introduced by intranasal inoculation into the lungs of mice in an attempt to produce infection. The organisms were eliminated from the three strains of mice used within 24 hours of challenge. Cyclophosphamide treatment of mice failed to render them susceptible although the organisms disappeared more slowly. The lungs of immunologically normal animals that had received either viable or heat-killed gonococci were acutely inflamed with infiltration of bronchioles and alveoli by polymorphonuclear and mononuclear leucocytes. Most of the changes had resolved after about four days. In cyclophosphamide-treated mice pulmonary infiltration by polymorphonuclear leucocytes was not evident, suggesting that these cells were not primarily responsible for the clearance of the gonococci. Despite the failure to produce a sustained infection, this model may be valuable for studying the local inflammatory effect of gonococcal endotoxin.


Cryosurgery of genital warts in cases in which podophyllin treatment failed or was contraindicated.

A total of 56 cases with warts in which podophyllin treatment was either contraindicated or a failure, were treated with nitrous oxide using a Keymed 500 cryosurgical appliance. Forty-three patients who completed treatment were followed-up for three months. Thirty-seven of these had received applications of podophyllin twice weekly for an average period of three months before cryosurgery. The remaining cases in whom podophyllin was considered to be contraindicated included five with vulval warts (two were pregnant, two were bronchial asthmatics taking oral prednisolone, and one was taking oral clomiphene citrate), and a diabetic patients with penile warts. Thirty-two were cured and 11 relapsed. The latter were re-treated at the end of the follow-up period with two freezing cycles of 45 seconds at an interval of 30 minutes. Seven were cured and the remaining four men who failed to respond belonged to the podophyllin-resistant group and included three with metal warts and one homosexual with anogenital warts. Cryosurgery gave a cumulative success rate of 91%. A single freezing cycle was free from complications but a double freezing cycle was often followed by severe local reaction.


Giardia lamblia infection in homosexual men.

Epidemic Giardia lamblia infection has usually been associated with contaminated water. In this paper, five proved and one presumed case of G. lamblia infection among homosexual men are reported. The sequential onset of their clinical illnesses and their sexual interrelationships suggest that this outbreak could have been caused by the direct faecal-oral transmission of G. lamblia. Other parasitic diseases with possible venereal transmission have been described, and parasitic diseases should be considered in homosexual men with diarrhoea or other gastrointestinal symptomatology.


Giant keratocanthoma on the inner surface of the prepuce.

Gian keratoacanthoma on the inner surface of the prepuce was observed in a 45-year-old man. First symptoms had appeared three months earlier. The tumour was surgically removed. The main histological features of the tumour were enormous, but relatively regular, acanthosis of rete pegs revealing no similarity to the squamous-cell carcinoma, and an exclusively parakeratottic eleidine-containing central plug. The name parakeratoacanthoma is suggested for this type of tumour.


The ultrastructure of the developing medial preoptic nucleus in the postnatal rat.

The postnatal maturation of the medial preoptic area (MPOA) of male and female rats was studied by means of light and electron microscopy. In Golgi-Kopsch preparations, bi- and multipolar cells were present at birth in both sexes; the perikarya of most of these cells, as seen with the electron microscope, exhibited an immature appearance characterized by a sparse organelle content. During the next 5-10 days, an increase in cell size and cytoplasmic differentiation occurred in each sex. By 10 days, many of the MPOA neurons displayed an increased organelle density with the most prominent change being a proliferation of rough endoplasmic reticulum. Further neuronal development was also evidenced by a greater frequency of dendritic spines than seen at either birth or 5 days. Lastly, the number of synapses per unit area increased rapidly in each sex during the first two weeks of postnatal life. Thus, a period of increasing cytological maturation and synaptic organization closely paralleled previously demonstrated stages of functional differentiation of gonadotrophin regulatory mechanisms in the rat brain.


Longitudinal changes of brain amino acid content occurring before, during and after epileptic activity.

In cats affected with cortical epileptogenic foci induced by penicillin application to and cobalt implantation into the pericruciate area, the brain amino acids contents were determined in the focus as well as in extrafocal areas. In different groups of animals, brain removal for biochemical determinations was performed at different times before, during and after epilepsy and the values compared to controls. The only amino acid to show a significant change before appearance of spikes in both types of epilepsy was taurine, which decreased. Cobalt epilepsy was accompanied by changes in a larger number of amino acids than penicillin epilepsy: in the former the brain content of taurine, GABA, aspartate, glutamate, serine, threonine, glycine and alanine was altered. The changes were proportional to the severity of epilepsy and more prominent in the focus area. After disappearance of spikes the levels of most amino acids returned to normal except for some amino acids, previously unaffected by penicillin epilepsy, which were decreased. It is proposed that the decrease in brain taurine, occurring before the appearance of penicillin and cobalt epilepsy, could increase the excitability of a certain neuronal population and thus, by potentiating the effects on neurons of penicillin and cobalt, contribute to the initiation of epilepsy.


Morphology of the facial nucleus of the rat.

The facial nucleus of the rat can be divided into 5 morphological subdivisions. Using a method for the correlation of the observed subdivisions with antidromic field profiles, the orgins of the major muscle branches of the facial nerve in the motor nucleus were determined. The posterior auricular branch is in the medial, the cervical in the ventromedial, the inferior and superior buccolabiales in the lateral, the zygomatic in the dorsal and the temporal and digastric in the intermediate subdivision. The results are consistent with an organization of the motor nucleus reflecting a corresponding topographic organization of the facial musculature.


The kinetics of extracellular potassium changes during hypoxia and anoxia in the cat cerebral cortex.

Extracellular potassium activity, [K+]0, was continuously measured using potassium specific microelectrodes in the cerebral cortex of cats before and after hypoxic or anoxic insults. Two patterns of [K+]0 increase were seen. A slow, linear rise occurred during hypoxia and hypothermia and was correlated with changes in mean blood pressure (B/P). A fast, complex, exponential rise resembling spreading depression occurred during anoxia and was unassociated with B/P changes. The fall of [K+]0 after reversal of the insult was described by a single exponential function with rate constants from 0.009 to 0.0194 sec-1. It is suggested that the linear rise is primarily a result of sodium pump inhibition and that the exponential rise is due to a superimposed sudden increase in cell membrane permeability perhaps secondary to transmitter release. The kinetics of the fall of [K+[0 is consistent with the normalization of the sodium and potassium gradients across the cell membranes secondary to Na+-K+ATPase activity.


Daily variations of various parameters of serotonin metabolism in the rat brain. I. Circadian variations of tryptophan-5-hydroxylase in the raphe nuclei and the striatum.

Daily changes in tryptophan-5-hydroxylase (TrH) activity have been studied in six different 5-HT-containing cell groups (B3, B4, B5, B6, B7, B8,) in the brain stem of rats maintained in a regular cycle of 12 h of light and 12 h of darkness. Significant circadian alternations of TrH activity were observed in most of the raphe nuclei tested, although the changes were not identical from one structure to another. The striatum showed daily variations in TrH activity in opposite phase to the nucleus raphe dorsalis which projects specific terminals into this area. Monoamine oxidase (MAO) activity was simultaneously estimated in these nuclei but did not exhibit and significant rhythm, suggesting a specific regulation of TrH. Total protein levels were also subject to daily changes.


Effects of undernutrition on cell formation in the rat brain and specially on cellular composition of the cerebellum.

In 35-day-old rats which were undernourished by quantitative restriction of the mother's diet from the 6th day of gestation, the wet weight and the DNA content of the cerebellum were slightly more decreased than those of the cerebrum. Cell growth (estimated from the DNA concentration and form the ratios of RNA and protein to DNA) was significantly affected by food deprivation only in the cerebellum. In the cerebullar cortex, the number of Purkinje, Golgi and stellate cells were unchanged. The numbers of other cell tyes were affected to various extents: there were significantly less granules and basket cells per Purkinje cell, and a still more marked hypoplasia of glia involving the glial cells of the molecular layer, as well as the astrocytes of the internal granular layer and the Bergmann cells of the Purkinje cell layer. Finally, the total number of glial cells within the cortex was decreased by 44% against 13% for neurones. These effects of undernutrition on cell acquisition within the brain, and on the cellular composition of the cerebellum, contrast with those of thyroid deficiency.


Daily variations of various parameters of serotonin metabolism in the rat brain. II. Circadian variations in serum and cerebral tryptophan levels: lack of correlation with 5-HT turnover.

Rats submitted to regular 12 h cycles of light and darkness for three weeks were sacrificed at various times of the day. 5-HT, 5-HIAA and tryptophan levels were estimated in the fronto-parietal cerebral cortex. Tyrosine and free and total tryptophan levels in serum were estimated in parallel. Significant circadian variations in 5-HT and 5-HIAA levels were found in cerebral tissues. The peaks of 5-HIAA levels were dectected during the lignt and dark periods respectively, the maximal fluctuations being seen between 17.00 h and 21.00 h, two times separating the light off. Important significant circadian variations in free and total serum tryptophan levels were also observed. In both cases, the maximal levels were found during the middle of the dark phase after the peak of 5-HIAA levels. The circadian rhythm of tyrosine levels in serum was in opposite phase with that of tryptophan (free or total). The diurnal changes in tryptophan content in cerebral tissues seemed thus related to those found in serum. Taking in consideration results obtained in previous studies 16,17 carried out in similar experimental conditions, it was concluded that the parallel increase in serum free tryptophan and in tissues 5-HIAA levels seen during the night were not related to a stimulation of 5-HT turnover. Indeed 5-HT synthesis is minimal at this time16.


Proteolytic enzymes in ordinary, hyperacute, monocytic and passive transfer forms of experimental allergic encephalomyelitis.

The changed patterns of proteolytic activity in brain and spinal cord of Lewis rats were examined in  4 different morphological variants of EAE: ordinary induced by the standard emulsion, hyperacute induced by an emulsion plus pertussis vaccine, passive induced by donor EAE cells, and monocytic induced by treatment of passive EAE with the immunosupressive drug tilorone. The  following enzymatic changes were found: firstly, in ordinary EAE there was a 2--3.5-fold increase in cathepsins A and C (E.C. 3.4.14.1) in spinal cord one day following the appearance of paralysis with a smaller change in hindbrain, and none in the forebrain regions. With recovery from paralysis, levels of cathepsin A remained high in upper cord, and cathepsin C levels fell to about half. In contrast, increase in cathepsin D(E.C. 3.4.23.5) was smaller and occurred only 4--5 days after paralysis with the largest change in spinal cord areas and with only a small decrease on recovery from paralysis. Secondly, in hyperacute EAE, the increase in all cases was smaller with the largest change in cathepsin A level in upper spinal cord. In passive EAE, the most significant increase occurred only in the lower spinal cord for cathepsins A and C, and fourthly, in monocytic EAE induced by tilorone, there was an exceptionally large, 3-fold increase in cathepsin C in lower cord as compared to a 1.5-2 fold increase for other cathepsins. No major differences were observed on comparison of antigens from different sources (guinea pig and bovin spinal cord myelin peptide). An attempt is made to relate enzymatic changes to the morphological features of each variant with special reference to the nature of the infiltrating cells.


Early cortical histogenesis in the primary olfactory cortex of the mouse.

The primary olfactory cortex of mouse embryos varying in age from the 13th to the 15th day of gestation is investigated with the aid of several techniques: Nissl and Golgi preparations, autoradiography and electron microscopy. It is observed that the earliest cells to complete their migrations are diffusely scattered at all levels of the emerging cortical plate. The dendrites of these cells are predominantly tangentially aligned. Subsequently these early formed cells are subdivided into two groups. One group  remains superficial in close relation to the lateral olfactory tract while the second is displaced to the deepest level of the cortex. The dendrites of many cells which remain at superficial cortical levels become realigned in a radially upward direction. "Maculae adherens diminutae" are abundant at points of apposition of membranes of cells of all classes at superficial cortical levels. It is suggested that these serve to stabilize cell position and that the upward dendritic realignment is an expression of radially directed stresses. Synapses appear relatively late and probably play no role as determinants of cell position.


Locomotor recovery after unilateral hindlimb deafferentation in cats.

After hindlimb deafferentation, recovery of locomotor patterns may be distinguished from recovery of accurate movements. Cats were timed while crossing wide runways requiring that locomotion be present, and narrow runways which require that it also be accurate. Locomotion recovers soon after deafferentation and becomes almost normal in speed, although accuracy is still absent. This accuracy returns 10 days postoperatively. Ventral root afferents with cell bodies in dorsal root ganglia are unnecessary for recovery. Postural reflexes (and other non-topographic feedback) are used as cues for limb guidance after removal of that limb's topographic feedback. Anatomical experiments show that a thoracic root sprouts during the recovery period. This sprouting may increase the potency of postural reflexes. Although lower thoracic roots contribute to recovery, they are not essential. Ipsilateral descending system are essential, and represent the final common path for all recovery after deaffernting a hindlimb. Contralateral descending and afferent systems alone cannot mediate overground locomotion. Thus there is a difference between the systems which mediate overground locomotion and those used by animals in treadmill locomotion or with L-DOPA or clonidine or brain stem stimulation. The proposed mechanism underlying recovery of accurate locomotion is behavioral substitution which may be faciliated by collateral sprouting of relevant systems.


Effects of spinal cord transections on lordosis reflex in female rats.

(1) Female rats with complete transections of spinal cord at low thoracic levels were not able to perform the lordosis reflex. (2) Females with bilateral transections of dorsal columns, dorsolateral columns or entire dorsal half of spinal cord performed lordosis in a normal way. (3) Bilateral transection of fibers in the ventromedial columns, added to transection of dorsal columns or entire dorsal half of the cord still allowed lordosis to be performed. (4) Large bilateral transections of the anterolateran columns caused severe loss in the strength and frequency of the lordosis reflex. Effective transections often included some ventromedial or dorsolateral column fibers, and were accompanied by abnormalities of locomotion. (5) We conclude that supraspinal control is required for the normal lordosis reflex, and that fibers necessary and sufficient for lordosis run in the anterolateral columns. These fibers are likely to be dispersed throughout the anterolateral columns, since large transections were required to eliminate lordosis, and also to be involved in (or interspersed with other fibers involved in) other aspects of motor control. Candidate ascending systems are the anterolateral fibers of Mehler. Candidate descending systems are the lateral vestibulospinal and reticulospinal tracts.


The pontine projection to the cerebellar vermal visual area studied by means of the retrograde axonal transport of horseradish peroxidase.

Following injections of horseradish peroxidase (HRP) in cerbellar vermal lobules VI, VIIA and B, VIIA and B in the cat, the distribution of labeled cells in the pontine nuclei was mapped in drawings of serial transverse and horizontal sections. The labeled pontine cells are distributed in 4 largely longitudinal columns, situated in the dorsolateral, peduncular, lateral and paramedian pontine nucleus (referred to as columns A, B, C and D, respectively). The majority of afferents to the vermal, visual areas come from colums A and B. To some extent cells projecting to the various sublobules have their preferential location within each column (Fig. 5). The majority of the fibers end in lobule VII. Available data from the literature show that only columns A, D and rostral part of B may be involved in the transmission of visual impulses to the vermal area, since these columns receive afferents from the superior colliculus, the lateral geniculate body and the visual cortex, respectively. The route via the superior colliculus-dorsolateral nucleus appears to be quantitatively the most important. As judged from data on fiber connections, impulses from various sources (inferior colliculus, cerebellar nuclei and "non-visual" parts of the cerebral cortex) are transmitted to certain parts of the 4 columns. The functional importance of this convergence and some general features in the organization of the pons are discussed.


Vestibular and medullary brain stem afferents to the abducens nucleus in the cat.

Brain stem neurons that project to the abducens nucleus (nVI) were labeled by the technique of retrograde transport of horseradish peroxidase (HRP). Following iontophoresis of HRP into nVI a large number of labeled cells are found in the ipsilateral vestibular nuclear complex, extending from the rostral medial vestibular nucleus into the ventral lateral vestibular nucleus. A smaller number of HRP-positive cells are also found in the contralateral medial vestibular nucleus. In addition, labeled cells are localized to the contralateral dorsomedial gigantocellular tegmental field as well as the nucleus praepositus hypoglossi of both sides, evidence that these neuronal groups may also be involved in eye movement control.


The role of the ventral lateral geniculate nucleus and posterior thalamus in intensity discrimination in rats.

The role of several subcortical structures in intensity discrimination was studies by examining the effects of localized lesions on intensity and orientation discrimination. In experiment 1 rats with lesions confined to the ventral lateral geniculate nucleus (LGNv) or posterior thalamus were specifically impaired on postoperative acquisition of the intensity discrimination compared with sham operated controls or rats with destruction of the superior colliculi. The lesions had no effect on the orientation discrimination unless the primary visual pathways were also damaged. The effects of LGNv damage on intensity discrimination were confirmed with much smaller lesions in experiment 2. In experiment 3 it was shown that postoperative retention of the intensity discrimination is also specifically impaired by destruction of LGNv. The results are related to the possiblility that information about intensity and pattern is coded in separate visual pathways.


Post-tetanic spontaneous spike activity in rat sympathetic neurons exposed to low potassium ion concentration.

Preganglionic tetanic stimulation (30 sec at 50/sec) of rat superior cervical ganglia, performed in the presence of reduced external potassium concentration (0-1 mM), is followed by a long-lasting postganglionic afterdischarge which fails to appear if stimulation is repeated in normal (5.6 mM) postassium solution. Intracellular recordings revealed that tetanus is followed by 15-30 mV membrane hyperpolarization when the neuron is exposed to normal concentrations of potassium. Conversely, after the ganglion is soaked in low potassium, stimulation results in long-lasting depolarization of the nerve cell with the consequent appearance of spontaneous spikes. This effect is reversed on returing to normal external potassium. Spontaneous activity also occurs after antidromic activation of the cell. It is suggested that tetanus causes sodium loading of the neuron, which leads to stimulation of an electrogenic sodium pump. If potassium is available, the membrane will hyperpolarize, whereas  depolarization and pacemaker activity ensues if external potassium is removed. The electrogenic sodium pump thus endows. the rat sympathetic neuron with a mechanism which enables it excitability to be controlled.


The effect of cholinergic drugs on [3H]acetylcholine release from slices of rat hippocampus, striatum and cortex.

Slices from rat hippocampus, striatum or cortex were incubated with l mum [3H] choline and following 75 min superfusion with Krebs solution the efflux of radioactivity was measured. The slices were stimulated either electrically (1 Hz) or with 25 mM potassium and the rate constant of the evoked release and the size of the releasable pool were estimated. The spontaneous efflux of radioactivity and the releasable pool but not the rate of evoked release correlated with the reported endogenous ACh content of the 3 areas. Raised potassium released radioactivity at a lower rate but from a larger pool than electrical stimulation from all 3 areas. In all 3 areas atropine alone potentiated while physostigmine, oxotremorine and carbamylcholine decreased the rate of evoked release. This depression was fully antagonized by atropine. The drugs had no effect on the size of the releasable pool. Findings suggest that muscarinic receptors located on cholinergic axons or terminals have a physiological role in the autoregulation of ACh release from these 3 areas.


Influence of p-chloroamphetamine on female sexual reflexes and brain monoamine levels.

The effect of p-chloroamphetamine(PCA) on female sexual reflexes was biphasic. Administration of PCA to receptive females initially terminated ongoing sexual behavior and this effect was correlated with the release of monoamines, particularly serotonin (5-HT). Sexual reflexes were abolished within 15 min of PCA injection. Other reflexes, including reciprocal forepaw treading, lateral head weaving, hindlimb abduction and Straub tail, were elicited by PCA. The long term infuence of PCA was the opposite. A facilitation of female sexual behavior occurred accompanied by a relatively specific depletion of 5-HT (10 mg/kg, 66% depletion; 20 mg/kg, 80% depletion) with both dopamine and norepinephrine depleted by less than 15%. This long term facilitation of female sexual reflexes was not blocked by dexamethazone suggesting that PCA was acting directly on the neural substrate for mating and did not produce it facilitation via adrenal progesterone. This biphasic infuence of PCA on mating reflexes, paralleling its effect on monoamine transmission, suggests serotonergic involvement in the integration of mating behavior.


Vesicular transport of horseradish peroxidase from brain to blood in segments of the cerebral microvasculature in adult mice.

The transfer of protein from the cerebral ventricles to the parenchymal bloodstream in mice was studied by electron microscopy. After perfusion with the protein tracer horseradish peroxidase (HRP; M.W. approx. 40,000) through the cerebral ventricles, the tracer penetrated the ependymal lining of the ventricles and was found in the extracellular space of the neuropil close to the ependyma. HRP was also seen in the vascular basement membrane and in endothelial vesicles opening at the abluminal endothelial surface, or situated within the endothelial cells in segments of the microvasculature (mostly small arterioles). In some of these segments HRP was also seen on the luminal surface of the endothelia and in surface-connected vesicles. The junctions connecting adjacent endothelial cells were never penetrated by HRP. It is concluded that vesicular transport of HRP across the endothelium of the cerebral microvasculature represents a possible mechanism for protein removal from brain extracellular space.


Nerve growth factor action on membrane permeation to exogenous substrates in dorsal root ganglionic dissociates from the chick embryo.

An experimental system has been described, in previous studies, where the ability of chick embryo dorsal root ganglionic cells to incorporate radiouridine into RNA declines in the absence of nerve growth factor (NGF), and is promptly restored by delayed supply of the factor. Following these early and fully reversible events, further NGF deprivation causes progressive irreversible damage. The early decline in RNA labeling and its reversion by NGF are accompanied by similar changes in the accumulation of acid-soluble radioactivity from the exogenous radiouridine substrate. In the present study, it is shown that the NGF-dependent accumulation of "soluble" radiomaterials is independent from, and responsible for, the NGF-dependent alterations in RNA labeling. Both changes are measurable with labeled cytidine and guanosine, as well as uridine, and in all cases accumulation of acid-precipitable and acid-soluble radioactivities are strictly proportional to each other. The acid-soluble responses to NGF are not prevented by actinomycin D or cycloheximide treatments, demonstrating that they require neither ongoing syntheses of RNA or protein nor prior effects of NGF on them. Chromatography of acid-soluble radiopools showed that the NGF-dependent increase was not due to a distortion in the intracellular phosphorylation of uridine; but involved corresponding increases in all the radiouridine derivatives including UTP. The time patterns of the acid-soluble response were comparable to those of the RNA labeling response, and maximal NGF effects occurred within minutes of its presentation. Finally, 2-deoxyglucose and a-aminoisobutyric acid, but not leucine, showed NGF-dependent accumulation patterns similar to those of the 3 nucleosides. It is proposed that regulation of selected membrane permeation properties could be the primary process through which NGF exerts its trophic role.


An ultrastructural study of cat petrosal ganglia: a search for autonomic ganglion cells.

It is not known whether cranial and spinal ganglia contain autonomic (motor) neurons in addition to sensory cells. Early light microscopic studies indicate the possibility of synaptic input to some nerve cells via perisomatic axon terminals and dendrites. It has also been suggested that visceromotor relay-type cells in the petrosal ganglion might be involved in the efferent control of the carotid body. The present ultrastructural analysis of 902 neurons in 17 levels from two cat petrosal ganglia provides no evidence for synapses on the cell somata or on their axonal extensions. Processes resembling dendrites were lacking although small surface projections typical of sensory cells were common. The petrosal ganglion thus appears to consist entirely of afferent unipolar neurons.


The isolation of cerebral neurons with partial retention of processes.

A novel tissue disaggregation technique has been devised which permits the isolation of neurons with fairly extensive processes attached. Cortex is dissociated by aspiration through nozzles of decreasing size followed by agitation on a vortex mixer, rather than by the usual technique of forcing tissue through sieves. After each aspiration step, dissociated cells are separated from undisrupted tissue by coarse filtration and the latter is subjected to repeated treatment. This prevents unnecessary trauma to the free cells. After disruption is complete, small pieces of undisrupted tissue are removed from the cell suspension by floating on the foam created by degassing the suspension under vacuum. Cells are purified by conventional velocity-gradient centrifugation. This procedure has been applied successfully to fresh rat brain, with or without a preincubation with trypsin, frozen human brain and frozen bovine brain. The cell yields from rat brain were comparable to or better than, those obtained by other procedures (37 X 10(6) cells/g brain) while the purity was comparable. Cell yields from human brain were similar to those from rat brain but the purity was lower. The lowered particle purity of human and bovine cells can probably be attributed to the conditions of storage of the tissue and to trapping of free nuclei in the meshwork of dendritic processes. Values are given for the amount of protein, RNA and DNA per cell.


Operant discriminative conditioning of vertical eye movements in the midpontine pretrigeminal cat.

In the acute midpontine pretrigeminal cat, either upward or downward eye movements above a certain preset amplitude were reinforced by electrical stimulation of the lateral hypothalamic (LHT) reward area, which did not induce a significant eye movement by itself. During the course of the reinforcement procedure, eye movements greatly increased. In a yoked control test where LHT stimulation was delivered to a cat, independently of its own eye movements, no significant enhancement of the eye movements was observed. However, when reinforcement was given contingently on each large eye movement, eye movement rate became much higher. When cats were trained for an operant discrimination between an S+ (light-off or light-on) and an S- (light-on or light-off), 5 cats acquired clearly differential responses to the S + and S-. They also learned a discrimination reversal. Furthermore, removal of the visual cue eliminated differential responses during the reinforcement and nonreinforcement periods. These data strongly suggest that, in its preparation, a real learning process in the form of a visual discrimination is maintained and an operant conditioning of eye movements with hypothalamic stimulation was achieved without feedback from the peripheral nerve or caudal central nervous system.


A hippocampal interneuron observed in the inferior region.

In the process of an extensive Golgi analaysis of the inferior region of the rat hippocampus, a hitherto undescribed cell type was discovered. The cell has a round, elliptical, or fusiform cell body and an apical dendritic plume reminiscent of dentate granule cells. The axon is thick, with many collaterals and ramifies within, above and below the pyramidal layer. The proximal dendrites have stubby spines whereas the distal dendrites have long thin spines. All impregnated cells of this type were found in the inferior region (CA3 and CA4 of Lorente de Nó) of the hippocampus and most were found in a circumscribed suprapyramidal region at the mouth of the hilus. The majority of impregnated cells of this type were found in the middle to temporal portion of the hippocampus. Nissl-stained sections confirmed the predominant occurrence of this cell type in the inferior region of the middle to temporal hippocampus. In these preparations, the cells have a large nucleus, several nucleoli and very scanty cytoplasm with Nissl substance essentially confined to the initial dendritic segements. The unique morphology of this cell type allows relatively easy identification using Nissl staining.


Synthesis and transport of newly formed proteins in dendrites of rat hippocampal pyramid cells. An electron microscope autoradiographic study.

The synthesis and transport of newly synthesized proteins in dendrites of rat hippocampal pyramid cells were investigated. Labelled leucine was injected into the left lateral ventricle and the hippocampal region was processed for light and electron microscopic autoradiography. To differentiate between the silver grains originating from 'sedentary' or 'migratory' proteins, the radioactivity in dendritic areas free of ribosomes and rich in ribosomes was determined separately. Several conclusions were reached. (1) Protein synthesis in dendrites takes place mainly in the proximal parts although a slight synthetic activity can be observed along the whole dendritic tress as well. (2) Newly synthesized proteins are transported toward the distal dendritic region; the data obtained suggest that cisterns of the smooth endoplasmic reticulum and the microtubular system may be involved in this transport. (3) Two phases of dendritic transport may be distinguished; a fast phase with a rate of 100-200 mm/day and a slow phase with a rate of 2.8-10 mm/day. It also seems probable that the majority of the proteins newly synthesized in dendrites are transported by the slow phase.


Maintained activity of single neurons in the cat visual cortex at different levels of retinal adaptation.

The influence of ambient illumination on the maintained electrical activity of single neurons of the cat visual cortex was studied by using the closed chamber technique for extracellular recordings. Several levels of light background within the scotopic-mesopic range were explored. Phasic and tonic changes in firing rate were observed following a background change. The former were irregular and unpredictable variations lasting up to 15-20 min. The latter, which usually followed the phasic changes, showed the constant characteristic of being in direct relation to luminance variations for neurons isolated in the striate area and in inverse relation for units recorded from the two non-striate areas of the visual cortex; in all cases, they lasted until a new luminous level was set. Changes in firing rate were not dependent upon either the neuron receptive field organization or the EEG pattern, simultaneously recorded. The background-locked firing rate variations recorded at the visual cortex seem to be the result of a particular cortical distribution of afferent fibers carrying luminance information. Applications to vision research are also suggested.


Unilateral storage of monocular engram in day-old chick.

Efficient interocular transfer of a one-trial passive avoidance task by the day-old domestic chicken, for whom the optic nerves decussate completely, raised the question of whether memory for the task was held in one or both sides of the forebrain. Intracranial injection of ouabain or cycloheximide to the trained hemisphere immediately after learning suppressed avoidance behaviour learned monocularly, while injection to the untrained side did not. Memory for the task was established in the side of the brain served by the eye used in learning. Interocular transfer was therefore achieved by the untrained hemisphere borrowing information from the other side's store. The presence of memories in the trained side was not sufficient to establish memory in the naive side.


Biosynthesis of rat brain phosphatidylethanolamines from intracerebrally injected ethanolamine.

[2-3H]Ethanolamine was injected intracerebrally into male rats and the brains of the animals immediately removed by particular procedures at regular intervals over the first 1200 sec. The incorporation of radioactivity into brain phosphorylethanolamine, cytidine-5'-diphosphate (CDP) ethanolamine and phosphatidylethanolamines was examined and quantitated. The nature of phosphatidylethanolamine molecular subspecies, which became labelled, was also investigated after isotope administration. Phosphorylethanolamine, CDP-ethanolamine and phosphatidylethanolamines were all labelled already 5 sec after the administration of labelled ethanolamine. The specific radioactivities of different phosphatidylethanolamine molecular subspecies varied according to the time elapsed from the injection to the sacrifice of the animals. This last result, together with the data on time course of labelling of ethanolamine phosphoglycerides and their precursors, provides indications that this base may be incorporated into lipids not only by net synthesis pathway, but also by base-exchange reaction.


Studies on the relationship of binding affinity to psychoactive and anticholingergic potency of a group of psychotomimetic glycolates.

A study was undertaken of the possible relationship of the binding affinity of a series of anticholinergic psychotomimetic drugs to their psychopharmacological and anticholinergic effects. Binding was measured to brain homogenates and nerve endings using [3H]quinuclidinyl benzilate (QB), a highly potent psychotomimetic agent presumably affecting muscarinic sites in the brain. The two stereoisomers of QB were compared; and although the L-isomer had 15 times the binding affinity of D-isomer, the L-isomer had over 200 times the psychopharmacological potency of the D-form. When the relative binding affinity of a homologous series of glycolate esters was compared with their relative psychoacitve potency, the correlation was excellent; however, when compounds with heterocyclic amino rings (e.g., tropanol) other than quinuclidine and piperidine were considered, the correlation was poor. The correlation between binding affinity and antagonism to acetylcholine-induced contraction of ileum was more consistent. A study was undertaken on the effect of added lipids on QB binding to nerve endings, and it was found that phosphatidyl serine had a significant enhancing effect while gangliosides were inhibitory.


An X-ray crystallographic examination of calcium phosphate formation in Ca(OH)2/H3PO4 mixtures.

Precipitates formed over a 10 day period by adding variable amounts of Ca(OH)2 to H3PO4 were examined chemically and by X-ray diffraction in order to determine and to relate the crystallographic changes observed during calcium phosphate formation in this system to those seen previously in dental plaque. In the lower Ca(OH)2/H3PO4 ratio mixtures the initial precipitates were amorphous or poorly crystalline. The latter deposits showed an apatite-like diffraction pattern which changed to brushite and decreased in Ca/P ratio from approximately 1.2-1.0. Since the amorphous precipitates showed a similar decrease in the Ca/P ratio and a transient appearance of apatite, it was suggested that these initial precipitates, like the poorly crystalline deposits, may contain brushite amorphous to X-rays. Precipitates from the higher Ca(OH)2/H3PO4 ratio mixtures changed from a poorly crystalline to a more crystalline apatite and the Ca/P ratio remained fairly constant. The relation between the pH, Ca and P on the one hand and the brushite and apatite contents and the pattern of crystallization of the precipitates on the other was strikingly similar to the same realtionship observed earlier in dental plaque in situ, suggesting that the system used in this study could be used to study certain aspects of plaque mineralization in vitro.


A quantitative study of the effects of prolonged calcitonin treatment on alveolar bone remodelling in the golden hamster.

This study was carried out on adult golden hamsters, to correlate the effects of porcine calcitonin on serum Ca and P concentrations with changes in osteoclastic resorption of bone. After 1 month of treatment with 5 MRC units/kg/day, there was little effect on these parameters. On the other hand, the hormone appears to have an effect on the remodelling sequence, as indicated by a large and very significant decrease in the extent of resorption lacunae unoccupied by osteoclasts. It is suggested that the duration of the reversal phase, separating the end of active resorption from the beginning of active bone formation in each remodelling focus, is greatly decreased. This shortening is associated with a prolongation of the bone formation phase, and the extent of osteoid tissue is markedly and proportionally increased in the treated animals. After a prolonged administration, calcitonin does not seem to impede the formation of new osteoclasts, their number being only slightly diminished, but it remains possible that it does continue to inactivate these cells. The effect on the bone remodelling sequence could be either due to direct action on the osteoblasts or their percursor cells, or an indirect action via the osteoclasts.


An electron microprobe analysis of osteofluorosis in the rabbit.

Osteofluorosis was induced in rabbits by the ingestion of 500 ppm F in their drinking water over a period of 30 days. The tibiae from experimental and control animals were selected for macroscopic, microscopic and microradiographic observation. Transverse sections of 100 mum thickness were prepared for an electron-microprobe analysis to determine Ca, P and F concentrations and to display the topographical distribution of F as revealed by the X-ray image of its Kalpha1 radiation. Variation in amount of periosteal and endosteal deposition was observed along the length of the bone. Changes, including numerous mottled osteones, were seen in the compact zone of bone which had been formed prior to the start of the experiment. The Ca/P ratio appeared to show a variation related to the F concentration.


Effect of local application of fluoride on healing of experimental bone fractures in rabbits.

The effect of local application of low fluoride concentrations on the healing of experimental bone-radii fractures in 20 rabbits was examined. No external fixation was required after the osteotomy and gelfoam being used as a medium for fluoride application. Histologic mineral and mechanical strength measurements were carried out on the healing callus. There were no significant changes in the ashpercentage and the fluoride concentration of the ash between the experimental and control callus. A significantly higher percentage of ossified tissue was found in the fluoride treated callus. The breaking strength was found to be significantly higher in the bone fractures treated with fluoride, whereas there was no notable difference between the surface areas. It is postulated that the greater amount of ossified tissues, the differences in organization of the bone trabecules, and/or an improved mineral crystallinity may be responsible for this result.


Isolation of osteoclasts by velocity sedimentation at unit gravity.

A method is presented for separating osteoclasts from the heterogeneous population of bone and marrow cells. Cell suspensions were prepared from femora of young rabbits by mechanical dispersion. The starting cell suspension typically contained only 1.0% +/- 0.5 osteoclasts. Following an initial 45 min of unit gravity sedimentation in a lucite chamber osteoclasts were primarily distributed in fractions 2-5. A second 45-min sedimentation of these pooled fractions yielded cell suspensions containing greater than 30% osteoclasts (as much as a 50-fold increase over starting percentages). Linear scan analysis, however, revealed that osteoclasts accounted for 73.14% +/- 0.58 of the cell colume. Subsequent in vitro experiments demonstrated linear incorporation of 3H-leucine into TCA precipitable protein for cells comprising the osteoclast fraction. Concomitant radioautographs revealed radioactive label in isolated osteoclasts.


Strain related electrical potentials recorded in vitro and in vivo.

Using wet dead specimens it was possible to show that the size and form of strain-related electrical potentials on the surface of sheep radii were related both to the amount of strain, and the strain rate, over the range of these recorded during locomotion. Using the same electrode and amplifier system in vivo changes in surface strain and surface charge were recorded from the radius of three sheep during locomotion. During slow locomotion electrical changes were negligible. At medium speed they were most variable, and profoundly influenced by small alterations in the timing and pattern of strain change. When locomotion was fast the electrical waveform reflected fairly faithfully the changes in strain on the bone surface.


Bone mineral content in the forearm after fracture of the upper limb.

The bone mineral content was measured by gamma absorptiometry in patients who had sustained fractures of the upper limb. Measurements were taken on the shafts of the forearm and in the trabecular bone immediately proximal to the wrist. Fractures of the surgical neck of the humerus and fractures of the shaft of the humerus did not significantly influence the bone mineral content of the ipsilateral forearm. Fracture of the radius and the ulna, however, caused a 15% loss of the bone mineral content in the trabecular bone proximal to the wrist, whereas the mineral content on the shafts of the fractured forearms increased or decreased depending on the fracture site. The findings suggest that measurements of bone mineral content of the forearm are not necessarily invalidated if there has been a fracture of the same limb. Only if the forearm itself is fractured should measurements on this site be avoided.


Acute intravenous administration of potassium chloride to furosemide pretreated dogs.

Twelve male mongrel dogs were used for this study; six were untreated (control) and six were given intravenous furosemide (1 mg/kg) daily for seven consecutive days before each study. Each animal received intravenous KCl 0.8, 1.6 or 3.2 mMol/kg/hr for one hour, but only one dose for each study and at least seven days were allowed between studies. The animals were given thiopentone for tracheal intubation and mechanically ventilated, maintaining a PaCO2 of 4.0 to 4.5 kPa (30-35 torr) and anaesthetized with nitrous oxide-oxygen and halothane. Daily administration of furosemide reduced serum potassium from 4.48 to 4.09 mMol/1 with no significant change in serum sodium. A greater number of furosemide-pretreated animals (6 vs 3) developed cardiac dysrhythmias during non-lethal intravenous KCl at 0.8, 1.6 mMol/kg/hr. The furosemide-pretreated group tended to succumb at a lower serum potassium concentration (12.2 vs 13.8 mMol/I, P less than 0.05) and developed earlier onset (44 vs 54 min, P less than 0.05) of cardiac standstill or ventricular fibrillation following intravenous KCl at 3.2 mMol/kg/hr. Cardiac output, heart rate and mean arterial pressure were significantly elevated during serum concentrations of 6.9-9.1 mMol/1, while no statistically significant changes were observed for stroke volume and peripheral resistance. There were no significant differences of urinary potassium excretion between the untreated and treated groups when like doses of KCl were infused. These data suggest that acute infusion of KCl in furosemide-pretreated dogs may not be an effective means of treating hypokalaemia and could be hazardous.


Dual action of pancuronium on succinylcholine block.

The effects of pretreatment with both sub-paralyzing and paralyzing doses of pancuronium and d-tubocurarine, on the onset and duration of succinylcholine-induced neuromuscular blockade were evaluated and compared in 225 patients. D-tubocurarine antagonized both onset and duration of succinylcholine block, while pancuronium produced a dual effect, antagonizing the onset and potentiating the duration of succinylcholine block. Pretreatment with d-tubocurarine (0.07 mg/kg, 0.3 mg/kg and 0.6 mg/kg) increased the time to onset of succinylcholine paralysis from 28 to 118%, and decreased the duration from 16 to 37%. Pancuronium (0.02 mg/kg, 0.04 mg/kg and 0.08 mg/kg) also antagonized the onset of succinylcholine paralysis with increases of 32 to 114%, but potentiated its duration from 30 to 103% compared with succinylcholine alone in the same patients. Although pancuronium markedly inhibited serum cholinesterase in vitro (I50=5 X 10(-7) mol) there was only a 10% inhibition of cholinesterase in vivo after pancuronium 0.08 mg/kg.


Clinical pharmacokinetics of local anaesthetics.

The present study has utilized a clinical model to compare the pharmacokinetics of four currently available amide local anaesthetic agents in theoretically equipotent concentrations. In addition to providing comparative data concerning the onset and duration of analgesia, anaesthesia, paresis, and paralysis, it has provided definitive confirmation of the clinical impression that under certain circumstances following the performance of a nerve block, motor blockade may actually precede sensory blockade, and an explanation for this seeming violation of established neurophysiological principles has been postulated. The study has also raised questions concerning the sequence of recovery from motor and sensory blockade which still await explanation.


[Anesthetic studies on trans-sphenoidal hypophysectomy: retrospective study].

This paper deals with the retrospective analysis of anaesthetic management of 31 cases of trans-sphenoidal hypophysectomy. Good management relies on the following points: (1) a precise diagnosis supported by thorough hormonal investigation, (2) adequate pre- and per-op. administration of steroids, (3) adequate monitoring, (4) a fail-safe airway. The authors recommend the combined use of Innovar and halothane under light hypocapnea for the maintenance of anaesthesia. The routine use of deliberate hypotension is not indicated. Diabetes insipidus usually results from this operation and consequently must be treated.


Preferential uptake of D-glucose by plasma membranes isolated from human adipose tissue.

A sensitive method for the measurement of the stereospecific uptake of D-glucose by plasma membranes isolated from human adipose tissue has been developed. The method is based on the difference in uptake of L-[14C]glucose and D-[3H]glucose as measured by the retention of radioactivity by the membrane preparation collected on Millipore filters. This D-glucose-uptake activity was reversible and did not involve any chemical alteration of the sugar. All uptake activity was lost upon boiling the membrane preparation for 5-10 min. All of the hydroxyl groups of D-glucose appear to be involved in a concerted fashion in the uptake reaction. The D-glucose-uptake activity was shown to be closely associated with glucose transport in adipose cells, since it exhibited the following properties characteristic of this carrier-mediated transport system. (a) The uptake was specific for the D-isomer of glucose. (b) Saturation of D-glucose uptake occurred with increasing concentrations of D-glucose, (c) The uptake activity was inhibited by N-ethylamleimide and phloretin, two reagents previously reported to inhibit D-glucose transport. We conclude that plasma membranes isolated from human adipose tissue retain the glucose transport activity of the intact cells and can be used in subsequent attempts at the isolation and characterization of this transport system.


D-Glucose uptake and insulin binding by the human adipose cell plasma membrane as a function of its polypeptide composition.

A preparation of plasma membranes isolated from human omental lipocytes is composed of about 15 major polypeptide components including three major glycoproteins with an apparent molecular weight range from 100000 to 23 000, as determined by sodium dodecyl sulfate - polyacrylamide gel electrophoresis. Extraction of this membrane preparation with sodium iodide or 2,3-dimethylmaleic anhydride solubilized 50 and 70% of the membrane protein, respectively, resulting from the extensive extraction of protein from all but two of the major membrane polypeptide components. This removal of protein did not affect the membrane's stereospecific D-glucose-uptake activity but did reduce its total specific [125I]insulin-binding activity by 46-67%. The binding of [125I]insulin to its specific receptor on lipocyte plasma membranes was detected at physiologic concentrations of the hormone and could be competitively displaced by increasing concentrations of native insulin. The kinetic behaviour of this reaction was approximated by Scatchard analysis, and both the affinity and binding capacity of the plasma membrane for insulin were increased at lower temperatures. These results suggest that D-glucose transport in human adipose tissue  is mediated by an intrinsic component of the hydrophobic structure of the lipocyte plasma membrane, and represent a partial purification of this component. In addition, these studies demonstrate and characterize the binding of insulin to the plasma membrane isolated from human lipocytes. A quantitative study of this binding reaction may provide further understanding of the mechanisms underlying the decreased insulin responsiveness characteristic of human diabetes.


Translation of protamine mRNA in a rabbit reticulocyte cell-free system.

Protamine mRNA isolated from the microsomal and postribosomal supernatant fractions of trout testis in poly A(+) (polyadenylated RNA)and poly A (-) (RNA devoid of poly A(+)) forms (GEDAMU, L. & Dixon, G.H. (1976) J. Biol. Chem. 251, 1446-1454 and 1455-1463) was translated in the heterologous rabbit reticulocyte cell-free system; the products were shown to be identical in mobility with authentic protamine by polyacrylamide and starch gel electrophoresis. Chromatography, on carboxymethyl cellulose (Whatman CM-52), of the labelled polypeptide products synthesized in this cell-free system in the presence of poly A (+) and poly A(-) mRNA fractions also showed that [14C]arginine was incorporated into all three protamine components resolved in this system, but there was an unequal and variable incorporation of label into the three components with different preparations of mRNA. These results were interpreted as showing that the population of subcomponents of the protamine mRNA coding for the three different protamine polypeptides varied in batches of trout testis at differing stages of development. In addition, the proportion of mRNA components varied between the poly A(+) and poly A(-) editions of the mRNA, and it appeared that the poly A(-) mRNA fraction might represent the product of deadenylation of an earlier population of poly A(+) mRNA.


Biosynthesis of arglecin and related compounds.

The requirements for maximum production of arglecin, 3-isobuty1-6-(3-guanidinopropyl)-2(1H)pyrazinone, by Streptomyces toxytricini grown on either yeast extract or synthetic medium were supplements of L-arginine and L-leucine. The arglecin produced was derived to a major extent from these amino acids, as was shown by comparison of specific activities in 14C-labeling experiments. Various compounds related to arglecin could be synthesized by the organism, and these were isolated and their structures determined primarily by natural-abundance carbon-13 and proton magnetic resonance methods. In old cultures which had produced arglecin, the metabolite 3-isobuty1-6-(3-aminopropy1)-2(1H)pyrazinone was found. In cultures grown on synthetic medium supplemented with L-leucine and L-homoarginine, the metabolit 3-isobuty1-6(4-guanidinobuty1)-2-(1H)pyrazinone was found, and in cultures that had been supplemented with L-norleucine and L-arginine, the metabolite 3-buty1-6-(3-guanidinopropy1)-2(1H)pyrazinone was found.


A Markov chain characterization of human neutrophil locomotion under neutral and chemotactic conditions.

The locomotion of human neutrophils is modelled by a continuous-time Markov chain model consisting of five states: state O, where the cell is stationary, and four motile states whose directions are defined by the four quadrants of a Cartesian plane. In this paper, the Markov property is verified experimentally in special cases. Further experimental evidence for the model is provided by the waiting-time distributions in each of the five states, which are well approximated by exponential distributions. Using the steady-state distribution of the Markov chain as a measure of the ultimate motion of the cells, it is possible to detect the effect of known chemotactic agents upon neutrophil locomotion. Other useful parameters describing neutrophil locomotion are presented.


Compensatory renal hypertrophy in dogs: single nephron glomerular filtration rate.

Sodium ferrocyanide was used to measure the intrarenal distribution of single nephron glomerular filtration rate (SNGFR) in remaining kidneys of dogs, 10 d after contralateral nephrectomy. It was first demonstrated that the renal function of both kidneys in situ was comparable. Following right nephrectomy, the urine volume, p-aminohippuric acid clearance, creatine clearance, osmolar clearance, fractional excretion of potassium, and sodium excretion of the left kidney increased. Fractional excretion of sodium, free water clearance, and filtration fraction remained unchanged. Following that 10-d period, left kidney weight exceeded that of the previously removed contralateral kidney by 50%, indicating that most of the compensatory hypertrophy had already occurred. No significant difference in the length of the proximal tubule nor in the diameter of the glomeruli of superficial (SUP) and juxtamedullary (JM) nephrons of either kidney could be demonstrated. Most importantly, the ratio of radioactivity in the SUP/JM nephrons of the residual kidney was comparable with that previously observed in normal dog kidneys. Thus, the increase in total kidney GFR is explained through a proportional increase in the SNGFR of the SUP and JM nephrons.


Regional cerebral energy metabolism in acute carbon monoxide intoxication.

The regional cerebral metabolic effects of 30 min of exposure to 0.5, 1.0, 1.5, and 2.0% carbon monoxide (CO) were studied in lightly anesthetized rats by measurement of energy phosphates and glycolytic - citric acid cycle substrates in the basal ganglia, hippocampus-thalamus, and cerebellum. In all three regions 0.5 and 1.0% CO gave rise to increases in tissue lactate, but since ATP and the energy charge of the adenylate pool (ECP) remained unchanged from control, it is concluded that energy state was unaltered at these levels of CO. At 1.5% CO the basal ganglia region showed decreases in ATP and ECP, whereas these values for cerebellum and hippocampus=thalamus were unchanged from control. At 2.0% CO all areas showed decreases in APT and ECP and increases in ADP and AMP. The patterns of change in glycolytic and citric acid cycle substrates were similar in all three areas. The results indicated that the energy homeostasis of the basal ganglia is less well maintained in this form of experimental hypoxia.


A progressive and cumulative suppression of the activity of spinal neurones in the nonspinal rat.

Electrical stimulation of the skin of the hindpaw of the rat, at frequencies ranging from 2 to 0.2 s-1, halted the tonic or evoked activity of spinal neurones. The duration of this effect increased with each successive stimulus until it outlasted the interstimulus interval. Tonic activity did not return immediately following termination of the stimulation, and activity was often depressed for periods of up to 5 min. Neurones displaying this behaviour were found in laminae 1 and 4--7 of the cord. Some neurones failed to demonstrate this behaviour following the administration of strychnine. This phenomenon provides a possible substrate for habituation of the flexor reflex that occurs with repetitive and noxious stimulation of the skin.


Metergoline as a selective 5-hydroxytryptamine antagonist in the cerebral cortex.

In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide, and oxygen, the depressant actions on the cerebral cortical neurones of iotophoretically applied 5-hydroxytryptamine (5-HT) but not of noradrenaline, histamine, AMP Ca2+, and gamma-aminobutyric acid were antagonized by metergoline. These observations indicate that metergoline may be a selective 5-HT antagonist in the cerebral cortex.


Fate of orally dosed linamarin in the rat.

Wistar rats, about 100 g in weight, were dosed by stomach tube with 30 mg of pure linamarin. No intact linamarin was identified in the feces or blood but 5.65 mg was excreted in the urine along with 0.823 mg of thiocyanate ion. A 50-mg dose of linamarin was lethal to 7 of 10 rats receiving this dose.


Inhibition of the immune response by rapamycin, a new antifungal antibiotic.

Rapamycin, a new antifungal antibiotic, was found to inhibit the immune response in rats. It totally prevented the development of two experimental immunopathies (experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA)) and the formation of humoral (IgE-like) antibody. It was about half as potent as cyclophosphamide in inhibiting EAE. In AA and on antibody formation, rapamycin and cyclophosphamide were about equipotent, whereas methotrexate was more potent. The immunosuppressant activity of rapamycin appears to be related to inhibition of the lymphatic system.


Effect of acute stress and ouabain administration on adrenal catecholamine content and cardiac function of rats pretreated with diazepam.

The experiments described were carried out in an attempt to determine the participation of adrenal catecholamines in the higher incidence of cardiac arrhythmias produced by acute stress or ouabain injections in diazepam-treated animals. The pretreatments of rats with diazepam (150 mg kg-1 d-1) increase significantly the adrenal catecholamine content. Consequently, the application of electrical and immobilization stress releases more catecholamines from the adrenal glands of the diazepam-treated rats and also produces higher incidence of ventricular extrasystoles. Furthermore, various pretreatments of rats with diazepam (5-150 mg kg-1 d-1) also lead to an increase in the catecholamine content of the adrenal gland. In diazepam-treated rats, the intravenous administration of ouabain produces a greater release of adrenal catecholamines as well as a greater incidence of cardiac arrhythmias. Several hypotheses are proposed to explain the elevation of adrenal catecholamines and also the higher incidence of ventricular arrhythmias.


The effect of SKF-525A and of altered hepatic blood flow on lidocaine clearance in the cat.

Hepatic blood flow and hepatic uptake of lidocaine were determined in cats during constant intravenous infusion of lidocaine. Lidocaine clearance is directly linked to hepatic blood flow with reductions in flow being reflected in equal reductions in hepatic clearance. Altered blood flow did not result in altered rates of lidocaine extraction. Lidocaine extraction ratio was 28%. Hepatic blood flow and lidocaine metabolism were measured before and 60 min after an intramuscular injection of SKF-525A (50 mg/kg). SKF-525A produced a reduction in hepatic clearance of lidocaine to 60% of control values, entirely as a result of a reduction in hepatic extraction ratios. Hepatic blood flow and vascular conductance were not affected by SKF-525A.


Electronic measurement of red cell flow in micropipettes.

The velocity of human erythrocytes in flow-through tubes of diameter less than 5 mum is measured as a function of driving pressure. The electrical resistance in the lumen of the tube increases when a cell is present, so a pulse can be generated of length inversely proportional to velocity. In the apparatus described the pulses and driving pressure are fed to a computer which derives the correlation between pressure and velocity. Experiments confirm that the resistance to flow of erythrocytes in a narrow tube is substantially the same as that of the suspending medium. The apparatus is being used to study the effects of changes in erythrocyte deformability on flow.


Effect of subacute dosing and phenobarbital and 3-methylcholanthrene pretreatment on the metabolism of acetaminophen in rats.

The metabolism of 14C-ring-labelled acetaminophen was studied in male Wistar rats. Pretreatment with phenobarbital increased the initial rate of elimination of 14C from the blood and increased the amount of acetaminophen glucuronide excreted in the urine. Pretreatment with 3-methylcholanthrene did not significantly affect the rate of elimination from the blood and decreased the amount of acetaminophen glucuronide in the urine. Daily dosing with acetaminophen for up to 3 weeks increased the rate of elimination of 14C from the blood after 4 h, and increased the urinary excretion of both total 14C and the glucuronide and sulfate conjugates. Subacute dosing with acetaminophen had a diuretic effect but this did not correlate with the increased excretion of the drug. It is concluded that acetaminophen elimination is increased by phenobarbital pretreatment and by subacute dosing with acetaminophen, but by different mechanisms.


The development of the hypothalamo-pituitary axis in the neonatal rat: pituitary and serum prolactin concentrations.

Using highly specific double-antibody radioimmunoassay techniques, we have measured pituitary and serum prolactin (PRL) concentrations in neonatal rats from birth to 60 d. Pituitary PRL concentration was low at birth in both sexes and peak prepuberal values were attained at 25-28 d. Following this time, pituitary PRL concentrations in females were significantly higher than those observed in males (p less than 0.01). Serum PRL concentrations were low at birth in both sexes and remained low until 15 d, when they rose to peak values just before puberty. There were no significant sex differences with respect to serum PRL concentrations. These data indicate that hypothalamic control of PRL secretion developes during the neonatal period of the rat. The relationship of this developmental process in the neonatal rat as a possible model for the study of the midgestational hypothalamic maturation of the human fetus is discussed.


The effect of fasting on the in vitro synthesis of amylase in rat exocrine pancreas.

Immunological methods were used to study the effect of fasting on the in vitro synthesis of amylase (EC 3.2.1.1) in rat exocrine pancreas. After 72 h of fasting, the amylase enzyme activity of the pancreas and the rate of amylase synthesis were reduced 50%. No significant change in the activities of trypsin or chymotrypsin were detected. The decrease in leucine incorporation in total pancreas protein was accounted for by the decreased amylase synthesis. No change in the rate of amylase breakdown was detected. These results indicate that the rate of synthesis of amylase is controlled by food intake and is not directly related to the tissue content of enzyme.


Left atrial thrombosis complicating mitral stenosis: results of surgical treatment.

In 343 patients treated surgically for mitral valve disease, there was thrombosis of the left atrium in 40. Massive atrial thrombosis was present in 32 of them, yet the diagnosis was suspected or established preoperatively in only 12, because of insufficient clinical signs. A transventricular mitral commissurotomy was performed in 32 patients and mitral valve replacement in the remaining 8. Surgical mortality was 23% in the patients with atrial thrombosis compared with 7% in the trombus-free patients: 66% of the deaths were due to cerebral embolism. Systemic embolism occurred in 17% of the patients who had a closed approach initially and in 27% following a planned open procedure. Among the survivors, 65% were asymptomatic or markedly improved; the average follow-up was 42 months. Atrial thrombosis increases the surgical risk because of the high incidence of operative embolism, a complication that is not avoided by the use of open procedures, but that could be prevented by earlier surgical treatment of mitral stenosis, before atrial thrombi develop.


Effect of unilateral pulmonary artery occlusion on the arterial oxygen pressure of children undergoing pulmonary systemic artery shunt procedures.

Of 20 children undergoing thoracotomy who had blood-gas analysis at various intervals during their operative procedure, 18 had congenital heart disease causing cyanosis. The venous admixture was apparent on compressing the lung to expose the mediastinal structures and was diminished upon clamping the pulmonary artery to the exposed lung. This observation may be of clinical value in raising the arterial oxygen pressure when sudden deterioration occurs during performance of a systemic pulmonary shunt in cyanotic children.


Percutaneous insertion of a permanent transvenous pacemaker electrode through the subclavian vein.

Insertion of transvenous permanent pacemaker leads through the subclavian vein is relatively safe and simple. This procedure was performed in 29 patients. The only serious complication was dislocation of the lead in eight patients. With this technique the endocardial lead can be positioned quite readily in the right ventricle. Use of the technique should be considered whenever the cephalic vein cannot be located readily or is too small to permit placement of an endocardial lead.


Actinomycosis of the gallbladder.

Actinomycosis of the gallbladder is rare, and the pathogenesis of the infection is poorly understood. The authors report the case of a 77-year-old man admitted to hospital because of abdominal pain. Clinical  and laboratory findings suggested the diagnosis of cholecystitis and cholelithiasis. At cholecystectomy the gallbladder was inflamed and contained many calculi. Gram staining of material from the mucosa of the gallbladder demonstrated gram-positive pleomorphic filaments, and Actinomyces israelii grew in pure culture, thus confirming the diagnosis of actinomycosis of the gallbladder. The pathogenesis of the condition is also discussed.


Actinomycosis of the colon.

A 44-year-old woman with severe pain in the right upper quadrant, simulating acute cholecystitis, was found to have a large tumour in the transverse colon. Cultures from the mass grew Actinomyces israelii. Actinomycosis may often be missed; involvement of the large bowel is not confined to the appendiceal and cecal areas and may simulate other intra-abdominal conditions.


Giant ovarian cyst in a dwarf.

The authors describe a case of giant mucinous cystadenoma in a dwarf. The cystadenoma weighed 32 kg, almost half the patient's normal weight, Such tumours are rare and are sometimes mistaken for ascites. They are usually benign, but care should be taken to remove them intact since malignant degeneration of mucinous cysts occurs in 5 to 15% of cases. Understanding of the possible complications allows for a favourable prognosis.


Methysergide therapy causing vascular insufficiency of the upper limb.

A 41-year-old woman, who was receiving methysergide maleate for the treatment of severe headaches, had occlusion of the left brachial artery, confirmed by arteriography. The occlusion was believed to result from the use of methysergide and the drug was therefore withdrawn. Within 4 days the distal pulses were normal, as confirmed by arteriography, and she was asymptomatic.


Subcapital fracture of the hip: a rare complication of intertrochanteric fracture of the femur.

Three cases of subcapital fracture of the hip that occurred after an intertochanteric fracture of the femur had been nailed have been described in the literature. The tip of the nail failed to penetrate the femoral head and a stress fracture occurred in two at the tip of the nail and in the other at the tip of a blade plate. This paper reports three further cases of this recently recognized and rare complication of intetrochanteric fractures. It is emphasized that the condition must be recognized and treated without delay.


Pheochromocytoma presenting with pulmonary edema and hyperamylasemia.

A 28-year-old woman was admitted to hospital with acute pulmonary edema, mild abdominal discomfort and hyperamylasemia. From the 2nd hospital day hypertensive episodes occurred daily. The furosemide screening test for renovascular hypertension revealed elevated plasma renin activity (PRA) but an intravenous pyelogram revealed a right suprarenal mass and no evidence of renovascular compression. Elevated values of plasma and urinary catecholamines indicated a pheochromocytoma, and a single chromaffin tumour was resected. It is important to monitor left ventricular filling pressure during operative removal of a pheochromocytoma. Postoperatively the patient had normal blood pressure and PRA. Decreased urinary amylase clearance and abnormal pancreatic and salivary amylase isoenzymes were found.


Coexistence of pheochromocytoma, adrenal adenoma and hypokalemia.

A 56-year-old woman had a 22-year history of hypertension. Investigation showed hypokalemia and kaliuresis without pronounced suppression of plasma renin activity or elevation of urinary aldosterone excretion. There was biochemical evidence of catecholamine metabolite excess but the usual clinical features of pheochromocytoma were absent. Laparotomy revealed a pheochromocytoma and adrenal adenoma in the right adrenal gland. Excision of the tumours was followed by resolution of the hypertension and metabolic abnormalities.


Hypoglycemia as a complication of removal of a pheochromocytoma.

In a patient with a solitary pheochromocytoma severe hypoglycemia developed following excision of the tumour. The possible causative mechanism was thought to be a reactive relative increase in insulin production secondary to increased endogenous production of glucose, induced by the large amounts of epinephrine produced by the tumour. Alternatively, epinephrine withdrawal following removal of the tumour under phentolamine infusion may have induced increased insulin production and hence potentiated the development of hypoglycemia. Careful monitoring of the blood glucose concentration during and after the operation is recommended to obviate this potentially fatal complication.


Hypoglycemia following excision of pheochromocytoma.

In two patients hypoglycemia developed in the immediate postoperative period after removal of a pheochromocytoma. In one patient the serum insulin value was elevated when he was hypoglycemic. Preoperative preparation of patients with pheochromocytoma requires use of an alpha-adrenergic blocking agent to decrease blood pressure and allow the plasma volume to expand; in the two patients referred to phenoxybenzamine was given orally. It is difficult to recognize hypoglycemia postoperatively because of the altered consciousness associated with a major operation, analgesics, anesthetic agents and the effects of adrenergic blocking medications; hence the physician must watch closely for this complication.


Management of pheochromocytoma during pregnancy.

To reduce the high maternal and fetal mortality in pheochromocytoma of pregnancy, therapy is advocated with phenoxybenzamine and propranolol to obtain adequate alpha- and beta-adrenergic receptor blockade. In early pregnancy control of symptoms may be difficult, but the patient may be carried to term with such medical therapy. Delivery should be by cesarean section before the onset of labour, with, if possible, simultaneous removal of the tumour. Additional preoperative preparation with phenoxybenzamine and propranolol and careful intraoperative management are essential. During her third pregnancy a 29-year-old woman was found to have a pheochromocytoma of the left adrenal gland. After the medical therapy and preparation described, the infant was delivered by cesarean section and the mother's left adrenal gland excised. Eight-year follow-up, including during a fourth pregnancy, showed no recurrence of tumour in the mother and only mild hypertension. The infant developed normally.


Acute fenitrothion poisoning.

A technician was accidentally exposed to the organophosphorus insecticide fenitrothion and subsequently treated with pralidoxime for the autonomic, somatic and psychiatric manifestations of intoxication. Although long-term therapy with pralidoxime is not recommended, this patient required and obtained symptomatic benefit from its prolonged use. Erythrocytic and plasma cholinesterase activities had been monitored prior to exposure and were monitored throughout treatment and following recovery. Continual monitoring of cholinesterase activities of individuals occupationally exposed to organophosphorus ester insecticides and early diagnosis are essential.


Heterogeneity of bilateral renal agenesis.

Bilateral and unilateral renal agenesis may be expressions of single dominant gene. Chromosome abnormalities may be present and the renal agenesis may be part of a syndrome of multiple abnormalities. Apparently normal relatives of affected individuals should be screened by intravenous pyelography before genetic counselling given.


Syndrome X: case report.

Transmural myocardial infarction occurred in a 48-year-old woman with syndrome X -- atypical angina pectoris and angiographically normal coronary arteries. Before the infarction her electrocardiogram had been normal at rest but showed ischemia after exercise. Angiography 3 months after infarction revealed a normal coronary tree but hypokinesia of the posterior left ventricular wall.


Recurrent hemorrhage from corpus luteum during anticoagulant therapy.

A 43-year old woman had recurrent massive intraperitoneal hemorrhage from rupture of a hemorrhagic corpus luteum in two successive menstrual cycles while receiving anticoagulant therapy. Left oophorectomy was performed on the first occasion and right salpingo-oophorectomy with left salpingectomy on the second. While the precise incidence cannot be determined, rupture from a hemorrhagic corpus luteum appears to be a rare but potentially catastrophic complication of anticoagulant therapy. Hence possible ovarian hemorrhage should be considered in women of reproductive age receiving heparin or sodium warfarin therapy.


The role of the head nurse in primary nursing.

Primary nursing brings about changing roles, responsibilities, and communication patterns for all members of the health care team. The head nurse, as she introduces new staff to primary nursing and its day-to-day applications, is in an ideal position to generate enthusiasm for the goals of the concept. In attempting to implement this new care pattern, she must continually promote the philosophy behind it by her support and recognition of its principles. In the long run, it is the positive attitude and high motivation of the head nurse that will determine the success or failure of the program wherever it is introduced.


A program that dares to be different.

In summary, we have attempted, in planning the Diploma Nursing Program at Okanagan College, to retain the positive aspects of existent hospital and college programs, while at the same time developing some unique features: a health promotion focus, a comprehensive curriculum framework and a cooperative education design. As yet, in this first year the program, it is too early to predict outcomes, but we anticipate that our students will be better equipped to deal with the reality of a work situation.


Characterization of a new continuous cell line derived from a human retinoblastoma.

A new continuous cell line derived from a human retinoblastoma has been established. This cell line, WERI-RB1, has been maintained in vitro since December 1974. The purpose of this investigation was to characterize WERI-Rb1 on the basis of morphology, growth, tumorigenicity, cytogenetics, and to compare this cell line with Y79, a human retinoblastoma cell line established at another institution. Morphologically, both cell lines were similar; each spontaneously grew as a suspension of small round cells in grapelike clusters. Each exhibited growth of cells in rosettes, as well as unusual chain formations. Growth rates differed: the population-doubling times for WERI-Rb1 and Y79 were 96 and 33 hr, respectively. When the negative surface charge on a plastic tissue culture flask was changed, each cell line grew as a monolayer. Y79 could be cloned in soft agar; WERI-Rb1 could not. An inoculm of 10(7) WERI-Rb1 or Y79 cells produced a retinoblastoma in test rabbits. Karyological examination showed each cell line to have a stable, near diploid chromosome number. Although large markers were observed in each line, they shared no common marker.