A computer-based radiotherapy clinical record system using mark-sense forms.

A computer-based system for radiotherapy clinical records is described. Its main features are the use of a single mark-sense form for input of data at all stages of the patient's progress, and the provision of a plain language print-out of the patient's record after each updating. The programs are written in Fortran and are implemented on a Rank Xerox Sigma 6 computer.


An on-line computer graphics terminal for radiotherapy treatment planning.

A programmed graphics terminal has been connected on-line to a large time-shared computer for calculating dose distributions in radiotherapy treatment planning and provides a viable alternative to dedicated systems and batch working. The terminal equipment is based on a mini-computer and includes a function-key devise for outline input, a large-screen refresh oscilloscope for viewing results and an X-Y plotter for hard-copy. Radiotherapy dose computation programs in standard Fortran are stored and run on a large remote computer with graphical interaction at the terminal. External beam programs can calculate dose distributions for most commonly used treatment situations and can compute in off-axis planes. Data input is fully interactive and easy to understnad. Dose distributions are displayed as isodose contours. Advantages of the system include accuracy, speed, ease of use and maintenance, and transferability of the programs between different host computers.


Persisting cyclic ovarian activity in cervical cancer after surgical transposition of the ovaries and pelvic irradiation.

The effect of surgical transposition of the ovaries on gonadal function was investigated in ten young women with carcinoma of the uterine cervix, stages I and II. Gonadotrophin-, oestradiol- and progesterone-levels were determined before and during pelvic irradiation. A control group consisted of seven patients with cervical cancer who did not undergo ovaria transposition. In the control group gonadotrophins began to rise after radiation doses of 560-2400 rad (FSH) and 1130-2600 rad (LH) respectively. The excessive secretion was not seen in patients who had ovarian lifting. Ovulatory cycles occurred during or after pelvic irradiation in seven women of the study group, either spontaneously or induced by clomiphene treatment. This indicates that transposition preceding radiotherapy is an effective means of preserving ovarian secretion in young women in whom malignancies of the pelvic region demand irradiation.


Long-term low-dose co-trimoxazole in prophylaxis of childhood urinary tract infection: clinical aspects.

Long-term low-dosage prophylaxis may be used in children with recurrent urinary tract infection to prevent reinfection of the urinary tract while the underlying cause of infection persists. Co-trimoxazole in a dose of 2 mg trimethoprin combined with 10 mg sulphamethoxazole per kg body weight daily has proved very effective: only six of 130 children receiving this treatment during a total period of 2637 months developed a reinfection. Co-trimoxazole was acceptable, compliance was good, and there were no important adverse effects. Supportive measures during prophylaxis are important. Sixty-five children were follow up after completion of their co-trimoxazole prophylaxis. Twenty-seven developed reinfections with fresh organisms, over two-thirds occurring within three months of discontinuing prophylaxis. Each one of these reinfections was sensitive to trimethoprin. The rectal flora were similarly sensitive.


Long-term low-dose co-trimoxazole in prophylaxis of childhood urinary tract infection: bacteriological aspects.

The bacteriological consequences of giving long-term low-dose co-trimoxazole to children to prevent reinfection of the urinary tract were studied. Only six "break-through" infections occurred during 2637 child-months of prophylaxis. The children complied well with treatment. During prophylaxis the number of rectal coliform bacilli recovered was greatly and rapidly reduced, but at least 70% of the surviving coliform organisms remained sensitive to the two components of co-trimoxazole. Changes in sensitivity pattern were evident within a month of starting treatment and the proportion of rectal organisms resistant to sulphonamide or trimethoprim did not increase with time. After stopping co-trimoxazole prophylaxis the number of rectal organisms recoverable returned rapidly to normal, as did their sensitivities to trimethoprim and sulphonamide. Further episodes of urinary tract infection developing after prophylaxis was stopped were caused by organisms sensitive to a wide range of antimicrobial agents, including trimethoprim.


Thyrotoxic vomiting.

In seven patients vomiting played an important part in the presentation of thyrotoxicosis. Vomiting does not always indicate severe thyroid disease, and the diagnosis in patients presenting with this symptom may be long delayed.


Mode of presentation of juvenile diabetes.

In a study of 66 children with juvenile diabetes symptoms had often present for over a month before diagnosis. Though polyuria, polydipsia, and weight loss were the commonest features, other important symptoms included tiredness lethargy, and malaise. A gradual onset of diabetes was commoner than is generally realised.


How trustworthy are bowel histories? Comparison of recalled and recorded information.

One hundred and fifty hospital outpatients were questioned about their bowel habits and then asked to record these in diary booklets for two weeks. Overall, recalled and recorded figures for frequency of defecation agreed fairly closely, but in 16% of patients there was a discrepancy of three or more bowel actions per week. This was usually an exaggeration of the difference from the norm of one a day. Patients were bad at predicting episodes of changed bowel frequency. These findings cast doubt on the value of population surveys of bowel habit based solely on questionnaires. They also suggest that the irritable bowel syndrome might be correctly diagnosed more often if patients were routinely asked to record their bowel actions.


Comparative study of ultrasound, 131I-19-iodocholesterol scintigraphy, and aortography in localising adrenal lesions.

Twenty-seven consecutive patients with endocrinological disease necessitating adrenal surgery underwent blind preoperative investigation with ultrasound, renal aortography, and adrenocortical scintigraphy for an adrenal lesion. Nine patients had pituitary-dependent Cushing's syndrome, five had pituitary-independent Cushing's syndrome, four had an adrenocortical androgenic excess, and nine had a preoperative diagnosis of phaeochromocytoma. The predictive value of preoperative ultrasound was 100% for a positive finding and 79% for a negative result. Preoperative aortography had a predictive value of 83% for a positive finding and 64% for a negative result; and the predictive value of adrenocortical scintigraphy was 100% for a positive finding and 85% for a negative finding. In localising biochemically suspected adrenal lesions ultrasound should be the first choice, since it is rapid, noninvasive, cheap, and reasonably accurate. Adrenocortical scintigraphy has a similar diagnostic value, especially in Cushing's syndrome, but it is time consuming. Nevertheless, it may be preferable for diagnosing small glucocorticoid-secreting adenomas. Aortography should be reserved for cases with inconclusive diagnoses and suspected extra-adrenal phaeochromocytomas.


Overnight urinary 11-hydroxycorticosteroid estimations in diagnosis of Cushing's syndrome.

Overnight specimens of urine were collected from control, obese, and hirsute women and from 11 women with Cushing's syndrome. Urinary 11-hydroxycorticosteroid levels in the group with Cushing's syndrome were significantly higher than in the other three groups. This simple test has proved invaluable when screening for Cushing's syndrome in a busy outpatient clinic.


Enhanced HBsAb production in pathogenesis of fulminant viral hepatitis type B.

The possible importance of humoral immunity in the pathogenesis of fulminant hepatitis was investigated by comparing 17 patients with fulminant hepatitis type B with 20 patients with severe but non-fulminant disease. Hepatitis B surface antigen (HBsAg) was cleared from the serum significantly faster (P less than 0-001) in those with fulminant hepatitis, and in 41% anti-HBsAg (HBsAb) was detectable by radioimmunoassay (RIA) at presentation. In all 11 sera from patients with fulminant hepatitis that were examined by electron microscopy aggregates of HBsAg and HBsAb were seen. In contrast, HBsAb was never detected by RIA in those with non-fulminant hepatitis, and in only one serum specimen (5%) were aggregates seen on electron microscopy. A significant sex difference between fulminant and non-fulminant hepatitis was observed, 65% of patients with fulminant hepatitis but only 15% of patients with non-fulminant hepatitis being women (P less than 0-01). An enhanced production of HBsAb in fulminant hepatitis, by leading to free HBsAb in portal blood, may cause an Arthus reaction in the sinusoids of the liver with ensuing ischaemic necrosis of hepatocytes.


Gastric emptying of solid meals in diabetics.

The gastric emptying rate of an isotopically labelled solid meal was compared in 29 insulin-dependent well-controlled diabetics and 18 normal controls. The diabetics were assessed for evidence of autonomic neuropathy. No significant difference in gastric emptying rate was found between controls and diabetics with or without autonomic neuropathy. Only three diabetics had greatly delayed gastric emptying, but in one of these the test had given a normal result on an earlier occasion.


The 14C-glycocholate test in diabetic diarrhoea.

Twenty-four insulin-dependent diabetics, including seven with diabetic diarrhoea, were studied by means of the 14C-glycocholate (14C-GCA) test and various tests for autonomic dysfunction. The breath component of het test was abnormal in four of the seven patients with diarrhoea and one of the other diabetics. Three patients with diarrhoea and a positive breath test result responded to antibiotics, whereas two with diarrhoea and a negative test result did not. High faecal 14C, suggesting bile acid malabsorption, was found in only one patient with diarrhoea and he had previously failed to respond to cholestyramine. These results suggest that bacterial overgrowth in the small intestine does occur in some but not all patients with diabetic diarrhoea and that the 14C-GCA test can predict the response to antibiotics. All the patients with diabetic diarrhoea had good evidence of autonomic dysfunction.


Haemophilia A and the blood transfusion service: a Scottish study.

The demand for blood products containing factor VIII for treating patients with haemophilia A in south-east Scotland was reviewed. From 1961 to 1975 the demand for fresh frozen plasma (FFP), cryoprecipitate (CP), and antihaemophilic factor (AHF) increased by seven and a half times, while total donations increased by only a third. Patients with severe haemophilia A treated at the regional haemophilia centre used about 85% of the factor VIII issued in 1971-4, most of which was used on demand. A patient with severe haemophilia A on unlimited ondemand home treatment would need about 500 units of factor VII/kg body weight/year, and a regional haemophilia centre, treating moderate and mild cases as well as severe ones, would use 15000 units/patient/year. Altogether about 50 million units of factor VIII will be needed each year in the UK. Although cryoprecipitate is much harder to store and administer than AHF, its yield from plasma may be far greater and its cost far smaller. Unless the blood transfusion services receive increased amounts of money and reappraise their functions and  operation, it seems likely that they will have to rely increasingly on commercial (and costly) sources for the major plasma fractions.


Deviation from prescribed drug treatment after discharge from hospital.

A study of 130 patients discharged from four hospital wards dealing mainly with acute medical cases showed that 66 deviated from the drug regimen prescribed on discharge. Of the patients, 46 did not have a clear understanding of the regimen (non-comprehension) and 20 of the remaining 84 patients understood the prescribed regimen but did not follow the instructions (non-compliance). The prescribing of complex drug regimens, and the availability of medicines prescribed before admission to hospital appeared to be the two main factors influencing non-comprehension and non-compliance.


Control of distension of varicose veins achieved by leg bandages, as used after injection sclerotherapy.

A study was performed to determine whether the pressures routinely produced by bandaging for compression sclerotherapy of varicose veins are adequate to maintain the superfical veins almost empty of blood. The results suggest that well-applied bandages can provide sufficient support to combat the high distending pressures found in varicose veins. The large variation among different surgeons, however, indicates that any clinical assessment of compression sclerotherapy should include measurement of the pressure at which the bandages are applied.


Effect of ethyloestrenol on fibrinolysis in the vessel wall.

Forty-nine patients with decreased fibrinolytic activity in the vessel walls or a decreased release mechanism, or both, were treated with ethyloestrenol for three to 17 months. Forty-five of the patients had had recurrent, phlebographically verified, deep venous thrombosis (DVT) and four had arterial thrombosis. Ethyloestrenol 8 mg/day was given to 31 patients and 4 mg/day was given to 12. The remaining six patients had been treated with a combination of phenformin and ethloestrenol. The phenformin was withdrawn but they were kept on ethyloestrenol 8 mg/day. Another 15 patients with a normal fibrinolytic system--four with recurrent DVT and 11 with severe arteriosclerosis--were given ethyloestrenol 8 mg/day. The spontaneous fibrinolytic activity, local fibrinolytic activity during standardised venous occlusion of the arms, and fibrinolytic activity of the vessel walls increased significantly after treatment with ethyloestrenol 8 mg/day for three months. No further increase occurred after three months, and ethyloestrenol 4 mg/day had no effect. No values rose significantly in the patients with a normal fibrinolytic system. One patient suffered a recurrence within three months of treatment, before the fibrinolytic system became normal. In one patient the fibrinolytic defect reappeared after 10 months in spite of continued treatment. Two of the three women of fertile age developed irregular cycles and intermenstrual bleeding, which disappeared when the treatment was withdrawn. No other side effects were observed.


Surgical audit: one year's experience in a teaching hospital.

For 12 months the surgical staff at Hope Hospital have operated a form of audit. The monitored information included work load, methods of treatment, complications, misdiagnoses, and deaths. The method described is suitable for any district general or teaching hospital provided adequate secretarial help is available. In addition to helping to maintain standards, an audit of this type has a positive educational role.


The curability of breast cancer.

The age-correlated survival rates for 982 women treated for localised breast cancer were analysed retrospectively. Analysis by size of the primary cancer showed that those with smaller cancers had a significantly higher survival rate and a significantly reduced probability of dying of cancer. Cured groups of patients were identified for all but those with the smallest tumours--2.0 cm in diameter or smaller. A long period of follow-up (to 25 years) is necessary to establish the presence of a large cured group in such cases.


Hormonal profiles after the menopause.

The endocrinological changes of the climacteric have been defined by studying the concentrations of follicle-stimulating hormone (FSH), luteinising hormone (LH), androstenedione, testosterone, oestrone, and oestradiol in 60 normal postmenopausal women of different menopausal ages. The women were studied in six groups, according to the number of years since their menopause. One year after the menopause androstenedione, oestrone, and oestradiol concentrations were reduced to about 20% of the values recorded during the early proliferative phase of the menstrual cycle. At the same time the mean concentration of FSH had risen by a factor of 13-4 and that of LH by a factor of 3-0. Concentrations of both gonadotrophins reached a peak of 18-4 and 3-4 times the proliferative phase value respectively after two to three years, and then gradually declined in the next three decades to values that were 40-50% of these maximal levels. Testosterone concentrations remained mostly in the normal range for premenopausal women but were depressed to 60% of these levels two to five years after the menopause, and the mean androstenedione levels showed a significant increase in the same group of women. The concentrations of both oestrone and oestradiol remained consistently low for 10 years after the menopause, but oestradiol concentrations inexplicably increased in the last two decades, with levels at the lower end of normal range for reproductive women in six patients.


Observations on electrocardiogram and plasma catecholamines during dental procedures: the forgotten vagus.

Emotional stress is conventionally considered to be associated with tachycardia and enhanced sympathetic activity. The electrocardiogram and plasma catecholamine and lipid concentrations were observed in 21 young healthy women undergoing dental procedures. Ten of these received premedication with the beta-blocking agent oxprenolol and 11 with a placebo, administered on a double-blind randomised basis. Mild tachycardia occurred in the placebo group a few minutes before and a few minutes after dentistry, but there was a reduction in heart rate immediately before and during the procedure. The pattern was similar in the group who received oxprenolol, though the heart rates at each stage were lower. Plasma adrenaline concentrations were much higher in the samples taken during the procedure than in those taken shortly before and after it. Plasma noradrenaline and lipid concentrations remained unchanged. A decrease in heart rate in the face of intense emotional arousal and an increased plasma adrenaline concentration suggest that the expectation or experience of pain may be associated with parasympathetic dominance despite greatly enhanced sympathetic activity.


Meconium ileus equivalent in adults with cystic fibrosis of pancreas: a report of six cases.

Eleven episodes of "meconium ileus equivalent" have been seen in six adults with cystic fibrosis of the pancreas. Three patients were initially treated surgically; one died and the other two developed serious postoperative chest infections. Six episodes were successfully treated medically with acetylcysteine orally and by enema, nasogastric suction, and intravenous fluids. Operation should be avoided if possible, and maintenance treatment with acetylcysteine may be necessary to prevent relapse.


General practice observed. Child abuse and general practice.

In a general practice of 9250 patients with 1841 children under 10 there were 12 cases of actual abuse during 1973-6. In March 1976 30 children were at risk. A preventive scheme was set up and the short-term outcome was good. There were no cases of serious abuse among the children at risk.


Distribution of nephrological services for adults in Great Britain. Report of the Executive Committee of the Renal Association.

A survey was performed to find out how many doctors in Great Britain were providing nephrological services. The number of such doctors in each region correlated closely with the size of population, but the relation between the numbers of sessions they provided and the size of population, though significant, was not nearly so close. The number of sessions provided correlated strongly with both the number of patients on dialysis and the number of outpatients seen each week. These findings indicated that nephrological services were unevenly distributed throughout the country, while patients with renal diseases are probably evenly distributed. Even in the regions providing the most sessions demand still exceeds supply. In Britain only 62-0 patients per million population were being treated for terminal renal failure at 31 December 1975, whereas over twice that number were being treated in Switzerland (136-1 per million) and Denmark (132-4 per million). Despite the deficiencies in the service, doctors attempt to see all patients with a renal disorder at least once and to treat acute renal failure, though many patients cannot be followed up.


Titanium-strip cranioplasty.

Titanium strips have been used to repair skull defects when preformed metal plates are not avilable and simple wiring would not be enough. The technique is simple, obviates the need to dissect the dura mater, and gives greater resistance to further impact injury than an inlay technique.


Treatment of candidal urinary tract infection with nifuratel.

Three patients with candidal urinary tract infections were successfully treated with oral nifuratel, a nitrofuran antimicrobial agent active against yeast and Trichomonas as well as urinary bacterial pathogens. The recommended dose is 400 mg thrice daily for a week. No side effects that could be attributed to the treatment were noted. Minimum ibhibitory concentration determinations for nifuratel against Candida strains of five species showed that 48 out of 59 organisms were inhibited by 50 mg/1 or less, the three strains of Candida species eliminated from our treated patients having MICs of nifuratel in the range of 10-50 mg/1.


Preoperative prediction of postoperative deep vein thrombosis.

A range of clinical data was obtained from 124 patients about to undergo operation and several coagulation tests were performed. No patient received prophylaxis for deep vein thrombosis, and isotopic scanning after operation showed that 20 patients had developed thrombosis. a simiple prognostic index for predicting which patients would develop postoperative deep vein thrombosis was constructed using the clinical and coagulation data obtained before operation. The five variables with the best predictive power-euglobulin lysis time, age, presence of varicose veins, fibrin related antigen, and percentage overweight-produced an equation that identfied 95% of those who developed deep vein thrombosis and misallocated only 28% of those who did not develop thrombosis. In view of the complications that low-dose heparin and dextran can cause, giving prophylaxis to under a third of the patients who will not develop deep vein thrombosis is clearly better than giving it to all.


Virus-like particles in paraspinal muscle in scoliosis.

Biopsy material from the skeletal muscle (paraxials) of 21 patients with scoliosis was examined by light and electron microscopy. Virus-like particles, 17 nm in diameter with a crystalline structure, were identified in the skeletal muscle fibres of four patients. Associated changes in the sarcoplasm included swelling of mitochondria, presence of lipid droplets, and vesicular structures. Serological studies and culture for virus isolation gave negative results. An excess of lipid (predominantly in type 1 fibres) was noted in the skeletal muscle of several other cases. The significance of these findings is obscure, but the morphology of the paraxial muscles of patients with scoliosis and controls is currently being investigated in greater detail.


Muscle changes in acromegaly.

Muscle biopsy specimens were obtained from 18 patients with acromegaly of varying degrees of severity. Half the specimens showed hypertrophy of type 1 fibres, while atrophy was most often seen in type 2 fibres. A direct correlation between muscle appearances and growth hormone levels was not observed. The needle biopsy technique is particularly suitable for determining the natural history of acrometalic myopathy.


A predischarge unit in a long-stay hospital for subnormality.

A newly built residential ward in the grounds of a long-stay mental subnormality hospital was converted into a predischarge unit to cater for those patients who could probably be discharged after some special training. So far 31 residents have been trained over the past two years; 18 (58%) have been discharged to community residences, and five were waiting for discharge. The high success rate shows the value and usefulness of a predischage unit in a long-stay hospital, and also shows that a purpose-built building is not necessary so long as the staff have the initiative and will to succeed.


Barbiturate prescribing: psychiatrists' views.

When questioned by post most of a one-in five sample of consultant psychiatrists replied that they did not favour the use of barbiturates as hypnotics or a sedatives.


Contribution of preterm delivery to perinatal mortality.

A detailed retrospective analysis was made of the records of 486 preterm infants, who accounted for 5-1% of all births during 1973 and 1974. Whereas preterm delivery did not contribute to perinatal mortality in terms of stillbirth, it outweighed all other causes in terms of early neonatal deaths. Preterm birth was responsible for 85% of the early neonatal deaths not due to lethal congenital deformities. Early neonatal mortality rates were closely linked both to gestational age and birth weight and to the reason for preterm birth. Early neonatal mortality was high (97 per 1000) when preterm labour was spontaneous, whether or not associated with material or fetal disease or with multiple pregnancy, but low (27 per 1000) when preterm delivery was elective. Preventing spontaneous preterm labour would considerably reduce neonatal mortality in our community.


Can phenformin-induced lactic acidosis be prevented?

Although patients taking phenformin are more likely to develop lactic acidosis in the presence of renal, cardiovascular, or hepatic disease, criteria for safe use of the drug are not well established. Eight diabetics died of lactic acidosis in Nottingham in 1972-5 and all were taking phenformin in therapeutic doses. Six had attended the diabetic clinic within a month of their terminal illness. Two patients had appreciable renal impairment and should not have been given phenformin. Four had hypertension and minimal evidence of renal disease, while in two no predisposing factor was identified. There are so many contraindications to the use of phenformin that it is doubtful whether patients on the drug can be monitored adequately. We suggest that phenformin should be withdrawn from general use.


Visual and nonvisual units recorded from the optic tectum of Gallus domesticus.

Units recorded from the optic tectum of Gallus domesticus were tested for responses to visual, auditory and somesthetic and stimuli. Units recorded from the superficial tectal layers (stratum opticum, stratum griseum et fibrosum superficiale) responded only to visual stimuli. On the basis of the unit's responsiveness to the directionality of a moving visual stimulus, three unit types referred to as pandirectional, unidirectional, and multidirectional units were identified. In the deeper layers (stratum griseum centrale, stratum album centrale) unimodal and bimodal units were encountered. These units responded to visual, auditory, and/or somesthetic stimuli. These results indicate that the tectal cortex of Gallus domesticus is subdivided into two functional divisions: the superficial layers which correlate visual information and the deep layers which correlate visual and nonvisual information.


Hyperemotionality and enhanced tonic immobility after septal lesions in the rabbit.

Large lesions of the septal region in the rabbit increased tonic immobility as measured by the number of successful inductions and by duration of immobility. Open field activity was also increased. Septally lesioned rabbits also exhibited increased emotionality, although the topography of the 'septal syndrome' in these rabbits was different from that described for rats. The septally lesioned rabbits exhibited increases in fear reactions such as thumping, escape responses and vocalization when caught, rather than increased aggressiveness. The results are discussed in terms of loss of inhibition of species-typical responses after septal damage.


Retinal projections in cyprinid fishes: a degeneration and radioautographic study.

The retinal projections of three species of cyprinid fish (Cyprinus macrolepidotus, Cyprinus carpio, Rutilus rutilus) were examined with Nauta and Fink-Heimer methods following enucleation and with radioautography following intraocular injection of [3H]-L-proline. Optic tract axons cross completely in the optic chiasma and are distributed to the hypothalamus (nucleus opticus hypothalamicus pars magnocellularis), the thalamo-pretectal region (11 distinct primary optic centers), and the tectum opticum (stratum fibrosum et griseum superficiale, stratum griseum centrale and stratum album centrale). No accessory optic tract was found. The experimental studies on visual projection of various teleosts are reviewed and discussed.


Vestibular projections to the thalamus of the pigeon.

Microelectrode recording in the thalamus of pigeons subjected to tilt and sinusoidal rotational stimuli around the vertical, longitudinal and transversal axes revealed vestibularly driven units in two thalamic nuclei, the nucleus posteroventralis and the nucleus principalis precommissuralis. Many of these units responded in a complex manner suggesting that inputs from contralateral and ipsilateral cupulae and maculae converged on them. A few units received additional visual or proprioceptive information. The homology relationship with a mammalian vestibular thalamic nucleus is discussed briefly.


An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. I. Magnitude and time course of degeneration.

Synapses in the rat dentate gyrus are rapidly lost after removal of the primary input from the entorhinal cortex. In this paper we describe the extent and time course of degeneration and in the subsequent paper the nature of the reinnervation processes. They synapses of entorhinal afferents are remarkably concentrated in their zone of termination. Unilateral removal of the rat entorhinal cortex results in the loss of about 86% of all synapses in the outer three-fourths of the molecular layer of the epsilateral dentate gyrus. Entorhinal synapses are all asymmetric (Gray type I) and terminate on dendritic spines. Analysis of the degeneration reaction provides a means to examine the characteristics of the loss of a relatively homogeneous afferent on a single cell type. The morphological characteristics of the the degenerating terminals showed some heterogeneity; both the electron lucent and electron dense types of degenerating terminals were identified. The electron lucent type was observed only at short survival times. The time course of the loss of degenerating terminals was resolvable into two components, each of which followed first order decay kinetics. Thus degenerating entorhinal terminals behaved as a population which disappeared randomly at a rate dependent on the fraction of terminals present at any time. The loss of degenerating terminals was accompanied by the loss of postsynaptic sites. At short survival times the majority of postsynaptic sites (defined by the presence of a postsynaptic density) had disappeared. There was also a loss of complex spines and some shrinkage of the molecular layer.


The mechanism of inhibition of neuronal activity by opiates in the spinal cord of cat.

Extra- and intracellular recordings from motoneurones, interneurones and dorsal horn neurones (laminae 4 and 5) were obtained from the lumbar segments (L6-L7) of spinalised (Th 9/10) or pentobarbital-anaesthetised and anaemically decorticated cats. In the majority of spinal neurones microelectrophoretically applied morphine and levorphanol reversibly depressed spontaneous as well as stimulus-evoked and L-glutamate- or acetylcholine-induced activity. There is evidence that opiates block L-glutamate-induced depolarisations by impairing the Na+-influx triggered at the postsynaptic membrane. These depressant effects of opiates could be antagonised by naloxone, and, except in a few cases, were not associated with hyperpolarisation of the cell. Dextrorphan, the D+ enantiomer of levorphanol, displayed no such depressant actions, indicating that stereospecific receptors mediate the depressant effects of opiates. Phoretically applied atropine, procaine and Ca2+ ions have anti-glutamate and anti-acetylcholine actions similar to opiates, but these actions were not antagonised by naloxone. The hyperpolarising effect of glycine was not influenced at dose levels of opiates sufficient to suppress depolarisation induced by L-glutamate or acetylcholine. Microelectrophoretically administered morphine and levorphanol slowed the rate of rise of mono- and polysynaptic EPSPs by a naloxone-antagonisable mechanism at dose levels where almost no alteration in spike shape was detectable. Increased doses of morphine and levorphanol reduced the amplitude of IPSPs and completely blocked or reduced the amplitude of both direct- and antidromically-evoked spikes. These effects of increased doses of opiates were not antagonised by naloxone. Intravenous injection of 2 mg/kg of morphine or 20 mug/kg of Fentanyl mimicked the suppression of spontaneous and evoked neuronal activity observed after phoretic administration. This depressant action of systemically applied opiates could be transiently antagonised by phoretic administration of naloxone. The results are discussed with respect to a stereospecific action of opiates at a postsynaptic receptive site in the spinal cord.


The effect of antisynaptosomal plasma membrane antibodies on memory.

Antisynaptosomal plasma membrane antibodies were introduced through an infusion cannula into rat brain and their effects on behaviour were tested. Four different learning paradigms were used, two appetitively and two aversively motivated, to show impairment in memory retrieval. No effects were found on aquisition, motor activity, or motivation.


An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. II. Reappearance of morphologically normal synaptic contacts.

Intact synapses in the denervated area of the rat dentate gyrus are reduced to 14% of those normally present 2-4 days following a unilateral entorhinal lesion. By 160-240 days after lesion, the former entorhinal terminal zone is repopulated with new synapses. In all, there is more than a 5-fold increase in the density of intact synapses in the denervated zone between 2 and 240 days post-lesion, and the denervated zone of the molecular layer is restored to 80% of control values. The synapses are Gray type I and are formed on simple and complex spines which closely resemble those normally present. A few boutons have an abnormally large number of synaptic junctions. Reinnervation seems to progress at differential rates. Synapses are rapidly regained up to 30 days after operation, but thereafter the reacquisition of synaptic connections is much slower. Reinnervation is more rapid in the portion of the denervated zone nearest the granule cells, where the maximal densities are attained within 30 days. The time course of reinnervation differed from that of degeneration. A portion of the new synapses in the reinnervated molecular layer appear to arise by the assembly of new synaptic junctions. Over time, the number of post-synaptic contact sites along a given length of dendritic surface recovers, suggesting the formation of new synaptic sites. Our data indicate that granule cells retain a capacity even into adulthood to manufacture, position and assemble postsynaptic components of a synapse and, in concert with reactive afferents, form normal-appearing synapses.


Fine structure of the olfactory bulb in the goldfish, Carassius auratus.

Ultrastructural studies have aided in identifying the principal cell types and the layers of the olfactory bulb in goldfish. The concentrically arranged four layers are: the primary olfactory nerve layer (most peripheral), the glomerular layer, the mitral cell layer, and the granule cell layer (deepest). Three types of cell bodies were differentiated by their size and cytoplasmic organelles: mitral cells, granule cells and short axon cells. The axons of the primary olfactory nerve formed synaptic contacts with mitral cell dendrites in the glomeruli. Reciprocal synapses were observed between the granule cell dendrites and the mitral cell dendrites in the mitral cell layer. Terminals of the centrifugal fibers forming synaptic contacts with the granule cell dendrites were identified in the granule cell layer. The relationships between the cellular and synaptic organizations and the neural mechanism of olfaction are discussed.


Tuning of single fibers in the cochlear nerve of the alligator lizard: relation to receptor morphology.

(1) The general anatomy of the peripheral portion of the cochlear nerve in the alligator lizard is described. (2) Spike discharges of single units were recorded with micropipets placed in the peripheral portion of the cochlear nerve of anesthetized lizards. (3) In response to tone bursts, each unit is maximally sensitive to a charactertistic frequency (CF). There are two distinct populations of units having different CFs: a low CF population (CF in the range 0.2-0.8 kHz) recorded in the portion of the nerve that enters the apical region of the basilar papilla and a high CF population (CF in the range 0.9-4.0 kHz) recorded in the portion of the nerve that enters the basal region. The low CF units are more sharply tuned than the high CF units. (4) Comparison of cochlear nerve units of the alligator lizard with those of mammals shows that the tuning of low CF units resembles that of mammalian units of the same CF. The tuning of high CF lizard units differs significantly from mammalian units. (5) The distinct differences in tuning of low and high CF units are correlated with distinct differences in the structure of the basilar papilla in the apical and basal regions rather than with differences in the width of the basilar membrane.


Stimulation of the dorsal noradrenergic dundle and field potentials in the locus coeruleus.

Field potentials were recorded from the locus coeruleus following electrical stimulation of the rat midbrain. Activation of a discrete area situated ventrolateral to the central gray evoked long-latency potentials in the locus coeruleus while stimulation of other midbrain sites did not. Damage to this discrete area resulted in a depletion of norepinephrine in the cerebral cortex suggesting that it is a segment of the dorsal noradrenergic bundle arising from the locus coeruleus.


Preparation of cell bodies from the developing cerebellum: structural and metabolic integrity of the isolated cells.

A method is described for the isolation from the developing rat cerebellum of cell bodies which display a high level of ultrastructural organization. The procedure, which utilizes isotonic conditions throughout, begins with a brief trypsinisation at low enzyme concentration (0.025%). Proteolysis is terminated by trypsin inhibitor and followed by short exposure to EDTA. The technique is effective with cerebella from rats up to 2 weeks after birth. Recoveries of cell bodies vary from 130-410 million/g wet weight of tissue, depending on age: this represents, in terms of recovered DNA, a mean value for yield of 33%. Suspensions contain little debris, free nuclei are rare and about 80% of the perikarya excludes trypan blue. Survey electron micrographs show that most cell bodies possess uninterrupted plasma membrane profiles and retain highly organised cytoplasmic and nuclear ultrastructure. Structural preservation is highlighted in the case of Purkinje cell bodies in which may characteristic features survive including, most notably, perisomatic spines. Metabolic integrity appears to parallel morphological preservation as judged by several functional criteria, including the ability to metabolise glucose, accumulate K+ ions and synthesize proteins. SDS-polyacrylamide gel electrophoresis shows that the tissue dossociation technique does not lead to major deletions of cell proteins and that the pattern of perikaryal protein synthesis in vitro closely resembles that in vivo. These perikaryal preparations therefore hold out great promise as a simplified system for metabolic studies and as a starting material for the derivation of purified sub-populations of cell bodies from developing cerebellum.


Silver impregnation of dopaminergic systems after radiofrequency and 6-OHDA lesions of the rat ventral.

Nauta and Fink-Heimer silver impregnation techniques were used to study the anterior degeneration produced by radiofrequency (RF) or 6-OHDA lesions in the medial and lateral ventral mesencephalic tegmentum (VMT), substantia nigra and dorsalis tegmental decussation (DTD) in rats. Both Nauta and Fine-Heimer impregnating methods showed that RF lesion of the VNT produced degeneration in three major pathways: a ventral pathway corresponding to the fasciculus medialis prosencephali (FMP), an intermediate pathway projecting to the ventral thalamus, and a dorsal pathway to the medio-dorsal thalamus and to the nucleus lateralis habenulae. In addition, the Fink-Heimer method demonstrated prejections of the dopaminergic A10 and A9 cell group in the VMT to the nucleus caudatus after RF or 6-OHDA lesions. Projections to nucleus accumbens, tuberculum olfactorium, stria terminalis, and cortex frontalis were observed only after 6-OHDA lesion of the A10 cell group. Degeneration in cortex cinguli and entorhinalis was seen mainly after 6-OHDA lesion of the A9 cell group. The limbic forebrain cortical projections of the A10 group provide a coherent anatomical basis for the behavioral syndrome provoked by RF and 6-OHDA lesions in the VMT.


Nucleoside triphosphate and cation requirement for dopamine uptake by plain synaptic vesicles isolated from rat cerebrums.

Plain synaptic vesicles were partially purified from rat cerebrums and their [3H]dopamine uptake was investigated. The addition of MgCl2 plus ATP and of CaCl2 plus ATP increased the uptake 16 times and 5.5 times, respectively, higher than the control level, whereas the separate addition of these agents augmented the level at most 2.5 times. GTP stimulated the uptake as well as ATP, whereas UTP was one-third as effective and CTP, ADP, and AMP were all ineffective. Adenylyl imidodiphosphate was not only ineffective, but strongly reduced the ATP-dependent uptake. The half-maximal level of the ATP-dependent uptake was reached within 1.5 min after the start of incubation at 25 degrees C. The incorporation peaked at 5-10 min, then gradually declined to half-maximum at 45 min. This decline was prevented by the further addition of small amounts of CaCl2. There was no uptake at  0 degrees C, and the incorporation rate was at least 2 times faster at 37 degrees C than it was at 25 degrees C. The apparent Michaelis constant for [3H] dopamine was 1.6 muM. The half maximal inhibition of uptake was obtained at 0.1 muM reserpine; neither colchicine nor ouabain showed significant inhibition. The ATP-dependent uptake was not affected by K+, Na+, and Cl-, but was drastically decreased by isotonic phosphate buffer.


Monosynaptic habituation in the vertebrate forebrain: the dentate gyrus examined in vitro.

The dentate gyrus of the hippocampus was examined for the presence of the parametric features of habituation. All 8 of the tested parameters were found in the dentate thus extending the observation of habituation to a monosynaptic junction in the vertebrate forebrain. The data are discussed in relation to hippocampal function and plasticity.


Lithium induced alterations in rat ganglionic lipids.

Superior cervical ganglia from normal or lithium fed rats were incubated in vitro with [U-14C]pyruvic acid, in Krebs-Ringer solution with or without lithium ion. Acute lithium incubations were performed on ganglia from normal rats with 25 mEquiv./l of lithium ion, while chronic incubations were performed on ganglia from lithium fed rats with 0.5 mEquiv./l lithium in the bathing solution. Lipids were extracted, separated by thin layer chromatography and specific activities of individual lipids and their fatty acids determined. In control ganglia shinogolipids contained 60-70% of the lipid radioactivity, glycerophospholipids 20-30% and neutral lipids 10-25%. Phosphatidylcholine contained 65% of the glycerophospholipid label and 40% of the lipid phosphorus, while sphingomyelin contained 90% of the sphingolipid label and exhibited the highest specific activity over all. Cholesterol was the major neutral lipid. Niety-five per cent of the glycerophospholipid label and 4% of the sphingomyelin label was localized in the fatty acids. The lipid and fatty acid compositions of all ganglia were similar. However the lipid radioactivity in chronic ganglia was lower than in control, with the sphingolipids most affected. In 80 min stimulated chronic ganglia stearic and oleic acid, radioactivity was depressed with respect to both control fatty acids and to the [14C]palmitate of chronic tissues. In both chronic and acute lithium ganglia stimulated for 80 min, the specific activities of phosphatidylinositol were significantly lower than in control. In contrast to control, the labeling of sphingolipids in resting acute ganglia was higher than in stimulated tissues.


Developmental studies of the compartmentalization of water and electrolytes in the choroid plexus of the neonatal rat brain.

Rats of various postnatal ages were utilized to study developmental changes in the distribution of Na, K and H2O between the various compartments of the lateral ventricular plexus (LVP). During the 3 weeks after birth, as the LVP grows from 0.5 to 0.8 mg, there is a significant increase in plexus K which is accompanied by a progressive decrease in Na and H2O. Also, during this postnatal period the decrease in [3h]inulin space in the plexus is proportional to the decrease in the Na space. Between 3 weeks and adulthood, the [3h]inulin and Na spaces are both augmented to a similar extent; moreover, during this same period of development there is a trebling of the residual [51cr]erythrocyte volume. Despite the substantial changes in the volume of the extracellular fluid and of the residual blood in the plexus with age, the calculated concentrations (mEquiv./kg H2O) of choroid cell Na (30-35) and K (145-155) are similar for all ages investigated. The derived data for cellular ionic concentration, together with the analysis of the ionic concentration gradients (cerebrospinal fluid/plasma H2O), suggest that the transport mechanism which translocates Na and K across the choroidal membrane is operative as early as 3-4 days postnatal. The important role of the choroid plexus in central nervous system homeostasis is discussed in relation to the developing brain.


Effect of auditory neocortex ablation on identification of click rates in cats.

Six experimental and 3 unoperated cats were trained with a go, no-go shock avoidance procedure to discriminate increases from decreases in the rate of presentation of all auditory cortex between the suprasylvian sulcus and rhinal fissure while 3 cats had bilateral auditory cortex lesions plus ablation of the cortex of the anterior lateral and anterior and middle suprasylvian gyri. A sixth 'naive' experimental cat received the present tests only after recovery from a bilateral auditory cortex ablation. After bilateral lesions, 5 of the experimental cats unexpectedly made no errors on no-go trials during retraining. This contrasts with their preoperative performance, as well as the performance of the 3 unoperated and the 'naive' operated cat, in which training was required for the successful discrimination of the two types of trials. This suggests that the neocortex may be more critical for mediating active 'go' responses to auditory stimuli than in preserving a memory for the difference between go and no-go stimuli. Further testing revealed that the thresholds of the operated cats did not differ from normal cats. All cats discriminated rates of 4/sec versus 6/sec clicks both with and without a neutral 5/sec background at levels significantly above chance.


Chronic changes in the response of cells in adult cat dorsal horn following partial deafferentation: the appearance of responding cells in a previously non-responsive region.

One side of the lumbar enlargement in adult cats was partially deafferented by cutting all dorsal roots caudal to L3 with the exception of the S1 dorsal root. At various times after the roots had been sectioned, the response of dorsal horn  cells to natural and electrical stimuli applied to the leg and flank were recorded through extracellular glass microelectrodes. When animals were examined up to 24 h after this partial deafferentation, no cells were located in a region between segments L4 and 5 which responded monosynaptically to cutaneous stimulation on the leg. By one week, cells began to appear in the L4-5 region which responded monosynpatically to peripheral stimuli. The numbers of these newly connected cells seemed to have stabilised by 1 month after the partial deafferentation, but the properties of these cells were abnormal in 6 ways. The location of the receptive field of the cells was characteristic either of the S1 dermatome or of segments rostral to L4. Some cells had double receptive fields, one on the leg and one of the abdomen. The size of the receptive field varied more than is observed in normal intact dorsal horn. In particular, certain cells had unusually small recpetive fields with abrupt edges and no associated inhibitory fields. The cells receive less convergence from high treshold afferents than normally observed. Associated inhibitory fields were rarely encountered. Habituation was observed and in some cells with doulbe receptive fields the response o onet area habituated while the response to the other area was unaffected. Slow wave recording on the surface of the cord showed that the effect of peripheral stimulation of the S1 dermatome spread far more extensively on the chronically deafferented side of the cord than it did on the intact side or in an intact cord. It was concluded that following partial deafferentation, the remaining afferents can establish connection with deafferented cells but the data presented did not allow a conclusion as to whether the new connections were produced by sprouting or by the unmasking of existing connections.


Responses of complex cells in the visual cortex of the cat as a function of the length of moving slits.

(1) As a step towards specifying the spatial selectivity characteristics of complex cells with spatially periodic substructures, we have studied single cell responses to narrow slits of variable length moved across the receptive field in the preferred direction. In general, the length-response curves were linear over a considerable and sometimes full range until an optimal slit length was reached. (2) In those cells in which the rate of rise of the slit length-response functions decreased before the optimal length was reached, at least 3 factors contribute to the shape of the curve. First, the receptive field shapes of some complex cells are more ovoid or rounded than rectangular, and the summation of responses from excitatory zones of varying optimal lengths itself results in a nonlinear slit length-response function at long slit lengths. Second, central regions may contribute more to cell response than do more lateral regions along the length dimension. Third, a nonlinearity in the slit length-response curve may occur in the upper range of slit lengths as a saturation effect because discharge rates may reach 600/sec, which appears to be close to a limiting firing rate. (3) Some cells believed to be complex during preliminary receptive field testing showed weak inhibitory regions beyond the region of the optimal slit length. Many of these cells also displayed periodic average response histograms to moving slits. The extent and magnitude of the inhibition were variable from cell to cell. In terms of receptive field properties, these cells and 'regular' complex cells seem part of a continuum.


The effects of pentylenetetrazol on molluscan neurons. I. Intracellular recording and stimulation.

The effects of the convulsant drug pentylenetetrazol (PTZ) were studied in neurons from isolated ganglia of the nudibranch molluscs, Archidoris montereyensis and Anisodoris nobilis, using conventional techniques of intracellular recording and constant current stimulation. PTZ was selected because it causes changes in the intracellularly recorded responses similar to the depolarization shifts recorded in mammalian epileptic neurons. When perfusate containing 120-140 mM PTZ is introduced, the intracellular recording is characterized by an initial silent period followed by small oscillations in membrane potential and irregular firing of spikes. Within 5-15 min, bursts of 2-3 spikes occurred followed by the appearance of episodic prolonged depolarizations with superimposed high-frequency spikes. In the presence of PTZ the prolonged depolarizations were evoked by intracellular stimulation and at the termination of conditioning hyperpolarizations. The prolonged depolarizations were also recorded in neurons isolated from all synpatic input by axonal ligation. Prolonged depolarizations showed threshold behavior since they can be terminated early by an intracellularly applied hyperpolarizing current.


The effects of pentylenetetrazol on molluscan neurons. II. Voltage clamp studies.

The effects of pentylenetetrazol (PTZ) upon the steady and transient outward ionic currents during PTZ-induced prolonged depolarizations were investigated using voltage clamp techniques. PTZ causes a 5-35% reduction in gL and a 40-60% reduction in steady-state gK. There is also a marked reduction in the activation of gA of Connor and Stevens6 at all clamp potentials; a shortening of the time constant for the inactivation of gA; and a 10-15 mV shift in the depolarizing direction of the curve relating the steady-state inactivation of gA to membrane potential. The equilibrium potentials for both gA and gK are depolarized by 20 mV in PTZ solution. Equation and voltage clamp data for normal repetitive firing were integrated with the normal and PTZ-alered data. Solution to these equations demonstrated: (1) normal repetitive firing in response to a constant current stimulus; and (2) PTZ-altered repetitive firing that was in the direction of, and for the most part, similar to the observed behavior.


Incorporation of tritiated leucine by axotomized rubral neurons.

Fourteen kittens, 7--10 weeks of age, were injected with [3H]leucine 0.5--24 h before sacrifice 1--30 days after unilateral high cervical rubrospinal tractotomy. Histoautoradiographs of the red nuclei were prepared and counterstained with thionin. Axon reaction, evident histologically 24 h after surgery, was manifested by central chromatolysis or diffuse cytoplasmic chromophobia. Partial reversion toward a normal cytologic appearance was apparent 10--30 days postoperatively. Nucleolar and nuclear shrinkage and cytoplasmic atrophy were conspicuous accompaniments of axon reaction in rubral neurons. Expressed per cell the radioactivity of axotomized rubral nerve cells was consistently less than controls in animals surviving operation from 5 to 30 days. The data indicate that axon reaction in red nucleus is regressive in character and early associated with diminished protein synthesis. The frequently regressive nature of axon reaction in intrinsic neurons, such as those of red nucleus, probably is important in accounting for failure of regeneration of many mammalian CNS fiber tracts after injury.


Regional distribution of substance P in the brain of the rat.

Using a sensitive radioimmunoassay we have studied the regional distribution of substance P. The level of substance P is higher in the mesencephalon, hypothalamus and preoptic area than in other regions of the brain. Substance P is found in especially high concentrations in the reticular part of the substantia nigra and the interpeduncular nucleus. It is present in large amounts in several septal, preoptic and hypothalamic nuclei as well.


The growth of the dendritic trees of Purkinje cells in irradiated agranular cerebellar cortex.

The heads of noenatal Wistar rats were irradiated with 200 rads daily from birth to the 10th day post-partum. Ten litters each containing 5 animals were killed at 30 days post-partum and their brains treated by the Golgi-Cox technique. The dendritic trees of 24 Purkinje cells were analysed using the quantitative technique of network analysis, and comparisons made between parameters obtained from 20 normal Purkinje cells. All dendritic trees in agranular irradiated cortex were markedly reduced in size (as indicated by total dendritic length and total number of segments) although mean path lengths were normal. Segment lengths were normal over proximal branches, but uniformly increased over distal branches. Abnormal appendages, called 'giant spines' were observed on many dendrites. They were often some 10 mum in length and their presence effectively reduced segment lengths, increased the frequency of trichotomy and deviated growth from the normal random terminal pattern so that long collateral branching topologies were formed. Nevertheless, trichotomy was uniformly reduced in those trees without 'giant spines' and the distribution of branching patterns suggested that growth had proceeded by random terminal dichotomy. These results demonstrate that the development of dendritic trees is retarded in the agranular irradiated cerebellum, where synaptogenesis is very greatly reduced below normal. The quantitative changes in segment lengths, size of trees, and trichotomy accord with those predicted by the filopodial synaptogenic hypothesis of dendritic growth formulated by Vaughn et al. 99, whilst the results of the topological analysis suggest that branching is established by a degree of non-random interaction between growing dendrites and their substrate. 'Claw-like' dendritic complexes within some Purkinje cell trees may have been induced by aberrent fibre bundles of few surviving granule cells.


Regional differences in the morphology of the rat subfornical organ.

Based upon scanning and transmission electron microscopy 3 regions are distinguished in the rat subfornical organ. The rostral region is dominated by nerve fibers interspersed with relatively few neurons and glial cells. Squamous to low cuboidal ependymal cells with flat ventricular surfaces bearing a few short microvilli line the center of this region; laterally, ciliated cuboidal ependymal cells predominate. The central region occupies the largest area of the organ and contains most of the neuronal perikarya and glial cells. Many perikarya and neuronal processes are located immediately underneath the ependymal surface. A dense capillary network with wide pericapillary spaces permeates the tissue. In the rostral two-thirds of this region the ependymal cells are either squamous or cuboidal, sometimes with slightly bulging ventricular surfaces bearing longer microvilli. Here supraependymal neurons are particularly numerous. The caudal one-third of the central region is characterized by squamous, cuboidal and columnar ependymal cells whose hemispherical ventricular surfaces are studded with long microvilli and occasional cilia and vesicular protrusions. The caudal region, like the rostral region, is dominated by nerve fibers between which neuronal perikarya and glial cells are present. At this level the choroid plexus is attached to the SFO through highly vascularized pial connective tissue. It is the major point of penetration of the SFO's capillary plexus. The possible significance of these observations and their importance in experimental interventions are discussed.


Convergence of the descending pathways of motor, visual and limbic cortex in the cat di- and mesencephalon.

Comparisons of the descending pathways of the motor, visual and limbic cortex in the cat revealed a number of structures in di- and mesencephalon that receive projections from all these fields. They are centrolateral (CL), paracentral (Pc), central medial (CeM) and centre median (CM), nuclei of the thalamus, zona incerta (ZI) and Forel's field H1 of the subthalamus, nucleus of the posterior commissure and anterior and posterior nuclei of the pretectum (Prt), stratum griseum intermedial and profundum of superior colliculus (CS), periaqueductal gray matter (GC) and pontine nuclei (NP). The projections from the striate field of the visual cortex to ventrobasal complex of the thalamus (VB) are shown. The results are discussed with recent data on the anatomy and physiology. A possible role of corticocortical and corticofugal fiber connections is dealt with.


Response plasticity in hamster olfactory bulb: peripheral and central processes.

It is a well-established fact that prolonged odor stimulation leads to marked sensory adaptation. This study demonstrates comparable electrophysiological phenomena occurring at the level of the olfactory receptor and at more central olfactory structures. Recordings of overall receptor response and of olfactory bulb unit responses were made during repeated odor stimulation. During the course of a single, continuous odor presentation response decrements were seen in the EOG (at the olfactory receptors) and were mirrored at the mitral cell layer of the bulb. When brief periods without stimulation were introduced between such odor presentations, receptor responsiveness rebounded to its original level, but mitral cell responses did not. On the basis of this dissociation it is suggested that the pattern of response decrement within the bulb represents a case of stimulus-specific habituation in a simple cortical subsystem and is well worth future investigation as a model of neural plasticity. Surgical disconnection of the olfactory bulb from one or more of its centrifugal inputs results in hyperactive, hyperresponsive mitral cells, which habituate more rapidly and show longer recovery times than do those in the intact bulb. In addition, the synchronization of such units to the inhalation cycle is markedly reduced as compared with normal preparations. These facts together suggest that the habituation of mitral cell activity does not depend on centrifugal inputs, although one or more of such inputs act indirectly in an inhibitory fashion to modulate and tune mitral cell response characteristics.


The contribution of local blood flow to the rapid clearance of potassium from the cortical extracellular space.

The transport of potassium to the blood stream following stimulation of the cortex in cats is evaluated by means of a potassium sensitive microelectrode technique. Potassium levels are measured in cortical veins, the sagittal sinus and the extracellular space during and after both pharmacological and electrical stimulation of the cortex. It is concluded that the potassium transport to the blood stream is not a significant factor in the rapid clearance of potassium from the extracellular space following stimulation.


On spinal noradrenaline receptor supersensitivity: correlation between nerve terminal densities and flexor reflexes various times after intracisternal 6-hydroxydopamine.

The noradrenaline (NA)-dependent hindlimb flexor reflex that can be elicited by pinching the foot of acutely spinalized rats given nialamide-DOPA or clonidine was evaluated different time intervals (14 days-6 months) after intracisternal injections of 6-OH-dopamine (6-OH-DA) and correlated to the degree of bulbospinal catecholamine (CA) denervation as seen by Falck-Hillarp fluorescence histochemistry. Six and 14 days after 6-OH-DA, when almost all NA nerve terminals of the spinal cord had degenerated, the NA receptors where supersensitive to stimulation with clonidine as evidenced by an increased flexor reflex. This supersensitivity gradually disappeared as new nerve terminals were formed in the grey matter of the spinal cord during the following 3-6 months. The supersensitivity phenomenon 14 days after 6-OH-DA could also be demonstrated by L-DOPA given to animals pretreated with 100 mg/kg nialamide. Using this relatively low dose of nialamide, almost no reflex response was seen in the control group. Using a higher degree of monoaminoxidase inhibition (nialamide 200 mg/kg) also non-supersensitive, NA receptors became maximally stimulated. Therefore, 6-OH-DA treated rats now showed a weaker reflex than controls, the reflex response being directly correlated to the number of nerve terminals present that could form NA from the precursor. Using 5,6-dihydroxytryptamine, which selectively destroys 5-hydroxytryptamine (5-HT) nerves, it was shown that the flexor reflex changes were specifically related to the NA nerves and unchanged by the simultaneous presence or absence of 5-HT nerve terminals. This was further supported by the finding of a correlation between amount of nerve terminals and flexor reflex responses in individual animals, especially at longer survival times both in the clonidine and the nialamide-DOPA experiments.


Long lasting changes in the spontaneous activity of hippocampal neurons following stimulation of the entorhinal cortex.

The spontaneous activity of hippocampal and denate units was investigated in acute and chronic experiments on adult rats. Spontaneous unitary discharges from both regions were measured before and after brief tetanic stimulation of the entorhinal cortex. An increase in the frequency of spontaneous unit activity was obtained in units recorded from the dentate gyrus and CA3 field of the hippocampus for up to 20 min following stimulation. In chronic recordings of physiologically identified dentate units from freely moving rats similar results were obtained. The findings are discussed with reference to long lasting potentiation of synaptic activity in the perforant path-dentate granule cell connection.


Effect of prenatal heat stress on brain growth and serial discrimination reversal learning in the guinea pig.

Exposure of pregnant guinea pigs to an environmental temperature of 42 degrees C for 1 hr daily on Days 20-24 of gestation resulted in a significant reduction in the birthweight and brainweight of newborn offspring. These deficits persisted to early maturity and were still evident at 250 days of age following behavioral testing. Although some degree of postnatal neurogenesis and brain growth had occurred, this was not sufficient to compensate for the retarding influence of prenatal hyperthermia. Heat stress was also observed to seriously impair learning performance on the original discrimination task and this tendency persisted over the subsequent 4 reversals for both initial and perseverative errors. Impaired learning performance was related to reduction in brainweight. Animals with lower brainweights made significantly more initial, perseverative and total number of errors over the 5 problems. In addition, 12 of the 14 behaviorally tested stressed progeny had brainweights that were at least 2 standard deviations below the mean of the controls and as a result were classified as micrencephalic. Although heat stressed animals showed a significant reduction in the number of amacrine synapses in the inner plexiform layer of the retina, performance differences were not atrributed to changes in synaptic organisation of the retinal circuitry or to visual or other ophthalmic defects, but brain function. Animals with higher mean maternal poststressing core temperatures gave birth to progeny which had smaller whole and part wet-brainweights. Examination of the effect of poststressing core temperature on brainweight revealed that brain growth, independent of bodyweight, was retarded when this temperature elevated above 41.5 degrees C. This represented a rise of approximately 2.1 degrees C above normal and for each 1 degree C rise above this temperature, brainweight was reduced by 0.4227 g of the control value. Analysis of the atmospheric content of the incubator during stressing sessions ruled out the possibility that changes in level of oxygen and carbon dioxide may have contributed to the retarding influence on fetal development and learning ability in the guinea pig.


Nucleus circularis: is it an osmoreceptor in the brain?

The nucleus circularis, in the anterior hypothalamus, is a group of magnocellular elements arranged in a ring around a capillary bed. The cells are predominantly monopolar, tightly packed, and are flattened at the outer border of the ring. The entire nucleus is surrounded or encapsulated by myelinated fibers. Electrical stimulation of this nucleus produced a short-latency, long-lasting and substantial antidiuresis in ethanol anesthetized rats. Water deprivation induced changes in numbers of nucleoli and cell size increases in these cells. The multiplication of nucleoli in this nucleus during water deprivation was more profound than that previously observed in the supraoptic nucleus. Decreases in multiple nucleoli accompanied voluntary rehydration. Seven criteria for status as an osmoreceptor are listed and the nucleus circularis was found to meet 6 of these criteria, the seventh being the demonstration of receptor potentials which has not yet been attempted.


Distribution of 3H-alpha-MSH in rat brain.

Radioactive synthetic alpha-MSH, prepared by selective tritiation of its dibromo-L-tyrosine-derivative, was injected into the carotid artery of intact, hypophysectomized or pinealectomized rats. More radioactivity was found in the occipital cortex, cerebellum, and pons-medulla than in most other brain parts of rats decapitated 15 sec and, to a less significant extent, 30 min after injection. Part of this radioactivity behaved like alpha-MSH in several identification procedures. After administration of 3H-tyrosine, the least radioactivity was consistently found in the pons-medulla. Large amounts of radioactivity after 3H-alpha-MSH were found in the pituitary and, particularly in the hypophysectomized rats, in the pineal. The half-time disappearance of the first component of radioactivity from the blood of each group of rats injected with tritiated-alpha-MSH was no more than 2.5 minutes, a time considerably shorter than the behavioral and EEG effects of this pituitary hormone on visual attention.


Acetylcholine, an inhibitory transmitter in the rat lateral hypothalamus.

Basolateral stimulation of the amygdala inhibited spontaneous firing of rat lateral hypothalamic neurons. The inhibition was augmented by eserine and blocked by atropine. Acetylcholine mimicked the inhibition and produced approximately 15 mV of hyperpolarization beyond the original resting membrane potential which stopped spontaneous firing. The ACh effects were reversible. Results indicate that ACh might be an inhibitory transmitter involved in LH inhibition by AL stimulation.


Evoked potential-unit relationships in behaving cats.

Adult cats were implanted with a movable microelectrode, and trained to respond differentially to two different frequencies of light flicker. Unit responses and evoked potentials were recorded along trajectories in the visual cortex and lateral geniculate nucleus. Although strong correlations are shown to exist between certain components of the evoked potential and peaks in the poststimulus histogram, it is demonstrated that it is impossible to specify a causal, predictive relationship.


Single cell activity in chronic unit recording: a quantitative study of the unit amplitude spectrum.

The ratio of standard deviation to mean, of the amplitude spectrum of well resolved single units, is shown to scale exponentially. This scaling is explained on the basis of a consideration of the relationship of extracellular voltage to voltage gradient, in a dendritic neuron model. A method is then advanced to extract, from multi-unit data, normally distributed amplitude spectra which are indistinguishable from those of well resolved single units. This method is suggested as a means of characterizing, in general, the unit activity obtained from chronically implanted preparations.


An examination of the participation of neurons in readout from memory.

Adult cats were implanted with a movable microelectrode and were trained to perform for food reward in response to diffuse light flicker at two different frequencies. After substantial overtraining, the patterns of cell response (poststimulus histogram) were obtained during generalization trials, using an intermediate frequency stimulus. An average of 29% of the cells examined in lateral geniculate nucleus and visual cortex traverses showed statistically significant differences in the late component of the neuronal response when different responses to the same generalization stimulus were compared.


Computer-determined EEG patterns associated with memory-facilitating drugs and with ECS.

Cortical EEG patterns of rats were analyzed by computer following administration of analeptic drugs at doses previously shown to facilitate posttrial memory processes. The drugs produced an increase in the power of the EEG primarily by increasing the amount of activity in delta and lower-theta frequency bands. The increase in lower frequency theta was accompanied by a decrease in higher frequency theta, thus increasing the regularity in the theta band. Electroconvulsive shock, which disrupts posttrial memory processes, also increased delta activity, but it greatly lowered amplitudes throughout the EEG frequency spectrum. It is concluded that if any consistent relationship between the cortical EEG and posttrial memory processes exists, then increased amplitude and regularity in the delta and theta bands are associated with increased amounts of memory storage--at least in alert animals. Further studies are required to determine if a causal influence is involved in this correlation.


Hypertrophy and redistribution of astrocytes in the deafferented dentate gyrus.

The response of the astroglial population of the dentate gyrus molecular layer to removal of that region's primary afferent was investigated using Cajal's gold sublimate method. Deafferentation caused the astrocytes to hypertrophy, an effect which was detectable at 24 hr and maximal at 72-96 hr post-lesion. Following this, the astroglia entered a lengthy period of gradual atrophy. Counts of the astrocytes in the various sublayers of the molecular layer led to the conclusion that these cells migrate into denervated dendritic areas from neighboring, nondeafferented zones.


Evidence for independent osmosensitivity of lateral preoptic and lateral hypothalamic neurons.

The purpose of the present study was to determine if a functional or modulatory relationship exists between osmosensitive neurons of the lateral preoptic (LPO) and lateral hypothalamic (LHA) areas. Unit activity was recorded from one neural area (LPO or LHA) following bilateral destruction of the opposite area, i.e., LPO recording site with LHA lesion site, and vice-versa. Bilateral destruction of the LPO or LHA did not eliminate the osmosensitivity characteristics of LPO or LHA units, demonstrating that units of either area do not require input from the opposite area for osmosensitivity.


Electrical stimulation of the tooth pulp in the study of pain.

Unit activity was recorded from bulbar neurons in the immobilized, lightly anesthetized cat following bipolar, electrical stimulation of the canine tooth pulp and the immediately proximal gingiva. When feasable, variations in neuronal responding were studied subsequent to the application of a topical anesthetic to the portion of the gingiva being stimulated. The results indicate that (1) stimulation of the pulp with insulated, embedded, dental electrodes does not excite receptors in adjacent, nondental tissue and (2) stimulation of the gingiva through insulated, concentric electrodes does not activate pulpal receptors in near-by teeth. In addition, the results corroborate previous demonstrations that current spread beyond the pulpal cavity is unlikely when appropriate stimulating procedures are used. Together, the data lend support to the position that electrical stimulation of the tooth pulp provides a unique means for the selective, parametric study of a known pain sensor.


Raphe neurons and barbiturate induced rhythmic activity in the subthalamic nucleus and ventral tegmental area.

A continuous rhythmic discharge in the subthalamic nucleus (STN), lateral habenular nucleus, and ventral tegmental area (VTA) is associated with tremor in cats lightly anesthetized with barbiturate. The pontine raphe nuclei centralis superior and inferior also show barbiturate dependent slow wave and unitary activity. Stimulation of the raphe region produces evoked potentials and synchronization of the oscillatory activity in STN and VTA. The latency of the evoked response is shortest in STN. Extensive raphe lesions abolish the rhythmic activity in STN and VTA, but lesions which do not completely destroy nuclei centralis superior and inferior are not effective. In single cell recordings 81% of 142 cells in the pontine raphe region and medial reticular formation are inhibited following VTA stimulation. Fifty-four percent of 129 cells in the same region were inhibited when tested with STN stimulation. Forty-seven raphe paramedian reticular formation cells showed convergence of inhibitory input from STN, VTA, and contralateral sciatic nerve (Group II and III fibers). Depletion of serotonin with rho-chlorophenylalanine did not affect the appearance of barbiturate rhythmic activity. It is concluded that the pontine raphe region is not essential for maintenance of the oscillatory activity in STN and VTA, and that the raphe region is on the output side of the system.


Pathologic effects of antimetabolites on the hippocampus of diet controlled mice.

Marked histological changes are observed in the hippocampi of mice maintained on a niacin deficient diet following a single injection of 3-acetylpyridine (antimetabolite of nicatinamide). Extensive neuronal damage occurs in areas H2, H3 and to a lesser degree in the dentate gyrus. The neurons appear to be shrunken, deeply basophilic and exhibit a loss of intracellular architecture. The neuronal response in pyridoxine deficient mice treated with 4-methoxypyridoxine (antimetabolite of pyridoxine) is not remarkable.


Instrumental avoidance conditioning in the spinal rat.

Spinal rats exposed to an instrumental avoidance routine in a counterbalanced Horridge paradigm were able to achieve successively higher criteria. Both experimental and yoked control animals were capable of instrumental avoidance conditioning to incremental criteria; experimental animals exhibited retention of the task when tested. During acquisition, naive experimental animals were superior in performance to previous control animals. Due to the use of a counterbalanced Horridge paradigm, the effectsof sensitization and response variability are probably not sufficient to explain all of the results of this experiment. The data suggest that both graded acquisition and retention occur at the spinal level.


A theory of the serial lesion effect.

The serial lesion effect is explained as a result of differentiation contingent upon induction by a spared residue. The induction can only take place when the lesion is made since the intact structures repress differentiation when some critical mass is reached. A distinction between the process giving rise to reorganization and reorganization as an outcome is made.


Superposition of binaural influences on single neuron activity in the medial superior olive elicited by electrical stimulation of the osseous spiral laminae.

The single unit response of medial superior olive (accessory nucleus) neurons was investigated, when elicited by electrical stimulation of nervous processes in the osseous spiral laminae in both cochleae and also by antidromic stimulation from the inferior colliculi. The osseous spiral laminae were stimulated at the first, second or third turns with grounding of one of the unstimulated turns. Time of signal arrival differences (delta tau) at the two cochleae and also intensity differences (deltai) were varied. (2) It is concluded that (A) binaural interaction in the MSO is not based on totally excitatory or inhibitory influences from either ear, but on cycles of excitation and inhibition; (B) these influences approximately obey the laws of superposition, i.e., the influences add linearly to determine discharge. (3) It is demonstrated that: (a) electrical stimulation, unlike acoustical stimulation, elicits a regular neural response; (b) the neural response functions elicited by changes in delta tau are deltai exhibit maxima and minima and are not smooth functions; (c) fine latency changes in the neural response are correlated with changes in delta tau and deltai; (d) the stimulation of different turns of the osseous spiral laminae (producing different current flows) elicits a different neural response depending on the turn stimulated, an effect reflecting the anatomical tonotopic arrangement of the medial superior olive; (e) changes in the stimulus differences delta tau and deltai are correlated with the ratio of the spike count in a short period following the stimulus, to the spike count in a longer total period; (f) changes in the stimulus differences delta tau and deltai elicit a neural response which varies according to the turn stimulated.


Effect of raphe lesions on brain serotonin in the cat.

A quantitative study of the regional distribution of serotonin (5-HT) in the forebrain, was performed in adult cats, following brainstem lesions. Seven to 10 days survival times were used to avoid nonspecific variations of the amine levels, as were observed in chronic preparations. Significant decreases of 5-HT levels were found after lesions of the nucleus centralis superior (CS), in hypothalamus, preoptic area, amygdala and hippocampus. After lesions of the nucleus dorsalis raphe (Dr), significant 5-HT decreases were also found in the hypothalamus and hippocampus. There was no change of 5-HT levels after lesions placed in the lateral midbrain, pontine tegmentum, or caudal pontine raphe, contrary to that was reported for chronic lesioned cats. These results suggest that CS and Dr may integrate different serotonergic subsystems and, probably, each one of these subsystems is related to specific functional phenomena.


Hypothalmic influences on the electrical activity of the olfactory pathway.

By means of evoked potentials a direct efferent connection was found to run from the posterior hypothalmus and medial forebrain bundle to primary olfactory structures (olfactory bulb, olfactory tubercle and prepyriform cortex). The pathway from the hypothalmus to the olfactory bulb follows in the lateral olfactory tract at a conduction velocity 5-10 m/sec. The olfactory tubercle functions as a relay station for the efferent fibers from various sources, running to the olfactory bulb. In animals with electrodes chronically implanted in the olfactory structures, hypothalamic stimulation gives rise to a prolonged train of hypersynchronous bursts of activity (40-50 Hz), which resemble the arousal reaction. This response is modified by transecting the cervical sympathetic trunk. By pathways still to be defined, potentials are evoked in the olfactory bulb by stimulation of the cervical sympathetic trunk and the termination of these sympathetic fibers shows a common postsynaptic neuronal pool with axons of hyopothalmic origin. Epinephrine topically applied to the olfactory mucosa induced hypersynchronous activity in olfactory structures, quite similar to that consequent to hypothalmic stimulation. These results suggest a multichanneled hypothalmic modulation of olfactory input.


Drug effects on sucessive discrimination learning in young chickens.

Chicks were trained to avoid pecking either a red or a blue bead in a one-trial avoidance task by coating one bead with methy anthranilate. They avoided the aversant bead on retention tests 10 to 180 min or 24 hr after learning, but not the neutral bead. Intracranial administration of ouabain or cycloheximide (CXM) 5 min before learning resulted in decay in retention after 10 and 30 min respectively following learning, discrimination being effective prior to those times. In a second experiment, chicks were trained on three physically distinct beads, two of which were made aversive during the learning period, the training trials separated by an hour. Saline-treated chickens retained memory of both aversive beads on retention trials 180 min later. CXM- and ouabain-treated chickens showed loss of memory for the bead associated with the drug but showed retention of the task which was not associated with the drug.


Hypothalamic Na+ and Ca++ ions and temperature set-point: new mechanisms of action of a central or peripheral thermal challenge and intrahypothalamic 5-HT, NE, PGEi and pyrogen.

The effects of changes in ambient and central temperature, amines, PGEu and pyrogen were investigated with respect to the mechanism of Na+-Ca++ ratio in the posterior hypothalamus of the unrestrained cat. Guide tubes were implanted bilaterally above the posterior hypothalamic area of 23 cats so as to accommodate push-pull cannulae. After a Na+ or Ca++ sensitive site was identified by perfusion at 50 mul/min of an artificial CSF containing 10.4 mM excess Ca++ ions or 13.6 mM excess Na+ ions, several types of experiments were undertaken with the results summarized as follows: if the cat was exposed to a cold or warm environmental temperature as the posterior hypothalamus was perfused with excess cation, the typical hypothermia was produced by Ca++ and hyperthermia by Na+ ions. However, if the cat was exposed to peripheral cooling or warming 30 min prior to the perfusion, the fall or rise produced by Ca++ or Na+ was attenuated or prevented. In other experiments, 1.0 muCi 45Ca++ was injected in the ion sensitive site in the posterior hypothalamus to label stores of the cation. Raising of ambient temperature caused a retention of 45Ca++ in this hypothalmic area, whereas a cold environmental temperature enhanced the efflux of 45Ca++ at the same perfusion site. The magnitude of change in 45Ca++ efflux depended upon the intensity of the thermal challenge. Similarly, warming of the anterior hypothalmic, preoptic area by means of implanted thermodes caused an immediate diminution in 45Ca++ efflux in the posterior hypothalamus, whereas cooling of this anterior region augmented the extrusion of 45Ca++ ions from the posterior area. When substances which produce a temperature change were applied to the same thermosensitive zone, the direction of shift in 45Ca++ flux in the posterior area corresponded to the signal for heat production or heat loss. That is, the microinjection of 5-HT, PGE1 or Salmonella typhosa into the anterior hypothalamus enhanced the efflux of 45Ca++ in the posterior hypothalamus as hyperthermia developed, whereas a similar microinjection of norepinephrine reduced the 45Ca++ output from the same sites. Finally, locally anesthetizing the cells of the anterior hypothalamus by the nerve blocker, procaine, prevented the cold and heat-induced 45Ca++ eflux and retention, respectively. These results suggest that if the Na+-Ca++ ratio in the posterior hypothalamus establishes and maintains the set-point for body temperature of 37 degrees -38 degrees C, the mechanism of lability of Ca++ through changes in binding characteristics, transport, or metabolism of the cation serves two purposes: (1) the active defense of the set-point temperature through gradations in ion shifts; and (2) the upward or downward change in set-point value, pathological or normal, triggered by virtue of impulses relayed from the anterior hypothalamus.


Peptides from pigeon cerebrum: two-dimensional fingerprinting and amino acid analysis.

The number and heterogeneity of endogenous peptides from pigeon cerebrum were studied by two-dimensional peptide fingerprinting. A highly consistent pattern of 8-9 peptides in the 1000-5000 molecular weight range was obtained from each cerebral sample. Amino acid analysis of the peptide material indicated that 30% of the identified residues were dicarboxylic amino acids and 30% were alphatic amino acids. There was no evidence for the presence of arginine or half-cystine in the peptide fraction.


Paraventricular nucleus: changes in the medial and lateral cell groups during dehydration and rehydration in the rat.

Cell area, percentage of cells with more than one nucleolus, and percentage of cells with the nucleolus apposed to the nuclear membrane (marginated) were compared in the medial and lateral magnocellular portions of the paraventricular nucleus (PVN) during water deprivation and voluntary rehydration. Lateral cells were larger and had a greater percentage of cells with multiple nucleoli in all conditions of deprivation and rehydration. In addition laterals were found to have more cells with marginated nucleoli in these cells with only one nucleoli. Medial and lateral cells showed similar responses to deprivation and rehydration.


Calcium inhibits catecholamine depletion by reserpine from carotid body glomus cells.

Histofluorescent and quantitative microfluorimetric studies have been performed on glomus cells of the rat carotid body, which fluoresce intently after treatment by paraformaldehyde vapor. Reserpine causes a reduction in intensity of fluorescence of about 90%. Subcutaneous injections of calcium chloride (100-300 mg/kg) were given before reserpine. Calcium prevents the depletion of catecholamies from the glomus cells by reserpine. This effect is dose related in that the depletion of catecholamines by heavy reserpine doses (15 mg/kg) cannot be overcome by calcium, medium doses (5 mg/kg) can be overcome but variably, and light doses (1 mg/kg) are always overcome substantially and can result in virtually complete inhibition of the depletion by reserpine. If calcium might counteract the effects of reserpine by occupying attachment sites of the vesicular membrane, thereby preventing reserpine from reaching its site of action, resulting in the usual uptake of catecholamines by the vesicles and suppression of the depleting action of reserpine.


Effect of visual stimulation on the evoked response recorded at the vertex.

Previous research on the visual evoked brain response (VEBR) recorded from the occipital scalp indicates that this response shows a high degree of stimulus control. An evoked brain response can also be elicited simultaneously from the vertex response is affected to the same degree by several different aspects of visual stimuli as is the corresponding occipital response. The VEBR was recorded from the vertex of 3 human subjects as a function of changes in stimulus size and intensity. The results showed that the amplitude of the first major positive component of the VEBR was not reliably related to the stimulus parameters. It was concluded that the VEBR recorded at the vertex probably has its source in a distinct cortical generator which is not specifically related to the parameters of visual stimulation.


"Twin peaks" papilledema: the appearance of papilledema with optic tract atrophy.

A woman with a right middle fossa meningioma causing right optic tract atrophy and papilledema had distinctive funduscopic changes. The ipsilateral eye showed temporal disc pallor and nasal edema. The contralateral disc showed edema of the upper and lower poles which was separated by a horizontal band of optic atrophy. The fluorescein angiographic changes clearly illustrate this pattern. Apart from its theoretical interest this appearance of papilledema and atrophy provides definite localizing information.


Pheochromocytoma and von Hippel-Lindau's disease.

Two families with von Hippel-Lindau's disease with associated pheochromocytoma are presented. We include a review of the literature on this association, and discuss its significance for the ophthalmologist.


Ophthalmic manifestations of multiple endocrine neoplasia, type three.

We report the case of a patient with multiple endocrine neoplasia type three, which was first diagnosed by members of the department of Ophthalmology. He was found to have multiple mucosal neuromata and medullary thyroid carcinoma. The ocular components of this syndrome include visible corneal nerves, conjunctival neuromas, thickened lids, anterior displacement of the cilia and a "dry eye" syndrome. The major systemic components are medullary thyroid carcinoma and pheochromocytoma. It is important that the Ophthalmologist recognize the ophthalmic manifestations of this syndrome so that early diagnosis and treatment may be possible.


Tonic pupil: a simple screening test.

The tonic pupil has a typical appearance and characteristic reactions to both light and the near reflex. Testing with Mecholyl (methacholine) is not possible since the drug is no longer manufactured. The reactions of a group of 25 patients with tonic pupil were studied using dilute pilocarpine, and compared with the pupil responses of a separate control group. We found that concentrations of 0.2% pilocarpine produced too many false-positive reactions in the control group and that 0.05% pilocarpine produced an insufficient response. The 0.1% concentration seemed suitable for ordinary clinical examinations and is recommended for pharmacologic confirmation of the diagnosis of tonic (Adie's) pupil.


Scanning electron microscopy of normal and lased rabbit retina.

This study presents the topography as seen by scanning electron microscopy of the rabbit retina in general and the photoreceptors in particular; and of large laser lesions in the retina.


The use of bank sclera to correct lid retraction.

Twenty-two scleral grafts were inserted in patients with retracted lids, the youngest patient was two years old at time of surgery. Two patients were operated on under local anaesthesia and the remainder under general anaesthesia. In the patients with thyroid disease larger grafts were required, the temporal side of the graft being 3 mm greater vertically than the nasal. Our first cases were undercorrected, so we used grafts of a size at least twice that required to lower the lid. Other complications were rare. For ptosis overcorrections, and congenital lid retraction, the graft should be 2 mm bigger horizontally and vertically than the amount required to lower the lid.


Lactic acid in human aqueous humour.

We wished to assess the contribution of the lens to the maintenance of the high level of lactic acid found in human aqueous humour. The lactic acid in aqueous humour was estimated by Pryce's modification of the Barker-Summerson method in 41 subjects who were divided into four groups: those with early cataract, those with advanced nuclear cataract, those with mature cataract and those with hypermature (morgagnian type) cataract. Statistical evaluation of the results showed that there was no significant difference in the lactic acid level between the four groups. We assume that the lens does not contribute significantly to the high concentration of lactate found in human aqueous humour.


Monocular elevator paresis, Argyll Robertson pupils and sarcoidosis.

A patient with sarcoidosis involving the central nervous system is described who developed monocular paralysis of elevation and Argyll Robertson pupils. A schema for the control system for vertical eye movements is presented as well as an explanation for monocular elevator palsy. The postulated lesion for monocular elevator palsy could well produce at the same time Argyll Robertson pupils and the cause of this papillary abnormality is discussed.


A 'black cornea' secondary to topical epinephrine.

We report a case of 'black cornea" secondary to topical epinephrine therapy and present the biochemical analysis of the lesion. The formed pigment is a melanin and not the intermediate substance, adrenochrome, as has been previously reported. The pathogenesis of melanin deposition is reviewed and a hypothesis of epinephrine-melanin binding is suggested.


Lack of a significant protective effect of augmented circulating glucose on the ischemic myocardium.BJ.

Infusion of glucose alone or glucose with insulin in cats subjected to acute myocardial ischemia did not alter the hemodynamic response of the cats to coronary artery ligation. Furthermore, determination of myocardial creatine phosphokinase (CPK) (ATP:creatine N-phosphotransferase, EC 2.7.3.2) activities failed to reveal a protective effect of glucose and insulin upon the status of the developing infarct in the ischemic myocardium. However, glucose and insulin apparently promote clearance of CPK from the plasma and inhibit proteolysis during the early phase of myocardial ischemia. These actions may be of value in generalized adaptive response of the animal to the stress of ischemia, but does not per se appear to diminish the spread of the ischemic damage within the heart not to limit the extension of the evolving infarct.


Induced rouleaux formation in interspecies populations of red cells.

A study was made of rouleaux formation between erythrocytes of different species when suspended in Ringer solution with polyvinylpyrrolidone added (PVP with M.W 360 000, 4.0 G/L). PVP was shown previously to be a suitable asymmetric macromolecule for promoting rouleaux formation. For the present study fresh samples of blood were obtained from humans, cats, rats, mice, dogs, rabbits and guinea pigs. Initally homogenous populations of cells were allowed to form rouleaux in the microscope chamber for the purpose of determining the average cellular dimensions for each species. Subsequently red cells from two species at a time were mixed in equal proportions to assess the degree of preference for the cells of one species to form rouleaux among themselves rather than with cells of the other species. The sequencing of the cells in the mixed rouleaux which formed on the coverslip was determined from photomicrographs, using the previously determined knowledge of the cellular dimensions. Although the visual impression was that the rouleaux were composed of a random selection of cells from the mixed population, a preferencnstrated statisically in nine of the ten combinations tested. Only the rat-mouse mixture of cells was excepted, perhaps because these animals are closely related members of the same family.