The role of feeding and nutrition in the pathogeny and prevention of diarrheic processes.

Diarrheic processes pose a grave health threat in much of Latin America, especially for small children. One reason for this is the close connection between diarrhea and lack of proper nutrition. The present article seeks to explore this connection by examining two of its main components: the protection against diarrhea resulting from breast-feeding and the increased vulnerability to diarrhea created by malnutrition. Breast-feeding helps prevent enteric infections in several ways. For one thing, the mother's colostrum and milk contain antibodies against some enterobacterial antigens. For another, the so-called "bifid factor" in human milk helps discourage growth of pathogenic enterobacteria in the intestinal lumen. Furthermore, children living in unhealthy surroundings become heavily exposed to common bacteria when breast-feeding stops, a circumstance deemed largely responsible for "weaning diarrhea." Proper nutrition in general is also important, since diarrhea tends to be more common and severe among malnourished children. Several processes that could contribute to this problem have been suggested. These include morphological alterations of the intestinal mucosa in malnourished children, poor intestinal absorption of fats and other nutrients, irritation caused by increased concentrations of free bile acids, and changes in the composition of the intestinal flora. Though not all these processes are well understood, it is clear that malnutrition favors development of diarrhea, while diarrhea in its turn precipitates and aggravates malnutrition. The sad plight of millions of children in the Americas is the result of this combined interaction. Many of those who experience it die, and the survivors fail to achieve their full potential growth and development. The control of diarrheic infections alone would greatly improve these children's nutritional status. Likewise breast-feeding in the early months of life, duly supplemented later and followed by a sound diet after weaning, would considerably reduce the danger and damage caused by diarrheic infections.


Patterns of infant and early childhood mortality in the California Project of a collaborative Inter-American Study.

The California Project of the Inter-American Investigation of Mortality in Childhood was carried out in San Francisco and three surrounding counties in 1969 and 1970. The study found infant death rates of 18.5 per 1,000 live births in San Francisco and 17.2 per 1,000 live births in the three counties. Mortality in the neonatal period (the first 28 days of life) accounted for two-thirds of these deaths. Low birth-weitht played a key role in neonatal mortality, one that was particularly marked during the first day of life. Overall, the study found that 77.7 per cent of the neonatal fatalities and 85.6 percent of those dying in the first day of life weighed 2,500 grams or less at birth. Mortality was also very high among infants of mothers under 20 and over 34 years of age., the risks being especially great in the case of young mothers. Moreover, the vast majority of babies that were born to young mothers and died the first day had very low birth-weights. It is therefore concluded that young mothers ran a relatively high risk of having low birth weight babies prone to dying in the first day of life. This demonstrates a clear need for special measures capable of reducing the health risk faced by both young mothers and their children. Besides providing a more detailed explanation of these points, the authors recommend various specific measures that should be taken and present data obtained by the California Project on other aspects of mortality among infants and preschool children 1-4 years of age


A quantitative analysis of oxygen release due to changes in P50 and venous PO2.

It is almost impossible to estimate the amount of oxygen released from hemoglobin on the basis of the P50 values without calculation, because of the shape of the oxygen dissociation curve. For this reason, we prepared two tables : one indicating the saturation of hemoglobin with oxygen in the venous blood as influenced by venous Po2 and P50 (Table I) and the other, the oxygen release from the arterial blood as influenced by venous Po2 and P50 (Table II). Both tables are based o- the Hill's equation and normal entry data. Values of P50 vary from 20 to 45 torr, while the range for venous Po2 is 5-50 torr. The discussion on possible use of the tables follows.


Metabolic and cardiovascular effects of isoprenaline and salbutamol in the dog.

1 The intravenous infusion of isoprenaline and salbutamol into the greyhound increased heart rate and levels of free fatty acids, lactic acid and glucose. 2 On terminating the infusions of isoprenaline the changes produced declined rapidly but the effects produced by salbutamol were more persistent. When high doses of salbutamol had been infused, glucose and lactic acid levels in fact increased during the 20 min following the infusions. 3 These results support suggestions that, in the dog, lipolysis is mediated by beta1-adrenoceptors and liver glycogenolysis by beta2-adrenoceptors. The beta-adrenoceptors mediating muscle glycogenolysis could not be assigned inequivocally to either subtype. 4 The differences in the behaviour of isoprenaline and salbutamol in the period following the infusions are considered to be due partly to slower removal of salbutamol. Increases in lactic acid levels after infusion of large amounts of salbutamol may be secondary to the persistence of high glucose levels.


Tryptamines and some other substances affecting waking and sleep in fowls.

1 Adult fowls (Gallus domesticus) with cannulae chronically implanted in the IIIrd cerebral ventricle and various other sites of the brain, received infusions or injections of tryptamines and catecholamines into the brain; effects of and interactions between these substances on behaviour, electrocortical activity and body temperature were studied. Reserpine-induced arousal, was investigated in young and adult fowls. 2 Tryptamine and alpha-methyltryptamine, given intraventricularly or into the hypothalamus of intact fowls evoked behavioural and bilateral electrocortical arousal, postural changes, elevation of body temperature and tachypnoea; behavioural and bilateral electrocortical arousal were obtained with infusions into the mesencephalon. Ipsilateral electrocortical arousal only, resulted from infusion of alpha-methyltryptamine into the hypothalamus or mesencephalon of fowl encephale isole preparations. The above effects in intact fowls were reduced or replaced by sleep following administration of noradrenaline or alpha-methylnoradrenaline into the IIIrd ventricle or hypothalamus. Pretreatment of intact fowls with an amine oxidase inhibitor surprisingly attenuated or reversed the excitant effects of intraventricular tryptamine. 3 5-Hydroxytryptamine (hydrogen maleinate, creatinine sulphate or oxalate) given intraventricularly or infused into the hypothalamus, elevated body temperature; tachypnoea and postural changes developed at some stage during the elevation of body temperature. Sleep also was induced, although with the oxalate this was succeeded by marked arousal. 4 Behavioural and electrocortical sleep induced by 5-hydroxytryptamine infused into the hypothalamus were replaced by arousal on infusing tryptamine into the hypothalamus, and vice versa. 5 Dexamphetamine infused into the hypothalamus induced drowsiness or sleep which even reversed arousal elicited by systemically administered dexamphetamine. 6 Reserpine-induced arousal was achieved in young and adult fowls pretreated with mebanazine; this arousal was attenuated or replaced by sleep following intraventricular noradrenaline or dopamine but not by 5-hydroxytryptamine nor by noradrenaline or dopamine applied to the hypothalamus. Prenylamine also induced arousal following pretreatment of chicks with mebanazine.


Indomethacin, ketoprofen and corpus luteum regression in the guinea-pig.

1 The accelerated regression of the corpora lutea normally produced by glass beads inserted unilaterally into the uterus of the guinea-pig early in the oestrous cycle was prevented when the beads were filled with indomethacin or ketoprofen. 2 Luteal regression was enhanced by the placement of beads in both horns of the uterus. When empty beads were placed in one horn of the uterus and drug-filled beads in the other, indomethacin blocked regression in both ovaries whereas ketoprofen was ineffective. 3 Indomethacin probably blocks luteal regression by inhibition of prostaglandin syntheses in the uterus.


Synthesis of kallikreins by rat kidney slices.

1 Four radioactive akllikreins were isolated from rat kidney slices incubated with (3H)-L-leucine. 2 The kallikreins were purified by procedures previously used for the isolation of rat urinary kallikreins (Nustad & Pierce, 1974), and by affinity chromatography on a column of insolubilized anti-rat urinary kallikrein. 3 The kidney kallikreins resembled the urinary kallikreins in their relative amounts, isoelectric points and electrophoretic mobilities on polyacrylamide disc gels. 4 The data indicate that the kidney synthesizes four kallikreins which are released into urine. The kallikreins are not changed by passage through the lower urinary tract.


The distribution of lithium, sodium and magnesium in rat brain and plasma after various periods of administration of lithium in the diet.

1 The tissue solubilizer Soluene-100 provides an efficient and easy means of preparing small amounts of rat tissue for cation analysis. 2 Administration of lithium ions to rats for two days to 42 days by the addition of lithium chloride to the diet at a concentration of 30 mmol/kg dry weight results in (a) the uniform distribution of lithium throughout the brain at a concentration comparable to that found in plasma; (b) decrease in the brain sodium concentration: (c) a decrease in brain magnesium concentration and an increase in plasma magnesium concentration; (d)no change in brain water content. 3 The inclusion of LiCl in the diet at a concentration of 30 mmol/kg dry food gives consistent and predictable plasma and brain levels of lithium in the rat without the occurrence of serious side effects over periods of up to 42 days.


Influence of cocaine and sodium on bretylium uptake by reserpine-treated guinea-pig left atrium.

1 The effects of cocaine and sodium on bretylium uptake into sympathetic nerve terminals were investigated in the reserpine-treated guinea-pig left atrium. The ability of bretylium pretreatment to increase the retention of noradrenaline was used as an index of bretylium uptake. Such increased retention has been assessed both by direct measurement and by the ability of tyramine to produce an inotropic response. 2 The restoration of the response to tyramine after incubation with noradrenaline was abolished when the atrium was pretreated with bretylium in the presence of cocaine. When bretylium was added before cocaine, or when alpha-methyl-noradrenaline (not a substrate for monoamine oxidase) was used for incubation, the responses to tyramine were restored in the normal way. 3 Bretylium greatly enhanced the retention of [3-H]-noradrenaline; when bretylium was added in the presence of cocaine, [3-H]-noradrenaline retention was severely impaired. 4 Pretreatment with bretylium in a low-sodium (25 mM) or sodium-free medium significantly decreased the retention of [3-H]-noradrenaline, as compared with the control. 5 Potassium deprivation did not modify the enhanced retention of [3-H]-noradrenaline induced by bretylium pretreatment. 6 Bretylium was released from the nerve terminals by exposure of the preparation to a sodium-free medium or to a solution containing calcium 50 mM, leading to a considerable decrease in [3-H]-noradrenaline retention. 7 The results are consistent with the view that both cocaine and sodium deprivation block the uptake of bretylium by the adrenergic nerve terminals, and that bretylium is probably taken up by a mechanism similar to or identical with the uptake system for noradrenaline and other amines.


Discrimination of monoamine uptake by membranes of adrenal chromaffin granules.

1 The accumulation of various radioactive monoamines by isolated membranes of bovine adrenal chromaffin granules was measured by equilibrium dialysis. 2 Adenosine-5'-triphosphate (ATP) in the presence of Mg++ stimulated the uptake of all the amines tested, but the accumulation of dopamine, (-)-noradrenaline (NA), 5-hydroxytryptamine (5-HT), (plus or minus)-adrenaline and (plus or minus)-octopamine was greater than that of tyramine, (plus or minus)-metaraminol, tryptamine, beta-phenylethylamine and histamine. 3 At the higher concentration levels of the amines in the medium the ATP-dependent accumulation of dopamine, NA, adrenaline and 5-HT in the membranes reached a saturation level, whereas in the absence of the nucleotide no saturation level was attained. 4 Octopamine and 5-HT competitively inhibited the ATP-dependent uptake of NA, 5 Decrease in the incubation temperature or the presence of N-ethylameimide greatly reduced the ATP-stimulated amine accumulation. Ouabain had no effect on uptake. 6 Reserpine virtually abolished the ATP-dependent uptake of dopamine, NA and 5-HT, caused a partial inhibition of the metaraminol, octopamine and tyramine accumulation, but did not interfere with the uptake of tryptamine. 7 The content of endogenous catecholamines of the membranes was changed very little by incubation of NA and 5-HT in the presence of ATP. However, the membranes lost over 80% of their endogenous amines if incubated for 30 min without ATP. 8 The ATP content of the medium progressively decreased during the incubation of granular membranes. 9 It is concluded that the membrane of adrenal chromaffin granules discriminates between the various monoamines with regard to the magnitude of their uptake and that two mechanisms of ATP-stimulated uptake, one responsive and the other resistant to reserpine, exist at the level of this membrane. The ATP-stimulated transport at the granular membrane level may be an important factor in determining the intraneuronal storage of a physiological or false neurotransmitter.


Role of extraneuronal mechanisms in the termination of contractile responses to amines in vascular tissue.

1 The role of the uptake and release of agonist from extraneuronal sites in the termination of responses of rabbit aortic strips to amines was studied. 2 Strips were contracted with adrenaline or noradrenaline and after response plateau was reached, the muscle chambers were washed free of agonist and the relaxation in Krebs solution recorded. After inhibition of catechol-O-methyl-transferase, monoamine oxidase and neuronal uptake the relaxation rate was greatly prolonged. Evidence is provided that this very slow relaxation resulted from the accumulation of intact amine at extraneuronal sites during exposure to the agonist and its subsequent release past receptors due to a reversal of the concentration gradient after washout. 3 Pretreatment with the haloalkylamine, GD-131 (N-cyclohexylmethyl-N-ethyl-beta-chloroethylamine), an inhibitor of extraneuronal uptake, returned the slow relaxation rate after enzyme inhibition towards that of control strips. By blocking the extraneuronal transport of amines their accumulation at intracellular loci after enzyme inhibition was prevented. 4 The effects of GD-131 and 17beta-oestradiol on the relaxation rate of untreated strips contracted by adrenaline and noradrenaline confirmed that extraneuronal uptake to sites of enzymatic activity is the major mechanism terminating their action. 5 Inactivation of extraneuronal transport sites by GD-131 was prevented by protecting them with 17beta-oestradiol or normetanephrine during exposure to the haloalkylamine, pointing to a common site of action of these agents on a specific carrier system for amines. 6 Evidence is presented that the relaxation from contractions induced by histamine and 5-hydroxytryptamine also involves extraneuronal accumulation and release, probably by an uptake process which is identical to the one for catecholamines.


Studies on the mechanism of action of a new Ca-2+ antagonist, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride in smooth and skeletal muscles.

1. The rabbit aortic strip, guinea-pig ileum and rabbit skeletal muscle sarcoplasmic reticulum preparations were used to determine at which sites and in what manner 8-(N,N-diethylamino)-octyl 3,4,5,-trimethoxybenzoate (TMB-8) interferes with Ca2+ availability in smooth and skeletal muscles. 2. TMB-8 (50 muM) significantly inhibited equivalent responses of the rabbit aortic strip to KCl and noradrenaline. 3. TMB-8 (65 muM) produced no significant alteration in the extracellular space of the guinea-pig ileum as measured with [3H]-sorbitol. 4. The resting cellular Ca2+ influx as well as the resting 45Ca2+ efflux in the guinea-pig ileum preparation were significantly inhibited by TMB-8 (65 muM). 5. TMB-8 (5 muM and 50 muM) had no significant effect on the uptake of 45Ca2+ by the sarcoplasmic reticulum preparation of skeletal muscle; however, TMB-8 (5 muM) did significantly inhibit the caffeine (20 mM)-induced release of 45Ca2+ from this preparation. 6. It is concluded that TMB-8 reduces Ca2+ availability in smooth and skeletal muscles by stabilizing Ca2+ binding to cellular Ca2+ stores and thereby inhibits the release of this Ca2+ by contractile stimuli.


Liver and brain tryptophan metabolism following hydrocortisone administration to rats and gerbils.

1 Liver tryptophan pyrrolase activity is low in the mongolian gerbil (Meriones unguiculatus) and is not induced by hydrocortisone (5 mg/kg). In contrast, there is measurable activity in the rat liver and this is induced by hydrocortisone. In vivo measurements confirmed the absence of induction in gerbils but suggested that they were able to metabolize tryptophan. However no detectable pyrrolase activity was found in any other tissues either before or after hydrocortisone. 2 In agreement with previous observations hydrocortisone decreased rat brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) 6 h after administration. Brain tryptophan concentrations were also decreased at this time. In contrast, hydrocortisone did not alter gerbil brain 5-HT, 5-HIAA or trytophan. alpha-Methyltryptophan activated hepatic tryptophan pyrrolase and decreased brain 5-HT and 5-HIAA in both animals. 3 Results suggest that the decrease in rat brain 5-HT and 5-HIAA following hydrocortisone may be associated with the rise in liver tryptophan pyrrolase and that the brain amine changes are mediated through the decrease in brain tryptophan concentration.


Prostaglandin production by a mild inflammatory lesion in sheep.

By implanting a Teflon chamber subcutaneously into a sheep a mild aseptic inflammatory lesion was produced from which wound fluid could be sampled daily. The prostaglandin content of this wound fluid was examined. Prostaglandin E2 activity was found in all samples, and a peak was apparent on the fourth or fifth day after producing the lesion. The amount of prostaglandin activity appeared to be unrelated to the total number of polymorphs in the fluid or to the volume of this exudate.


An ambiguity in receptor theory.

Two expressions for colculating receptor occupancy by antagonist in competitive drug antagonism are contrasted.


Thermoregulatory changes induced by cholinomimetic substances introduced into the cerebral ventricles of sheep.

1 Thermoregulatory responses have been recorded from Welsh Mountain sheep exposed to warm, neutral or cold environments while injections of cholinomimetic drugs and/or their antagonists have been given into a lateral cerebral ventricle. 2. Carbachol and physostigmine inhibited panting of animals at high ambient temperature (ta), caused vasoconstriction and initiated shivering at neutral ta, and accentuated shivering at low ta. Rectal temperature (tre) invariably increased. Oxotremorine had apparently identical effects. 3. Nicotine and another ganglionic stimulant, the quaternary methyl derivative of dopamine, had no effects on thermoregulation. 4. Atropine given 10 min before injections of carbachol, physostigmine or oxotremorine completely inhibited their hyperthermic effects, but pretreatment with the ganglion-blocking drug, pempidine, caused no inhibition. The cholinergic synapses that respond to cholinomimetic drugs injected into the lateral cerebral ventricles of sheep are therefore muscarinic and not nicotinic. 5. When atropine was given to sheep exposed to cold, no detectable reduction of shivering occurred and tre decreased only slightly, even with doses of atropine far greater than needed to inhibit shivering induced by physostigmine. This may be because shivering is controlled by neural pathways unaffected by drugs administered intracerebroventricularly or because the cholinergic synapses activated by physostigmine do not carry the input from cold sensors.


The effects of morphine on the release of noradrenaline from the cat isolated nictitating membrane and the guinea-pig ileum myenteric plexus-longitudinal muscle preparation.

1. Electrical field stimulation of either the cat isolated nictitating membrane or the guinea-pig ileum myenteric plexus-longitudinal muscle preparation caused the release of noradrenaline into the bathing medium. 2. In the cat nictitating membrane, the output per pulse of noradrenaline was constant at frequencies of stimulation from 0.5 to 15 Hz. In the guinea-pig myenteric plexus preparation the output per pulse of noradrenaline increased as the frequency of stimulation was increased from 2 to 16 Hz. 3. Phenoxybenzamine (29.3 muM) caused a marked increase in the noradrenaline output from both the cat nictitating membrane and guinea-pig myenteric plexus preparations. 4. Morphine (0.13-8 muM) inhibited the contractions of the cat nictitating membrane caused by electrical stimulation. This effect was greater at low (1Hz) than at high (15Hz) frequencies of stimulat The site of action is at the nerve-smooth muscle junction. 5. The action of narcotic analgesic drugs on the cat nictitating membrane showed stereospecificity. Naloxone (0.1 muM) reversed the inhibition caused by normorphine (3.2 muM). 6. Morphine (3 muM) reduced the noradrenaline output from the cat nictitating membrane stimulated at 1 Hz but not at 15 Hz. At 1 Hz, the inhibition of noradrenaline output by normorphine (muM) was reversed by naloxone (0.25 muM). 7. Morphine (1.5 muM) did not alter the noradrenaline output from the guinea-pig myenteric plexus preparation stimulated at 2 or 16 Hz.


Inhibitory effects of clonidine and BS 100-141 on responses to sympathetic nerve stimulation in cats and rabbits.

1. In pithed cats, the spinal sympathetic outflow was stimulated preganglionically at segments C7 and T1 and heart rate responses and nictitating membrane tone were measured in parallel. 2. Clonidine and a related drug, BS 100-141 (N-amidino-2(2,6-dichlorophenyl)acetamide hydrochloride), caused a dose-dependent inhibition of the stimulation-induced tachycardia but did not inhibit responses of the nictitating membrane. The inhibition of heart rate was antagonized by the alpha-adrenoceptor blocking drug, phentolamine. 3. In isolated hearts of rabbits, noradrenaline release in response to adrenergic nerve stimulation was reduced by clonidine and BS 100-141 and the effect was antagonized by phentolamine. 4. The results support the view that presynaptic alpha-adrenoceptors are involved in the regulation of transmitter release from adrenergic nerves. Cardiac adrenergic nerves appear more sensitive to alpha-adrenoceptor-mediated inhibition of inpulse transmission than the sympathetic nerves to the nictitating membrane.


An indirect sympathomimetic effect of burimamide on kitten isolated atria.

1. Burimamide (34-1080 muM) caused a concentration-dependent increase in the force and frequency of contraction of kitten isolated atria. 2. Metiamide (467 muM) had no stimulant action on kitten atria and did not modify the effects of burimamide. 3. The atrial stimulation produced by burimamide was reduced by (-)propranolol (34-68 nM) and by cocaine (3 muM). 4. The atrial stimulant effect of burimamide was prevented by pretreatment of kittens with reserpine (1 mg/kg, 24 h before the experiment). 5. It is concluded that burimamide causes atrial stimulation by releasing catecholamines.


Effect of acetylcholine on changes in contractility, heart rate and phosphorylase activity produced by isoprenaline, salbutamol and amino-phylline in the perfused guinea-pig heart.

1. Isolated perfused hearts of guinea-pigs were given graded doses of isoprenaline, salbutamol and aminophylline, both before and during acetylcholine infusion. 2. The three agonists produced increases in contractile force, heart rate and ventricular glycogen phosphorylase activity. 3. Acetylcholine, in the concentration used, had no effect on any of the measured variables but did antagonize the effects of the three agonists on contractility and phosphorylase activity. The positive chronotropic responses were unaltered by acetylcholine infusion. 4. The ratio of the dose required for a standard heart rate response to the dose producing a standard contractile force response was different for each agonist. 5. The selective antagonism of the contractile response to isoprenaline, salbutamol and aminophylline suggest that different mechanisms are involved in the initiation of positive inotropic and chronotropic responses.


A chemotactic role for prostaglandins released from polymorphonuclear leucocytes during phagocytosis.

1. Prostaglandin E1 is chemotactic at concentrations down to 10 ng/ml for rabbit polymorphonuclear (PMN) leucocytes. Prostaglandins E2 and F2alpha have little or no chemotactic effect at concentrations up to 10 mug/ml. 2. Washed PMN leucocytes produced a chemotactic agent during phagocytosis, but not in the presence of indomethacin (28 muM). 3. Phagocytosing PMN leucocytes produce up to ten times as much prostaglandin as do resting cells. Some of this is prostaglandin E1 as judged by thin layer chromatography and differential bioassay. This prostaglandin production by PMN leucocytes is abolished by indomethacin (28 muM). 4. Ultrasonicated suspensions of PMN leucocytes produced prostaglandin from arachidonic aicd. This synthesis is inhibited by indomethacin. 5. Homogenates of PMN leucocytes which have been pre-incubated withe bacteria for 30 min show more prostaglandin synthetase activity than homogenates from PMN leucocytes which have not been exposed to bacteria. 6. It is concluded that in some forms of inflammation, prostaglandin E1 may play a controlling role in cellular migration. 7. PMN leucocytes may contribute to the generation of prostaglandins found in some inflammatory lesions.


Enhanced inactivation of prostaglandin E2 by the rabbit lung during pregnancy or progesterone treatment.

1. The inactivation of prostaglandin E2 by the rabbit lung was estimated in vivo by comparing its depressor potency following intravenous and intra-aortic injections, and in vitro by measuring the rate of disappearance of smooth muscle stimulating activity when the prostaglandin was incubated with high speed supernatant fractions from lung homogenates. 2. The ability of the lung to inactivate prostaglandin E2 in vivo increased gradually throughout pregnancy, and then decreased rapidly during the three days post-partum. 3. An increased lung inactivation was also seen in pseudopregnant (day 12) rabbits, and in non-pregnant rabbits treated with progesterone for 12 days. A further increase occurred when progesterone treatment was prolonged to 26 days. 4. Treatment with oestradiol monobenzoate or cortisol for 12 days, and deprivation of ovarian hormones for 14-17 days by ovariectomy, were without effect on the lung inactivation of prostaglandin E2. 5. The in vitro experiments revealed a striking increased in the activity of lung prostaglandin metabolizing enzymes during pregnancy. 6. The results are discussed in relation to the hormonal changes occurring during pregnancy, and it is suggested than an enhanced lung inactivation of prostaglandins might have an important protective function at this time.


Effect of fenfluramine on 5-hydroxytryptamine uptake and release by rat blood platelets.

1. (+)-Flenfluramine reduces the central stores of 5-hydroxytryptamine (5-HT) by a poorly understood mechanism. 2. Rat blood platelets have been used in this study as a simple model for serotoninergic nerve endings. 3. (+)-Fenfluramine shows a dual effect: it inhibits the uptake of (14C)-5-HT by platelets and it releases newly absorbed (14C)-5-HT from platelets. 4. The inhibition of (14C)-5-HT uptake induced by (+)-fenfluramine appears very rapidly, is concentration-dependent and seems not to be competitive. (+)-Fenfluramine is ten times less effective than chloroimipramine but tem times more effective than (+)-amphetamine; (+)-fenfluramine is more active than its (-)isomer or its metabolite norfenfluramine ((+)- or (-)-form). 5. The release of (14C)-5-HT from platelets induced by (+)-fenfluramine is concentration-dependent but increases wtih increased incubation time. Both chloroimipramine and (+)-amphetamine are in comparison very poor release inducers; (+)-fenfluramine is more active than its (-)-isomer or its metabolites. 6. The effect on (14C)-5-HT uptake exerted by (+)-fenfluramine and chloroimipramine in vitro could not be observed in vivo. 7. The observed effect on fenfluramine on the uptake and release of 5-HT may explain the lowering action of fenfluramine on the brain 5-HT level, an effect considered of importance for the anoretic effect on this drug.


Antagonism of adenosine 5'-triphosphate-induced relaxation by 2-2'-pyridylisatogen in the taenia of guinea-pig caecum.

1. 2-2' Pyridylisatogen tosylate (PIT) (greater than 2.5 muM) relaxed the guinea-pig isolated taenia caeci by an unknown mechanism. 2. With higher concentrations of PIT (greater than 12.5 muM) subsequent applications of adenosine 5'-triphosphate (ATP) (2-600 muM) revealed a blockade of the ATP receptors. The antagonism was characterized by a delayed onset of action (greater than 10 min incubation with 50 muM PIT) and eventually became irreversible (greater than 50 muM PIT for greater than 30 minutes). The antagonism was specific for ATP, was not competitive, and was not dependent upon the relaxant effect. 3. The presence of either acetylcholine (0.05-1.0 muM) or carbachol (0.05-1.0 muM) increased the antagonistic effect of PIT (50 muM) approximately five-fold. 4. Following prolonged exposure, PIT (50 muM for 90 min) did not block the inhibitory effects of fiedl stimulation (2 Hz, 10 s) of the taenia caeci in the presence of hyoscine (0.33 muM). These results do not support the purinergic nerve hypothesis.


Effect of fluphenazine on tissue noradrenaline concentrations and its interaction with pargyline.

Fluphenazine caused a small decrease in the noradrenaline (NA) concentrations of the rat brain, possibly by impairing granular amine storage. The drug diminished the rise in brain and heart NA concentrations induced by pargyline, suggesting that it might posses inhibitory properties on neuronal uptake mechanisms and/or NA synthesis. Fluphenazine abolished conditioned avoidance responses in rats, an effect which was maintained after the concomitant administration of pargyline, when NA concentrations remained high. This suggests that the fluphenazine-induced sedation is not mediated via its effect on brain NA content, but is possibly due to the effect of the drug on NA turnover rates in the brain.


Indomethacin potentiation of the response of the rabbit portal vein to electrical stimulation: effect of stimulus frequency and train length.

The response of the rabbit isolated portal vein to electrical stimulation was potentiated by indomethacin (10 mug/ml). This potentiation was dependent upon frequency but independent of the number of pulses in a train. It is concluded that these results add further support for the idea that indomethacin increases the release of newly synthesized noradrenaline as a result of inhibition of prostaglanding synthesis.


Effect of tetramethylenedisulphotetramine on the membrane conductance increase produced by gamma-amino-butyric acid at the crab neuromuscular junction.

The effect of tetramethylenedisulphotetramine (TETS) on the increase in membrane conductance produced by gamma-aminobutyric acid (GABA) at the hermit crab neuromuscular junction was investigated. TETS produced a dose-dependent antagonism of GABA, which was characterized by a non-parallel shift of the log dose-conductance curve for GABA with a reduced maximal conductance change.


Factors affecting the cerebrovascular response to noradrenaline in the dog.

1 Noradrenaline infused into the internal carotid artery of the dog (0.01-1 mug kg(-1) min(-1)) constricts the blood vessels of the cortex. This constriction is mediated by the action of noradrenaline on alpha-adrenoceptors of the cerebral arteries.2 Intravenous (1 mug kg(-1) min(-1)) or intra common carotid arterial (0.01-1 mug kg(-1) min(-1)) infusions of noradrenaline cause an increase in cortical blood flow that can be dissociated from changes in blood pressure.3 The effect of intravenous noradrenaline on the cortical blood vessels and metabolism is blocked by high PaCO(2) levels, or by the prior administration of (+/-)-propranolol. (+)-Propranolol is without such effect.4 Following section of both vagi and both sinus nerves, intravenous noradrenaline fails to cause an increase in cortical blood flow.5 In another series of animals the area of the carotid bifurcation was vascularly isolated and perfused with blood from a second dog. Chemoreceptor and baroreceptor activity was shown to be intact.6 Administration of 5% CO(2) to the donor dog caused an increase in cerebral blood flow in the recipient dog.7 Administration of intravenous noradrenaline (1.0 mug kg(-1) min(-1)) to the donor animal caused an increase in cerebral blood flow, cerebral O(2) and glucose utilization of the recipient.8 Administration of 5% CO(2) and intravenous (-)-noradrenaline (1.0 mug kg(-1) min(-1)) caused a further increase in flow and metabolism.9 This evidence suggests that the cerebrovasodilatation observed following intravenous noradrenaline is reflex and is triggered by chemoreceptor activity.10 The evidence also suggests that the antagonism of the cortical dilatory effects of intravenous noradrenaline by raised PaCO(2) in the intact animal must be at a site different from the peripheral chemoreceptors.


Role of catecholamines in the central mechanism of emetic response induced by peruvoside and ouabain in cats.

1 Peruvoside, (a glycoside obtained from the plant, Thevetia neriifolia Juss) and ouabain produce emesis in cats. Vomiting is not produced by these drugs in animals pretreated with catecholamine depleting drugs like reserpine, tetrabenazine or syrosingopine. Chloropromazine hydrochloride, mepyramine maleate, or BOL-148 administered intravenously or intracerebro-ventricularly do not afford protection.2 Phenoxybenzamine produces partial protection against peruvoside-induced emesis.3 Haloperidol (1 mg/kg i.v.) prevents vomiting induced by peruvoside or ouabain. Intracerebroventricularly administered haloperidol is ineffective.4 Cats pretreated with SKF-525-A, are not protected by haloperidol. Animals pretreated with phenobarbitone in a dose of 25 mg/kg for a week were protected by haloperidol, 250 mug/kg i.e. one quarter of the effective antiemetic dose in normal cats.5 It is postulated that catecholamines are involved in the mechanism of vomiting induced by cardiac gycosides. Further, a metabolite of haloperidol seems to be responsible for its effective antiemetic action.


Hyperglycaemia produced by drugs with analgesic properties introduced into the cerebral ventricles of cats.

1 The effects on blood glucose of four substances with analgesic properties (apomorphine, pethidine, codeine and etorphine) and of prostaglandin E(1) were examined in unanaesthetized cats. They were applied by the intraventricular route being either injected into a lateral ventricle or infused into the fourth ventricle through implanted Collison cannulae.2 Apomorphine gave rise to pronounced hyperglycaemia in a dose of 0.75 mg which produced scarcely any hyperglycaemia on intravenous injection. It was more effective on infusion into the fourth ventricle than on injection into a lateral ventricle and was approximately half as potent as morphine in provoking hyperglycaemia.3 Codeine produced no hyperglycaemia in doses of 0.75 and 1.5 mg.4 Pethidine had a weak hyperglycaemic action in doses of 0.75 and 1.5 mg, but the effect was not regularly obtained. Potency of the drug was at most only a third to a sixth that of morphine.5 Etorphine produced strong hyperglycaemia on infusion into the fourth ventricle in a dose of 10 mug. Unlike apomorphine or morphine it was more potent on injection into a lateral ventricle when it produced a strong hyperglycaemic response in doses of 5 or 1 mug, which were subthreshold on infusion into the fourth ventricle. However, this response may have been brought about indirectly as a result of severe asphyxia and of convulsions associated with the injections. On infusion into the fourth ventricle, etorphine was about 75 times as potent as morphine in producing hyperglycaemia.6 Prostaglandin E(1) had no hyperglycaemic action when infused into the fourth ventricle in a dose of 400 ng.


Alternative approaches to analgesia: baclofen as a model compound.

1 It is suggested that analgesia could be produced by drug action at the spinal level through (a) interference with neurotransmission at primary afferent terminals; (b) enhancement of the ;gate control' of the sensory input to the spinal cord mediated through descending spinal tracts; or (c) increased presynaptic inhibition of primary afferents by a direct action.2 Baclofen (9.4-70.3 mumol/kg, i.p.), which may mimic spinal presynaptic inhibition, produced a dose-dependent increase in the response times of mice in a hot-plate test, but high doses also impaired motor function.3 Morphine hydrochloride (5.3-40 mumol/kg, i.p.) increased the response time of mice in the hot-plate test and had little effect on motor function.4 Combination of baclofen (9.4 or 23.4 mumol/kg) with morphine (13.3 mumol/kg) produced greater increases in response time than either drug administered alone but with little concurrent effect on motor function.5 The possibility that baclofen may have some analgesic action and a potentiating effect on other analgesics is discussed.


Characterization of an inhibitory receptor in rat hippocampus: a microiontophoretic study using conformationally restricted amino acid analogues.

1 Pyramidal cells in rat hippocampus were used to study the molecular dimensions of a receptor for inhibitory amino acids in the central nervous system. The inhibitory potencies of gamma-aminobutyrate (GABA), beta-alanine and glycine were compared by standard microiontophoretic techniques. Subsequently, rigid cyclopentane and cyclohexane amino acid analogues were applied by iontophoresis and their relative efficacies were compared with those of the naturally occurring amino acids.2 GABA was the most effective of the small aliphatic amino acids in producing inhibition of the firing of hippocampal pyramidal neurones. beta-Alanine was less effective and glycine was the least effective. GABA-induced inhibition was antagonized by concurrent iontophoresis of picrotoxin or bicuculline, whereas strychnine did not antagonize GABA inhibition.3 The ability of the series of substituted aminocyclopentane and aminocyclohexane carboxylic acids to produce inhibition of pyramidal cells was a direct function of the separation of amino and carboxylic acid groups. In both series of the cyclic amino acids the most potent inhibition was demonstrated when the spatial separation was similar to that of the extended GABA molecule (4.74 A). Additionally, the inhibition of hippocampal pyramidal cells by (+/--cis-3-amino-cyclopentanecarboxylic acid, like that produced by GABA, could be blocked by simultaneous application of picrotoxin or bicuculline, but not by strychnine.4 The present results suggest that the physiologically active conformation of GABA is the fully extended molecule, and additionally indicate that one dimension of the postsynaptic receptor site is within the range of 4.2 to 4.8 ångströms.


The effects of prostaglandins on guinea-pig isolated intestine and their possible contribution to muscle activity and tone.

1 Prostaglandins F(1alpha) and F(2alpha) caused contraction of the longitudinal muscle of both guinea-pig isolated ileum and colon, apparently by acting directly on the muscle and on cholinergic nerves. They had little effect on ileal circular muscle.2 Prostaglandins E(1) and E(2) caused contraction of the longitudinal muscle of guinea-pig isolated colon, apparently by acting directly on the muscle and on excitatory nerves which are non-cholinergic. Prostaglandin E(1) seems more effective than E(2) in stimulating these nerves.3 It seems likely that prostaglandin release in vitro maintains the tone of the longitudinal muscle of guinea-pig colon, whereas release of a prostaglandin E compound inhibits circular muscle tone.


The responses of the isolated, blood-perfused spleen of the dog to angiotensin, oxytocin and vasopressin.

1 The responses of the smooth muscle of the capsule and blood vessels of the isolated, blood-perfused spleen of the dog to angiotensin, oxytocin and vasopressin have been investigated and compared to the actions of the catecholamines, adrenaline and noradrenaline.2 Increasing doses of each of the three polypeptides cause graded increases in splenic vascular resistance and reductions in spleen volume.3 Doses of the polypeptides which evoked increases in splenic vascular resistance not significantly different from increases produced by chosen doses of each catecholamine caused significantly smaller reductions in spleen volume.4 The time-course of action of the polypeptides on the splenic vascular smooth muscle is different since the time to 50% recovery from vasopressin is highly significantly longer than that for equieffective doses of either angiotensin or oxytocin.5 Phenoxybenzamine, in a dose which almost blocked the actions of the catecholamines, increased the responses of the vascular and capsular smooth muscle to oxytocin, vasopressin and angiotensin. This increase was not observed with another alpha-adrenoceptor blocking agent, phentolamine.6 The significant species variation in the responses of the smooth muscle of the spleen to polypeptides and catecholamines are discussed and the results are considered in the context of the possible physiological roles of the polypeptides in haemorrhage.


Suicide in Dublin: II. The influence of some social and medical factors on coroners' verdicts.

This paper presents an analysis of the factors which influence coroners in their decision to classify some deaths as suicides and others as accidental or "open". The most important influence on coroners' behaviour was seen to be the manner by which the person died. Those who died by cutting, hanging, drugs or gas were significantly more likely to receive a suicide verdict than those whose deaths were due to drowning, jumping, shooting or poisoning. If the deceased left any intimation of a suicidal intent, this increased the likelihood that a suicide verdict would be returned. Finally, persons aged under 40 were significantly more likely to be returned as suicides than older victims, especially those aged over 70. All of these results show that coroners operate by observing the law as it defines suicide, that is, by looking for evidence of intent of self-inflicted death. Our findings concerning the factors associated with the suicide verdict help to clarify the meaning of the official data on suicides in Ireland, and illuminate the reasons why, using clinical rather than legal criteria, a much higher rate is obtained.


The urban distribution of non-fatal deliberate self-harm.

1. The incidence of non-fatal deliberate self-harm throughout the City of Bristol during 1972 and 1973 was assessed by means of a survey of patients presenting to Accident and Emergency Departments of hospitals in the area. Fatal or repeated acts of self-harm were not included in the survey. 2. The rates for females exceeded those for males at all ages, with peak incidence of 645 per 100,000 females (age group 15-29 years) and 334 per 100,000 males (age group 25-29 years). Ninety-three per cent had taken a drug overdose of some kind. 3. The problem was found in all electoral wards of tE CITY, THOUGH ITS DISTRIBUTION WAS MARKEDLY CENTRIPETAL, WITH A CENTRAL AREA HAVING MORBIDITY RATES UP TO 2-8 TIMES THAT FOR THE CITY AS A WHOLE. 4. The socio-economic correlates of deliberate self-harm were examined by reference both to a series of 368 patients interviewed soon after the event and to the pattern of its distribution throughout the city. A significant positive association was found with areas of overcrowding, lack of exclusive domestic amenities and high proportion of foreign born residents, but there was no correlation with the proportion of persons living alone nor with the type of accommodation. 5. The central high rate area was found to be heterogeneous in socio-economic terms, ranging from a student and young professionals' bed-sitter area to one with a high proportion of unskilled manual labourers and New Commonwealth immigrants. 6. The aetiological implications of the ecological findings for deliberate self-harm throughout the city are discussed.


Mental and psychomotor speed in depression and mania.

Mental and psychomotor speed scores were obtained for three affectively ill groups of bipolar depression, unipolar depression and bipolar mania, and three corresponding recovered groups. Comparisons were made among ill groups, among recovered groups, and between ill and recovered groups for each illness type. The following conclusions were drawn: 1. Though manic patients solve problems quicker than those of either depressed group, they do not differ much from normals. 2. With stress to work faster, the pateints in the two depressed groups can quicken their speed of work and bring it up to the level of the manic patients, even thought the latter also increase their speed. 3. On a psychomotor speed task, the bipolar dipressives are significantly slower than the manics and the unipolar depressives, who do not differ. 'Internal distraction' causes a slight  increase in speed in all three groups, with no significant difference, but 'external distraction' speeds up the bipolar groups and slows down the unipolar depressives resulting in significant differences between the bipolars on the one hand and the unipolars on the othbr. 4. All recovered groups perform at the same level on all measures. 5. Comparison between ill and recovered groups seems to indicate that a manic illness does not affect mental ro psychomotor speed significantly when tested objectively. Unipolar depression also does not seem to affect speed functions very significantly. Thus only bipolar depressive patients seem to show true retardation, and manic patients do not show the opposite of retardation.


The first seventy admissions to an adolescent unit in Edinburgh: general characteristics and treatment outcome.

1. The clinical functioning of the Young People's Unit, Edinburgh is described. This involves a relatively permissive, democratic "milieu". Psychotherapeutic efforts are devoted to the resolution of family psychopathology and the achievement of maturational progress for the adolescent. 2. Data on the first seventy admittions to the Unit were examined. Two-thirds of the patients were diagnosed "developmental crisis"; the majority of these also had a personality disorder. 3. Assessments of family functioning showed high levels of disturbance and psychiatric morbidity among the parents. The adolescents had mutually good, positive relationships with their opposite-sexed parents, but markedly negative ones with the same-sexed parents. This was not in accordance with the usual findings in "normal" families. Delinquent and impulsive patients showed uniformly negative family attitudes. 4. A simple estimation of treatment outcome at discharge gave results comparable to those of other units, with 70 per cent of patients rated as improved. Neurotic and psychotic patients had a relatively better outcome. Tension-discharge personality disorder and a history of very disruptive or antisocial behaviour were associated with poor outcome. 5. The poor response of very disturbed, impulsive adolescents to this type of therapeutic regime is discussed. These individuals do not appear to have sufficient personality resources and organization to benefit from this type of treatment. Emerging from this is a suggestion for an increased provision of specialized units offering containment and intensive care to the very disturbed adolescent.


The peripheral retinal 'map'.

The condition of the periphery of the retinal field of the human eye is of considerable significance, it is suggested, to those participating in various sporting activities.  Its boundaries shrink and expand depending upon the physiological conditions imposed both upon the eye and upon the organism as a whole.  Consequently its message to the brain may be impaired under stress with resulting danger owing to delayed response.


Variability of corticosteroid responses during exercise stress in active and sedentary middle-aged males.

Two groups of middle-aged male subjects (both N=11), one active (mean age 44.6 years) and one sedentary (mean age 43.7 years), undertook a graded exercise stress test on a bicycle ergometer in the post-absorptive state.  Blood serum corticosteroid levels were measured at the following stages of metabolism; at rest, under conditions of submaximal and "maximal' exercise and during recovery.  The active group showed no significant change in mean serum corticosteroid levels from resting values, during exercise and recovery.  However the sedentary group displayed a significant increase in mean serum corticosteroid levels from a resting value of 5.81 plus or minus 0.41 mub-g/100 ml. (mean plus or minus S.E.) to 7.83 plus or minus 0.71 mug/100 ml. during "maximal' exercise (p smaller than 0.05), which was maintained throughout recovery 7.82 plus or minus 0.70 ug/100 ml (p smaller than 0.05).  Futhermore the active group demonstrated significantly lower mean serum corticosteroid levels compared with the sedentary group under conditions of submaximal (p smaller than 0.05) and "maximal' (p smaller than 0.01) exercise and during recovery (p smaller than 0.01).  It was concluded that the variability in the response patterns of serum corticosteroids during exercise stress in active and sedentary middle-aged males, reflected the physiological differences observed between the two groups of subjects.


Thermography of the female breast: a five-year study in relation to the detection and prognosis of cancer.

More than 12,000 women have been examined thermographically in the Breast Unit of the Royal Marsden Hospital, London. Of these women 1,464 had biopsy and histology; 363(25 per cent) were found to have carcinoma and of these 68 per cent had abnormal thermograms, 13 per cent has some thermal asymmetry of doubtful significance and 19 per cent had normal thermal patterns. Fifty-seven per cent and 62 per cent of patients with Stage I and Stage II cancer, respectively, had abnormal thermograms whereas 83 per cent of patients with Stage III cancer had abnormal thermograms. Of 1,101 women who had benign lesions, 63 per cent had normal thermal patterns, 15 per cent had thermal asymmetry of doubtful significance and 22 per cent had abnormal thermograms. The subsequent histories of 172 cancer patients examined thermographically have been analysed and three-year survival rates have been correlated with thermography report, the clinical stage of the disease and the histotogical grade (Bloom, 1950) of the excised tumour. The mean three-year survival rates for patients with Stage II or Stage III cancer are 84 per cent for those with normal and 61 per cent for those with abnormal thermograms.


Time/dose relationships in abdominal irradiation: a definition of principles and experimental evaluation.

We have drawn upon the work of numerous investigators to formulate a model describing the principles governing the acute response of the intestinal epithelium to cytotoxic agents. Tolerance (exposure required to kill 50 per cent of the animals) to abdomen-only irradiation was measured experimentally in the mouse using a total of 17 time/dose fractionation schedules. The principle determinants of intestinal response to fractionated radiation therapy were magnitude of each fraction and the introduction of regular recovery intervals during the course of treatment. The roles of exposure per week, exposures per day, and radiation days per week were also examined. The log-log plots of endpoint v. either number of fractions or overall treatment time yielded straight lines with slopes of 0 with 54 and 0 with 59 and y intercepts of 1,270 and 812 rets respectively. The single dose for 50 per cent acute intestinallethality (LD50/6 days) was 1,610 R. It would appear that the acute intestinal tolerance to fractionated irradiation is, in the mouse, extremely dependent upon fraction number and overall treatment time. The biological basis for intestinal tolerance to cytotoxic agents is discussed in light of the results of these studies and the model initially described.


Prolonged drip-infusion cholangiography.

Previous experimenttal work in animals has shown that the hpatic excretion of iodipamide and ioglycamide is subject to a transport maximum (TM). Doses in excess of this TM are largely excreted in the urine. In the present study the TM for man was estimated in three subjects with indwelling T-tubes: figures of 19-23 mg/minute for ioglycamide were obtained. It was thought that prolonged administration of contrast at levels slightly above the TM might have advantages in patients with impaired liver function. In obstruction the gradual excretion of contrast could improve the chances of filling the ducts completely, while in hepato-cellular disease the gall bladder might have time to concentrate the contrast. Ioglycamide was therefore given by slow overnight infusion, equivalent to 35 mg/minute, to patients in whom standard cholangiography had been unsuccessful. The overall success rate was 75 per cent with similar improvement in obstructive and hepatocellular disease.


Cure, regression and cell survival: a comparison of common radiobiological endpoints using an in vitro tumour model.

Multicell spheroids of Chinese hamster V79-171 cells grown in suspension culture display many of the characteristics of solid tumours in vivo, and can be used as an in vitro tumour model. Two populations of spheroids differing in age and radiosensitivity were exposed to single doses of gamma-radiation and their response assayed by several techniques: (1) spheroids were reduced to single cells by trypsinization at various times post-irradiation, and viability of the single cells determined by colony formation; (2) entire spheroids were placed in petri dishes and observed for cellular outgrowth; (3)spheroid volume and cell content were monitored as a function of time after irradiation. It was found that spheroid volume changes could not be correlated with either the amount of radiation given or with the relative radiosensitivity. In contrast, the number of cells per spheroid, or cellularity, decreased exponentially with exposure dose at sufficiently long times after irradiation. Radiosensitivity was then quantified by calculating the per cent decrease of cellularity per rad. "Cure" of spheroids as defined by lack of outgrowth when entire spheroids were placed in petri dishes, correlated well with single cell survival, and was achieved 50 per cent of the time after 2,630 rads for the smaller spheroids and 3,750 rads for the larger ones. Since these spheroids contained an average of similar 7,600 and similar 30,700 cells respectively, comparison of cure data with single cell survival data showed that cures were achieved only when every cell was killed. This result may have significant therapeutic implications, since cells of the most radioresistant population of the spheroid, the chronically hypoxic internal cells, were capable of proliferation even when the spheroid was not reduced to single cells after irradiation.


Measurement of the focal spot size of diagnostic x-ray tubes--a comparison of pinhole and resolution methods.

The pinhole camera technique has been compared with resolution and other methods for measuring the focal spot dimensions fo diagnostic X-ray tubes. These comparisons show that the resolution method offers an accurate estimation of the focal spot dimensions without the difficulties normally encountered in pinhole camera techniques. Accuracy and reproducibility of the "star-test" resolution method is examined. The current standard specifications for pinhole camera measurements are also discussed, and in the light of results obtained, changes in these specifications are suggested, particulary with regard to correction factors for non-uniformity of the intensity distribution and manufacturing tolerances.


Relative effectiveness of 12-hourly fractionation and a non-uniform x-ray schedule in the optimum fractionation of C3H mouse mammary tumours.

In previous experiments the highest proportions of tumours controlled for 150 days at a particular level of skin reaction were obtained with five or nine fractions of X rays in nine or ten days respectively. Poor results were obtained for the same numbers of fractions given in 4 or 18 days respectively. The present work reports results of three "non-standard" fractionation schedules: two with equal doses given at 12-hour intervals over four or nine days and one with eight decreasing doses given at decreasing intervals over 11 days. The two 12-hour interval schedules gave results which were equal to the best obtained by any other schedule tested. The 8F/11d non-uniform schedule, however, gave mediocre results in spite of being close to the previously optimum overall time. When these results are compared with previously published results from the same tumour system two, phases of optimum fractionation are demonstrated. At short overall times, up to four days, the situation is finely balanced, so that fraction size and interval matter greatly and results of the schedules vary from good to bad. At longer overall times, of nine days or more in these tumours, the response is no longer so variable. Eighteen days (two to three times the average volume doubling time) is too long for any successful treatment with this system, presumably because of proliferation in the tumour.


An assessment of the value of spleen scanning in the staging of Hodgkin's disease.

The value of non-invasive spleen scanning with 51Cr-chromate heat damaged red cells has been assessed in 68 patients with histologically proved Hodgkin's disease in whom pre-treatment laparotomy with splenectomy was performed. The scans were reported independently by two observers. Following this, the uptake pattern of the radioactive tracer and size of organ on the scan were compared with the post-operative weight and pathology of the spleen. From these results it is concluded that this method of spleen scanning is an unreliable technique in staging Hodgkin's disease.


A 170Tm gamma scattering technique for the determination of absolute bone density.

A new technique for the determination of absolute bone density is described. The procedure is based on the measurement of both transmitted and scattered photons emitted from a 650 mCi radioisotope source of 170Tm in a narrow beam geometry. The method takes into consideration the change in the effective Z/A as a function of bone density which is due to the changing of the elementary composition of bone when bone material is resorbed. The experimental results show that the density of homogeneous materials can be measured with a reproducibility of 2 per cent. The bone density values for the 24 bone specimens measured by the new method show a good correlation (r=0 with 94) with results obtained by application of Archimedes' principle.


Umbilical portogram in a case of Schistosomiasis japonicum.

The life cycle of shistosomes in their human host contributes to protean pathologic changes in many organs. One of these, pre-sinusoidal hepatic fibrosis in the case of S. Japonicum, was studied by an umbilical portogram during the work-up before haemofiltration. Intrahepatic portal block, with rapid tapering and marked tortuosity of portal branches as well as a very inhomogeneous and variable parenchymal pahse with poorly marginated underperfused areas and reversal of extrahepatic portal flow, was demonstrated.


The residual renal stone.

A study of the observer error built in to contact preoperative radiography for renal stones shows that particles less than 2 mm in diameter are likely to be missed. The radiographic follow-up of 100 patients from whom 120 large staghorn calculi have been removed over a period of up to 10 years shows that new calculi may form in kidneys which have been completely cleared, and that residual stones do not always grow, but equally often pass spontaneously, or remain unchanged.


Some data on urinary stones which were passed.

Out of a group of 979 patients with urinary calculi, 175 had passed their stone(s). Comparison of data for stones which had been passed with data for the whole group shows many significant differences. Calculi composed entirely of calcium oxalate are more likely to be expelled than any other composition variety. The chance of this happening is 1 in 3 and it is even higher when the person is under 50 years of age. The probability of calculi composed of calcium oxalate+calcium phosphate being expelled is 1 in 5 and this also increases for younger patients. Infection stones consisting of calcium phosphate+struvite have only 1 in 19 chance of being passed. Many of the stones passed (130) are under 0.10 g in weight. However, there is a similar relationshp between composition and weight among both the stones that were passed and the whole group. In both groups, pure oxalate stones are the lightest, infection stones are the heaviest and stones composed of calcium phosphate and calcium phosphate+calcium oxalate are of intermediate weight.


Atraumatic rupture of the kidney. A case report with autopsy.

A case of atraumatic rupture of the parenchyma of the right kidney with gross retroperitoneal haemorrhage is reported in an old woman. The underlying vascular lesion was probably arteriosclerotic and associated with hypertension.


Bilateral pelvi-ureteric avulsion following closed trauma.

A 9-year-old girl suffered severe multiple injuries in a road traffic accident. Following a period of anuria an intravenous pyelogram was performed indicating bilateral pelvi-ureteric rupture. Continuity was eventually achieved on both sides following two attempts at ureteral anastomosis. One year after the accident the child is well and the kidneys and ureters are functionally normal. Early diagnosis and treatment is essential in order to achieve a good functional result. This is aided by an awareness of the condition and is confirmed by intravenous and retrograde pyelography. The anastomosis is performed over a polythene splint, supported by a defunctioning nephrostomy for several weeks. The aetiology remains obscure, although there have been many suggestions regarding the mechanics of pelvi-ureteric avulsion.


The congenital refluxing megaureter: experiences with surgical reconstruction.

A series of 17 children with congenital refluxing megaureters underwent ureteric tailoring and reimplantation. The results obtained suggest that such surgery should be restricted to those cases in which an obstructive element is introduced as a result of the reflux or in which ascending infection is further damaging the already prenatally defective kidney parenchyma.


Urodynamic observations following spinal trauma.

A method of the urodynamic investigation of paraplegic and quadriplegie patients is described. Serial measurements of the urethral pressure profile in patients with developing reflex micturition demonstrate a rising pressure at the external urethral sphincter with time following spinal trauma. Patterns of micturition with detrusor-sphincteric imbalance are described in patients with both early and well-established reflex micturition.


The distribution and retention of cadmium 115m in the rat following injection into the prostate.

The gonadal effects produced by injection of cadmium in the rats are well known. The effects of direct injection into the prostate are less well understood. The present experiments indicated the retention of cadmium by the various lobes of the rat prostate following direct injection of radioactive cadmium into the organ. The cells of the prostate are capable of retaining cadmium in measurable amounts up to at least 6 weeks following the injection. The subcellular fractions were measured with respect to cadmium activity and these are indicated. In addition measurements were made in organs which are known to be affected by cadmium, that is, kidney and the testicle. The affinity of the kidney for cadmium is confirmed. The areas of the prostate gland with a high zinc content appear to retain less cadmium than areas of the gland which are known to have a low zinc content. This suggests a possible zinc protective mechanism.


Adrenergic and cholinergic receptors in the human prostate, prostatic capsule and bladder neck.

The adrenergic and cholinergic receptors of the human prostatic capsule, prostatic "adenoma", and bladder neck, were investigated by the in-vitro isometric technique. The prostatic capsule was found to be very rich in both alpha-adrenergic receptors and cholinergic receptors. The prostatic adenoma was moderately rich in alpha-adrenergic receptors, but cholinergic receptors were absent. Beta-adrenergic receptors were absent in the prostatic adenoma, and there was an equivocal response in less than half the specimens of the prostatic capsule. An attempt was made to distinguish between the trigonal component at the posterior bladder neck, and the true bladder neck muscle both posteriorly and antero-laterally. The results indicat that the "posterior bladder neck" seen at operation is predominantly trigonal muscle, and is poor in cholinergic receptors. The adrenergic response is variable in the true bladder neck muscle, but is present and strong in the trigonal muscle. This response is characteristically gradual in its development. In view of the findings in this investigation, it is suggested that certain instances of acute retention of urine in prostatic patients are due to over-stimulation of the alpha-adrenergic receptors, particularly those in the prostatic capsule. Similarly, the accepted clinical contraindication to the use of cholinergic drugs for retention in the prostatic patient is supported by the distribution of the cholinergic receptors in the tissues examined.


Treatment of Peyronie's disease with procarbazine.

The treatment of 10 cases of Peyronie's disease with procarbazine, a cytotoxic drug, is presented. The results were disappointing.


The effect of hepatic ischaemia on liver function and the restoration of liver mass after 70 per cent partial hepatectomy in the dog.

Partial hepatectomy was performed in dogs either as the only procedure or following a period of ischaemia of liver remnant produced by inflow occlusion for periods of 30-60 minutes before partial hepatectomy. Temporary portal decompression was maintained through the portion of liver subsequently excised. 1. Survival in dogs subjected to partial hepatectomy and ischaemia to the liver remnant was similar to that in animals after partial hepatectomy alone. 2. Metabolic changes were similar in both groups but dogs submitted to partial hepatectomy and ischaemia to the remnant had higher serum alkaline phosphatase and alanine amino-transferase levels with increased bromsulphthalein in the fourth to sixth post-operative weeks. 3. Replacement of liver mass proceeded rapidly in all groups of animals. It is concluded that ischaemia of the liver remnant for up to 60 minutes preceding partial hepatectomy in the dog is consistent with survival and produced little change in postoperative liver function or in the rate of restoration of liver mass.


Early management of corrosive burns of the oesophagus.

One hundred and sixteen patients with early corrosive burns of the oesophagus treated by the author are reviewed. It is emphasized that the all important aspect of management of these patients is prophylactic treatment to avoid stricture of the oesophagus. Early treatment consists of intravenous fluid therapy, broad spectrum antibiotics, sedation, parenteral hydrocortisone and more importantly maintaining the patency of the oesophagus followed by dilatation. The importance of early barium meal studies and oesophagoscopy is stressed.


The management of peptic oesophageal stricture.

Eighty-three adult patients with peptic oesophageal stricture are reviewed with regard to diagnosis and treatment. Sliding hiatus hernia was present in 94 per cent of cases. The strictures were graded according to the degree of stenosis encountered at initial oesophagoscopy, but several other factors influenced the management of each case. Bouginage should always be attempted before proceeding to surgery. Thirty-eight patients were treated by bouginage alone, with 21 (55 per cent) good results and 3 deaths. Forty-five patients came to surgery, with 32 (71 per cent) good results and 3 deaths. Six patients sustained instrumental perforation of the oesophagus with 1 fatality. There was in addition 1 case of silent perforation following self-bouginage, which is believed to be unique. Hiatal herniorrhaphy combined with simple bouginage is recommended where reflux oesophagitis dominates the clinical picture. Local plastic repair (oesophagoplasty) has proved a simple and effective method of treating low annular strictures. Oesophagogastrostomy was carried out in 12 patients without operative loss and with good results in 8 cases; the addition of a pyloroplasty is believed to lessen postoperative reflux.


The effect of raising the concentration of potassium in the blood or intestinal lumen on the transport of potassium in the dog intestine.

The rates of transport of potassium, sodium and water across the intestinal mucosa of Thiry-Vella fistulas of colon and ileum, were studied in dogs in two experimental situations; (1) following intravenous infusion of potassium (15 mEg) over 30 minutes and (2) during variations in the intraluminal concentration of potassium in the range 0.8-16.0 mEg/l. Following intravenous infusion of potassium the rates of potassium secretion into the colon were usually increased; the rates of sodium and water absorption were either unchanged or decreased. The unidirectional rate of movement of potassium into the lumen increased as the concentration difference across the mucosa increased; the movement of potassium in the opposite direction remained relatively constant. The undirectional movement of sodium and water into the lumen of the colon also increased but to a lesser extent. The effect on potassium transport in the ileum was not so marked. With increase in the intraluminal concentration of potassium there was a decrease in the rate of net potassium secretion in both colon and ileum. The rates of net absorption of sodium and water were not significantly altered. Unidirectional potassium movement into the body increased in all the ileal fistulas.


Environmental tests of linear flow ventilation for an operating theatre.

Criticisms have been levelled against linear air flow operating enclosures because of their alleged physical and biological conditions and the effects of these, both on the surgical team and on the patient's tissues.


Bilateral idiopathic parotid duct strictures.

Details of 2 patients with idiopathic bilateral parotid duct strictures are presented. The possible aetiology and treatment are discussed.


General anaesthesia during early pregnancy.

General anaesthesia in the early stages of pregnancy may carry an increased risk of embryotoxicity. One hundred and six women scheduled for non-emerency surgery were interviewed preoperatively and their menstrual history taken. Forty-three (41 per cent) were considered to be using adequate contraceptive therapy. Thirty-one (29 per cent) of the patients could have been in the early stages of pregnancy, and of these women, 19 (61 per cent) were undergoing surgery of a minor nature. Simple history taking identified the women 'at risk' and it is suggested that surgery could have been delayed without detriment in many cases.


Injuries caused by rubber bullets: a report on 90 patients.

The injuries in 90 patients caused by rubber bullets are described. There was 1 death and 17 people in the series had permanent disabilities or deformities. In 41 patients the injuries necessitated admission to hospital. One fatality outside this series is known. Injuries to the head and neck were frequent and severe.


Incidental appendicectomy with laparotomy for trauma.

Incidental appendicectomy was performed in 83 of 206 patients undergoing laparotomy for abdominal trauma. No organs were injured in 42 per cent of the appendicectomy patients and in 17 per cent of the non-appendicetomy patients, thus making comparison between the groups unreliable. While the incidence of intestinal perforation was 21 per cent in the appendicectomy patients, the rate of wound infection was only 7 per cent. One complication (pelvic abscess) was possibly attributable to incidental appendicetomy. Since males below the age of 50 face a significant risk of future appendicitis and represent the majority of patients with abdominal trauma, it may be advisable to perform incidental appendicectomy with laparotomy for trauma in such patients. Specific indications for incidental appendicectomy during laparotomy for trauma are suggested.


Nitrogen mustard as adjunctive chemotherapy for breast carcinoma.

A retrospective study is reported of 38 patients with breast carcinoma treated by radical mastectomy and a short course of nitrogen mustard. They were followed up for an average of 10 years. There were no serious untoward reactions to the drug. The 5- and 10-year correct survival rates were 71 and 71 per cent respectively. There would appear to be a renewal of interest in adjuvant chemotherapy for patients with breast carcinoma.


Immune status of children with and without severe infection during remission of malignant disease.

The immune status of children with malignant disease in remission was assessed usingvarious immune function tests.  Children with infections had significantlymore neutropenia, hypogammaglobulinaemia, and impaired cell-mediated immune responses than those without.  These two groups combined had much more absolute lymphopenia and impairment of both cell-mediated immunity and antibody-producing capacity thancontrol children with non-malignant conditions.  Regular immunological evaluation isrecommended for children with malignant disease when new intensive treatment schedules are under trial and for individual patients particularly prone to develop infections during treatment.


Variations in leucocyte count during menstrual cycle.

The neutrophil counts of seven women, three tkaing oral contraceptives and four nottaking them, showed cyclical variations during the menstrual cycle, most consistentlya fall in the neutrophil count at menstuation.  The neutrophil count in women not taking oral contraceptives rose to a peak twice during each cycle.  One womennot taking oral contraceptives was studied in detail over eight consecutive menstrualcycles.  She showed two neutrophil peaks per cycle and a similiar variation in themonocyte count.  The eosinophil count showed a reciprocal relation with the neutrophil count and the basophil count fell in mid-cycle.  The changes in her neutrophil count seemed to follow changes in oestrogen level with a delay of one to two days.  Oestrogen probably promotes release of neutrophils from the bone marrow rather than from the marginated pool.


Relative contributions of history-taking, physical examination, and laboratory investigation to diagnosis and management of medical outpatients.

To evaluate the relative importance of the medical history, the physical examination, and laboratory investigations in the diagnosis and management of medical outpatients some physicians recorded their diagnosis and a prediction of the method of managementafter reading the patient's referral letter, again after taking the history, and againafter performing the physical examination.  These diagnoses and predictions were compared with the diagnosis and method of management which had been adopted two months after the patient's initial attendance.  A diagnosis that agreed with the one finally accepted was made after reading the referral letter and taking the history in 66 out of 80 new patients; the physical examination was useful in only seven patients, and the laboratory investigations in a further seven.  In only one of six patients in whom the physician was unable to make any diagnosis after taking the history and examining the patient did laboratory investigations lead to a positive diagnosis.


Recurrent aphthae: treatment with vitamin B12, folic acid, and iron.

A series of 130 consecutive outpatients with recurrent aphthous stomatitis were screened at the oral medicine department, Glasgow Dental Hospital, for deficienciesin vitamin b12, folic acid, and iron.  In 23 patients (17.7%) such deficiencies werefound; five were deficient in vitamin B12, seven in folic acid, and 15 in iron.  Four had more than one deficiency.  Out of 130 controls matched for age and sex 11 (8.5%) were found to have deficiencies.  The 23 deficient patients with recurrent aphthaewere treated with specific replacement therapy, and all 130 patients were followed up for at least one year.  Of the 23 patients on replacement therapy 15 showed complete remission of ulceration and eight definite improvement.  Of the 107 patientswith no deficiency receiving local symptomatic treatment only 33 had a remission or wereimproved.  This difference was significant (P less than 0.001).  Most patients withproved vitamin B12 or folic acid deficiency improved rapidly on replacement therapy;those with iron deficiency showed a less dramatic response.  The 23 deficient patientswere further investigated to determine the cause of their deficiencies and detect the presence of any associated conditions.  Four were found to have Addisonian perniciousanaemia.  Seven had a malabsorption syndrome, which in five proved to be a gluten-induced enteropathy.  In addition, there were single patients with idiopathic proctocolitis, diverticular disease of the colon, regional enterocolitis, and adenocarcinoma of thecaecum.  We suggest that the high incidence of deficiencies found in this series andthe good response to replacement therapy shows the need for haematological screening of such patients.


Hostility to kith and kin.

Ten male patients who shared a similar behaviour disorder have been seen. Their behaviour was characterized by extreme hostility towards close members of the family without aggressiveness towards others. The first manifestations of an increase in hostility may be acts aimed to injure of denigrate the spouse or close members of the family. The dynamics of Capgras's syndrome may be similar. This behaviour disorder must be recognized as one of many causes of conjugal conflict.


Identification of high risk labours by labour nomogram.

The labour stencil representing the expected cervimetric progress of normal labour was used in 741 consecutive spontaneous labours to identify high-risk labours which needed oxytocic stimulation. Uterine contractions were stimulated if progress extended two hours past the nomogram, which resulted in shorter labours, fewer instrumental deliveries and caesarean sections, and babies with higher Apgar scores than in those dysfunctional labours which were not stimulated. According to the protocol used 36% of primigravid and 13% of multigravid labours needed acceleration. The remaining patients did not need any oxytocic interference during the first stage. This selection of patients is important to prevent a major obstetric advance being abused and discredited at a time when the profession and public are questioning the safety of active labour.


Arterial occlusion after cannulation.

The occurrence of ischaemic changes, arterial occlusion, and other complications which may follow percutaneous arterial cannulation was assessed in a survey of 155 patients. No patient complained of or had signs of ischaemic damage though signs of arterial occlusion were found in 33 patients (22%). These signs were significantly more common after periods of cannulation greater than six hours (43%) than after less than six hours cannulation (17%). During recovery from occlusion all patients had palpable pulsation over the artery even though blood flow seemed to be absent. By the end of follow-up blood flow had returned in 19 of the 33 occluded arteries.


Pyogenic cocci in infantile eczema throughout one year.

To determine the source of pyococci causing attacks of sepsis in infantile eczema 20 patients with continuing eczema were followed up for one year, regular swabs being taken from the skin, nose, throat, and family contacts. The staphylococci were phage typed and the streptococci serologically typed. Staphylococci of the same phage type in most cases remained in reservoir sites on the skin and coincidently in the nose. Staphylococci causing attacks of clinical sepsis arose from these persistently colonized sites. Staphylococci of the same phage type were also common in family contacts. Streptococci of the same group in most cases did not remain on the skin. Streptococci causing attacks of clinical sepsis arose as new infections from external sources, sometimes from throat infections in the patient or family contacts. Strains of streptococci which are known to be associated with glomerulonephritis were isolated. It has been confirmed that staphylococci resistant to neomycin and sodium fusidate quickly emerge after the topical use of these antibiotics. Streptococci are highly resistant to neomycin and gentamicin, and moderately resistant to sodium fusidate, so the use of these antibiotics in topical steroid preparations will have little effect in preventing further attacks of clinical sepsis in these patients.


Excessive use of psychiatric services by suicidal patients.

The use of psychiatric services by patients with a suicidal history was examined to see if they placed a greater long-term burden on these services than other types of patient. Suicidal patients spent significantly more days in hospital and made more outpatient attendances; suicide attemptors in particular not only needed more emergency consultations but also spent more days in hospital. A more economical yet more effective treatment policy for the suicidal patient is needed.


Who cares for head injuries?

Patterns of management for head injury in the acute and late stages are reviewed in respect of both mild and severe injuries. Because so many disciplines are involved, continuity of care if often difficult to achieve; and no one discipline is concerned with planning for the care of head injuries in a strategic way. The needs of head-injured patients are defined and suggestions made for improving care by the reorganization of existing facilities. What is most needed is to concentrate on patients with head injuries, both in the acute and in the late stages. Only then can medical, nursing, and paramedical personnel become skilled in dealing with the many problems which such patients present.


Maturity onset diabetes mellitus: response to intensive dietary management.

Analysis of the first six months of intensive dietary management of 57 maturity onset diabetics showed that a large proportion of such patients could be satisfactorily controlled without the need of either oral hypoglycaemic agents or insulin. A dietitian's assessment of the patient's adherence to the prescribed diet allowed groups of good and poor dieters to be selected. Among the poor dieters the plasma insulin and triglyceride levels were significantly increased though plasma glucose levels were not significantly higher. Dietary adherence may thus be an prognostic risk factor in this group of diabetic patients.


The Tower of London bomb explosion.

After the detonation of a bomb in the Tower of London 37 people were brought to St. Bartholomew's Hospital. The explosion caused numerous severe injuries of a type rarely seen in peacetime.


Analysis of services available for total joint replacement surgery.

The use of a total joint replacement surgery has been growing in a manner which is poorly understood. This growth is more likely to be limited by saturation of the available medical services than by a limit to the number of people who could benefit from the treatment. Present indications are that services will be saturated in 1974 or 1975, after which 4600 extra people a year will go on to the waiting lists if demand continues as at present. Stability can then be achieved by either raising the clinical criteria for surgical treatment or making about 300 extra orthopaedic beds available each year, buffered from the demands of acute trauma admissions.


Paroxysmal attacks in multiple sclerosis.

Twenty-two out of 235 patients with undoubted or suspected MS, treated at the Neurological Clinic, Uppsala, during the eight-year period, 1966-1973, had paroxysmal symptoms during the course of their disease. Paroxysmal dysarthria and ataxia (7 cases), and tonic seizures (5 cases) were the most common types of attacks. Some types of attacks (paroxysmal hemiataxia and crossed paraesthesiae, paroxysmal itching, diplopia as the single, paroxysmal symptom) do not seem to have been described previously. A patient with tonic seizures caused by a localized, traumatic lesion of the cervical spinal cord is also described. It is suggested that the paroxysmal phenomena in MS are caused by a transversely spreading ephaptic activation of axons within a partially demyelinated lesion in fibre tracts somewhere in the central nervous system. The different paroxysmal phenomena are discussed in the light of this hypothesis.


The effects of acetylcholine and dopamine on the caudate nucleus depleted of biogenic amines.

Because it has been proposed that the reduction of the striatal biogenic amines in Parkinson's disease leads to an imbalance between the actions of acetylcholine and dopamine, we have studied the effects of these substances, liberated from multibarrelled micropipettes, on the firing of single neurons in the feline caudate nucleus depleted of biogenic amines by long-standing nigrostriatal lesions. Compared with neurons in intact cats, those in cats with lesions were more easily excited by acetylcholine and less easily supressed by dopamine. These results suggest that the depletion of the striatal amines decreases the neuronal susceptibility to dopamine and increases that to acetylocholine, possibly by changing the sensitivity or the number of the neuronal receptors of these agents.


Ideogram reading in alexia.

A case of alexia with agraphia in a Japanese patient is presented. Reading difficulty was severe in words composed of phonograms (Kana), while reading of words composed of Ideograms (Kanji) was better preserved. Writing was severely impaired in both types of characters. Occlusion of the angular branch of the left middle cerebral artery was demonstrated by carotid arteriography and was considered responsible for the symptoms. Two additional cases of alexia with agraphia from the Japanese literature are reviewed. Their linguistic features were similar to the present case. A hypothesis of a functional disconnexion between visual and auditory-oral systems is proposed to explain why Kana processing was more severly affected than Kanji processing.


Intrahemispheric cortical connexions and visual guidance of hand and finger movements in the rhusus monkey.

An attempt has been made to elucidate in the rhesus monkey the role of intrahemispheric cortico-cortical connexions in visual guidance of relatively independent hand and finger movements which are governed mainly from the precentral motor cortex. These movements were tested by requiring the animals to retrieve with their fingers small food pellets from a special test board in which the pellets were easily visible but were more difficult to palpate. Unilateral occipital lobectomy combined with a commissurotomy impaired the performance of the contralateral hand. The same was true for the parietal leucotomy of Myers et al. (1962) which transects the bulk of the intrahemispheric occipitofrontal cortical fibres. Tests of the visual discrimination of the leucotomized hemispheric showed that the motor impairment after this leucotomy did not represent a visual defect. In control animals no impairment was found after ablation of the cortex on the surface of the postcentral gyrus and the superior parietal lobule. A mild impairment occurred, however, when the lesion either involved also the inferior parietal lobule or was accompanied by a white matter infarct deep under the postcentral gyrus. The findings make it likely that the intrahemispheric cortical fibres to the frontal lobe play a role in visual guidance of relatively independent hand and finger movements. This conclusion is also supported by some preliminary findings after frontal lobe lesions, but further experiments are necessary to establish it firmly.


Visual evoked responses in the diagnosis and management of patients suspected of multiple sclerosis.

Averaged visual evoked responses to pattern reversal stimuli have been recorded in 54 control subjects, 51 patients with multiple sclerosis, and 55 patients with other neurological diseases which might involve the visual apparatus. The latency to the peak of the major positive potential in normal subjects under the age of 60 was 104 msec or less (mean 90-5 msec+3 SD). The latency of the VER was prolonged above this value in one or both eyes in 67 per cent of the patients with multiple sclerosis (in 84 per cent of those with definite multiple sclerosis, in 83 per cent of those with probable multiple sclerosis, and in 21 per cent of those with possible multiple sclerosis). The latency of the VER was also prolonged in 25 percent of those with an acute spinal cord lesion of unknown cause; in 46  per cent of those with an isolated brain-stem lesion unknown cause; and in 49 per cent of patients presenting with a progressive spastic paraparesis. The extra delay in latency varied from a few msec to as much as a 100 msec. In patients with multiple sclerosis, a delayed VER was found in the affected eye in all with a previous history of optic neuritis, and in 47 per cent of those with no such history....


Use of the Pulfrich pendulum for detecting abnormal delay in the visual pathway in multiple sclerosis.

(1) Pulfrich's pendulum has been developed as a method for detecting abnormal delay in the visual pathway of patients with suspected multiple sclerosis. (2) Forty-one normal subjects gave a mean interocular latency difference of 2-4 +/- 1-8 msec on Pulfrich's pendulum. This mean +2 SD (6 msec) was taken as the limit of normal interocular latency difference by this method. (3) The test was assessed on 58 patients. Eighteen of these had definite multiple sclerosis, 9 had probable multiple sclerosis, and 8 had possible multiple sclerosis, according to clinical criteria. The remaining 23 patients did not conform with clinical criteria for multiple sclerosis, and served as neurological controls. Thirteen of these 23 patients had abnormal signs in the visual system. All the 58 patients also had visual evoked responses (VERs) recorded. (4) Interocular latency difference was outside the normal range in 9/18 with definite multiple sclerosis, in 3/9 with probably multiple sclerosis and in 2/8 with possible multiple sclerosis. (5) Interocular latency difference was outside the normal range in 2/23 patients with other neurological disorders. (6) There was a strong correlation between abnormality on the Pulfrich pendulum and on the VER for the multiple sclerosis group. (7) Individual results are compared with those from the VER. There was no significant correlation of the size and direction of the interocular latency difference obtained from the Pulfrich pendulum with that obtained from the VER, for any group. Possible reasons for this are discussed. (8) It is concluded that Pulfrich's pendulum is an easily performed and potentially useful subjective test for detecting abnormal dealy in the visual pathway in multiple sclerosis.


The cerebral pathways of optokinetic nystagmus: a neuro-anatomical study.

Abnormalities of optokinetic nystagmus are described in a patient with pathologically proven bilateral infarcts in the middle cerebral artery territories. There were no other central nervous system lesions. These abnormalities of eye movement are interpreted as indicating an inhibitory effect of the frontal eye fields upon the occipital lobes.


Vestibular dysfunction in hereditary ataxia.

A kindred with a unique autosomal dominantly inherited ataxia of late onset is described. Manifestations of the condition include defective optokinetic nystagmus and absent or abnormal oculo-vestibular responses, in association with normal cochlear function. It is possible that these latter features may serve as "markers" to indicate the presence of the disease in presymptomatic young adults, thereby facilitating important genetic counseling.


Simple reaction time: evidence for focal impairment from lesions of the right hemisphere.

Simple reaction time is significantly increased in patients with unilateral lesions of either cerebral hemisphere responding with the hand ipsilateral to the lesion, but the effect is much greater when the lesion is in the non-dominant hemisphere. This difference cannot be attributed to asymmetries in the size or type of lesion. It applies over the complete distribution of reaction times as well as to the means, and is not diminished by practice. Neither the classical conduction model of reaction time nor the mass-action hypothesis proposed by De Renzi and Faglioni (1965) can account for the findings. Although the increase of about 100 ms observed with lesions of the dominant hemisphere probably represents a non-specific effect of brain disease, the much larger increases resulting from lesions of the non-dominant hemisphere appear to be of focal origin. The critical areas cannot yet be specified with certainty, but maps of the brain scans for patients with the highest reaction times suggest that structures in or near the basal ganglia and the posterior parietal region of the non-dominant hemisphere are involved, and other studies show that the focal effect is not found when patients with contralateral motor involvement are excluded.


Timing of activity in cerebellar dentate nucleus and cerebral motor cortex during prompt volitional movement.

The discharge of neurons in cerebellar dentate nucleus and cerebral motor cortex was recorded on alternate days in each of 3 monkeys in association with prompt arm movement in response to a light signal. The time of change of the discharge of each neuron in relation to arm movement was computed. The distributions of the time of change for cerebellum and cerebrum overlapped, but the cerebellar distribution was shifted slightly earlier.


The effects of lesions of the superior colliculus on locomotor orientation and the orienting reflex in the rat.

The effects of bilateral removal of the superior colliculus or visual cortex on visually guided locomotor movements in rats performing a brightness discrimination task were investigated directly with the use of cine film. Rats with collicular lesions showed patterns of locomotion comparable to or more efficient than those of normal animals when approaching one of 5 small doors located at one end of a large open area. In contrast, animals with large but incomplete lesions of visual cortex were distinctly impaired in their visual control of approach responses to the same stimuli. On the other hand, rats with collicular damage showed no orienting reflex or evidence of distraction in the same task when novel visual or auditory stimuli were presented. However, both normal and visual-decorticate rats showed various components of the orienting reflex and disturbance in task performance when the same novel stimuli were presented. These results suggest that although the superior colliculus does not appear to be essential to the visual control of locomotor orientation, this midbrain structure might participate in the mediation of shifts in visual fixation and attention. Visual cortex, while contributing to visuospatial guidance of locomotor movements, might not play a significant role in the control and integration of the orienting reflex.