Re-innervation of fast and slow twitch muscle following nerve crush at birth. 1. The frequency of miniature end-plate potentials (m.e.p.p.s) was significantly greater in the fast twitch extensor digitorum longus muscle (extensor) than in the slow twitch soleus, even though end-plate surface area was greater for fibres in the latter muscle. 2. Crush of the sciatic nerve at birth did not prevent the appearance of this difference in m.e.p.p. frequency. However, the frequency of the potentials in the re-innervated muscles was less than normal, even though the regenerated neuromuscular junction was qualitatively normal in morphology. 3. Though the re-innevated muscles were differentiated with respect to twitch time course, the extensor muscle was more responsive than normal to the contracture-inducing action of caffeine. 4. The Z line of the re-innervated extensor muscle was similar to that of the normal soleus in thickness. 5. Resting potential, passive electrical properties and action potential generating mechanism of the sarcolemma were normal. 6. Since the re-innervated muscles lacked muscle spindles, a role of sensory feed-back in the function of the neuromuscular junction as well as the neutrotrophic regulation of muscle is discussed.


Load clamp analysis of maximal force potential of mammalian cardiac muscle. 1. Abrupt alterations in load (load clamps) have been imposed on cat papillary muscle during isotonic shortening and relaxation of afterloaded twitch and tetanic contractions, to assess the maximal force potential for a given contractile state. 2. These load clamps were accompanied by an initial fast lengthening reflecting an undamped series compliance. Even when exceeding isometric twitch and tetanic force, these loads could be borne for a considerable time, accompanied by a slower lengthening after the initial extension of the series compliance. At sufficiently high loads the muscle was pulled out very rapidly; a maximal supra-isometric force potential was defined as the load the muscle could bear momentarily and this was measured at times throughout contraction and relaxation. 3. This maximal force potential was determined at different initial muscle lengths. Depending on the instantaneous loading conditions, various length-force relations were obtained from : (a) peak force values of isometric twitches at different starting lengths, (b) the shortest length reached during after loaded isotonic twitches, and (c) the forces obtained in overloaded isotonic twitch contractions. 4. These results are consistent with a crossbridge model in which the delayed lengthening during isotonic overloading is due to back rotation and detachment of attached crossbridges and in which the inital phase of spontaneous isotonic relaxation is governed by the same mechanism.


Cation movements in normal and short-term denervated rat fast twitch muscle. 1. The earliest known change in rat fast muscle following denervation is a fall in resting membrane potential unaccompanied by change in membrane resistance. The present study tested the hypothesis that increased Na permeability (P(Na)) accounted for this early depolarization.2. In all experiments, rat extensor digitorum longus muscles were studied in vitro at 25 degrees C. Li uptake in vitro, used as a measure of P(Na), was greater in 1- and 2-day denervated muscles (and in 2-day denervated diaphragm) than in paired controls.3. The extra Li taken up by denervated muscle was not sequestered in an extracellular or freely exchangeable compartment, nor was it irreversibly bound.4. Measurements of resting membrane potential and of internal Na, K, and Li in Krebs solution before and 2 hr after replacement of NaCl by LiCl, were used to compute the ratios P(Na)/P(K) and P(Li)/P(K) for normal or denervated muscles. P(Na) and P(Li) were similar relative to P(K) within each class of muscle.5. Both P(Na)/P(K) and P(Li)/P(K) ratios were elevated more than twofold in denervated muscle, as were most estimates of relative P(Li) approximated by the flux equation.6. These data, and measurement of resting membrane potential of normal muscle in 1 mM external K-Krebs solution, support the view that an electrogenic Na-K pump does not substantially contribute to this potential of normal or denervated muscle, and that the early depolarization after denervation results from increased P(Na).7. The Na-K pump of denervated muscle was as sensitive to ouabain as normal muscle. An effect of ouabain on P(Na) may explain previously noted differential effects of ouabain on normal and denervated muscle.


The effect of indomethacin on autoregulation of renal blood flow in the anasthetized dog. 1. Renal blood flow autoregulation was studied in anaesthetized greyhounds, using an electromagnetic flowmeter, before and after the administration of the prostaglandin-synthesis inhibitor, indomethacin, or phosphate buffer. 2. Indomethacin caused a reduction in renal blood flow at all levels of perfusion pressure, but did not affect the ability of the kidney to autoregulate. 3. The aburpt reinstatement of renal perfusion pressure from previously reduced levels caused a triphasic transient response in flow. Peak hyperaemia at the beginning of the transient was not affected by indomethacin. After indomethacin, the second phase of this flow transient showed an oscillatory pattern during which flow fell initially to levels significantly lower than control. 4. It is concluded that although indomethacin did not abolish steady-state autoregulation, renal prostaglandins may damp rapid oscillations in renal blood flow and thus contribute to the efficiency of autoregulation.


Inhibitory processes underlying the directional specificity of simple, complex and hypercomplex cells in the cat's visual cortex. 1. The iontophoretic application of bicuculline, an antagonist of GABA, the putative inhibitory transmitter in the visual cortex, has been used to examine the contribution of post-synaptic inhibitory processes to the directional selectivity of simple, complex and hypercomplex cells in the cat's striate cortex.2. The directional selectivity of simple cells was significantly reduced or eliminated during the iontophoretic application of bicuculline. This supports the view that the selectivity is derived from the action of a GABA-mediated post-synaptic inhibitory input modifying their response to a non-directionally specific excitatory input.3. Complex cells were subdivided into three categories on the basis of the action of iontophoretically applied bicuculline on their directional selectivity, receptive field characteristics and distribution in terms of cortical layer. They are referred to as type ;1', ;2' and ;3' complex cells.4. The directional specificity of type ;1' complex cells was eliminated during the iontophoretic application of bicuculline. It seems likely, therefore, that they receive a non-directionally specific excitatory input and that, as for simple cells, the directional specificity derives from the action of a GABA-mediated post-synaptic inhibitory input. No type ;1' complex cells were recorded below layer IV.5. The directional specificity of type ;2' complex cells was unaffected by the iontophoretic application of bicuculline, despite increases in response magnitude, a block of the action of iontophoretically applied GABA and, in some cases, changes in other receptive field properties. It is suggested that these cells receive a directionally specific excitatory input. The type ;2' complex cells were found both superficial and deep to layer IV with the majority in layer V.6. Type ;3' complex cells appear to have very similar receptive field properties to those of the cells described by other workers as projecting to the superior colliculus. They were found predominantly in layer V. Their directional specificity was not eliminated by the iontophoretic application of bicuculline. However, they exhibited a powerful suppression of the resting discharge in response to stimulus motion in the non-preferred direction. Iontophoretic application of ammonium ions revealed a small excitatory response in place of the suppression. It appears from these observations that the directional specificity of the type ;3' complex cells could be determined, at least in part, by an inhibitory process which is not GABA-mediated.7. The directional specificity of hypercomplex cells found in layers II and III was unaffected by the iontophoretic application of bicuculline, and they showed no suppression of their background discharge level in response to stimulus motion in the non-preferred direction. This evidence is consistent with the view that they receive a directionally specific excitatory input.


Effects of 5-hydroxytryptamine on pial arteriolar calibre in anaesthetized cats. 1. The responses of individual pial arterioles and small arteries to perivascular injections of 5-hydroxytryptamine were studied in anaesthetized cats.2. Pial arteriolar calibre was measured by a television image-splitting technique.3. At normotension, the average response of pial vessels was dilatatory at injected 5-hydroxytryptamine concentrations between 10(-10) and 10(-4)M.4. These pial vascular changes were, however, dependent upon the resting vessel calibre: those arterioles < 70 mum dilated universally, whereas small arteries >/= 200 mum in resting diameter tended to constrict in response to 5-hydroxytryptamine.5. The 5-hydroxytryptamine-induced dilatation of pial arterioles < 70 mum in resting calibre was directly dependent on mean arterial pressure, although no such relationship was observed with the larger cerebral vessels.6. It is concluded that the specific cerebrovascular actions of 5-hydroxytryptamine are largely tone-dependent. The greater the resting tone of a pial arteriole, then the greater will be the tendency of that vessel to dilate in response to 5-hydroxytryptamine, and vice versa.7. The direct vascular actions of 5-hydroxytryptamine are in contradistinction to the observed changes in cerebral tissue perfusion and it would therefore appear that the effects of this amine on cerebral metabolism and neuronal activity outweigh its cerebrovascular actions under physiological conditions.


Differential enhancement of early and late components of the cerebral somatosensory evoked potentials during forced-paced cognitive tasks in man. 1. Cerebral potentials evoked by random sequences of electrical stimuli to four fingers were recorded in intact man performing selective attention tasks. Eye movements and other artifacts were excluded from the averaged traces. Different finger stimuli were designated as targets to be mentally counted in alternate runs of each experiment. The high mean random rate of stimuli (150/min) fully involved the processing capacities of the subject. Vigilance changes or differential expectancy effects were excluded by the reciprocal random design with four different sensory channels. Task-related enhancements of somatosensory evoked potentials (s.e.p.) components were estimated by comparison with the s.e.p.s to physically identical finger stimuli recorded in runs when the subject attended signals in the opposite hand. The experimental design avoided subject's fatigue.2. The primary s.e.p. components N(20) and P(45) were not significantly influenced and this excluded centrifugal gating of the corticipetal signals as a mechanism.3. The earliest task-related changes in s.e.p. occurred 55-135 msec (mean 77.7 msec) after the target finger stimuli. In most cases the negative N(140) component was markedly enhanced both for target signals and for non-targets in the adjacent finger of the same hand. However, in several subjects the targets elicited a positive P(100) component instead. Both N(104) and P(100) were larger at the contralateral parietal focus than ipsilaterally. They were definitely smaller at the vertex and frontal scalp locations.4. Enhancements of N(140) were not observed in similar random four-finger experiments carried out at a 4 times slower mean rate, but they occurred in a bisensory paradigm with finger shocks and acoustic clicks at that slower rate.5. A large positive P(400) component was only elicited by target stimuli. Its voltage was maximum over the parietal region and was equal on both sides.6. At least three categories of components can be differentiated in the cortical s.e.p. on the basis of their time domains (roughly 18-70 msec, 70 to 200-250 msec and over 200 msec after the finger stimuli), cerebral hemispheres topography and cognitive parameters. Verbal instructions defining specific perceptual tasks can to a large extent switch on and off the components of the second and third categories when the processing resources of motivated subjects are fully committed in a well designed forced paced paradigm. In certain individuals physiological evidence for a different ;stimulus set' processing of target (P(100)) and non-target (N(140)) signals was documented for the first time.


A long-lasting potentiation of transmitter release related to an increase in transmitter stores in a sympathetic ganglion. 1. High frequency preganglionic nerve stimulation increases the acetylcholine (ACh) stores of the cat superior cervical ganglion. The increase reaches a maximum 20 min following 60 min conditioning stimulation at 20/s. The effect of this conditioning on ACh release in ganglia perfused with plasma and test stimulated at 4 or 5/s has been studied, and the relationship of ACh stores to ACh release in conditioned ganglia determined.2. The rate of ACh release in response to test stimulation at 5/s for 15 min, starting 20 min following conditioning, was 174% of the rate found in unconditioned ganglia. The ACh stores of the conditioned ganglia at the end of the test were calculated to be 173% of the control ganglion stores.3. When test stimulation at 4/s was started 5 min following conditioning, the rate of ACh release showed a variable pattern of increase and decrease over a 75 min period. The mean peak rate of release was about 150% of the control rate, and the duration of potentiation was about 75 min.4. When conditioned, unperfused ganglia were tested by stimulation at 4/s the ACh stores were found to increase and decrease in parallel with the increase and decrease in ACh release rates found in the perfusion experiments.5. It was found also that the magnitude of the increase in ACh stores and ACh release was related to the amount of ACh in the ganglionic stores at the onset of conditioning, being greater for the ganglia with the smaller initial stores.6. It is concluded that the potentiation of ACh release in ganglia conditioned in this way is directly related to the accompanying increase in ACh stores.7. The possible significance of alterations of ACh stores and ACh release as a mechanism of modulatory control of ganglionic transmission is discussed.


Muscular nociceptors.

Muscular nociceptors. The discharge characteristics of various types of muscle afferents in response to mechanical and chemical painful stimulation were studied in cats anaesthetized with chloralose. In a few experiments, heat was used as an additional stimulus. The results indicate that only among the fibre groups III and IV, units are regularly found that have high thresholds on mechanical and thermal stimulation, and that response to administration of algesic agents in pain-producing doses. The response behaviour of individual group III and group IV afferent units to the various stimuli was very similar, but when the fibre populations are compared, the group III afferents appeared to be more sensitive to the mechanical and chemical stimuli of this study. It is concluded that both the fibre groups III and IV include afferent units possessing receptive properties enabling them to serve as muscular nociceptors.


A pharmacological approach to elucidation of the role of different nerve fibres and receptor endings in mediation of pain. Capsaicin, after initial stimulation, induced a long-lasting insensitivity to chemical pain stimuli without reducing the sensitivity to mechanical pain. The effect was peripheral as shown by recording action potentials from sensory nerves. In order to throw light on the receptors responsible for chemogenic pain, the specificity of the capsaicin effect was analysed. 1. In cats, capsaicin given in close arterial injection excited the slowest conducting C2 fibres as measured by the collision technique on the saphenous nerve. In rats, the frequency of action potentials evoked by s.c. injection of capsaicin was sensitized by rapid warming of the skin area, while sudden cooling had a blocking effect. On the human skin, the threshold of thermal pain was shifted from 45 degrees C to 30-31 degrees C; below this skin temperature, the burning pain and hyperalgesia induced by capsaicin treatment disappeared and cold sensation remained unimpaired. 2. On the human tongue, local capsaicin desensitization resulted in an elevated threshold of warm discrimination, while gustatory sensitivity as well as the capacity for discriminating cold or tactile stimuli remained unimpaired. 3. It is concluded that capsaicin is a selective sensory blocking agent which acts by stimulation and subsequent sensory blockage of polymodal nociceptors and warm receptors.


The terminal arborization pattern of primary afferent fibers in the substantia gelatinosa of the spinal cord in the cat. The spinal cords of adult cats were impregnated using the Golgi-Kopsch technique and cut in the sagittal plane. Richly arborizing axon-trees were found in the substantia gelatinosa (lamina II of Rexed). Axon arborizations, characterized by a long rostro-caudal course, a single-stem fiber, multiple-arborizing side branches and large terminal and en passant boutons, were subjected to a semi-quantitative and later to a computer-aided analysis. These arborizations, presumably of primary afferent origin (Réthelyi, 1977), are arranged in narrow sheets. The sheets of the individual arborizations are tilted with respect to the sagittal plane (the dorsal edge of the sheet having a more lateral position than the ventral edge), and tilted with respect to each other's plane, but they are rigorously oriented in the rostro-caudal direction. The average thickness of the sheets encompassing the terminal and en passant bulbs of these arborizations is 16.65 micrometer (S.D. = 2.86; n = 10). Occasionally, the side branches and terminal bulbs of a single stem fiber arborize into two separate sheets. These anatomical results suggest that the activity of the peripheral fibers spreads in long and narrow neuropil fields in the substantia gelatinosa. This pattern suggests a fine scale somatotopic arrangement.


Sympathetic reflex responses presumably specific for nociceptive stimulation. 1. In superficially anaesthetized and in unanaesthetized decerebrate cats, tetanic stimulation of A or A + C afferent fibres of the tibial nerve evoked in renal and inferior cardiac nerves a three-phasic change of activity, which consisted of a short powerful burst of discharges, followed by an inhibitory pause and then, by a moderate excitation. When such a command appeared in sympathetic nerves, reflex rising of systemic arterial pressure was extremely fast. 2. The latencies of the three-phasic command and of the so-called very late A response are almost the same. The very late A response is evident if the central nervous system is in the same state as when repetitive stimulation of A afferents evokes the three phasic command in sympathetic nerves and a steep rise of systemic arterial pressure. This permits the assumption that the very late A response reflects the excitation of just those central structures that on repetitive stimulation organize the three-phasic command. 3. A command of this kind is shown to ensure the optimal-time-control of the heart and blood vessels. Such a control (three-phasic command) is supposed to be evoked by nociceptive stimulation, i.e., to be specific for the defence reaction.


Visceral pain: responses of the reticular formation neurons to gallbladder distension. Visceral projection (gallbladder distension) to the gigantocellular nucleus of the reticular formation of the cat was tested in neurons classified as pain (P), nonpain-pain (NP-P) and nonpain (NP) units, according to their responses to noxious and/or innocuous natural stimuli from the somatic areas. 96% of P neurons (23 out of 24) responded to gallbladder distension. Quantitative criteria showed comparable effectiveness of the somatic and visceral inputs. NP-P neurons reacted to the gallbladder stimulation in 71% of cases (22 out of 31); NP neurons were activated less effectively. Stimulation of either the central tegmental field or "nonspecific" thalamic nuclei evoked direct responses in 38% of P and 26% of NP-P units, which, in most of the P neurons were followed by excitatory and inhibitory phases. The duration of the latter was approximately one second and it greatly affected the responses of the units to somatic as well as to visceral inputs. A large proportion of P neurons responding to a visceral input documents the important role of the reticular formation in the mechanisms of visceral pain. Findings concerning comparable modifying influences upon reactions of P units both in the case of visceral and painful somatic afferentation indicated that similar control mechanisms could be involved.


Thalamic and mid-brain responses to dental pulp afferent messages in awake cats. 1. Central projections of messages evoked by dental pulp stimulation have been searched for in awake cats and recorded at unitary level. A head-top frame screwed to the skull served to fix the animal in the stereotaxic instrument precisely and in the usual orientation. 2. Three types of responses could be distinguished, each with characteristic thalamic localization: --one was of the specific type: it occurred at short latency, followed rapid rates of stimulation, and was localized in VPM and SG; --a second type had longer latency, did not follow rapid rates of stimulation, was frequently bilateral, and was localized in VPM, CM-Pf and Posterior Group; --the third type was a complex response, exhibiting inhibitory and excitatory phases; extremely labile, it disappeared during wakefulness; it was found in LP and CM-Pf. 3. The responses elicited by dental pulp stimulation and recorded in the periaqueductal grey matter mostly originated from face muscle messages provoked by the jaw opening reflex. 4. The possible contributions to pain perception made by each of the different thalamic responses is discussed, as well as the adequacy of dental pulp stimulation for producing a purely nociceptive signal.


Spinal trigeminal tractotomy and nociceptive reactions evoked by tooth pulp stimulation in the cat. The effect of transection of the descending root of the spinal trigeminal tract on nociceptive and aversive reactions evoked by stimulation of the tooth pulp nerve was studied in cats. The transection was performed 1-1.5 mm caudally to the obex. 1. The nociceptive reaction, characterized by wide opening of the jaw, dorsiflexion and rotation of the head and by signs of affective behaviour, remained unchanged after transection of the descending root of the trigeminal nerve (n = 6). 2. The instrumental escape reaction was elaborated in three cats before transection of the descending root of the trigeminal nerve and in three cats after transection. The escape reaction was retained after transection of the descending root and the speed of learning to escape the tooth pulp stimulation did not significantly differ in these two groups of animals. 3. It is to be concluded that the transection of the descending root of the spinal trigeminal tract in the cat does not result in dental analgesia.


Synaptic control of an endogenous pacemaker network. 1. The present study consists of an analysis of the coordinating effects of monosynaptic EPSPs and IPSPs on the discharge of the endogenous pacemaker neurons which drive the pyloric motor system of the spiny lobster. The experiments were performed on isolated nervous systems. 2. An analysis of the characteristic phase response curves to both classes of input (fig. 1) shows that the pyloric oscillator possesses the necessary characteristic for entrainment: i.e. a periodically varying sensitivity to synaptic drive. 3. By repetitive stimulation of either input at frequencies near the endogenous frequency of the PD slow wave, it was possible to entrain the discharge of the pacemaker system to the cyclic stimulus (figs. 2b and 3b). The pyloric discharge tends to occur at different characteristic phase relations in response to the two inputs (figs. 2c and 3c), which reflect features of the corresponding phase response curves (fig. 1). 4. It is argued that the periodic sensitivity of these neurons to synaptic input reflects interactions between the synaptically induced currents and the endogenous currents which underlie the slow wave.


Neural circuitry underlying oscillatory motor output. 1. The stomatogastric nervous system of lobsters can be used as a model network with which to study the mechanisms involved in the generation of rhythmic behaviour. 2. The stomatogastric ganglion contains about thirty neurons and produces two rhythms, the gastric and the pyloric. 3. The gastric rhythm appears to be derived from the global properties of a twelve-cell network. 4. The pyloric rhythm is driven by a group of three endogenous bursters. 5. Both rhythms are assisted by phasic excitatory input from the two commissural ganglia. 6. Synapses found in this network appear to be located on the finest dendritic branches and are multiterminal.


[Walking in Crustacea: motor program and peripheral regulation (author's transl)]. 1. Rock lobsters can walk in all directions. In the present study, we report the organization of the motor output of the three muscles which control the mero-carpopodite joint (M-C): the extensor E, the flexor F and the accuracy flexor FA, during unrestrained locomotion (fig. 1). 2. During lateral walking, movements of the M-C joint provide most of the propulsive force, whereas during forward and backward walking this joint function more as a strut (fig. 2). Corresponding differences are observed in the motor discharge in the different walking modes. During lateral walking, discharge in the M-C extensor and M-C flexor alternates, whereas during forward and backward walking these antagonists are coactivated (fig. 3 and 4). 3. We have also examined the effects of alterations of proprioceptive feedback: the FA tendon has been cut to eliminate MCO afferents during walking. This ablation does not modify the burst period and the temporal structure of the output pattern is largely unaffected (fig. 5, 6 and 7). MCO may influence the motor output of a given muscle depending upon whether it participates in the return stroke or the power stroke.


[Induced release of neurosecretion from the median neurosecretory cells of the African locust in vitro (author's transl)]. Induced release of neurosection from the median neurosecretory cells of the African locust in vitro.


Comparison of the WISC-R and culture fair intelligence test in a juvenile delinquent population. Culture Fair and WISC-R scores were obtained of 51 delinquent juveniles. Comparison of mean scores on the two tests for minority and white juveniles demonstrated the Culture Fair to be less culturally biased than the WISC-R. On analysis of variance there was a significant difference due to ethnicity and test used, and a significant interaction of those two factors. The interaction was due to the elevation of the score of minority juveniles on the Culture Fair compared with WISC-R scores. Correlations between the WISC-R scores, subtest scale scores, and Culture Fair scores were significant at the .01 level which provides further validation of the WISC-R.


Personality characteristics of men with liberal sex-role attitudes. The present study was conducted to provide some initial information on the personality attributes of men oriented toward liberal sex-role views. Fifty-one male college students were given the Attitudes Toward Women Scale and divided into conservative, moderate, and liberal groups. Personality differences among the groups were assessed by comparing scores on nine scales from the Adjective Check List. Findings for liberal men were found to parallel results reported for liberal women on some personality dimensions and complement them on others. As with liberal women, liberal men were found to be more spontaneous, action oriented, risk taking, individualistic, and unconventional than the other male groups. There were also some indications of less self-control. Sex-role attitudes and heterosexuality were curvillinearly related. In direct opposition to results for liberal women, male liberals evidenced the least need for achievement and dominance.


General anxiety and death imagery in Catholic seminarians and college students. General anxiety and evoked imagery of death as a person were measured in 75 male Catholic college students and seminarians. College students most frequently described death as a macabre figure, and seminarians mostly conceived death as a wise and sympathetic individual. Hither anxiety was more characteristic of college students than seminarians.


Perceived appraisals by others, self-esteem, and anxiety. Questionnaire data from 595 male and female college students were used to test four hypotheses regarding interpersonal sources of anxiety--i.e., that high anxiety occurs as a function of (a) low subjective public-esteem (perceived negative appraisals of self by others); (b) low self-esteem; (c) discrepancies where subjective public-esteem is more negative than self-esteem; and (d) absolute discrepancies between subjective public-esteem and self-esteem, regardless of evaluative direction. The results suggested that level of self-esteem and absolute discrepancies between subjective public-esteem and self-esteem are important and relatively independent factors in anxiety.


Distance and location cues in retention of movements by a congenitally blind subject. Retention of linear arm-positioning movements in a congenitally blind university student was tested with either distance or location cues and under retention conditions of rest, location, and distance interpolated tasks. Results revealed a consistent superiority for retention with location cues. The conclusion is drawn that these data would support a dual proprioceptive storage mode hypothesis.


Assumed personality characteristics of counseling center growth group participants. Two hundred students enrolled at Eastern Kentucky University were administered a questionnaire designed to measure attitudes toward fictitious students. The "students" were described as being engaged in several kinds of activities including a growth group at the counseling center of the university. The results indicated that growth group participants were rated more negatively than control stimulus persons on several personality dimensions. Ratings of individuals engaged in two kinds of psychotherapy were also discussed.


Extraversion and risk preference in portfolio theory. One hundred seventy-eight male and female undergraduates completed the Eysenck Personality Inventory and indicated their risk preference assessed under the assumptions of Coombs' portfolio theory. Extraverts preferred higher risk significantly more than did introverts, and also showed significantly greater risk preference change as expected value increased. It was suggested that a theoretically defensible selection of both personality variables and a risk assessment model may lead to greater personality-risk predictability.


[Gayet-Wernicke encephalopathy].

[Gayet-Wernicke encephalopathy]. We have reviewed the aetiology, symptomatology, biology and clinical course of 61 cases of the Gayet-Wernicke encephalopathy. Our results do not differ fundamentally from those of Victor et al. (1971). Nevertheless, our study shows fewer oculomotor palsies in the acute stages, lower mortality and a lower incidence of residual anmesic syndromes. These results demonstrate the importance of early diagnosis and of starting the specific therapy in the initial stage of reversible biochemical lesions.


[Acute alcoholic hepatitis].

[Acute alcoholic hepatitis]. Acute alcoholic hepatitis is an anatomical (fatty liver with sclerosing hyaline necrosis) and a clinical (hepatomegaly with a variety of symptoms of hepatic failure) entity arising out of chronic alcoholism, and of a typically 'pre-cirrhotic' state. Although fatal in 25% of acute cases due to failure of homeostasis, it often leaves a centrilobular scarring necrosis which in more than 60% of cases progresses to nodular cirrhosis. Continued alcoholism worsens the prognosis. Alcoholic hepatitis may be confused with acute abdominal catastrophes or with a hepatoma. The characteristic Mallory bodies found on liver biopsy are found rarely in non-alcoholic hepatitis. There is no effective treatment for this disease except reduction of alcohol intake; indeed, the disease may become self-perpetuating.


Insulin levels in the amniotic fluid and in maternal and fetal blood. The effects of excessive maternal weight gain during pregnancy (five cases) and of glucose infusion in the mother (five cases) on insulin levels are compared with the insulin levels in a control group (19 normal pregnancies) by radioimmunologic determination of insulin levels in the amniotic fluid and in maternal and fetal blood. The mean values for insulin in the control group were as follows: mother, 23.9 +/- 2.23 muU per ml; fetus, 9.86 +/- 2.11 muU per ml; and amniotic fluid, 5.08 +/- 2.27 muU per ml. In patients with excessive weight gain during pregnancy, maternal insulin mean values were 38.45 +/- 4.16 muU per ml; fetal, 19.99 +/- 9.8 muU per ml; and amniotic fluid, 11.25 +/- 2.58 muU per ml. After an infusion of 25 mg of glucose in the mother, the mean maternal insulin values were 53.6 +/- 13.74 muU per ml; fetal, 24.7 +/- 6.67 muU per ml; and amniotic fluid, 14.3 +/- 5.52 muU per ml. Insulin concentrations in maternal blood (p less than 0.001), fetal blood (p less than 0.001) and amniotic fluid (p less than 0.001) were higher in pregnancies with excessive weight gain as compared to those in the control group, whereas the glucose infusion in the mother increased the concentration of insulin in the three components studied.


Postobstructive diuresis after reduction of an incarcerated gravid uterus. An incarcerated gravid uterus is a dangerous but fortunately infrequent complication of pregnancy. Many sequelae may result from this condition. The purpose of this paper is to present an unusual complication after repositioning of the gravid uterus and to discuss management of the incarcerated uterus in pregnancy.


Atypical cytology in tubal pregnancy.

Atypical cytology in tubal pregnancy. The V-C Pap smears taken from five cases of tubal pregnancy revealed dyskariotic endometrial cells characterized by clear, finely vacuolated, abundant cytoplasm with indistinct cellular borders and finely hyperchromatic nuclei. These cells, the cytologic counterpart of A-S reaction, may be interpreted as malignant by the unwary observer. Critical evaluation of their cytologic characteristics, however, is not likely to confirm this impression. The proper recognition of these atypical cells may be a valuable aid in suggesting the presence of ectopic pregnancy.


Outcomes of elective home births: a series of 1,146 cases. Medical records of 1,146 elective home births from five home delivery services in northern California were reviewed. Three of the services consisted of family physicians and nurses, whereas two consisted of lay midwives without immediate physician supervision. Rates of medical complications in both groups were low. Perinatal morbidity and mortality were lower than California averages. Fifteen premature infants (1.3%) were delivered successfully. Apgar scores were high. Four infants (0.3%) were neurologically abnormal at follow-up. The perinatal mortality rate was 9.5 per 1,000 total births. There were no maternal deaths. These figures demonstrate that in a self-selected, medically screened, low-risk population, home delivery with medical facility back-up can be a reasonable alternative to hospital delivery. Possible reasons for the good results obtained are cited.


Cell mediated immunity in rheumatoid arthritis: Imparied lymphocyte responsiveness, humoral immunosuppressants, and correlations with clinical status in patients off drug therapy. Cell mediated immune functions were studied in 17 patients with rheumatoid arthritis (RA) at times off all drug therapy, and were correlated with clinical findings. Cellular immunity was evaluated by (1) skin testing to antigens and (2) measuring peripheral blood lymphocyte (PBL) and effusion lymphocyte tritiated thymidine (3H-TdR) uptake in in vitro cultures containing 20 percent autologous or 20 percent AB plasma and various concentrations of mitogens or antigens. Cutaneous and in vitro reactivity were decreased in RA patients: (1) RA PBL spontaneously incorporated more 3H-TdR than normals; (2) 3H-TdR uptake by RA PBL, cultured in AB plasma, in response to mitogens and antigens was markedly reduced when compared with normals; (3) RA PBL responses were further diminished when cells were cultured in autologous plasmas; (4) effusion lymphocytes similarly often had high unstimulated 3H-TdR uptakes and poor responses to stimulation; and (5) decreased proliferative responses of RA PBL (in AB plasma) correlated with class and stage III-IV, increasing age, number of tender or swollen joints, rheumatoid factor titer, total protein, decreased grip strength, and poor skin test reactivity.


Synovial calcification in a patient with collagen-vascular disease: light and electron microscopic studies. Unusual articular as well as periarticular calcifications are reported in a patient with collagen-vascular disease. Tiny crystals visible in electron micrographs in synovial membrane and in synovial fluid cell vacuoles resemble apatite and appear most consistent with apatite on electron probe studies. The inflammatory synovial effusion also contained chylomicrons. Other joint diseases associated with synovial calcification or suspected synovial apatite are discussed.


Colchicine in the treatment of scleroderma. We treated 10 patients with well established scleroderma with colchicine in the highest tolerated dose for one year. We could determine no clinical or laboratory improvement in any patient. Progression of disease was suggested by the development of new skin ulcers and telangiectasia, by an increase in musculoskeletal complaints, and by a significantly diminished ability to make a fist. In addition, there was deterioration of pulmonary function as demonstrated by a statistically significant fall in FEV1, and diffusing capacity. Colchicine was not of value in the treatment of scleroderma in this group of patients.


Psoriatic spondylitis: a clinical, radiological, and scintiscan survey. Thirty-three per cent of patients with psoriatic spondyloarthropathy referred to a rheumatic disease unit were found to have radiological sacroiliitis. The majority of these patients had definite or probable spondylitis according to the New York criteria. Abnormal sacroiliac uptake of 99mTcPP on bone scan correlated well with the radiological finding of sacroiliitis. In addtion, eight patients with normal radiographs had an abnormal uptake of radionuclide over the sacroiliac joints, indicating sacroiliitis. Patients with sacroiliitis tended to have more severe psoriasis. Sacroiliitis occurred in association with all of the patterns of peripheral joint involvement which may occur in psoriatic arthritis. Although the HLA antigen B27 was present in only 21 percent of the total group and in 33 percent of those with sacroiliitis, 8 out of 10 with this antigen had sacroiliitis.


The sacroiliitis of acute Reiter's syndrome. Sacroiliitis can be demonstrated radiologically in over one-third of patients with chronic Reiter's syndrome. We have used a bone scan technique with digital analysis which will quantitatively assess the sacroiliac joints, and have found abnormalities in 24 of 33 patients with active Reiter's syndrome. It seems likely therefore that sacroiliitis is a common feature in patients with early Reiter's syndrome and while in most patients it resolves with resolution of disease activity, in some it may persist with the development of overt radiological changes.


Ankylosing spondylitis with selective IgA deficiency and a circulating anticoagulant. A patient with ankylosing spondylitis was found to have selective IgA deficiency and a non-heparin, immediate-acting antithrombin (antithrombin V). T cells were decreased, and serum IgG was increased. In vitro synthesis of IgG by peripheral blood lymphocytes was very high. This association of ankylosing spondylitis with the T cell and protein abnormalities is probably fortuitous but does demonstrate that severe spondylitis may evolve in the absence of IgA.


Acute pseudogout in the absence of synovial fluid Leukocytes. A case of acute pseudogout that occurred in the absence of synovial fluid leukocytes is described. This finding implies that there may be an alternative inflammatory mechanism for acute pseudogout that does not depend on polymorphonuclear leukocytes.


Granulomatous liver disease and giant cell arteritis. Case report and literature review. A case granulomatous liver disease associated with the polymyalgia rheumatica-giant cell arteritis syndrome is presented. Treatment with corticosteroids resulted in prompt improvement in both the polymyalgia rheumatica-giant cell arteritis syndrome, as well as the tests of liver function. It is suggested that polymyalgia rheumatica and giant cell arteritis may involve the liver and should be included in the differential diagnosis of granulomatous liver disease.


HLA antigens in patients with giant cell arteritis and polymyalgia rheumatica. The frequency of 24 HLA antigens was determined in 43 patients with giant cell arteritis (25 of whom had polymyalgia rheumatica) and 12 others with polymyalgia rheumatica without evident arteritis. No haplotype was present in significantly increased frequency above controls in the total group nor when the patients were separated according to the presence or absence of polymyalgia rheumatica.


Synthesis and biological action of two glucocorticoid alkylating agents. Two alkylating glucocorticoids have been synthesized in order to test the possibility of alkylating glucocorticoid receptors. The title compounds are 9alpha-fluoro-11beta,16alpha,17alpha,21-tetrahydroxypregna-1,4-diene-3,20-dione 21-[bis(2-chloroethyl)carbamate] 16,17-acetonide (I) and 11beta,17alpha,21-trihydroxypregn-4-ene-3,20-dione 21-[bis(2-chloroethyl)carbamate] (II), prepared from triamcinolone acetonide and cortisol, respectively, through the reaction of the C-21 hydroxyl group with phosgene and di-2-chloroethylamine in the presence of triethylamine. Both compounds are biologically active as inhibitors of the growth of cultured mouse fibroblasts and are able to compete for the specific binding of radiolabeled triamcinolone acetonide to the L929 cell receptor. The bis(2-chloroethyl)carbamate moiety is capable of reacting with nucleophilic groups as evidenced by the colorimetric reaction with 4-(p-nitrobenzyl)pyridine. Both the interaction with the receptor and inhibition of cell growth by these two glucocorticoids are reversible.


Quantitative relationships between steroid structure and binding to putative progesterone receptors. Relationships between chemical structure of androst-4-en-3-one derivatives and their affinity for putative progesterone receptors are described. The binding affinity for 55 derivatives can be expressed by the equation log relative binding affinity (rabbit receptor) = 1.79 + 0.18 (+/-0.11) pia + 1.45 (+/-0.21) pib + 0.010 (+/-0.002) (surface area in hydrophobic pockets) - 0.012 (+/-0.003) (surface area out of hydrophobic pockets) - 0.99 (+/-0.21) MK - 0.33 (+/-0.08) (conformational changes). For this equation, r=0.88. The equation successfully predicts the affinities of other compounds in the literature. The importance of the surface area terms is discussed.


Synthesis and gastric antisecretory properties of 15-deoxy-16-hydroxyprostaglandin E analogues. The preparation and gastric antisecretory activity of a series of 15-deoxy-16-hydroxyprostaglandin analogues are described. The compounds were tested intravenously in histamine-stimulated Heidenhain pouch dogs in relation to the reference standards PGE1 and PGE1 methyl ester (PGE1ME). The parent compound of this seris, (+/-)-15-deoxy-16alpha,beta-hydroxyprostaglandin E1 methyl ester (3), was found to be equipotent to the reference standard PGE1ME. Methylation at C-16 of 3 produced 8 which was found to be some 40 times more potent than PGE1. In sharp contrast, addition of two methyl groups to 3 at C15 or C17 markedly reduced the antisecretory action. The 16-ethyl analogue of 3 also showed reduced potency. Removal or epimerization of the C-11 hydroxy group of 8 reduced the activity. Likewise, hydrogenation or changing the stereochemistry of the 13,14 double bond from trans to cis decreased the activity. On the other hand, omega-homologation of 8 or the introduction of a cis-5,6 double bond did not affect the potency. From these studies, it appears that 8, 16, and 17 possess optimum gastric antisecretory effects in this series.


[1-(L-2-hydroxy-3-mercaptopropanoic acid)] analogues of arginine-vasopressin, [8-D-arginine]vasopressin, and [4-valine,8-D-arginine]vasopressin. [1-(L-2-Hdroxy-3-mercaptopropanic acid)]arginine-vasopressin (hydroxy-AVP), [1-(L-2-hydroxy-3-mercaptopropanoic acid),8-D-arginine]vasopressin (hydroxy-DAVP), and [1-(L-2-hydroxy-3-mercaptopropanoic acid),4-valine,8-D-arginine]vasopressin (hydroxy-VDAVP) were synthesized by a combination of the solid-phase and solution methods of peptide synthesis. Protected octapeptides synthesized by the solid-phase method were further acylated by 1 + 8 couplings in solution to furnish the key intermediates. Hydroxy-AVP has antidiuretic potency of 470 units/mg and activity in the rat vasopressor assay of 550 units/mg, representing a small enhancement of activity over that of arginine-vasopressin (AVP) in each case. Hydroxy-DAVP and hydroxy-VDAVP have essentially the same high antidiuretic activity (900 units/mg) and very low vasopressor potencies (0.9 and less than 0.02 units/mg, respectively). Hydroxy-AVP, hydroxy-DAVP, and hydroxy-VDAVP thus have antidiuretic-pressor selectivity (A/P) of 1, 1000, and greater than 45 000, respectively. These data are compared with those of other vasopressin analogues. Hydroxy-VDAVP is a highly specific antidiuretic peptids and may be useful in pharmacological studies of antidiuresis.


2-pyridylimidazoles as inhibitors of xanthine oxidase. A series of 28 4-substituted and 4,5-disubstituted 2-pyridylimidazoles was synthesized and evaluated in vitro for inhibition of xanthine oxidase. Included within this group are examples of 2-pyridylimidazopyridines and halo-substituted 2-pyridylbenzimidazoles. Five compounds exhibited inhibitory activity in the same range as the standards, 4-hydroxypyrazolo[3,4-d]pyrimidine and 2-(4-pyridyl)-4-trifluoromethylimidazole (22). Two examples, 2-(4-pyridyl)-4,5-dicyanoimidazole (16) and 2-(4-pyridyl)-4-nitroimidazole (3), were at least an order of magnitude more active than the standards and therefore rank among the most potent known inhibitors of the enzyme.


Inhibitors of hepatic mixed function oxidase. 3. Inhibition of hepatic microsomal aniline hydroxylase and aminopyrine demethylase by 2,6- and 2,4-dihydroxyphenyl alkyl ketones and related compounds. A series of 2,6- and 2,4-dihydroxyphenyl alkyl ketones has been investigated as inhibitors of hepatic microsomal aniline hydroxylase and aminopyrine demethylase activities. Structural alterations in both series did little to enhance the inhibitory activity of the parent compounds 2,6-dihydroxyacetophenone (3) and 2,4-dihydroxyacetophenone (27). In the 2,6 series activity against both microsomal systems varied only over a relatively narrow range, 6-allyloxy-2-hydroxyacetophenone (19) being the most potent inhibitor. In the 2,4 series, activity against aniline hydroxylase was poor or absent in most cases. tthe most potent inhibitor was 5-ethyl-2,4-dihydroxyacetophenone (31). In contrast, high activity against aminopyrine demethylase was frequently displayed in this series, 3,5-dibromo-2,4-dihydroxypropiophenone (36) showing greatest inhibitory potency. The effects of some compounds on hexobarbital sleeping times and zoxazolamine paralysis times in mice were also examined.


Oxime ether derivatives, a new class of nonsteroidal antiinflammatory compounds. A series of new 2-hydroxyethyl and carboxyalkyl ethers of aromatic oximes was found to possess pronounced antiinflammatory activity in the carrageenan-induced edema test in the rat. The activity was limited mainly to derivatives of p-haloacetophenone oxime and of p-halobenzaldehyde oxime. Nevertheless, the hydroxyethyl and carboxyalkyl groups may be converted into many derivatives with maintenance of activity. Some structure-activity relationships are in contrast to those of the well-known antiinflammatory arylacetic acids. The activity is limited to the E stereoisomers. The hydrochloride of 2-(dimethylamino)ethyl (E)-[[(p-chloro-alpha-methylbenzylidene)-amino[oxy]acetate (36, INN name Cloximate) was chosen for clinical evaluation. The first results agree with the pharmacological prospects.


Electronic factors in the structure-activity relationship of some 1,4-benzodiazepin-2-ones. Some significant correlations are observed between the CNS activities of a series of 59 benzodiazepines and some calculated electronic indices. The parameters concerned are the net charge on the carbonyl oxygen atom of the lactam ring and the total molecular dipole moment, correlations with the latter index being superior. The utility of the observed relationships is discussed.


Potential long-acting anticonvulsants. 2. Synthesis and activity of succinimides containing an alkylating group on nitrogen or at the 3 position. The synthesis of succinimide derivatives in which alkylating groups have been attached to the imide nitrogen or to the 3 position of the ring is described. The synthesis of one bis-alkylating derivative 19 is also described. The alkylating groups used were (a) alpha-haloacetyl, (b) alpha-haloacetamido, (c) maleamyl, and (d) maleimido. These compounds were prepared as potential long-acting anticonvulsants. None of the compounds showed activity against maximal electroshock or metrazole-induced seizures.


Effect of the solvent-dependent conformational system of hydroxyureas on predicted vs. observed log P. Calculated and observed log P values are reported and compared with in vivo and in vitro biological action (L1210 leukemia ILS % and ribonucleotide reductase ID50) for hydroxyurea, the 1-N methyl and ethyl, and the 3-N ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, phenyl, and p-chlorophenyl analogues. The log P values were calculated via the method of Hansch and Leo from literature f values and the observed log P values were obtained by direct determination after equilibration between octanol and water. Calculations of log P for hydroxyurea were found to be appreciably more hydrophilic than the values obtained experimentally. Differences in calculated and observed log P (delta log P) for the substituted analogues were lowest with the 1-N and the bulky 3-N substituents and greatest with the 3-N-substituted straight-chain analogues (delta log P = 0.70). Different structural species were observed by infrared spectroscopy in dry octanol vs. octanol after water equilibration and drying, and this is proposed as due to changes in conformational equilibrium in the hydroxyurea systems. Differences between calculated and observed log P are explained via the stabilization of internally hydrogen-bonded conformers in the case of 1-N or bulky 3-N analogues or destabilization of various conformers allowing maximal interactions with solvent or water which is the case with straight chain 3-N analogues.


4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide, a new, potent fasciolicide. The synthesis and fasciolicidal activity of 4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide are reported. A single dose of 15 mg/kg was effective in removing over 90% of immature Fasciola hepatica from sheep (6 weeks after infection) and calves (8 weeks after infection). A 2.5 mg/kg dose removed over 90% of mature (16 weeks old) liver fluke from sheep. Single oral doses up to 400 mg/kg were tolerated by sheep without gross toxic symptoms.


[1-deaminopenicillamine,4-valine]-8-D-arginine-vasopressin, a highly potent inhibitor of the vasopressor response to arginine-vasopressin. In attempting to design an antagonist of the antidiuretic response to arginine-vasopressin (AVP) [1-deaminopenicillamine,4-valine,8-D-arginine]vasopressin (dPVDAVP) was synthesized by the solid-phase method and assayed for antidiuretic, vasopressor, and oxytocic activities. dPVDAVP has an antidiuretic potency of 123 +/- 22 units/mg, one-tenth that of its parent [deamino,4-valine,8-D-arginine]vasopressin (dVDAVP). Like dVDAVP its antidiuretic effect in conscious diabetes insipidus rats is greatly prolonged when compared to AVP. dPVDAVP causes a prolonged inhibition of vasopressor responses to AVP but not to norepinephrine or angiotensin II. It has an antivasopressor pA2 value of 7.82 +/- 0.05 when tested against AVP. Thus the penicillamine substitution at position 1 in dVDAVP increased its antivasopressor activity sixfold (dVDAVP has a pA2 value of 7.03 +/- 0.11). dPVDAVP is thus the most potent vasopressor antagonist yet reported. dPVDAVP was also found to be a potent inhibitor of the in vitro oxytocic response to oxytocin (pA2 value = 7.23 +/- 0.04). dPVDAVP with its potent and specific ability to antagonize the vasopressor effects of AVP should be a useful pharmacological tool with which to explore the possible participation of AVP's potent vasoconstrictor properties in cardiovascular regulation in physiological and pathological states.


Focus: current issues in medical ethics. The current debates about seat belts in motor cars and the evils of smoking may only be straws in the wind if the scenario sketched in this paper were translated into a social, political programme. Then 'illness would increasingly be seen as a failure to keep healthy and thus culpable. The failures [the patients] ... must either be irresponsible and hence punishable at least by the imposition of financial penalties or insane and thus in need of corrective therapy.' If this sounds like 1984 the reader must read the whole argument set out in this paper and make his own judgment. He may not be encouraged by what he reads but he will be forewarned. There is no answer to the question, What shall I do, if this prophecy is true?


The General Medical Council: frame of reference or arbiter of morals? Many members of the public think of the General Medical Council (GMC) as the body which tries doctors: the doctors' law courts, as it were. And, except in the more sober of newspapers and news reports, the 'offences ' which receive the most publicity are those concerning alleged improper relations between doctors and patients. Professor Sir Denis Hill, in the following paper, which he read in the spring of this year to the annual conference of the London Medical Group devoted to a discussion of human sexuality, chose to examine the whole function of the General Medical Council as a frame of moral reference for doctors. Judging allegations of professional misconduct by doctors is the function of the Council's Disciplinary Committee. Judging sexual misconduct forms only a small part of their work. The GMC's responsibility covers the whole notion of morals and morality as it concerns doctors in their professional work. Sir Denis Hill stresses the modern thinking that morality must be learned and that attitudes are always shifting as society alters its norms of what is moral conduct. That is not to say that all that was previously considered not to be moral has now become acceptable but rather that other concepts have entered the field of moral debate. Therefore the GMC must constantly review the frame of reference it offers to doctors and the public may be surprised to learn that that process is never static. Sir Denis Hill in this paper is speaking personally and not as a member of the General Medical Council or of any of that body's special committees.


Royal College of Nursing (Rcn) code of professional conduct: a discussion document. We are printing in its entirety the discussion document which sets out a code of professional conduct for nurses published by the Royal College of Nursing in November 1976 together with commentaries by the Assistant Secretary of the British Medical Association, a professor of nursing studies, student nurses and a lawyer. The image of the nurse is still that of one of Florence Nightingale's young ladies or of a member of a religious order who is wholly dedicated to caring for the sick. Today, as this document and the comments upon it show, 'dedication' is still part of the motive which leads a man or woman to become a nurse but in addition, and this is where the public may be ignorant or choose to be ignorant, nursing offers a career where intellectual achievement and the satisfaction of a demanding job bring their proper financial reward and place in the professional community. We are grateful to the Royal College of Nursing for permission to publish this document.


Tacit components of medical ethics: making decisions in the clinic. When a patient visits his doctor there is, as well as a spoken dialogue, also an unspoken, or tacit, dialogue between them. This may not be evident unless that dialogue breaks down when the psychological or moral terms of reference of each are seen to be different. The author of this paper tries to elucidate the framework in which physician and patient think, and in so doing allow an understanding of why the physician may appear to be rigid and authoritarian in his dealing with his patients and the patient uncooperative.


False belief and the refusal of medical treatment. May a doctor treat a patient, despite that patient's refusal, when in his professional opinion treatment is necessary? This is the dilemma which must from time to time confront most physicians. An examination of the validity of such a refusal is provided by the present authors who use the case history of a patient refusing treatment, for cancer as well as for a fractured hip, to evaluate the grounds for intervention in such circumstances. In such a situation the patient is said to have a 'false belief' and it is the doctor's duty to try to change that belief in the patient's interest. The false belief is considered here in terms of the liberty principle, the patient's mental competence and on what is called the 'harm principle' (harm to other individuals or to society). Finally the concept of paternalism is examined. The authors conclude that the doctor must attempt to change a false belief, and if this fails he must examine the patient's mental competence to make the decision to refuse treatment. But in the last analysis the doctor may be under an obligation to respect the patient's refusal. Readers might like to look at (or read again) the papers on 'Liberty' and 'Conscience' published in this Journal under the heading Analysis.


G gamma delta beta thalassaemia and g gamma HPFH (Hb Kenya type): comparison of 2 new cases. Two new cases of G gamma delta beta thalassaemia and G gamma HPFH (Hb Kenya type) have been characterised in detail and compared with regard to haematological data, globin chains biosynthesis, and intracellular distribution of Hb F. The similarities and differences between these two conditions are discussed in relation to the possible underlying defects at the molecular level and to the control of the gamma delta beta gene complex in general.


Haemoglobin D Ouled Rabah (beta 19[Bl] asn leads to lys) in a Tuareg tribe of the Southern Sahara. Haemoglobin Ouled Rabath found only once before in an Algerian has been discovered at high frequency in the Kel Kummer Tuaregs in Mali. The tribe represents a 'genetic isolate'.


Sister chromatid exchange in dyskeratosis congenita lymphocytes. Sister chromatid exchange (SCE) frequency in chromosomes from lymphocytes of a patient with dyskeratosis congenita was 12-2 per mitosis. Our 33 normal controls had a mean of 5-4 SCE per mitosis and 5 patients with Fanconi's anaemia averaged 7-6 SCE per mitosis. The rate of chromosome breakage was only 0-5% in the dyskeratosis congenita patient and 0 to 2-5% in controls, while the Fanconi's anaemia patients showed higher values.


Partial trisomy 7p associated with familial 7p;22q translocation. A newly described partial trisomy of the short arm of chromosome number 7 is reported in a familial translocation between 7 and 22. The unbalanced translocation was found in one family member, the propositus, and the balanced form in 5 other members. The possibility of this translocation being a rare telomeric attachment previously undescribed in humans is discussed. Prominent clinical features include general mental and motor retardation, microbrachycephaly, and cardiac and oral abnormalities.


X/XYq - mosaicism and mixed gonadal dysgenesis. A non-fluorescent Y chromosome was observed in a phenotypic male with 45,X/46,XYq-mosaicism and mixed gonadal dysgenesis. Q-banding of the father's chromosomes showed a normally fluorescent Y. Measurements of the Y chromosomes in the father and the patient showed a significant difference in length. Evidence for translocation of the Y fluorescent segment to another chromosome was lacking in the present case.


'Complete 5p' trisomy: 1 case and 19 translocation carriers in 6 generations. A description is given of a female infant with multiple malformations and mental retardation who died at 31 months. Cytogenetic studies indicate trisomy of the complete short arm of chromosome 5, resulting from the unbalanced segregation of a balanced translocation in the mother whose karyotype was interpreted as 46,XX,t(5; 15)(p11; p12). The karyotype of the proband was designated 46,XX, der(5)t(5; 15)(p11; p12)mat. Family studies indicate that the translocation has been present in the family for at least 6 generations.


Echinocytes in families with Duchenne muscular dystrophy. The results of the present investigation have failed to confirm the suggestion that there is a significant increase in the proportion of echinocytes in preparation of fresh erythrocytes in patients with Duchenne muscular dystrophy and heterozygous carriers of this disorder.


A further example of human blood group chimaerism. Blood group chimaerism was detected in a healthy fertile woman, not known to be a twin. Her peripheral lymphocytes had a male karyotype (46/XY); fibroblasts cultured from her skin had a female karyotype (46/XX). The mechanism of chimaerism could not be established.


The r(20) syndrome.

The r(20) syndrome. A 21-year-old woman with a ring-20 chromosome is described. The clinical findings, behaviour problems, epilepsy, and low grade mental retardation are the same as in the 3 cases described earlier. It seems to be justified to speak of a specific ring-20 syndrome.


Economic and racial disadvantage as reflected in traditional medical school selection factors. Medical College Admission Test scores and undergraduate grade-point averages show that both lower income applicants in general and minority applicants in particular are at a competitive disadvantage in gaining admission to medical school. This study examines the extent to which income and race, viewed independently of one another, affect these selection factors. By analyzing data collected by the Association of American Medical Colleges on applicants to the 1976-77 entering class, factors associated with race were found to have a far more significant influence on applicants' credentials than factors associated with lower family income. An admissions policy based exclusively on GPAs and/or MCAT scores would proportionately exclude minority applicants from medical education but would have no similar effect on lower income white applicants.


Undergraduate education in primary care: the Rockford experience. Four years of experience with an undergraduate program in primary care in a new community-based medical school are described. Students are intimately involved over a two-and-a-half-year period in the delivery of primary care in rural and semi-rural community health centers. Despite problems of financing and, especially, faculty recruitment and development, the program has been enthusiastically endorsed by students and patients and appears to represent a viable new model for medical education.


The myth of professional isolation among physicians in nonurban areas. Forty-six physicians practicing in nonurban areas of California were interviewed. A majority reported that they rarely or never felt professionally isolated. Measures describing the current community and professional activities were not found to predict feeling of professional isolation. The only background variable found to be significantly related to feelings of professional isolation was mean rating by admissions interviewers. It was concluded that applicants with high ratings were more likely to acquire a strongly academic, research view of medicine and, as a result, to feel professionally isolated when practicing in nonurban areas.


A microprocessor controlled multi-channel evoked potential data acquisition system. A stored program control system is described for the acquisition of evoked potential (EP) data. It is a small, portable and flexible system with a variety of input and output possibilities. The system presents a low cost solution to the problem of acquisition of evoked potential data. A novel method of converting and reducing sixteen channels of EEG analogue data to their digital equivalent is shown. It is adaptable for the inter active control of experiments and is sophisticated enough to deal with the complexities of experimental control as well as data manipulation. One of the major advantages of the system is that both the sequencing of the functions and their detailed make-up can be readily altered by programming to meet the individual requirements of any given situation.


Elements of hip joint prosthesis reliability. The performance of a total hip prosthesis is considered in terms of reliability. The causes requiring removal of the prosthesis are considered and methods of avoiding these difficulties are outlined. It is pointed out that most attention must be focused on the areas of low reliability. The goal of increasing prosthesis lifetime must be shared between the surgeon and manufacturer.


Effects of nystatin on membrane conductance and internal ion activities in Aplysia neurons. Two methods were used to study effects of the antibiotics, nystatin, on giant neurons of Aplysia. In the first method the effects of various concentrations of nystatin on the current-voltage relationship were evaluated at a fixed time after exposure to the antibiotic using a two-microelectrode voltage clamp. Nystatin increased membrane conductance in a dose-dependent manner. The dose-response relation was very steep, with little or no effect below 15 mg/liter and an effect too large to measure at concentrations greater than 30 mg/liter. Upon return to antibiotic-free solution, membrane conductance returned to pre-treatment levels within 30 minutes. The second type of experiment involved use of ion-specific microelectrodes to measure changes of intracellular univalent ion activities which attended the nystatin-induced permeability. Nystatin-induced permeability changes mainly involved univalent cations, but Cl permeability was also increased. Nystatin may therefore be used to selectively rearrange the internal ionic milieu to study the effect of such a change on membrane transport or electrical properties.


IQ decline in mentally retarded adults: a matter of fact or methodological flaw. While it has generally been assumed that intelligence in the retarded decreases with age, the institutional research supporting this premise, whether cross-sectional or longitudinal, is methodologically flawed by selective sample attrition. This paper demonstrates that in an institutional population those leaving, at every age level, are indeed the brightest. When the IQ data is viewed cross-sectionally there is the appearance of decline, but when the same population is studied semi-longitudinally, not only is there no decrease in IQ with age but there are regular increments, particularly in performance scores.


Medical diagnosis and intelligence levels in young mentally retarded children. The relationship of diagnosis to initial and subsequent intelligence test levels in 282 young retarded children was investigated through repeated psychometric evaluation on the Bayley Infant Scales of Mental Development or the Stanford-Binet. It was found that although aetiology relates to first test scores (or rate of initial progress), it has no bearing on changes in scores (or course of development). The implications of the surprisingly stable scores for this heterogeneous population are discussed.


A fragile secondary constriction on chromosome 2 in a severely mentally retarded patient. A case is presented of an eighteen-year-old girl suffering from severe mental retardation associated with a fragile secondary constriction on the long arm of chromosome 2. The question of the relationship between the phenotypic and chromosomal abnormalities is discussed. We acknowledge the co-operation of Dr M. E. Elsarag and Dr K. M. Laurence in allowing this investigation to be made.


Inhibition and axial deviation of limb regeneration in the newt by means of a digit implanted into the amputated limb. This research was designed to follow up the observation of Thornton and Kraemer ('51) that regressed, denervated limbs of Ambystoma larvae will not regenerate upon reinnervation if all digits on the limbs were not completely resorbed. The object of this experiment was to determine whether the presence of an apical structure, protruding past the amputation surface, would affect the regenerative process. Both forearms of adult newts were amputated midway between the elbow and the wrist. One limb served as a normal regeneration control, and in the other limb the third digit from the removed hand was implanted in place of the removed radius, so that the three distal phalangeal segments protruded past the plane of amputation. Blastema formation in the experimental limbs was delayed by several weeks as compared with control limbs. Approximately one third of the experimental limbs did not regenerate. The regenerates that did form were strongly deviated (45-90 degrees) radially from the longitudinal axis of the limb. Experimental analysis showed that the delay in regeneration is due largely to the projecting part of the digit. The radial deviation of the regenerates is not due to the digital implant, but rather to the removal of the radius. Trauma alone does not account for this phenomenon.


Exogenous hormones, reproductive history, and breast cancer. We studied 284 patients (20-74 years of age) with carcinoma of the breast and 367 controls; all were admitted to one hospital between 1969 and 1972. The disease was associated with nulliparity, first pregnancy over 20 years of age, premenopausal status, and a lower frequency of artificial menopause. After adjustment for these factors, no significant difference was found between the breast cancer patients and controls in their prior use of either estrogens or oral contraceptives, but the confidence limits on the relative risk, especially for oral contraceptives, were large.


Dentition, diet, tobacco, and alcohol in the epidemiology of oral cancer. Interview and dental examination data were gathered on 584 males with cancer of the oral cavity and on 1,222 control patients with nonneoplastic diseases at Roswell Park Memorial Institute, Buffalo, New York. No dietary characteristics distinguished cancer patients from controls. However, a higher risk of developing oral cancer was associated with heavy smoking, heavy drinking, and poor dentition. When controlled for the other factors, each factor carried a higher risk. Moreover, heavy smokers and heavy drinkers with poor dentition and males with all three traits had a substantially higher risk than would have been expected, if the traits were considered additively. The risk for males with all three traits was 7.7 times that of men with none of these traits.


Carcinogenic effects of niridazole on rodents infected with Schistosoma mansoni. The carcinogenicity of 1-(5-nitro-2-thiazolyl)-2-imidazolidinone (niridazole), a widely used schistosomicide, was examined in Swiss mice and Syrian golden hamsters. Schistosoma mansoni infection was evaluated as a cofactor. High incidences of drug-related neoplasms of the forestomach, lungs, mammary glands, urinary tract, and ovaries were found in mice, and tumors of the forestomach and urinary tract were found in hamsters. Infection with schistosomes had no apparent influence on tumor incidence. The results indicated a need for reevaluation of the possible carcinogenicity of this drug in man and suggested that care should be taken during its clinical use.


In vitro lysis of tumor cells by antibody and complement: detection of antibody with low cytotoxic reactivity. The factors affecting the in vitro lysis of PARA-7 tumor cells mediated by antibody and complement were examined with the use of the 51Cr-release assay. The addition of immune syngeneic hamster antisera (HA) to 51Cr-labeled PARA-7 target cells 30 minutes before the addition of guinea pig complement (GPC) failed to produce significant levels of lysis. Similarly, the addition of rabbit anti-PARA-7 serum (RAS) 30 minutes prior to the addition of GPC resulted in low levels of lysis. Longer incubations in the presence of RAS, but not RAS and GPC, increased levels of lysis. Extended incubation in the presence of RAS increased the amount of antibody bound to the target cells. This increase did not appear to be due to the expression of additional antigen, because the increase occurred at 4 degrees C and was not sensitive to inhibitors of protein synthesis. The inability to obtain increased levels of lysis by extended incubation in the presence of both RAS and GPC appeared to be due to the inhibitory effects of GPC on the interaction of antibody and antigen. Similar inhibitory effects could be produced by inactivated GPC and various other substances. When extended incubations in the presence of antiserum were used for the reexamination of the cytolytic activity of syngeneic immune HA, significant lysis was detectable.


Time of appearance and histology of tumors induced in the dorsal skin of C3Hf mice by ultraviolet radiation from a mercury arc lamp. The time course of skin tumor induction was determined in hair-clipped inbred agouti C3Hf mice irradiated three times per week with a medium-pressure quartz-mercury lamp; 4 different UV doses were used. Although the ears were also exposed to the radiation, in the 3 groups given the highest doses no ear tumors were observed by the time each animal had developed at least 1 tumor on its back. No tumors were found in the animals receiving the lowest UV dose. In the group receiving the highest dose, males developed tumors earlier than did females; this trend continued in the lower dose groups. Many tumors that developed in the back skin were well-differentiated squamous cell carcinomas. Others were less well-differentiated squamous cell carcinomas. Others were less well defined so that the cell of origin was difficult to determine. In the group receiving the highest UV dose, the squamous cell carcinomas were few, whereas at the lower doses they predominated.


Epidemiological relationship between steroid hormones and liver lesions. In the past 3 yr, over 140 cases of benign liver cell adenomas in young women who have used oral contraceptives have been reported in the world's medical literature. In the past, these tumors have been considered rare. Although hepatic cell tumors are benign, reports have indicated that the onset of the disease is of a critical nature--victims are frequently subject to sudden pain, shock, and hemorrhage, and a fatality rate of 10% was recorded in the aforementioned reports. In light of these facts, an epidemiological study was initiated in Nebraska. As a result, 20 new cases have been recorded of hepatic cell tumors in oral contraceptive users.


Liver lesions and oral contraceptive steroids. Two strains of mice, CF-LP and Swiss-Webster random-bred, were evaluated for liver neoplasia after administration of oral contraceptive steroids. No increased incidence of hepatocellular tumors was found beyond the variation expected by chance. The overall tumor incidence in treated and untreated groups was identical. No significant increase in tumor size was observed in the treated animals. Liver weights progressively increased in several of the treated groups. In both treated and untreated animals hepatocellular neoplasia was usually accompanied by intracytoplasmic inclusions similar to those observed in human liver tumors. Vascular lesions were observed in some of the animals receiving large doses of contraceptive steroids. While these may be the result of local toxicity, their similarity to lesions observed in benign liver tumors warrants further investigation. No evidence was found to suggest that contraceptive steroids act as initiators of liver neoplasia.


Metabolism of zearalenone by Fusarium roseum. Twenty products associated with the metabolism of zearalenone by Fusarium roseum were analyzed with respect to time and culture conditions. By statistical analysis a set of six metabolites possibly related to zearalenone were selected. These products were characterized by gas chromatography--mass spectrometry and other methods. The chemical structures of these six confirmed the statistical relationships, and evidence for the formation of these materials from zearalenone is presented. A suggested scheme of metabolism of zearalenone by F. roseum includes the formation of the two isomers of 8'-hydroxyzearalenone, 6',8'-dihydroxyzearalene, 6-(carboxypentyl)-beta-resorcyclic acid, and phenylacetic acid derivatives.


Metabolism cage for carbon dioxide trapping studies. This report describes the design and construction of a metabolism cage that allows for separation of urine and feces and for trapping expired CO2. Such a cage could find use in pharmacokinetic studies of drug excretion rates where potential metabolism to CO2 should be considered. To demonstrate the separation qualities of this cage design, the radioactivity appearing in the urine, feces, and exhaust gases was determined daily for 14 days after the single oral administration of 26-[14C]cholesterol. Less than 1% of the administered radioactivity appeared in the urine, whereas 61% appeared in the feces and 19% in the expired CO2.


Effects of a new rodenticide, benzenesulfonic acid hydrazide, on prenatal mice. Benzenesulfonic acid [(3-amino-2,4,6-trichlorophenyl)methylene] hydrazide, a candidate rodenticide coded as DRC-4575, was administered by gavage to pregnant female BALB/c mice. Each dose (5.5, 28.0, 42.0, 62.0 and 94.0 mg/kg) was given to one of five groups of ten mice on day 8 of gestation, making a total of five different dose groups on day 8. This same procedure was followed for days 9, 10, 11, 12, and 13. This made a total of 30 dose-day treatment groups. Six control females were dosed each day. Dam survival to day 18 declined as the dose increased; only 2% of the dams survived at 94 mg/kg. When the surviving females were killed at day 18, no significant differences were found between treatment and control animals in the number or weight of live fetuses, or in the ratio of male to female fetuses. However, the percentage of live fetuses was significantly lower and the number of resorptions was significantly higher for the treated dams at the 62 mg/kg dose level than for the control dams. Skeletal anomalies were limited primarily to unossified phalanges, which were probably related to the lower weights of those fetuses. Slight hydrocephalus occurred infrequently at all dose levels and in the controls, and was not dose-related. These data indicate that DRC-4575 would be embryotoxic only at doses of 62 mg/kg or higher and would not be teratogenic.


Increase in calcium binding activity in renal cortex of rats treated with stannous chloride. The effect of tin on the calcium binding activity in renal cortex was studied in rats administered stannous chloride intraperitoneally. The calcium concentration in the soluble fraction of renal cortex was elevated about 30-fold over that in controls 2 days after administration of tin (3.0 mg/100 g). The calcium binding activity in the soluble fraction of renal cortex increased significantly at any of the time intervals between 6 and 72 hr after administration of tin, and this increase preceded an elevation of the calcium concentration in the renal cortex. The increased calcium binding activity produced by administration of tin was strikingly reduced by treatment with actinomycin D (100 microgram/100g). A significant increase in calcium binding activity was not exhibited after administration of zinc, manganese, calcium, or lead. These results suggest that the calcium accumulation in the renal cortex caused by administration of tin is closely connected with an increase in calcium binding activity.


Heart morphological changes in rats placed in a crowded environment. A group of rats were stressed by placing them in a crowded environment. Examination of the hearts showed the following anatomic changes: (1) increased weight; (2) occlusion of capillaries by platelet thrombi; (3) endothelial swelling of capillaries; and (4) swelling and deformity of mitochondria.


Impairment of thymus-dependent immune functions by exposure of the developing immune system to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The effects of TCDD exposure on the developing immune system were investigated in F344 rats. Fetal and neonatal rats were exposed to TCDD through maternal dosing (5 microgram/kg) on day 18 of gestation and on days 0, 7, and 14 of postnatal life (group I). Another group of neonatal rats was exposed to TCDD through maternal dosing on days 0, 7, and 14 of postnatal life only (group II). Body weights and thymus/body weight ratios were found to be suppressed up to 145 days of age in group I, but only up to 39 days of age in group II. Parameters of cell-mediated and humoral immune function were investigated. TCDD suppressed cell-mediated immune function without affecting humoral immune function. Suppression of T-cell function was selective in that "helper" cell function was not suppressed.


Absorption, distribution, and excretion of [14C]patulin by rats. Adult rats of both sexes were given a single oral dose of [14C] patulin and were sacrificed at various time intervals from 4 hr to 7 days following administration of the mycotoxin. Two groups of rats were employed; the treated group had been exposed to daily oral doses of unlabeled patulin (dissolved in pH 5.0 citrate buffer) in utero and for 41-66 wk after weaning, while the controls were given the buffer only throughout gestation and for 38-81 wk after weaning. Approximately 49% of the administered 14C radioactivity was recovered from feces and 36% from urine within 7 days after dosing. Most of the excretion of labeled material occurred within the first 24 hr. All of the 14C activity detected in the urine samples was either metabolites and/or conjugates of the original [14C]patulin. About 1-2% of the total radioactivity was recovered as 14CO2 from expired air. Carbon-14 radioactivity in various tissues and organs was determined throughout the 7 day period; the most significant retention site was the red blood cells.


Effects of pentachlorophenol on the development of estuarine communities. Pentachlorophenol affected the composition of communities of estuarine organisms developed in sand from planktonic larvae in estuarine water that flowed through ten control aquaria and ten aquaria per exposure concentration averaging 7, 76, or 622 microgram/liter. Annelids, arthropods, and mollusks were the numerically dominant phyla when animals were collected in a 1-mm-mesh sieve after 9 wk of exposure. Mollusks were markedly fewer at 7 microgram/liter; annelids and arthropods at 76 microgram/liter. Almost no animals occurred at 622 microgram/liter. The total numbers of individuals and species were significantly less (alpha=0.01) in aquaria exposed to 76 microgram/liter than in those unexposed or exposed to 7 microgram/liter.


Effects in rats and guinea pigs of short-term exposures to sulfuric acid mist, ozone, and their combination. Ozone and the oxides of sulfur are common environmental pollutants. The acute pulmonary lesions caused by ozone and sulfuric acid mist in rats and guinea pigs have been characterized. Rats are not affected by sulfuric acid mist in concentrations up to 100 mg/m3 except for reduced body weight at the higher doses. A true alveolitis develops in guinea pigs exposed to more than 20 mg/m3 sulfuric acid mist. The ozone lesion is primarily confined to the terminal bronchioles and proximal alveoli. In combination studies with up to 2 ppm ozone and up to 10 mg/m3 sulfuric acid mist, the pulmonary lesion and lung/body weight data were essentially the same as in exposure to ozone alone, and the number of statistically significant synergistic effects in rats and guinea pigs was about what one would expect to observe by chance alone.


Immune response in aged mice exposed to lead. Mice were exposed to 0, 13, or 1,300 ppm lead in drinking water for 18 months. The immunological assays examined were mitogen (lipopolysaccharide E. coli, concanavalin A, and phytohemagglutinin-P) stimulation of lymphocytes; erythrocyte-antibody (EA), erythrocyte-antibody-complement (EAC), and phagocytosis of macrophages; and EAC of splenic lymphocytes. As measured by the majority of these assays, the low dosage (13 ppm) of lead tended to stimulate certain immune responses (lymphocyte mitosis, EA, and EAC) while the high dosage (1,300 pm) did not provoke an appreciable alteration. The results were interpreted by comparing data on aged mice with data on young adult mice. It was apparent from this comparison that the aged mice were naturally immunosuppressed. Therefore, the results obtained from lead-exposed mice were unpredictable.


Effect of anemia on blood and tissue lead in rats. The effect of anemia on the lead content of blood, red cells, and tissue was studied in rats given oral lead, 54 mg/kg-day for 6 days. The 16 rats made anemic (hematocrit, 26%) by bleeding on days 1, 3, and 5 had significantly higher concentrations of lead in the kidney, liver, red cells, blood, and brain (but not in the bone marrow). Increases in blood lead in anemic subjects were correlated with the concentrations in red cells, kidney, and liver. The greater increase in the lead content of all tissues of the anemic rats is consistent with increased lead absorption in anemia and is considered relevant to the clinical coexistence of anemia and lead poisoning.


Effect of 2-chloroethanol on hepatic microsomal enzymes in the rat. The effect of 2-chloroethanol on the activities of hepatic microsomal enzymes in the rat has been studied. A significant reduction in activities of drug-metabolizing enzymes (aminopyrine N-demethylase, coumarin 3-hydroxylase) and a marked decrease of glucose 6-phosphatase were seen in both sexes given dose levels of 20 mg/kg sc daily for 7 days. Inosine diphosphatase activity remained unaltered. In male rats given 3 or 10 mg/kg, a trend in the inhibition of drug metabolism was found. A single dose of 50 mg/kg caused no apparent change in the activities of the enzymes measured.


Single lead acetate insult, testosterone therapy, and erythropoiesis in mice. Lead acetate (PbAc) was tested for its effects on the production and release of erythrocytes-that is, erythropoiesis-in ICR mice. Dose-survival data indicate that a dosage of 20 mg PbAc/100 g body weight represents the maximum tolerable treatment level. No differences in survival at the various levels of the salt were observed with regard to sex or age. For erythropoietic effects of PbAc, mice were injected on day O, and radioiron (59Fe) incorporation percentages were determined at daily intervals through day 8 for both erythrocytes and splenic tissue. Control mice received isotonic saline as the injectate. On day 3, the percentages obtained from PbAc-treated mice showed a decline, reaching their minimum value by day 4. Recovery from erythropoietic suppression appeared to be complete by day 6 or 7; no positive overshoots in 59Fe percentages were found following recovery. These trends were typical for both peripheral red blood cells and spleen. Testosterone was administered to mice receiving saline or PbAc on two consecutive days (days -1 and O). Radioiron uptake percentages for females receiving testosterone and saline showed an abrupt increase on day 4. No accelerative effect due to testosterone was found in recipient males. For females treated with testosterone and PbAc, the radioiron percentages for erythrocytes and spleen paralleled those for females receiving saline only. Male mice treated with both androgen and PbAc demonstrated 59Fe percentages typical of males treated with PbAc alone.


Strain differences in the response of the mouse to diethylstilbestrol. BALB/c StCrlfC3Hf/Nctr, C57BL/6/, C57BL/6 X BALB/c F1 hybrid (B6CF1), and monohybrid-cross offspring from the breeding of B6CF1 mice were examined with respect to uterine, vaginal, and thymus responses to diethylstilbestrol (DES). About 400 mice of each genetic population were used. Weanling mice were fed DES at dietary concentrations of 2.5 to 1,000 ppb (microgram/kg feed) for 6 days and were killed by cervical dislocation about 20 hr after removal of the feed. C57BL/6, B6CF1, and the monohybrid-cross offspring did not differ in the uterine-weight response to DES, but the slope of the dose-response line was shallower for the BALB/c than for the other strains. Dietary DES concentrations of 250 ppb or more inhibited the uterotrophic response in all populations. Vaginal cornification occurred at lower concentrations of DES in the C57BL/6 strain than in the B6CF1 animals. BALB/c and monohybrid-cross offspring were indistinguishable from each other in their vaginal response to Des and were less sensitive to DES than the other mouse populations. The use of ethanol or corn oil as the solvent for mixing DES into the diet had no apparent effect on the uterine weight or vaginal response in any of the mice. DES depressed thymus weight in a dose-related fashion at dietary concentrations of 100 ppb and above in all genetic populations.


Social studies of destitutes (beggars) in Nigeria: Lagos experience. A study of 183 beggars and destitutes in Lagos is presented. Their mean age was 36.3 years; and there was a preponderance of male over female. Majority of the beggars were Hausa and their religion was Muslim. Seventy-three (51.8%) of the beggars and destitutes attended Arabic (Koranic) schools only while 53 (37.6%) had no schooling at all. There was a statistically significant difference between the educational attainment of males and females (p less than 0.001). Monogamous marriage was popular among the beggars even though their religion (Islam) permitted polygamous one. The number of children was two per beggar which was minimal compared with the large families reported among beggars in Zaria. Child wastage was common among these children maybe because of their parents' ignorance, poverty and disease. The urgent establishment of a National Rehabilitation Centre, among other measures, is recommended as a lasting solution to the problem of begging and destitution in Lagos.


Resolution time of amoebic liver abscess by micro-opaque barium sulphate. Resolution time of amoebic liver abscess in 20 males aged 20-80 yrs. as studied by intra-cavitary micro-opaque barium sulphate ranged from 24-284 days (mean 74.8 S.D. +/- 8.4). Sic of these patients also underwent Indium11m scanning. The resolution time by scanning varied from 24-114 days (Mean 58.3 days S.D. +/- 4.6). No correlation was found between the size of abscess and resolution time. Resolution time studied by two methods was statistically significant. Instillation of micro-opaque barium sulphate is an inexpensive, reliable and a safe method which does not require sophisticated equipment.


Uric acid lithiasis in the Sudan.

Uric acid lithiasis in the Sudan. Fifty-seven per cent of Urinary Calculi in the Sudan contain Uric Acid, 20 per cent in the pure form and 37 per cent mixed with other constituents mainly calcium oxalate. The peak age presentation of urolithiasis is 30-40 years with more prediliction to males than females. An earlier study documented a high incidence of hyperuricaemia in Sudanese people. It is probable that "voluntary dehydration" and hyperuricaemia acting together may help in the formation of uric acid stones on the surface of which other crystals mainly calcium oxalate may be deposited to form the bigger calculi which are commonly encountered in this country.


Cutaneous cladosporiosis due to Cladosporium trichoides. A case of cutaneous cladosporiosis due to Cladosporium trichoides, manifesting as a chronic discharging ulcer near the wrist of the left arm in a farmer with ascites and hypoalbuminaemia is described. The isolate was neurotropic in experimentally infected mice. The present case constitutes one of the few reports of cutaneous cladosporiosis.


Carcinoma of the hypopharynx--a five year follow-up. This is a study of 339 patients with carcinoma of the hypopharynx, seen in Toronto from 1960-72. Patients were grouped according to the U.I.C.C., T.M.N. classification but a modified staging method was employed since there is no generally accepted procedure for stage-grouping at the present time. Patients treated by primary radiation were compared to a group treated by combined therapy (radiation followed by surgery). The results show that the overall crude survival of all hypopharyngeal lesions was approximately 20 per cent. A high percentage of patients had advanced lesions at first presentation and almost 30 per cent of patients were treated palliatively. Analysis indicated that combined therapy is the treatment choice for Stage I and II hypopharyngeal lesions. Patients with more advanced lesions do poorly regardless of the treatment modality. The morbidity and mortality rates are high in the combined therapy group but the risks were doubled when salvage surgery was undertaken for failed primary radiotherapy.


Treatment of carcinoma in situ of the larynx. The treatment of choice for carcinoma in situ of the larynx is radiotherapy. Forty-three patients were seen with this condition between 1940 and 1972 and are now suitable for five year follow-up. Thirty-seven of these patients were treated with a tumoricidal dose of Cobalt 60. Three died in less than five years--without evidence of laryngeal disease. Of the remaining 34, all but one are free of disease for five to 17 years. The only failure in this group had co-existing invasive carcinoma. The high incidence of radiotherapy failures previously reported is probably related to the frequency of co-existing invasive carcinoma. We do not feel that there is a true increase in the incidence of carcinoma in situ in recent years. The increased frequency of diagnosis is probably due to increased awareness of the disease and the routine use of microlaryngoscopy.


The radiologic diagnosis of malignant tumors of the larynx. A variety of radiologic examinations are used to assess malignant tumors of the larynx. The primary role of radiographic examination is the pretreatment classification of laryngeal cancer, necessary to select the appropriate modality of treatment. The major radiologic modalities comprise conventional lateral radiography, anterior-posterior tomography, laryngography, xeroradiography, and high KV selective filtration radiography. Advanced radiologic modalities such as CT scanning and transverse B-mode gray scale ultrasound may also prove useful. It is the purpose of this presentation to define the role of these modalities in pretreatment definition of laryngeal cancer. Additionally, some comment is made as to the role of radiology in the diagnosis of post-radiation therapy recurrence of laryngeal cancer.


Malignant tumors of the salivary glands. The incidence of malignant salivary gland tumors is influenced by geographic and racial factors. Some etiological aspects and diagnostic pitfalls are discussed. The treatment of salivary gland malignancies is primarily surgical but the extent of the surgery should be dependent on the availability and application of routine postoperative high or supervoltage radiotherapy on a "regional" basis of invasive low-grade and all high-grade malignant tumors.


Upper alveolar carcinoma--a 30 year survey. Primary malignancy of the upper alveolus is an infrequent type of intra-oral carcinoma. This study reviews in detail 50 patients with a primary tumor of the upper alveolus who were treated at the Cancer Control Agency of British Columbia and Vancouver area hospitals, between 1940-1970 inclusive. Sixteen per cent had exposure to possible industrial carcinogens; 34 per cent had previous leukoplakia. The common presenting symptoms were pain (78 per cent) and swelling (64 per cent). Only 22 per cent had tumors confined to the upper alveolus. Fifty-two per cent had extensive lesions (i.e. T3 and T4). Twenty-six per cent had palpable cervical lymph nodes with potential metastatic disease. Treatment consisted of surgery, radiotherapy, or a combination of both. Complications are detailed. The five year survival rate is 44 per cent; and the 10 year survival rate 24 per cent. Treatment rationale is discussed.


The radiologic diagnosis of malignant tumors of the paranasal sinuses and related structures. Paranasal sinus and related malignancies affect air-containing mucosal-lined bony structures which can only be studied by appropriate radiologic examination. Pre-treatment staging by radiologic study, primarily utilizing tomography with complex motion, is essential for election of proper treatment modalities. It is the purpose of this presentation to define the conventional tomographic and advanced radiologic modalities which can be used in paranasal sinus radiologic examinations. The indications for the studies as well as their limitations are demonstrated. Finally, the role of radiology in post-therapy evaluation is noted.