Effect of anti-inflammatory drugs on the membrane potential of vascular endothelial cells in vitro. 1 Cells of the aortic endothelium isolated from the guinea-pig and bathed at 37 degrees C with a calcium-free superfusion fluid had membrane potentials of minus 41 plus or minus 7 mV (mean plus or minus s.e mean). 2 Depolarization was produced by addition of potassium (50-200 mM) or certain other monovalent metal cations to the superfusion fluid. Depolarization was rapidly reversed on return to the original superfusate. 3 Several divalent metal cations, notably calcium (16 mM), caused depolarization which was only slowly and incompletely reversed on return to the original calcium-free superfusate. 4 Repolarization after exposure to calcium was accelerated and made more complete by addition of indomethacin (0.25 mM) to the superfusate, 5 The trivalent cations of lanthanum, aluminium or iron (0.1 mM) inhibited the depolarizing effect of calcium (16 mM). 6 Exposure to histamine (100 mug/ml) or heating to 45 degrees C for 1 h caused depolarization in the presence but not in the absence of calcium. Subsequent removal of histamine or cooling again to 37 degrees C in the continued presence of calcium permitted only slow and partial repolarization. However, repolarization was more rapid and complete in the presence of indomethacin (0.25 mM). 7 Heating to 45 degrees C for 5 h in the presence of calcium caused progressive and almost complete depolarization. Lanthanum, cinchocaine, indomethacin, flufenamic, meclofenamic and salicylic acids, phenylbutazone and aminopyrine each reduced the depolarization, but hydrocortisone, chloroquine, benzindamine, isoprenaline and aminophylline did not.


Inhibition of 5-hydroxytryptamine-induced human blood platelet aggregation by chlorpromazine and its metabolites. 1 Blood platelets from normal human subjects were isolated and aggregated in vitro with adenosine diphosphate (ADP) or 5-hydroxytryptamine (5-HT). 2 The effects of chlorpromazine and 7 major metabolites upon 5-HT-induced aggregation were investigated. 3 All the phenothiazines inhibited 5-HT-induced aggregation when added to platelet rich plasma 3 min prior to 5-HT. 4 There were no qualitative differences in the inhibitory effects, but inhibitory potency varied over a wide range. The decreasing order of potency was monodesmethylchlorpromazine, chlorpromazine, 7-hydroxychlorpromazine, didesmethylchlorpromazine, 3,7 -dimethoxy-chlorpromazine, didesmethylchlorpromazine sulphoxide, chlorpromazine sulphoxide, chlorpromazine nitroxide.


An analysis of the phenomenon of acute tolerance to morphine in the guinea-pig isolated ileum. 1 The observations which Paton (1957) interpreted as 'acute tolerance' and 'dependence' have been confirmed for coaxially stimulated segments of guinea-pig ileum and extended to the contractions evoked by field stimulation in the myenteric plexus-longitudinal muscle preparation. Evidence is adduced that the morphine receptors of the myenteric plexus are not involved in the two phenomena. 2 The contraction of the longitudinal muscle depressed by low concentrations of morphine, or levorphanol, can be restored to control level not only by high concentrations of morphine but also by levorphanol and equally well by its (+)-isomer, dextrorphan, which does not fulfil the stereospecific requirements of the morphine receptor. Acetylcholine output was not increased. 3 When, after restoration of the twitch by high concentrations of morphine, the drug is washed out, contractions become depressed. This effect cannot be due to 'dependence' because either morphine or its antagonist, naloxone, restore the twitch again. 4 In the concentrations used, morphine, levorphanol and dextrorphan inhibit the cholinesterase of homogenates of the myenteric plexus-longitudinal muscle preparation by 10-15%. Since a concentration of physostigmine which causes a similar inhibition also restores the twitch, it is concluded that the described phenomena are best explained by the anticholinesterase effects of the drugs.


Use of the logistic function for the calculation of dose-ratios and potency ratios. 1 Dose-ratios and potency ratios, obtained with the guinea-pig isolated ileum by calculating matching concentrations from a least-squares fit using a logistic relationship between response and dose, differ from those obtained with the more usual assumption that response is a linear function of log dose over a limited range. 2 The differences are not due to the mathematical treatment of the results but arise from changes in sensitivity associated with the production of very high or very low responses. 3 With this preparation there is no advantage in avoiding the linear transformation and fitting the results to the complete dose-response curve though this might not apply to results obtained from other tissues with less variable sensitivity.


The effect of oxytocin on blood vessels of cremaster muscle of the rat. Oxytocin administered intravenously to the anaesthetized rat produced dilatation of the blood vessels of the cremaster muscle at concentrations ranging from 2.5 times 10-minus 11 to 2.5 times 10-minus 9 M. When applied topically to the exposed vessels it produced constriction at concentrations ranging from 2.5 times 10-minus 12 to 5.0 times 10-minus 8 M. Oxytocin was thus similar to adrenaline in eliciting opposite effects when applied to the serosa or to the intima of skeletal muscle blood vessels.


Kinetics and some characteristics of uptake of noradrenaline by the human umbilical artery. The uptake of exogenously added noradrenaline (NA) (0.5-2.5 mug/ml) by the human umbilical artery was linear with time up to 10 minutes. The uptake was saturable and could be described by the Michaelis-Menten equation. The uptake was cocaine-resistant, normetanephrine-sensitive, was considerably inhibited in the cold and was partially inhibited by Na+- deficiency. Of NA accumulated in the artery 31% could be washed out by NA-free medium. It is concluded that the mechanism of uptake of NA by the human umbilical artery is similar to the uptake2 mechanism.


The effect of tricyclic antidepressants on cholinergic responses of single cortical neurones. 1 The technique of microelectrophoresis was used in order to study the effects of tricyclic antidepressants on responses of single cortical neurones to acetylcholine. 2 Both potentiation and antagonism of excitatory responses to acetylcholine could be observed after a brief application of imipramine or desipramine. A higher dose of the antidepressant was required to evoke antagonism than to evoke potentiation. 3 Responses to carbachol were affected by desipramine similarly, suggesting the inhibition of cholinesterase is not responsible for the potentiation of cholinergic responses. 4 A brief application of atropine also had a dual effect on responses to acetylcholine. 5 It is suggested that the potentiation of excitatory cholinergic responses by atropine and the antidepressants may be due to the blockade of masked inhibitory receptors.


The effect of sympathomimetic amines on the ventricular fibrillation threshold in the rabbit isolated heart. 1 The ventricular fibrillation threshold (VFT) was measured in the isolated heart of the rabbit perfused via the aorta with McEwen's solution at 37 degrees C by applying a single 10 ms pulse of current during the vulnerable period of late systole. The arrhythmia induced was either fibrillation or a rapid tachycardia. 2 The catecholamines adrenaline, noradrenaline and isoprenaline, but not dopamine, when infused at rates which produced similar moderate effects on cardiac rate and force, significantly lowered the VFT; it was reduced slightly more by adrenaline than by the other two. Phenylephrine and methoxamine were ineffective. Only those sympathomimetic amines which lowered the VFT also shortened the vulnerable time, i.e. minimal time after the R-wave of the ECG at which the pulse had to be applied to induce the arrhythmia. 3 The lowering effect of adrenaline on the VFT was not influenced by phentolamine but was blocked by propranolol and pindolol. 4 Chloroform potentiated the lowering effect of adrenaline, but not that of isoprenaline, on the VFT. Carbachol did not alter the effect of adrenaline on the VFT. 5 The results indicate that adrenaline, noradrenaline and isoprenaline lower the VFT by a direct action on the cardiac musculature and that this effect is mediated via beta-adrenoceptors.


Some central effects of 5-hydroxytryptamine in young chickens at and below thermoneutrality. 1 Three salts of 5-hydroxytryptamine, the hydrogen maleinate, the oxalate and the creatinine sulphate were infused into the hypothalamus of 10-18 day old chickens at ambient temperatures in and below the thermoneutral range. Body temperature was recorded and behaviour observed. Electrocortigrams were recorded in experiments in which 5-hydroxytryptamine hydrogen maleinate was used. The effects of a monoamine oxidase inhibitor and methysergide on these responses were similarly studied. 2 At thermoneutrality (31 degrees C) all 3 salts produced behavioural sleep. 5-Hydroxytryptamine oxalate had inconsistent effects on body temperature. 5-Hydroxytryptamine creatinine sulphate produced hypothermia at small doses and mild hyperthermia at higher doses. 5-Hydroxytryptamine hydrogen maleinate produced hypothermia at all doses tested; the falls in temperature induced by this salt were intensified in magnitude and duration by monoamine oxidase inhibition unlike the responses to the other 2 salts. 3 At temperatures below thermoneutrality (16 degrees C) all 3 salts produced behavioural sleep and electrocortical sleep was recorded with 5-hydroxytryptamine hydrogen maleinate. All 3 salts produced hypothermia, which was intensified in magnitude and duration by monoamine oxidase inhibition. 4 The hypothermia produced by 5-hydroxytryptamine hydrogen maleinate was prevented by equimolar doses of methysergide. 5 The position of the cannula in the hypothalamus was found to be crucial. 6 The results contrast with those found in the adult fowl. No conclusion is drawn as to the relationships of the actions of these salts when infused compared with the effects of endogenous 5-hydroxytryptamine release.


A further investigation into the energy dependence of angiotensin II-induced contractions of isolated smooth muscle preparations. 1 The energy dependence of angiotensin and acetylcholine-induced contractions of rat descending colon and uterus was investigated. 2 Differences were observed in the effect of anaerobic substrate depletion upon responses of colon and oestrous and dioestrous uterus. These were attributed to differences in the energy metabolism of the tissues and were correlated with differences in tissue levels of glycogen. 3 The preferential reduction of angiotensin responses of dioestrous uterus and descending colon when exposed to 2,4-dinitrophenol, was evidence for an energy dependent stage in the angiotensin response distinct from the contraction process itself. 4 The absence of a preferential reduction of the angiotensin response of oestrous uterus when exposed to 2,4-dinitrophenol appeared to be related to the ability of this tissue to generate ATP by anaerobic glycolysis. 5 It was concluded that the energy for the angiotensin response may be derived either anaerobically or aerobically, depending upon the tissue.


Stimulation of the hypothalamo-pituitary-adrenal axis by compounds formed in inflamed tissue. 1 Rat paws were injected with carrageenin, and their subcutaneous tissue perfused 135 min later. These perfusates were injected intravenously into receptor rats in which they caused an attenuation of inflammatory responses. 2 The effect was not observed in adrenalectomized receptor rats nor in receptors with electrolytic lesions in the median eminence of the hypothalamus but persisted in adrenal-demedullated animals. 3 The active perfusates also induced eosinopenia in normal or adrenal-demedullated animals, but not in adrenalectomized rats, and produced an increase in blood corticosterone with a concomitant decrease in the amounts of adrenal ascorbic acid. 4 The active perfusates did not affect the responses of isolated preparations to histamine, bradykinin, prostaglandins and 5-hydroxytryptamine neither did they elicit changes of the arterial blood pressure in receptor animals. 5 The anti-inflammatory activity present in perfusates from inflamed paws seems to be formed slowly at the site of the developing inflammatory reaction, since perfusates collected 30-65 min after the injection of carrageenin were ineffective, as was plasma taken from donor rats at various time intervals after carrageenin injections. 6 It is suggested that the anti-inflammatory factor present in the active perfusates exerts its action by stimulation of the hypothalamo-pituitary-adrenal axis.


The possible occurrence of endogenous anti-inflammatory substances in the blood of injured rats. 1 Using the carrageenin rat paw oedema test as an assay, an attempt has been made to confirm the presence of anti-inflammatory activity in the blood of rats with a chronic inflammatory lesion induced by a polyester sponge, and to relate such activity to the systemic anti-inflammatory effect exerted in situ by the lesion. In addition, plasma from rats given acetic acid intraperitoneally has been examined for anti-inflammatory properties. 2 The activity of serum obtained from sponge-bearing adrenalectomized Wistar rats did not differ significantly from that obtained from animals without implants. Furthermore, implanted sponges exerted no systemic anti-inflammatory effect. 3 Similar experiments were performed in sponge-bearing adrenalectomized Sprague-Dawley rats, plasma instead of serum being examined for anti-inflammatory activity. The plasma removed from such animals possessed no anti-inflammatory activity, whilst implanted sponges exerted a small, yet significant, systemic inhibitory effect. 4 When the irritancy of sponge implants was augmented with croton oil, more marked systemic anti-inflammatory effects were observed. However, the plasma obtained from rats injured in this manner exerted no anti-inflammatory effect. 5 No anti-inflammatory activity could be detected in plasma samples obtained from rats treated with doses of acetic acid capable of producing pronounced systemic anti-inflammatory effects. 6 It was concluded that the induction of these inflammatory lesions in rats does not appear to lead to a detectable release of endogenous anti-inflammatory substances into the circulation.


The prevention by sulphydryl compounds of the toxicity in the cat of 2,6-dimethoxyphenol and its morpholinopropionyl ester. 1 Intravenous (minus)-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride (M&B 16,573) produced anaesthesia of short duration in the mouse, rat, rabbit, cat, dog and monkey. In the cat but not in other species, a severe and usually fatal toxic reaction was seen 1-2 h after administration. 2 This toxic reaction but not the anaesthetic properties of M&B 16,573 was prevented by the intravenous administration of cysteine or N-acetylcysteine. Cysteamine or dimercaprol were ineffective. 3 Intravenous administration of 2,6-dimethoxyphenol or 2,6-dimethoxyquinol in the cat produced a response similar to the delayed toxic effects of M&B 16,573 but not preceded by anaesthesia. The toxic effects of these compounds were prevented by cysteine. 4 Intravenous 4-allyl-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride produced anaesthesia in the cat without the delayed toxic effects seen after M&B 16,573. 5 The acute toxicity of 2,6-dimethoxyquinol in mice was reduced by the administration of cysteine or N-acetylcysteine. 6 It is postulated that the delayed effects produced by M&B 16,573 in the cat are due to the formation of 2,6-dimethoxyquinol and 2,6-dimethoxybenzoquinone in this species, the toxicity of the latter being reduced by sulphydryl compounds.


Studies on the kinetics of (3H)-ouabain uptake and exchange in the isolated papillary muscle of the guinea-pig. 1 The uptake, wash-out and exchange of [3H]-ouabain was studied in isolated, resting, and electrically stimulated papillary muscles of the guinea-pig. 2 At the equilibrium level of uptake, a different tissue/medium ratio was obtained for each of the concentrations used, i.e. 3.4, 1.8 and 0.82 for 1 times 10-minus 7M, 7.7 times 10-minus 7M, and 5 times 10-minus 6M ouabain, respectively. Equilibrium was reached more rapidly at high concentrations of ouabain. 3 The maximum number of binding sites for ouabain was estimated to be 1 times 10-15 binding sites/g wet weight. 4 No difference in [3H]-ouabain uptake could be detected between resting and electrically stimulated papillary muscles. 5 The kinetics of the ouabain uptake, wash-out and exchange are discussed. The results suggest that there is a saturable compartment in papillary muscle which can best be demonstrated if low concentrations of ouabain are used. Because of its small size, the saturable compartment submerges in the process of the filling of the extracellular space at high concentrations (5 times 10-minus 6M).


Multivariate analysis: the need for data, and other problems. Multivariate analyses are an aid to, not a substitute for critical thinking in the area of data analysis. Meaningful results can only be produced by these methods if careful consideration is given to questions of sample size, variable type, variable distribution etc., and accusations of subjectivity in interpretation can only be overcome by replication. The computer revolution has produced many problems for statisticans, not least of which is the ease with which experiments may access packages of programs for multivariate analysis, and so bypass a "difficult" (by which is meant one who will not do simply as he is told) statistician. Of course there are many abusers of univariate statistical methods. Here, however, the abuses are not likely to lead to such seriously misleading results as in the multivariate case. Perhaps a major cause of the continuing misuse of statistical methods is the insistence of many journal editors in psychology and related areas, on articles being laced with multivariate analyses, and on encouraging the pedantic use of signifance levels, i.e. the inevitable p less than minus, as if such inclusions lent an air of respectability to their journal which it might not otherwise have had. Research workers in these fields would be better encouraged to devote more time to an initial screening of their data using simple graphical techniques, to ensure that their data are at least approximately suitable for more complicated multivariate analyses.


Stress in schizophrenics and normals.

Stress in schizophrenics and normals. This paper presents findings related to the measure of stress in 641 schizophrenics(125 acutes and 516 chronics) and 95 comparable normals. Stress was defined as an imbalance between environmental demands and the respondent's ability to meet that demand successfully, and was measured in terms of level of stress experienced in relation to specific problem situations. Twenty-one dimensions of stress were measured, subsumed under thefollowing four general areas: social performance, family interaction, social interpersonal interaction, and social maladaptive activities. Results indicated that, in general,normals experience significantly less stress in dealing with life events than do schizophrenics. Within the schizophrenic group, the pseudoambulatory chronic patients evidenced more stress than did their acute counterparts, a finding not previously described in the literature. Implications of these findings do not support the present community after-care concepts. Discharged chronic schizophrenics appear unable to remain in the community for any reasonable period of time because of the high level of stress under which they function.


The brain stem in psychosis.

The brain stem in psychosis. The brain stems of 24 mental hospital patients and 10 control patients were examined. Ten mental hospital patients were either deluded or auditorily hallucinated in clear consciousness, and of this group 8 presented with a diagnosis of schizophrenic syndrome. The nature and significance of lesions found in the midline reticular nuclei and the trigeminal n. are discussed. The results, and the dearth of other published material on this subject, indicate the need for further work in this field.


Information leading to accurate diagnosis in the elderly. Psychiatric diagnosis in the elderly has been examined in order to extract the information which leads to later modification of the diagnosis. Initial diagnoses of neuroses and toxic states were least stable, 14 out of 29 changing to a different category. Information from relatives and further interviews contributed most to the modification of the initial diagnosis, though affective and neurotic syndromes were particularly susceptible to change resulting from conceptual differences, and dementia to change consequent on physical examination. It is concluded that an adequate initial interview of a patient and his next of kin will achieve a diagnosis which is correct in its major category on 95 per cent of occasions.


Educational attainment in adolescent school phobia. The educational attainment of 100 school-phobic youngsters was compared to that of 100 other psychiatric patients, using the reading quotient as the main measure. Age and IQ were allowed for. RGs were, on average, higher in the school phobic group than in the other subjects, except in a small number of younger children of high IQ. Additional comparisons with another group of psychiatric patients and with the general population,using regression equations, failed to provide any evidence of poor educational attainment in school phobia.


Observations on the dose regime of fluphenazine decanoate in maintenance therapy ofschizophrenia. An analysis of the drug regimes prescribed to two separate groups of unselected schizophrenic patients indicates certain trends of clinical importance. The results demonstrate a need for the adoption of a personalized dose regime. The scatter of dose regimes found effective is too great to recommend a standardized approach to the prescription of L.A.P. injections. Two other results of particular significance are that the dose of drug required to control symptoms can be gradually reduced in nearly half of patients,and that helpful trends in prescribing were identified that will help the clinician to abolish side-effects.


Accidents and drug treatment in a psychiatric hospital. A survey of 351 accidents occurring in a two-year period in a psychiatric hospital showed that 77 per cent of the accidents involved female patients and 48 per cent involved patients with organic psychoses; 236 accidents were falls and 280 occurred in the ward setting. In 277 instances adequate controls were available. Seventy-five per cent of the accident patients had received a psychotropic drug on the day of the accident as opposed to 61 per cent of the controls. The possibility that the side-effects of psychotropic drugs may have contributed to some of these accidents is discussed.


A technique of insight-directed psychotherapy for health service use. A technique of psychotherapy seemingly compatible with psychoanalytical knowledge is described, and compared and contrasted with psychoanalysis. Its mode of action, efficacy, advantages and difficulties, and its suitability for once-a-week individual or group psychotherapy and therefore for Health Service use is discussed.


Evaluation of group therapy: correlations between clients' and observers' assessments. An attempt to compare observers' evaluations of aspects of group psychotherapy with the patients' assessments of the same selected variables (i.e. 'acceptance', 'abreaction'and 'improvement') is described. Correlation coefficients between the observers' and clients' rankings of these factors were obtained, and the implications of the findings are discussed in relation to each group.


Segmental intervertebral anastomosis in subclavian steal. Segmental intervertebral arterial connections originate from normal vascular channels which are commonly seen on selective vertebral arteriography. In subclavian steal, these vessels can hypertrophy and form important collateral pathways. The significance of their haemodynamic contributions may be assessed by their multiplicity and calibre. Lateral or oblique projections in addition to frontal visualization may be required to differentiate the various transcervical channels which lie either anterior or posterior to the vertebral bodies.


Left coronary artery contrast transit time. With our method for selective left coronary arteriography it is possible to determine the time interval between the start of the contrast injection into the artery and the appearance of the contrast in the coronary sinus. This time-interval, coronary contrast transit time (CCTT), has been determined in patients with or without obstructing coronary artery disease. The average CCTT was about four seconds with some individual variations. The CCTT tended to decrease with advancing age. There was no significant difference between the CCTT in patients with normal angiograms compared to the CCTT in patients with coronary stenoses or occlusions. In the latter patients, there was no correlation between the degree of narrowing on the angiograms and the time-measurements. Alternative explanations for these findings are discussed.


Urinary ascites and obstructive uropathy. Seven infants with urinary ascites caused by obstructive uropathy are reported. The extravasation occurs in the kidneys and produces an opaque halo, best seen in delayed films at excretory urography. The common cause is a posterior urethral valve which forms an obstructive sail-like structure.


Radiotherapy by several sessions a day.

Radiotherapy by several sessions a day. The early clinical experience with external beam radiotherapy using three treatment sessions a day is briefly reported. Thirty-seven patients suffering from advanced malignant disease, mostly of the breast or neck, were treated. The normal tissues tolerance was similar to the tolerance of daily fractions using the same doses.


A comparison of the effects of radiation on tumour growth delay and cell survival. The effect of radiation quality. Measurements have been made of the effects of 250 kV X-rays and cyclotron produced neutrons on the delay in growth of a rat fibrosarcoma (RIB5C) and on tumour cell survival assayed in vitro after irradiation in vivo. For doses above 300 rads of neutrons the RBE for cell survival was greaer than that for tumour growth delay. This may be due to X rays causing a greater delay in cell proliferation than neutrons for a given level of cell survival. This would be the opposite effect to that found by BBarendsen and Broerse (1969), irradiating a rat rhabdomyosarcoma. Another possibility is that meassurements of cellular radio-sensitivity which involve removal of cells from their normal environment may lead to incorrect estimates of cell survival in situ. A plot of the RBE for growth delay against the reciprocal of the neutron dose indicated that the dose level at which the RBE became dependent on the fraction of hypoxic tumour cells was larger than that for cell survival, indicating a smaller "effective" hypoxic fraction than that estimated from the cell-survival curves.


Mechanism of radioactive iodine uptake depression following intravenous urography. The radioactive iodine (RAI) uptake examination is a standard test for the evaluation of thyroid diseases. For many years it has been known that the results of the RAI are depressed following administration of iodinated contrast media, such as that used for intravenous urography (Williams, 1968; Beierwates, 1956; Slingerland, 1957). The mechanism of this depression is not well documented. It is presumably due to inorganic iodide since it is only inorganic iodide that can be extracted from the blood by the thyroid gland. To study this problem we measured inorganic iodide in bottled contrast media.


Ionizing radiation as a carcinogen: practical questions and academic pursuits The Silvanus Thompson Memorial Lecture delivered at The British Institute of Radiology on April 18, 1974. Cancer is naturally very common, and practical questions about the possibility of radiation-induced harm are often questions about what in other contexts would be called background noise. Central to the question of whether small radiation exposures are carcinogenic is the effect of antenatal radiography. A comparison of singleton and twin births with radiography rates of 10 and 55 per cent respectively showed that radiography must be the main cause of the elevated frequency of malignant disease. In Japanese bomb survivors, most radiation-induced cancer has been found in those irradiated in adult life, less in those irradiated in childhood and adolescence, and least for exposure in utero. Specific biological differences between different kinds of malignant disease in their induction by ionizing radiation are becoming increasingly evident. When dose-response relationships for observed cancer frequencies are to be used as evidence about dose-response relationships for cancer induction, it will always be necessary to allow for the concomitant cell sterilization. When this is done, there is little support for linearity as the method of extrapolation when making predictions about possible effects of low doses but the absence of threshold seems scientifically inescapable. In cellular terms, radiation induction of cancer must be a very rare phenomenon, so rare compared with cell sterilization or mutation induction, that the general corpus of radiobiological understanding may be inapplicable.


Tomography of the petrous bone in keratosis obturans. Three cases of keratosis obturans, which were studied by tomography of the petrous temporal bone, are described. The widening of the deep bony part of the external auditory canal by pressure erosion of an impacted benign slowly-growing mass is the key radiological finding. Erosion was so severe as to involve the facial nerve canal in one and the temporo-madibular joint in two cases. The theories of causation are reviewed. Tomography using elliptical tube movement was valuable in diagnosis, pre- and post-operative management.


Histiocytosis-X of the hypothalamus.

Histiocytosis-X of the hypothalamus. Hypothalamic masses associated with histiocytosis-X may be mistaken for neoplasms. As a result radiation therapy will often be administered rather than chemotherapy, which appears to be the treatment of choice for histiocytosis-X of the hypothalamus. Particularly in young people, the possibility of granulomatous disease should be entertained and biopsy should be considered in the presence of a hypothalamic mass.


The measurement of regional ventilation during tidal breathing: a comparison of two methods in healthy subjects, and patients with chronic obstructive lung disease. Regional ventilation has been measured in 17 healthy volunteers, and 24 patients with chronic obstructive lung disease during tidal breathing using 133-Xe. The wash-in and wash-out of 133-Xe were recorded by a gamma camera interfaced to a small digital computer. Regional ventilation was calculated as the distribution of tidal volume per unit lung volume-a measure of relative ventilation--and from the wash-out curves as the fractional exchange of air per second. Determination of the regional fractional exchange of air showed a significant difference between the patients with chronic obstructive lung disease and normal subjects for all regions. The distribution of tidal volume per unit lung volume did not effect such a clear separation. Significant correlations were found between the whole-lung fractional exchange of air in the patients with chronic obstructive lung disease and their FEV1 r equal 0-70, MMFR r equal 0-70, FVC r equal 0-56 and FEV1/FVC r equal 0-57. It is suggested that measurement of regional ventilation as the fractional exchange of air is more realistic than methods that determine relative ventilation or only make use of the early part of the wash-out 133-Xe.


Liver and pancreas scanning in extrahepatic obstructive jaundice (with special reference to tumours of the bile and hepatic ducts). 198-Au-gold colloid liver scans and 75-Se-selenomethionine pancreas scans in 72 patients with extrahepatic obstructive jaundice were assessed by blind marking. They were compared with liver and pancreas scans from 20 control patients and liver scans from 33 patients with diffuse liver disease. 56 per cent of the liver scans in extrahepatic obstructive jaundice showed a filling defect in the hilar region of the liver. This was most frequently seen in the most deeply jaundiced patients, and was reported in 80 per cent of patients with a serum bilirubin greater than 15 mg/100 ml. The liver scan alone cannot distinguish between different forms of extrahepatic obstructive jaundice although severe loss of left lobe uptake appeared to favour a diagnosis of carcinoma of the bile or hepatic ducts. A normal pancreas scan virtually excludes a pancreatic carcinoma as the cause of obstructive jaundice. A pancreas scan showing severely reduced uptake suggests a carcinoma of the pancreas or of the lower end of the common bile duct.


Post-irradiation proliferation kinetics of a serially transplanted murine adenocarcinoma. The proliferation kinetics of the transplanted adenocarcinoma 284 of C3H mice from the first to the sixth day after 600 R and from the first to the eigth day after 1,200 R has been studied by repeated labelling of the tumour cells in vivo with 3-H-thymidine and measurement of the labelling index and the percentage of labelled mitotic cells. The time course of the post-irradiation synchronization was followed during the first day. Later, the mean generation times of the tumour cells were usually prolonged and the spread of the generation times increased. Three to four days after irradiation, the tumour increased its growth fraction to twice the normal value by triggering resting cells (Go cells) into cycle.


In vivo testing of hypoxic radiosensitizers using the KHT  murine tumour assayed by the lung-colony technique. The KHT transplantable tumour of C3H mice has been used as a model tumour for the invivo study of hypoxic cell sensitizers. Eleven sensitizers comprising four nitrofuran five nitrobenzene and two nitroimidazole derivatives, which have been shown to be effective on hypoxic mammalian cells in vitro, have been investigated. Two of these compounds, metronidazole (2-methyl-5-nitroimidazole-1 ethanol) and tinidazole (ethyl [2-(2'-methyl-5'-nitro-1'-imidazolyl) ehtyl] sulfone), showed signs of hypoxic cell-sensitization in vivo when given systemically by intraperitoneal injections. In addition, preliminary testing of the nitrobenzene NDPP (P-NITRO-3-DIMETHYL-PROPRIOPHENONE HYDROCHLORIDE) INDICATED THAT WHEN IT WAS INJECTED DIRECTLY INTO THE TUMOUR AND IRRADIATION WAS COMPLETED WITHIN TEN MINUTES AFTER INJECTION, APPRECIABLE SENSITIZATION WAS OBTAINED. More detailed studies indicated that both metronidazole at 1,500 mg/kg and tinidazole at 750 mg/kg given intraperitoneally gave an enhancement ratio of 1-5 for a chronically hyopix cell population in this solid tumour in air-breathing mice. Measures of plasma levels of metronidazole and enhancement ratios obtained in the present in vivo system seem in relative agreement with the in vitro and in vivo results of others.


Detection of hepatitis B surface antigen among Scottish blood donors: evaluation of sensitive tanned-cell haemagglutination-inhibition test. A total of 70 224 blood donations were tested at three Scottish blood transfusion centres for hepatitis B surface antigen /HBsAg) by an economical haemagglutination-inhibition method (E.H.A.I.) and the results compared with those of counterelectrophoresis (C.E.P.). A further 4086 donations were tested using the Wellcome turkey cell haemagglutination test, C.E.P., and E.H.A.I.E.H.A.I. was also compared with commercial haemagglutination and radioimmunoassay reagents for sensitivity and specificity against several established antigen panels and used to reinvestigate counterelectrophoresis-negative blood donations implicated in post-transfusion hepatitis. E.H.A.I. combines the inherent specificity of an inhibition reaction with a sensitivity equal to that of commercial radioimmunoassay and haemagglutination kits but at a fraction of the cost. The assessment of 70 224 blood donations in three regions showed that E.H.A.I. detected more antigen-positive blood donations than C.E.P. Results of retesting more than 100 blood donors implicated in 10 cases of post-transfusion hepatitis suggested that the use of E.H.A.I. or a test of similar sensitivity in place of C.E.P. may significantly reduce the incidence of this complication.


Which techniques should be used to screen blood donations for hepatitis B surface antigen? Preservation of all donor sera already tested for Hepatitis B surface antigen (HBsAg) by counterimmunoelectrophoresis (C.I.E.P.) allowed C.I.E.P., reversed passive haemagglutination (R.P.H.A.), and radioimmunoassay (R.I.A.) to be evaluated as screening techniques. Out of 165 811 donors tested for the first time 207 were found by C.I.E.P. to be positive for HBsAf-a prevalence of 0-12%. At the next donation 10 of those apparently negative on first screening were HBsAg positive by C.I.E.P., and nine of these were shown by retesting with R.P.H.A. and R.I.A. to have been positive at the earlier donation. These nine false negatives caused four cases of transfusion-transmitted HBsAg-positive hepatitis. On comparative screening of 22 239 donations C.I.E.P. detected 27 sera positive for HBsAg, R.P.H.A. 39, and R.I.A. 41. Thus R.I.A. increased the detection rate by more than half over C.I.E.P. From these 14 further false-negative donations by C.I.E.P. six cases-one fatal-of HBsAg-positive hepatitis occurred. The number of false positive reactions when using R.P.H.A. or R.I.A. for screening was less than 1%. As many as 700 donations in one day have been tested by R.P.H.A. or R.I.A. R.P.H.A. is faster and less expensive than R.I.A., but R.I.A. is more objective. Either R.P.H.A. or R.I.A. should replace C.I.E.P. as the routine method of screening donor sera for HBsAg.


Cushing's syndrome and pituitary-adrenal suppression due to clobetasol propionate. Widespread application of clobetasol propionate resulted in suppression of the hypothalamic pituitary axis in four patients. Three patients showed Cushigoid features and developed symptoms of adrenocortical insufficiency on withdrawal of clobetasol.


Attitudes towards self-poisoning.

Attitudes towards self-poisoning. Self-poisoning now constitutes one of the prime emergencies in hospital medical practice. This paper describes the results of the study of the attitudes of physicians and senior nurses towards several common illnesses in the medical wards. The junior doctors and the nurses who frequently have primary responsibility for the care of the self-poisoners tend to show unfavourable attitudes towards these patients.


Attitudes towards alcoholism.

Attitudes towards alcoholism. An attitude survey of psychiatrists has shown that alcoholism is the least favoured of the organic and psychiatric illnesses. They considered that this attitude was shared by general physicians and surgeons. The unfavourable attitudes towards alcoholism are unlikely to improve the success of treatment programmes. It is suggested that education within the professions is needed.


Effect of teaching on students' attitudes to self-poisoning. The attitudes of students, resident house physicians, and medical social workers towards 10 medical conditions were assessed in relation to both personal attitudes and the opinions expressed of the attitudes of the medical profession. Final-year students and house physicians showed unfavourable attitudes towards self-poisoning in contrast to fourth-year students and medical social workers. The fourth-year students were given the opportunity to admit patients referred to hospital with self-poisoning and visited the family doctor and the patient after discharge. After this exposure there was a subjective impression that the students became more interested in the problems of use self-poisoned patients, and this was supported by a review of their attitudes at the end of the teaching project.


Comparison of debrisoquine and guanethidine in treatment of hypertension. A cross-over trail of debrisoquine and guanethidine in 32 patients showed that both drugs were equally effective in lowering both systolic and diastolic blood pressure. The degree to which they were tolerated by the patients, however, differed greatly. After three months on each drug 18 patients preferred debrisoquine, nine preferred guanethidine, and five showed no particular preference. At current prices the cost of daily treatment to the patient was cheaper with debrisoquine than with guanethidine.


Detection of continuing gluten ingestion in treated coeliac patients. To assess the incidence and effects of continuing gluten ingestion in coeliac disease 51 adult coeliac patients were studied after four to 132 (mean 63) months on a prescribed gluten-free diet. Each patient completed a prospective dietary questionnaire, underwent a repeat jejunal biopsy, and gave serum for gluten antibody estimation. Altogether 65% of patients were still ingesting gluten, often inadvertently. Direct questioning on dietary habits had failed to uncover most of this consumption. The gluten antibody test proved a useful screening test for detecting continuing gluten ingestion and patients with both persistent subtotal villous atrophy and gluten antibodies were almost certain to be taking large amounts ( more than 2 g/day). The presence of persistent partial villous atrophy was found, however, to be an unreliable guide to gluten intake.


Outbreak of idiopathic erysipelas in a psychiatric hospital. In an outbreak of idiopathic erysipelas ten women patients, aged 42-74, in a long-stay unit of a psychiatric hospital were simultaneously affected. Group A streptococci M-type 1 were isolated from two isolated from two patients with erysipelas and 18 carriers, but subsequent serological tests for type-specific antibody, antistreptolysin O, and anti-deoxyribonuclease B showed that the infection had been widespread in the unit. Treatment with ampicillin proved ineffective and to prevent relapse it was substituted by a standard course of intramuscular penicillin. This seems to be the first epidemic of this type to be reported and certainly the first outbreak of idiopathic erysipelas to be investigated by modern serological techniques.


Untoward effects associated with practolol administration: oculomucocutaneous syndrome. Keratoconjunctivitis sicca, conjunctival scarring, fibrosis, metaplasia, and shrinkage developed in 27 patients as an adverse reaction to practolol. Rashes, nasal and mucosal ulceration, fibrous or plastic peritonitis, pleurisy, cochlear damage, and secretory otitis media also occurred in some cases. Three patients suffered profound visual loss though most retained good vision. Symptoms and signs improved on withdrawal of the drug, but reduction of tear secretion persisted in most patients.


Myasthenia gravis associated with penicillamine treatment for rheumatoid arthritis. Four patients with rheumatoid arthritis (R.A.) developed myasthenia gravis after taking penicillamine. In one patient withdrawal of the drug was followed by spontaneous remission of the myasthenia, and in two the dose of anticholinesterase was subsequently reduced. In the fourth patient continuing penicillamine treatment was associated with increasingly severe myasthenic features, but on withdrawal of the drug these resolved. As myasthenia gravis rarely complicates R.A. its onset in these patients shortly after the start of penicillamine treatment suggested that penicillamine may have precipitated this condition.


Surgery of violence. V. Missile wounds of the head and spine. The patient with a cerebral gunshot wound has a very unstable condition. In Belfast emphasis has been laid on rapid evacuation and on starting resuscitation within a few minutes of injury. Early and adequate transfusion combats shock; controlled ventilation helps limit the rise in intracranial pressure. Intracranial haematomata should be sought by early operation. Operation seldom improves neurological function in missile wounds of the spine.


Indications for angiography and surgery in carotid artery disease. The results of angiographic investigation of 211 patients suffering from transient cerebral ischaemic attacks in the carotid territory have been reviewed. The greatest proportion of patients with carotid stenosis and who were referred for endarterectomy were those with a neck bruit ipsilateral to the affected hemisphere. Ocular involvement (amaurosis fugax) was associated with a still higher prevalence of angiographic abnormality, and carotid occlusion was commonest in this group. The implications for the management of patients with transient ischaemic attacks are discussed.


Plasma immunoreactive beta-melanocyte-stimulating hormone and skin pigmentation in chronic renal failure. Plasma immunoreactive beta-melanocyte stimulating hormone (beta-MSH) concentrations were greatly increased in patients with chronic renal failure. There was no correlation between the severity of the renal failure or the degree of pigmentation and the plasma beta-MSH levels.


The trainee year--a critical appraisal.

The trainee year--a critical appraisal. Answers to questionnaires distributed to all trainees in the Scottish south-east region in 1972 and 1973 showed a wide variation between the standard of teaching in individual practices. This was partly due to a failure of the organizing bodies to give proper guidance on the modern concepts of training to the trainers, and partly to a lack of enthusaism by some of the trainers. It is particularly important that the training practices are well equipped with equipment and books and journals relating to general practice. For the trainee vocational training programmes, attendance at day release courses, contact with fellow trainees, and appropriate "on call" duties are similarly important. If these and other recommendations were brought to the attention of the trainers by an effective, co-ordinating committee, the standards of general practice teaching would rise, as would the quality of patient care in the community.


Cellular and humoral immunity to hepatitis-B surface antigen in active chronic hepatitis. The hepatitis-B surface antigen (HBsAG) may be persistently present in the serum in a few cases of active chronic hepatitis but the cause of the disease in most patients is unknown. In a study of 39 HBsAg-negative cases cell-mediated immunity to HBsAg was observed in 24 (62%), suggesting a high frequency of previous infection with the hepatitis-B virus. Hepatitis-B surface antibody was detectable by radioimmunoassay in six patients, in all of whom complexes of HBsAg were present in the serum on electron microscopy. Out of 12 patients with HBsAg-positive active chronic hepatitis who were also studied eight, including all those untreated at the time, showed a cellular response to the antigen. Evidence of sensitization to a liver-specific cell surface lipoprotein was found with similar frequency in the two groups. These results are consistent with the hypothesis that hepatitis-B virus infection is important in initiating the disease in many cases of active chronic hepatitis and that sensitization to the liver cell membrane antigen is the autoimmune process responsible for the perpetuation of the liver injury.


Highly selective vagotomy for duodenal ulcer: do hypersecretors need antrectomy? Two to five years after highly selective vagotomy (H.S.V.) for duodenal ulcer the results were similar in patients with high preoperative maximal acid outputs and those with lower acid outputs. Pain of ulcer type was experienced at some time by 6% of patients from each group, but it was mild and transient in some. No patients had recurrent ulceration at endoscopy or laparotomy, while incidence of individual symptoms was about equal in the two groups. Hence H.S.V. is adequate surgical treatment for patients with both duodenal ulceration and high levels of acid secretion. Antrectomy in such patients is not necessary provided that the incidence of incomplete vagotomy can be kept low.


Depression of sublingual temperature by cold saliva. Sublingual and oesophageal temperatures were compared at various air temperatures in 16 subjects. In warm air (25-44 degrees C) sublingual temperatures stabilized within plus or minus 0-45 degrees C of oesophageal temperatures, but in air at room temperature (18-24 degrees C) they were sometimes as much as 1-1 degrees C below and in cold air (5-10 degrees C) as much as 4-4 degrees C below oesophageal readings. The sublingual-oesophageal temperature difference in cold air was greatly reduced by keeping the face warm, but it was not reduced in two patients breathing through tracheostomies and thereby eliminating cold air flow from the nose and pharynx. Parotid saliva temperature was low and saliva flow high during exposure, and cold saliva seemed to be mainly responsible for the erratic depression of sublingual temperature in the cold. These results indicate hazards in the casual use of sublingual temperatures, and indicate that external heat may have to be supplied to enable them to give reliable clinical assessments of body temperature.


Effects of truncal, selective, and highly selective vagotomy on glucose tolerance and insulin secretion in patients with duodenal ulcer. Part I-Effect of vagotomy on response to oral glucose. An oral glucose tolerance test was performed in patients who had undergone truncal vagotomy and pyloroplasty, bilateral selective vagotomy and pyloroplasty, or highly selective vagotomy without a drainage procedure at least six months earlier. The results were compared with those from patients with chronic duodenal ulcer before operation. In all three groups of patients after vagotomy more rapid rates of rise of blood glucose and higher peak concentrations were observed than in patients who were tested before operation. These differences were statistically significant only in patients who had undergone truncal or selective vagotomy with pyloroplasty and were probably due to more rapid rates of gastric emptying after these operations. Plasma insulin concentrations were lower after truncal vagotomy than after selective or highly selective vagotomy, the difference between truncal vagotomy and highly selective vagotomy being statistically significant. Truncal vagotomy resulted in a diminished insulin response to oral glucose, which could have been due to vagal denervation of the pancreas or, more probably, impaired release of small-bowel hormones which normally augment the pancreatic insulin response.


Effects of truncal, selective, and highly selective vagotomy on glucose tolerance and insulin secretion in patients with duodenal ulcer. Part II-Comparison of response to oral and intravenous glucose. Paired oral and intravenous glucose tolerance tests were carried out in patients who had undergone truncal vagotomy and pyloroplasty, selective vagotomy and pyloroplasty, or highly selective vagotomy at least six months earlier. Intravenous glucose tolerance was similar in all three groups. Oral glucose elicited significantly higher concentrations of plasma insulin in patients who had undergone selective and highly selective vagotomy than in those treated by truncal vagotomy. When the same amount of glucose was given intravenously, however, plasma insulin concentrations were similar in all three groups of patients. The insulin secreted in response to intravenous glucose expressed as a percentage of that secreted in response to oral glucose was 112% for truncal vagotomy, 51% for selective vagotomy, and 52% for highly selective vagotomy. Truncal vagotomy thus led to a diminished insulin response to oral glucose, which was probably due to impaired release of small-bowel hormones.


Use of oxytocin and incidence of neonatal jaundice. A retrospective controlled study using data from the Cardiff Births Survey examined a possible relation between oxytocin administration to induce or accelerate labour and the subsequent development of neonatal jaundice. Among 10 591 infants born in Cardiff between 1970 and 1972 the incidence of neonatal jaundice was higher in infants born after oxytocin administration than among others. Analysis by gestational age at delivery, birth weight, Apgar score, length of labour, sedative and analgesic therapy during labour, and suppression of lactation showed that this association held within all these categories except among small immature infants, who are at high risk of jaundice in any case.


Placental scanning with computer-linked gamma camera to detect impaired placental blood flow and intrauterine growth retardation. By retrospective analysis of 65 placental localization studies by a computer-linked gamma camera the isotope studies by a computer-linked gamma camera the isotope uptake patterns were correlated with the eventual outcome of the pregnancies. The uptakes by anterior and lateral placentae were reduced in pregnancies which resulted in growth-retarded babies and statistically unrelated to the gestation of the pregnancy. This simple representation of placental blood flow could be a clinically useful index of placental function.


Patient-orientated gastroenterology.

Patient-orientated gastroenterology. Analysis of the first year's working of a combined gastroenterology clinic in a district hospital has shown that the major benefit was improved patient management. Hospital attendances were reduced, the diagnostic process accelerated, and unnecessary radiological investigations and surgical operations avoided. There were no obvious major disadvantages.


Cost to National Health Service of social outcasts with organic disease. The hospital medical records of a patient with chronic lung disease and intractable social problems have been analysed. Multiple admissions resulted in the patient spending nearly three years out of seven and a quarter years in Edinburgh hospitals and in the performance of repeated and ofter unnecessary medical investigations. Such patients are a source of considerable uneconomic expense to the National Health Service, but at present it is difficult to see how their medical and social demands can be met in any other way.


Hydroxyproline excretion in patients with breast cancer and response to treatment. The urinary excretion of hydroxyproline, measured as the hydroxyproline: creatinine ratio, was useful in monitoring the progression of metastatic cancer of the breast. After new treatment was started changes in the hydroxyproline excretion occurred earlier than other clinically observable responses. The test could therefore be used for predicting the response to treatment and early detection of the sensitivity of the tumour to hormone therapy.


Occult pulmonary haemorrhage in leukaemia. Through gleeding into the lung parenchyma is responsible for morbidity and mortality in patients with leukaemia pulmonary haemorrhage is seldom diagnosed during life.  We diagnosed occult pulmonary haemorrhage in five leukaemic patients with unexplained infiltrates on chest roetgenograms by examining alveolar macrophages retrieved by bronchopulmonary lavage. Macrophage haemosiderin content was greatly increased in the patients with pulmonary haemorrhage as compared to normal and thrombocytopenic control subjects. Haemoglobin and intact erythrocytes in alveolar macrophages were taken as evidence of recent haemorrhage. Intrapulmonary bleeding may occur often in patients with leukaemia, and bronchopulmonary lavage offers a safe approach to diagnosis and allows for concomitant identification of pulmonary infection.


Gastro-oesophageal reflux complicating highly selective vagotomy. An unacceptably high incidence of gastro-oesophageal reflux was observed in a small series of patients with duodenal ulcer who had been treated by highly selective vagotomy. Possibly this is due to an altered angle of entry of the oesophagus into the stomach, and we now routinely narrow this angle at operation.


Hypersecretion of glucagon and gastrin in severely burnt patients. Hyperglucagonaemia and hypergastrinaemia were observed in some severely burnt patients during their illness. Hyperglucagonaemia seemed to be related to the severity of illness rather than to the burn itself, and the close correlation of glucagon concentrations with glucose and urea and its inverse correlation with bicarbonate concentrations suggest that glucagon might contribute to the hypercatabolic state. One patient developed high levels of gastrin and massive bleeding from a stress ulcer of the duodenum. Possibly gastrin hypersecretion may have a role in the pathogenesis of Curling's ulcer.


Successful pregnancy in patient on regular dialysis. A pregnancy in a patient undergoing regular dialysis treatment was successfully managed. Premature labour occurred at 32 weeks. Fetal nutrition was satisfactory and the infant developed normally and showed no congenital abnormality during 12 months' observation.


Patterns of incidence in acute pancreatitis. A review of acute pancreatitis occurring over a 20-year period in the Bristol clinical area is reported. A total of 590 cases were available for analysis. The yearly incidence was 53-8 per million population at risk, with a mortality of 9-0 per million. This compares favourably with 11-4 deaths per million for England and Wales as a whole during the same period but the difference is not statistically significant. When the deaths occurring in the Bristol clinical area were expressed in terms of case mortality rate the figure was 17%. In contrast the mortality for recurrent acute pancreatitis was only 1-5%, and the benign nature of this second condition is confirmed. Aetiological factors and age and sex distribution were also analysed in relation to each other and to mortality. An increase in acute pancreatitis secondary to chronic alcoholism was confirmed and steroid pancreatitis also emerged as a definite entity in this survey. The pattern of recurrence in patients with idiopathic pancreatitis was studied in detail and is analysed on an actuarial basis.


Trimethoprim-sulphamethoxazole in gonorrhoea. A comparison with privampicillin combined with probenecid. 419 patients with uncomplicated gonorrhoea were treated with sulphamethoxazole 4 g. combined with trimethoprim 0-8 g. divided into two doses with an 8-hr interval. The failure rate was 1-9 per cent. Parallel with this trial, 319 patients received pivampicillin 1-4 g. combined with probenecid 1 g,; the failure rate was 0-9 per cent. Side-effects were few, four patients in the first group and one in the second group developing a rash. No recurrences were noted in nine patients treated for tonsillar gonorrhoea with the trimethoprim-sulphamethoxazole schedule, while two recurrences were found in thirteen patients treated with pivampicillin-probenecid. The frequency of post-gonococcal urethritis was 7-7 per cent. in the pivampicillin-pro-benecid group against 3-4 per cent. in the trimethoprim-sulphamethoxazole group, a difference which was not statistically significant.


Gonorrhoea in 1972. A 1-year study of patients attending the VD Unit in Uppsala. During 1972 a total of 2,090 men and 1,489 women were seen in the VD clinic in Uppsala, Sweden. The most frequent diagnosis among the men was non-gonococcal urethritis (38 per cent.) and among the women non-gonococcal vaginitis (34 per cent.), N. gonorrhoeae was found in 22 per cent. of the men and in 33 per cent. of the women, 68 per cent. of the men with gonorrhoea attended because of symptoms, but 67 per cent. of the men without gonococcal infections came for the same reason. 39 per cent. of the women with gonorrhoea attended after being told by their sexual partner; it was found that women coming because of symptoms were most likely to have non-gonococcal infection. Gonorrhoea without subjective symptoms was found in 23 per cent. of the men and 50 per cent. of the women. Gonorrhoea was found in association with scabies in 9 out of 18 men and in 3 out of 5 women. A rising incidence of pharyngeal gonococcal infections has been noticed at the clinic and the figures for 1972 were 6 per cent. of the men and 9 per cnet. of the women with gonorrhoea. The route of infection was usually oro-genital contact, but in some cases other routes had to be considered. It was not possible to define a promiscuous group of patients suitable for a planned study of prophylactic treatment, as only 2 per cent. of the men and 1 per cent. of the women had had nore than one gonococcal infection during the preceding year. The standard treatment for genital gonorrhoea (ampicillin 2 times 1 g. orally with a 5-hour interval) was very satisfactory and gave a 98 per cent. cure rate. This was possible because there were few gonococcal strains with decreased panicillin sensitivity. There were considerable problems in treating the pharyngeal infections, the standard treatment failing in 61 per cent.


Effect of althesin on renal perfusion in anaesthetized dogs. Since Althesin affects not only the systemic circulation but also certain regional blood flows autoregulated by intrinsic mechanisms, such as cerebral and coronary blood flow, the purpose of this study was to investigate the effect of Althesin upon renal blood flow. After an injection of 2.0 mg/kg Althesin, heart rate (63 per cent) and cardiac output (21 per cent) increased, while total peripheral resistance (25 per cent), mean aortic pressure (9 per cent) and the maximum rate of change of left ventricular pressure (31 per cent) decreased. In spite of the large renal fraction of cardiac output (17.4 per cent) the renal blood flow remained unchanged. Althesin is believed not to be contra-indicated in the presence of renal dysfunction.


[Effects of postoperative decurarization with neostigmine on digestive anastomoses]. A prospective study was undertaken to assess the influence of neostigmine, a reversal agent for curarimimetic myorelaxants, on the incidence of postoperative disruption of anastomotic sites. Over a period of one year, 400 patients had surgery, including anastomosis, on the digestive tract for a variety of surgical conditions (Table II). At the end of anaesthesia, 200 patients received doses of atropine and neostigmine, usually 1 mg and 2.5 mg of each, as indicated on clinical basis and neuromuscular stimulation. The other patients did not recieve these drugs and were ventilated till the myorelaxation vanished spontaneously. During the postoperative period of incidence of anastomotic breakdown was assessed by the surgeon, unaware of the use or the omission of neostigmine in his patients. Anastomotic leakage was classified in four groups, namely: proved, absent, likely and unlikely. In this series and according to these clinical criteria, both groups had an incidence of anastomotic breakdown which was not significantly different (Table III). Neostigmine as used in this work does not seem to compromise the normal healing of anastomotic sites on the digestive tract.


Post-operative renal failure caused by disseminated intravascular coagulation. A 22-year-old man suffered a stab wound of the femoral artery and vein. This was followed by disseminated intravascular coagulation. Renal failure then occurred presumably due to fibrin deposition in the small vessels of the kidney. The D.I.C. was successfully treated with heparin and the renal failure with peritoneal dialysis. It is suggested that D.I.C. and consequent alterations in regional blood flow following trauma are not uncommon, and search should be made for these phenomena in every case of major trauma.


Effect of triphenylmethane derivatives on cell-free macromolecular synthesis. I. Aminoacyl-tRNA synthetase. The inhibitory effect of aurintricarboxylic acid (ATA) on phenylalanyl-tRNA synthetase is demonstrated in the rabbit-reticulocyte system. This inhibition is not specific to ATA; other triphenylmethane derivatives are also potent inhibitors of this enzyme reaction. The site of inhibitory action is in the enzyme itself, not in the tRNA molecule. It thus appears that the skeletal structure of ATA, not the side chains, is responsible for its inhibitory action, and that ATA is a nonspecific inhibitor of the reactions involving polynucleotides.


Effect of triphenylmethane derivatives on cell-free macromolecular synthesis. II. mRNA-ribosome binding. The specific inhibition by aurintricarboxylic acid (ATA) of mRNA binding to ribosomes was re-examined. Among triphenylmethane compounds, all of which are potent inhibitors for phenylalanyl=tRNA synthetase, ATA is the most potent inhibitor. Two other dyes, Aurine and Azure Blue B, inhibit the reaction, but the concentration for 50% inhibition is far higher than that for ATA. It appears that the presence of the carboxyl group on the skeletal-triphenylmethane structure enhances the inhibition of the mRNA-binding reactionmthis feature is slightly different from that of the phenylalanyl-tRNA synthetase reaction, in which the skeletal structure of the dye itself is essential to its inhibitory action.


Excretion of radioactive diadzein and equol as monosulfates and disulfates in the urine of the laying hen. The phytoestrogen, diadzein, was injected intramuscularly as [4-14-C]daidzein into two laying hens. The radioactive materials in the urine for the succeeding 23 (hen 1) or 14 (hen 2) days were fractionated on a DEAE-Sephadex column by a gradient of NaCl and the fractions thus separated were further analyzed by solvent partition, susceptability to enzymic cleavage and thin-layer chromatography. The sic following components were identified and quantitated: [14-C]diadzein, [14-C]equol, [14-C]diadzein monosulfate, [14-C]equol monosulfate, [14-C]diazein disulfate, and [14-C]equol disulfate. The urine from hen 2 yielded also the sulfate of an unidentified conversion product of [14-C]daidzein. Repeared tests for glucuronides of [14-C]daidzein or its conversion products gave negative results, excluding the possibility that any appreciable proportion of the radioactivity in the urine was in the form of beta-glucuronide. It is concluded that the diadzein and the equol excretion in the urine of the laying hen are present for the most part as monosulfates and disulfates.


Studies on molecular weights of two peptide hormones from the urophysis of white sucker (Catostomus commersoni). The molecular weights of two active principles extracted from the urophysis of the teleost fish Catostomus commersoni in 0.1 N HC1 or in 0.25% acetic acid have been investigated by gel filtration chromatography and SDS-polyacrylamide gel electrophoresis. Two peptides with urotensin I Tlong-acting rat hypotensive) activity and two peptides with urotensin II (fish smooth muscle stimulating) activity were found by these procedures. The smaller of the two urotensin I peptides (molecular weight 1200-1700), designated urotensin Is, was shown to be a fragment of the larger peptide (molecular weight 2300-3000) which is produced by acid hydrolysis withour loss of rat hypotensive activity. The two urotensin II peptides are suggested to represent either a monomer and a dimer or open and closed forms of a peptide.


Acid proteases from species of Mucormii. partial characterization of the acid protease produced by a strain of Mucor miehei isolated in Cuba. The acid protease produced by a strain of Mucor miehei isolated in Cuba was purified by column electrofocusing and partially characterized as to amino-acid composition, molecular weight, helical content, total carbohydrate content, and approximate isoelectric point; A detailed comparison of these results was reported previously for Mucor miehei protease (Ottesen, M. & Rickert, W;S. (1970) C.R. Trav. Labmcarlsberg 37, 301) suggested that the two enzymes are similar but not identicalmthis conclusion was reinforced by an analysis of circular-dichroism spectra.


The reaction of chymotrypsin with 2,3-butanedione trimer;. A method for the preparation of the trimer of 2,3-butanedione has been developed; The reaction of this trimer with chymotrypsin A alpha was examined in the presence or absence of light. Under conditions of exclusion of light, modification of one to two arginine residues and of a similar number of lysine residues could be achieved without any loss of enzymatic activity. The trimer facilitated a rapid photoinactivation of the enzyme with little or no modification of the above amino acid residues. Such photoinactivation was not found to react with proflavine and diiosopropylfluorophosphate to an extent greater than that expected on the basis of residual activity presentmproflavine protected the enzyme from the trimer promoted photoinactivation.


Characterization and composition of the purple and red membrane from Halobacterium cutirubrum;. The purple membrance (bacteriorhodopsin) isolated from cells of Halobacterium cutirubrum grown anaerobically in the light was shown to contain 77% protein and 20% lipils by weight. The protein component consisted of a single protein moeity, having a molecular weight of (19.6 plus or minus 0.8) times 10-3, complexed with retinal in  mole ratio of 2:1, respectively. The protein moeity is not glycosylated but may be phosphorylated (ca. 2 mol of phosphate per mole of protein). The red membrance contains 56%protein and 38% lipids, including bacterioruberins. Several polypeptide components are present including some which may be glycosylated and/or phosphorylated. The lipids of both membranes contained phosphatidyl glycerophosphate (52%) and phosphatidyl glycerol (3-4%) but the sulfated lipid components, glycolipid sulfate and phosphatidyl glycerosulfate, were present exclusively in the purple membrane, the red membrane containing instead two unidentified glycolipids. Neutral lipids (squalenes, vitamin 75-8, etc.) were present in both membranes to the extent of 7-9%.


The diglycoside of 17 alpha-estradiol from rabbit urine: comparison with material prepared by synthesis. Two synthetic routes to methyl estra-1,3,5(10)-trien-17 alpha-yl-2'-trifluoroacetamido-3',4',6'-tri-O-acetyl-2'-deoxy-beta-D-glucopyranosid-3-yl-2',3',4'-tri-O-acetyl-beta-D-glucopyranosidyl  uronate are described, with the 3-acetyl or the 17 alpha-trifluoroacetyl derivatives of 17 alpha-estradiol as starting materials. Physical characteristics of the fully acetylated double glycoside were determinedmthis compound was converted to sodium estra-1,3,5(10)-trien-17 alpha-yl-2'-acetamido-2'-deoxy-beta-D-glucopyranosid-3-yl-beta-D-glucopyranosid-3-yl-beta-D-glucopyranosidyl uronate, which was found to be identical with the sodium salt of material isolated from rabbit urine.


Formation and repair of papain sulfenic acid. The inactivation of highly purified papain (2 times 10- minus 5M-minus 1 min-minus 1) for papain: peroxide molar ratios of 1:1 or 2:1. Loss of activity is accompanied by a parallel loss of sulfhydryl; however, the sulfhydryl losses, as determined with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNG) or p-hydroxymercuribenzoate (pHMB), are anomalously either too large or too small, respectively. These discrepancies resulted from the reaction of inactive papain with either the thiol anion product of the DTNB reaction, or with the pHMB reagent itself. The addition of 1.2M urea to the DTNB reaction mixture significantly decreased this error. Inactive papain reacted with high concentrations of cysteine or cyanide to yield completely repaired active papain, and with benylamine to yield non-repairable, inactive papain. Sodium arsenite, which is capable ofreducing sulfenic acids but not disulfide bonds, readily repaired peroxide-inactivated papain. A completely inactive but repairable papain fraction was isolated by virtue of its lessened ability to bind to a tetrapeptide inhibitor immobilized on Sepharose. The cumulative results indicate that the peroxide inactivation of papain is due almost exclusively to the formation of papain sulfenic acid (Cys25-SOH).


S-adenosylhomocysteine metabolism in various species. Eleven microorganisms, four plants, and major organs from the chicken, dog, rat and rabbit were assayed for the presence of S-adenosylhomocysteine hydrolase, S-adenosylhomocysteine nucleosidase, and S-ribosylhomocysteine-cleavage enzyme. All bacteria (procaryotes) were found to possess S-adenosylhomocysteine nucleosidase and S-ribosylhomocysteine-cleavage enzyme but not S-adenosylhomocysteine hydrolase; All eucaryotes tested, including yeasts, plants, birds, and mammals, possessed S-adenosylhomocysteine hydrolase but not S-adenosylhomocysteine nucleosidase or S-ribosylhomocysteine-cleavage enzyme. Of all the organs assayed in the vertebrates, the level of S-adenosylhomocysteine hydrolase was highest in liver, pancreas, and kidney, lower spleen and testis, and very low in brain and heart; In all systems tested, equilibrium of the hydrolase reaction always favored synthesis over hydrolysis. We studied some of the kinetic properties of the hydrolase from rat liver; In the direction of synthesis, the Km value was 1.5 mM for adenosine and 4.5 mM for L-homocysteine, whereas marked substrate inhibition was observed with L-homocysteine. The condensation reaction is subject to product inhibition, and was inhibited by adenine. Results from in-vivo experiments revealed that the cells of the various organs of the dog are impermeable to the exogenously administered S-adenosylhomocysteine.


Wheat-embryo ribonucleates. IV. Factors that influence the formation and stability of a complex between 5S rRNA and 18S rRNA. Under the conditions used in this study, wheat-embryo 5S rRNA complexes with its homologous 18S rRNA from wheat embryos and with heterologous 18S rRNA from other eukaryotic source materials such as yeast, L cells, and HeLa cells, but it does not complex with heterologous 16S rRNA from a prokaryote such as Escherichia coli or with homologous or heterologous 26S (23S) rRNA of either eukaryotic or prokaryotic origin. If a solution of wheat-embryo rRNA is simply made 0.3 M with respect to NaCl and then heated at 60 degress C for 3 min before quick cooling to room temperature (ca. 20 degrees C), there is both preferential and efficient complex formation between 5S and 18S rRNA. The 'laboratory-prepared' complex between wheat-embryo 5S rRNA and its homologous 18S rRNA is more thermostable in 0.1 M NaCl solution than is the 'natural' complexes 'melt' over a narrow range of temperature. The possible physicochemical and physiological importance of both homologous and heterologous rRNA complexes is the subject of a brief discussion.


Magnetic resonance studies of concanavalin A:CONFORMATIONAL CHANGES INDUCED BY Ca2+ and alpha-methyl-D-mannopyranoside. Three independent solution spectroscopic techniques (solvent proton relaxation enhancement, circular dichroism, and high resolution 220 MHz proton magnetic resonance spectroscopy) have been utilized to demonstrate mental ion- and monosaccharide inhibitor-induced structural perturbations for the dimeric form of the plant lectin concanavalin A (Con A). The results indicate that (i) the occupation of the transition metal ion site S1 by Mn-2+ or Zn-2+ does not detectably perturn the demetallized protein conformation, (ii) the binding of Ca=2+ to the Con A-Mn-2+ or Con A-Zn-2+ complexes perturbs the protein structure in the vicinity of the S1 site as well as at points remote from the S1-S2 double ion site, and (iii) the binding of the monosaccharide inhibitor alpha-methyl-D-mannopyranoside to the fully metallized Con A complex also significantly perturbs the structural features of the protein. A detailed radio frequency dependence analysis of the Ca-2+ effect on the solvent proton relaxation enhancement properties of the Con A-Mn-2+ complex indicates that the considerable reduction in the observed enhancement upon Ca-2+ binding principally results from an approximate 120-fold decrease in the single Mn-2+ water of hydratio- exchange rate; The 220 MHz proton magnetic resonance spectra for Con A indicate that this form of spectroscopy is the most useful of those utilized in detailing the solution structural features of this lectin, and a tentative assignment for the C-2-H proton of histidine residue 24 (the S1 site ligand) has been proposed.


Transient kinetics of the acetylcholinesterase catalyzed hydrolysis of N-methylindoxyl acetate. An experimental study has been made of the kinetics of the hydrolysis of N-methylindoxyl acetate catalyzed by electric-eel acetylcholinesterase, both in the steady state and the pre-steady statemstopped-flow and temperature-jump experiments revealed a fast transient and a slow one. The fast transient is correlated with the conventional mechanism E+A in equilibrium EA yields X-yieldsEA' YIELDS E+Y. The slow transient is attributed to conformational changes involving E or EA. Analysis of it revealed two exponential terms of the form e- minus lambda t, and the two lambda values were obtained over the temperature range 5Yand 25Ydegrees C. The results are interpreted in terms of two alternative mechanisms; in one, the enzyme undergoes a conformational change before it adds on the substrate molecule; in the other, the conformational change occurs after the substrate addition. Both mechanisms may be involved, but the results exclude a concerted mechanism in whivh the conformational change occurs concurrently with the addition of substrate. Kinetic parameters (delta S not equal to and E) are obtained for this conformational change and for the conversion of EA into EA'+X.


The demonstration of O-acetylated sialic acids in colonic epithelial glycoproteins. Glycoproteins have been isolated from a 1 M sodium chloride extract of the colonic epithelial cells of man and rat by a combination of Agarose gel and DEAE-cellulose chromatography; The glycoproteins contain O-acetylated or O-esterified sialic acids of at least four types: (a) unsubstituted or possible at position C-9, (b) substituted at C-4 and possibly at C-9, (c) substituted at C-7 and/or C-8, and (d) substituted at C-4 as well as at C-7 and/or C-8.


Effects of hormones and drugs on phosphoribosyl pyrophosphate concentrations in mouse liver. Concentrations of phosphoribosyl pyrophosphate (PP-ribose-P) in mouse liver were studied as a function of time of day and following injection of a number of metabolites and drugs. A twofold diurnal variation in liver PP-ribose-P concentration was observed. Liver PP-ribose-P concentrations were elevated following injection of glucagon, insulin, epinephrine, and ethylaminothiasiazole.


The metabolism of 4'chloro-4-biphenylol in the rat. 4'Chloro-4-biphenylol, the major metabolite of 4-chlorobiphenyl in the rat, was given intraperitoneally to rats, and the urine and feces were examined for possible metabolic degradation products. The structure of the major urinary metabolite was elucidated by mass and nuclear magnetic resonance spectroscopy and shown to be 4'-chloro-3,4-biphenyldiol. Two chloromethoxbiphenylols (m-4) were also identified in the urine extracts but they could not be separated by chromatographic procedures. Demethylation of the mixture gave 4'-chloro-3,4-biphenyldiol as the sole product, thus indicating that the two components of the mixture were 4'-chloro-3-methoxy-4-biphenylol and 4'-chloro-4-methoxy-3-biphenyldiol. No 4'-chloro-4-biphenylol metabolites were isolated in the fecal extracts, and mass spectrometric analysis of the crude urine and feces extracts did not reveal any chlorine-containing degradation products that could be derived by oxidative fission of the biphenyl nucleus.


Electrophoretic characterization of porcine pancreatic (pro)elastases A and B. Two porcine pancreatic zymogens can be separated by free electrophoresis on a sucrose gradient. After activation by trypsin, both enzymes can hydrolyze completely the fibrous protein elastin. One of the two proteins, proelastase B, has, in addition, an esterolytic activity towards N-acetyl-L-tyrosine ethyl ester. The other, proelastase A, does not possess it. The activation products of the zymogens have been tagged with radioactive diisopropylfluro-phosphonate and separated by polacrylamide-gel electrophoresis. Proelastase A gives only one active species, pancreatopeptidase E, but three distinct proteins can be obtained from proelastase B. Elastases A and B exhibit an important synergism when acting together upon a purified elastin lacking microfibrils. Trypsin has considerably less synergistic activity, and chymotrypsin has practically none.


The development of kinetic parameters of hepatic drug-metabolizing enzymes in perinatal rats. The development of the apparent kinetic parameters K-  m and V-max was studied in perinatal Wistar rats for three functionally diverse, hepatic enzymes (p-nitroanisole O-demethylase, carboxylesterase and bromosulphophthalein-glutathione conjugating enzyme), the period studied being from 3 days prepatum to 35 days postpartum. The kinetic parameters underwent marked quantitative changes during development, which appeared to be independent of sex for the first 5 weeks postpartum.


Biosynthesis of gliotoxin and mycelianamide. Mycelium of Penicillium terlikowski was permeable to both L-[carboxyl-14C]phenylalanine and cyclo L-[carbonyl-14C]phenylalanyl-L-seryl. The former compound was incorporated well and the latter poorly into gliotoxin produced by stationary cultures of the organism. Mycelium of Penicillium patulum was permeablt to L-[CARBONYL-14C]tyrosyl and cyclo L-alanyl-d-[carbonyl-14C]tyrosyl. These cyclic depeptides were not incorporated into mycelianamide produced by stationary cultures of the organism, but both1carboxyl-14C]tyrosine were incorporated. The latter was incorporated in a specific manner into part of the mycelianamide molecule. The results did not support the postulate that the appropriate cyclic dipeptides, as outlined above, were free intermediates in the biosynthesis of gliotoxin or mycelianamide.


The incorporation of -14c from [1-14C] PALMITATE INTO GLUCOSE AND GLYCOGEN IN MICE. The incorporation of -14C FROM [1-14C]palmitate into blood glucose and liver and kidney glycogen in postnatal mice has been studied. Incorporation of -14C FROM [1-14C]palmitate into blood glucose and hepatic glycogen is relatively high in suck ling mice. Incontrast, the incorporation into kidney glycogen is low in suckling mice and high in adults. The study indicates the possible utilization of palmitate for glucose synthesis.


Use of the brucellosis card test for screening cattle in Saskatchewan. One group of 28,714 bovine sera were tested by both the brucellosis tube serum agglutination test and the brucellosis card test. The tube serum agglutination test confirmed 99.8% of the negative brucellosis card test results. The brucellosis card test identified 63% of the tube serum agglutination test reactors. In a second group of 496 sera reacting to either the tube serum agglutination test, complement fixation test, plate serum agglutination test or acid antigen serum agglutination test the brucellosis card test identified 99.1% of the complement fixation test positive sera and 91.3% of the sera reacting to any of the other serological tests. The brucellosis card test showed satisfactory agreement with both the complement fixation test and tube serum agglutination test. It appears to be a useful screening test in operations involving large numbers of animals since under these conditions the reactors can be quickly identified and isolated.


Mycoplasma species recovered from the reproductive tracts of western Canadian cows. Samples of cervico-vaginal mucus from 633 animals from 110 herds were cultured and yielded the following mycoplasmas: T-strain--88: Mycoplasma bovigenitalium--79, Mycoplasma spp. (Leach Group 7)--7, Acholeplasma laidlawii--4, Mycoplasma bovirhinis--2 and one not typable. Uterine exudates and endometrial scrapings from 80 infertile cows in two herds were examined. Four animals were positive, M. bovigenitalium was isolated three times, A. laidlawii and Mycoplasma arginini once each. Sixty-five normal uterine contents from pregnant cows were examined, one yielded M. bovigenigalium and the same organism was recovered from the fetal kidney. T-strain mycoplasma, M. bovigenitalium and other Mycoplasma spp. appear to be a part of the normal flora of the cervico-vaginal region of clinically normal one and two year old bred heifers in Alberta and Saskatchewan. Although M. arginini was not recovered from the cervico-vaginal region, a single recovery was made from the uterus of an infertile cow.


Adequacy of commercial lentogenic vaccines against Canadian strains of viscerotropic Newcastle disease virus. Three field strains of Newcastle Disease virus, designated S20, S21 and S23, isolated from chickens or turkeys in Ontario during the 1971-72 epizootic, were characterized as velogenic viscerotropic viruses. No significant antigenic differences were demonstrated among B1, LaSota and a field strain (S23) of velogenic vescerotropic virus by haemagglutination inhibition or protection tests. Primary water vaccination of chicks with commercial B1 and LaSota vaccines at five weeks of age and aerosol revaccination with the same strains four weeks later resulted in protection that lasted 16 weeks after revaccination against experimental challenge with strain S23. The differences in haemagglutination inhibition titres noted when the homologous or the heterologous viruses were used as haemagglutinating antigen were not statistically significant. The rates of decay of virus neutralizing and haemagglutination inhibition antibodies in vaccinated birds showed a divergence indicating the possible duality of antibodies measured in serum neutralization and haemagglutination inhibition tests.


Experimentally induced Faciola hepatica infection in white-tailed deer. I. Clinicopathological and parasitological features. Six white-tailed deer (Odocoileus virginianus) and six sheep were inoculated with metacercariae of Fasciola hepatica. Two animals of each species were given 100, 500 or 2500 metacercariae. Clinicopathological features of these infections were determined by analyses of blood samples collected each week from inoculated deer and sheep as well as from two noninoculated animals of each species. One animal in each inoculated group was killed and examined at six weeks postinoculation and the remainder at 15 weeks postinoculation. Compared with the values obtained from noninoculated controls, eosinophilia, hyperproteinemia and hyperglobulinemia occured in inoculated deer. There were no other significant changes in hematological values or in serum aspartate aminotransferase levels. Marked leukocytosis and eosinophilia, with hyperproteinemia, hyperglobulinemia, hypoalbuminemia, elevated serum aspartate aminotransferase levels and mild macrocytic normochromic anemia characterized the infection in lambs. Although approximately 29% of the inoculum was recovered from the hepatic parenchyma of the sheep, F. hepatica was found in only one of six inoculated deer. A patent infection was established in this deer and constitutes the second report of mature F. hepatica in this host.


Experimentally induced Fasciola hepatica infection in white-tailed deer. II. Pathological features. Six white-tailed deer (Odocoileus virginianus) and six sheep were inoculated with metacercariae of Fasciola hepatica. Two animals of each species were given 100, 500 or 2500 metacercariae. One animal in each inocluated group was killed and examined at six weeks postinoculation and the remainder at 15 weeks postinoculation. At six weeks postinoculation the parietal surface of the livers from inoculated deer was covered with gray fibrous plaques and rust colored patches. Fibroplasia with mononuclear cell infiltration characterized Glisson's capsule on the parietal surface. Granulomas were found in the hepatic parenchyma and on the dorsal surface of the lung. Fresh and healing tracks were occasionally found in the liver. In the sheep fibrinous exudate and numerous subcapsular tracks were found on both surfaces of the liver. Inflammatory changes in portal areas and numerous fresh and healing tracks in the hepatic parenchyma were prominent features. At 15 weeks postinoculation inflammatory changes in Glisson's capsule of inoculated deer were less marked than at six weeks but portal fibrosis and hyperplasia of bile duct epithelium were more advanced. A zone of hemorrhage surrounded ducts that contained mature F. hepatica in one deer. The livers from the sheep were rough, pitted and covered with fibrous tags and adhesions to the diaphragm and greater omentum were common. Hemorrhagic tracks were common in the sheep given 500 and 2500 metacercariae. Portal fibrosis and hyperplasia of bile duct epithelium were seen in the sheep (100 metacercariae) that harbored mature F. hepatica.


The protective effect of milk diet on Toxoplasma gondii infection in mice. The effect of an all milk diet on resistance to Toxoplasmagondii infection in mice was studied. Mice fed an all milk diet were more resistant than conventionally fed mice to T. gondii. It was shown that this effect was due to a dietary deficiency para-aminobenzoic acid.


A pharmacological study of chloramphenicol in horses. Pharmacological disposition of chloramphenicol was studied in horses. Minimum levels of the antibiotic (greater than or equal to 5 mu g/ml) in blood or plasma recommended to combat infections could not be achieved by 4.4 and 8.8 mg/kg I.V. or 30 and 50 mg/kg I.M. or 30 mg/kg oral (as palmitate salt) doses of chloramphenicol. Increasing the dose to 19.8 and 26.4 mg/kg I.V. provided such levels for about two and three hours respectively. A combination of 20 mg/kg I.V. and 30 mg/kg I.M. administered simultaneously did not provide more prolonged levels than 26.4 mg/kg I.V. alone. Chloramphenicol succinate produced higher but not more prolonged levels in blood and plasma than those produced by pure chloramphenicol. Succinate salt is very little, if at all, bound to red blood corpuscles. Plasma half life and the apparent volume of distribution of chloramphenicol in horses were determined as 0.98 hours and 0.92 L/kg, respectively. At 5-10 mu g/ml concentrations in equine plasma approximately 30 percent of the chloramphenicol is bound to plasma proteins. From these studies it is concluded that the biological half life of chloramphenicol may be too short for therapeutic application against systemic infections in horses.


Labrador keratopathy: clinical and pathological findings. The clinical and pathological features of Labrador keratopathy are described. Some indication is given of the frequency of the condition in Northern Newfoundland and Labrador. The histopathology, based on light and electron microscopy of five specimens, is illustrated. The findings support an origin for the globular deposits in the stroma and Bowman's layer rather than the epithelium.


Ocular findings in nevus flammeus.

Ocular findings in nevus flammeus. We examined the eyes of 50 patients with nevus flammeus of the face (port wine stain). Of 26 patients with nevus flammeus involving the area of both the first and second sensory branches of the trigeminal nerve, 4 had glaucoma and 8 were glaucoma suspects. Because the age at which glaucoma develops is uncertain, these patients require periodic ocular assessment. When the nevus flammeus involved the area of V1 alone or V2 alone, there was no associated glaucoma.


Three hundred and sixty degree scleral buckling. A three hundred and sixty degree scleral buckling procedure is proposed for treating difficult and complicated cases of retinal detachment. This procedure has been used successfully in more than 242 cases with an anatomic re-attachment rate of greater than 90%. The overall re-operation rate was about 11%. Complications directly attributable to this procedure were minimal.


Fibrillopathia epitheliocapsularis (pseudoexfoliation): a clinical and electron microscope study. The light microscopic and transmission and scanning electron microscopic findings from two cases of fibrillopathia epitheliocapsularis (pseudoexfoliation) are presented. The ciliary processes, posterior iris and preequatiorial lens capsule were found to be covered with a fine, white, flocculent material. Light microscopic examination revealed feathery, eosinophilic deposits on all three tissues; electron microscope studies showed the exfoilative deposits to be composed of a fine meshwork of fibrils ranging in size from 200-300 A. Fibrils were found on the apical surfaces of the epithelial cells, as well as on and throughout the epithelial cell basement membranes. The general distribution and possible sources of the pseudoexfoilative material are discussed with respect to other recent investigations. The value of the scanning electron microscope as a tool in pathological studies is presented.


The effects of the catecholamines and related drugs on intraocular pressure. This review offers a short summary of present knowledge of the physiology and pharmacology of the sympathetic system with particular reference to its role in the control of intra-ocular pressure. The ocular effects of epinephrine and some related amines are discussed as as new and interesting developments which promise significant increase in the efficiency of drugs in the treatment of glaucoma.


The management of magnetic intraocular foreign bodies. The management of 34 intracocular foreign bodies is reviewed. When possible the removal of the foreign body was carried out in the quadrant closet to where the foreign body was located and through a site 4-5 mm from the limbus. A circumferential incision was made after tenting had been demonstrated while the magnet was applied to the sclera. Sweet localization and B-scan ultrasound were helfpul in patients with opague media. In particular, ultrasound was used to confirm the magenetic qualities of the foreign body when it could not be visualized ophthalmoscopically. Visual results were surprisingly gratifying, even when the foreign body had damaged the cornea and lens as evidenced by the fact that 26 patients (77%) utimately achieved a vision of 20/50 or better.


Retinal changes in sarcoidosis.

Retinal changes in sarcoidosis. In this series, ten patients with systemic sarcoidosis presented with retinal changes as the initial manifestation of the disease. The diagnosis was suspected on the basis of the retinal findings, and subsequently substantiated by medical evaluation. Anterior uveitis, the best-known finding in ocular sarcoidosis, was overshadowed by the retinal changes. The retinal findings in this condition are characteristic and should alert the ophthalmologist to evaluate the patient for systemic sarcoidosis.


Iridoplegia and aqueous flare due to acute herpetic keratouveitis. Functional disturbances due to herpetic keratouveitis in rabbits were investigated. Measurements of pupillary reactivity and exudative processes in the anterior chamber with marked elevations of aquenous proteins and enzymes (LDH and GOT) were used to determine virus-induced pharmacodynamic changes by application of several autonomic and antiviral agents. Characteristic features included the earlier occurrence of hyperreactivity to Mecholyl and epinephrine and the later development of iridoplegia unreponsive to cocaine or atropine. An increase of aqueous proteins causing aqueous flare was suppressed by application of PPP. These patterns were compared with those of acute ocular responses to various types of injuries caused by fromalin, bacterial endotoxins and immunological sensitization with bovine albumin. This experimental herpetic keratouveitis in rabbits appeared similar to Wellings' ocular syndrome,which is suspected to be of herpetic etiology.


Errors in the diagnosis of choroidal malignant melanoma. A 10 year review of enucleations at the University of Ottawa affiliated hospitals revealed that of 29 eyes with a visible fundus lesion diagnosed as choroidal malignant melanoma only one was incorrectly diagnosed.


Induced corneal astigmatism with hydrophilic contact lenses. Changes in keratometer readings were measured in 87 patients, wearing hydrophilic contact lenses for three to more than eighteen months. Twenty-four eyes in the group had an increase of +0.75 or more in the keratometer readings, which invariably involved the vertical reading and was often associated with a distortion of the mire reflex. The change was high as +2.75 diopters. If greater than +1.00 diopter, it was associated with decreased visual acuity with forward correction and with the hydrophilic contact lenses. All but one of the patients who showedchanges of greater than +0.75 diopters over their baseline keratometer readings, were wearing their lenses on an average of 14-16 hours a day. The keratometer readings reverted to the baseline levels with a loss of the distrotion, if the patient reduced the wearing time to less than 12 hours daily. We believe that a maximum average daily wearing time of 12 hours is the safety limit required to minimize the development of induced corneal astigmatism.


Clinical trail of intravitreal C F in retinal detachment surgery. A mixture of 40% octafluorocyclobutane (C4F8) and 60% air was used clinically in eight patients with long-standing retinal detachment. In seven cases the retina reattached after intravitreal injection of C4F8 and intrascleral diathermization of the retinal tear. The one failure was due to massive vitreous retraction and preretinal proliferation prior to the surgery. Except for a slight postoperative iritis when 4 cc of gas lasted for  12 to 30 days after intravitreal injection. On the basis of this and our previous studies, we recommend the use of C4F8 in retinal detachment surgery.


The clinical significance of a single unilateral temporal pterygium. A rare case of a single temporal pterygium is reported. The etiology of pterygium and its predilection for the nasal side is discussed. A hypothesis is presented to explain why a pterygium never extends beyond the center of the cornea. Whenever a single temporal pterygium is noted it should be excised to determine the true nature of the lesion.