Testicular function, secondary sexual development, and social status in male mandrills (Mandrillus sphinx). Positive correlations between dominance rank and plasma testosterone levels have been described for adult males of several primate species in captivity, but the relevance of such observations to free-ranging animals is unclear. CIRMF in Gabon maintains a breeding group of 45 mandrills in a six hectare, naturally rainforested enclosure. This study describes correlations between dominance rank (in agonistic encounters), levels of plasma testosterone, testicular volume, body weight, and development of secondary sexual characteristics (red and blue sexual skin on the muzzle and rump areas) in male mandrills under semifree ranging conditions. Two morphological and social variants of adult male mandrill were identified. Large-rumped or fatted adult males (n = 3) remained in the social group and exhibited maximal development of sexual skin coloration as well as large testicular size and highest plasma testosterone levels. By contrast, slimmer-rumped or nonfatted males (n = 3) lived a peripheral or solitary existence and these exhibited less development of their secondary sexual coloration and had smaller testes and lower plasma testosterone levels. Longitudinal studies of gonadal development in these six males revealed that testicular volumes and plasma testosterone levels increased most rapidly during pubertal development (4-5 years of age) in the three animals which proceeded to the fatted condition. These included the highest ranking, group-associated male which exhibited the most intense sexual skin coloration and had higher testosterone levels, although this was not correlated with testicular volume. This study shows that in the male mandrill social factors and reproductive development are interrelated.(ABSTRACT TRUNCATED AT 250 WORDS)


Naloxone prevents interruption of parturition and increases plasma oxytocin following environmental disturbance in parturient sows. Experiments in rodents have suggested that environmental disturbance can disrupt parturition through an opioid-mediated inhibition of oxytocin secretion. To test this hypothesis in a large animal model, 14 primiparous female pigs were allowed to commence parturition in a strawed pen. Five of these gilts were allowed to continue parturition undisturbed in this pen, while the remainder were moved to a farrowing crate immediately after the birth of the first piglet. At this time, pigs were injected subcutaneously with either the opioid antagonist naloxone (n = 4; dose 1 mg/kg body weight) or saline (n = 5). Whereas the undisturbed pigs all gave birth to a second piglet within 53 min, in three of the five disturbed and saline-treated pigs no further births occurred for 2 h, at which time oxytocin was administered subcutaneously to restart parturition. By contrast, all of the naloxone-treated pigs gave birth spontaneously within 2 h, although mean interbirth intervals were still prolonged compared to undisturbed pigs. In a second experiment, nine primiparous female pigs with chronic catheters preplaced in the external jugular vein were similarly moved after the birth of their first piglet and either injected with naloxone (n = 5) or saline (n = 4). Again, parturition was interrupted in three out of four saline-treated animals for at least 2.5 h, but resumed promptly when exogenous oxytocin was administered. Plasma concentrations of oxytocin in these pigs were significantly lower than in naloxone-treated pigs, five out of six of which gave birth spontaneously to one or more piglets within 2.5 h.(ABSTRACT TRUNCATED AT 250 WORDS)


Diminished luteinizing hormone release in prenatally stressed male rats after exposure to sexually receptive females. Prenatally stressed (P-S) males show reductions in male sexual behavior, medial preoptic area volume, and levels of circulating testosterone. We examined the luteinizing hormone (LH) response to the presence of a sexually receptive female, a known index of sexual arousal. Adult male offspring from mothers stressed on days 15-22 of pregnancy (thrice-daily exposures to heat, light, and restraint) were implanted with an intraatrial catheter. Forty-eight h later they were placed into test chambers divided by a wire mesh partition; the catheter was extended outside the chamber. Thirty min later a baseline blood sample (time 0 min) was taken and a sexually receptive female was then placed on the side of the partition opposite the male for 60 min. Blood samples were collected 5, 10, 15, 30, 60 min, and 24 h after introduction of the female. Prenatally stressed males exhibited significantly lower LH levels following exposure to the female at each time point, 5 min to 24 h. Furthermore, at no point were P-S males' LH levels significantly increased above baseline levels. These data suggest that attenuations in female-induced LH release are associated with the marked reductions in male sexual behavior characteristic of the P-S male.


Taste preferences, body weight gain, food and fluid intake in singly or group-housed rats. Two behavioral experiments were performed to determine if the housing conditions modify taste preferences, body weight gain, food and fluid intake, and alimentary diurnal pattern in adult male rats. In Experiment 1, a two-bottle 24-h preference test (salt, sweet, sour, bitter solutions versus deionized water) was performed in singly, dually or multiply housed rats. In Experiment 2, the same sapid solutions as Experiment 1 and water were contemporaneously offered to singly, dually, or multiply housed rats. Crowded rats drank more water, sweet solution, and total fluid, but less salt solution than singly or dually housed rats during dark and whole-day periods. All rats preferred sour solution, but not bitter solution, to water. In both experiments, crowded rats gained less body weight and ate less food than dually or isolated rats. These results suggest that the housing conditions influence taste preferences, food and fluid intake, body weight gain, but not alimentary diurnal pattern in rats. An important implication of these results is that in experiments in which appetite and taste are dependent variables, all rats should be housed under the same social and environmental conditions.


Characterization of stress-induced long-term behavioural changes in rats: evidence in favor of anxiety. Recently, we reported that rats exposed to one brief session of inescapable footshocks showed a gradually developing and long-lasting decrease in behavioural activity and an increase in defecation in an open field. The aim of the present study was to further characterize the long-lasting changes in behavioural responsiveness to environmental stimuli. For this purpose, behavioural paradigms validated as tools in the preclinical study of the psychobiology of depression were used. Footshocked rats (S) showed a decreased response latency in an one-way avoidance-escape task and decreased immobility in a forced swim test as compared to nonshocked control rats (C) 14 days after shock exposure. These S rats showed decreased behavioural activity and increased defecation as compared to the C rats in an open field test carried out 28 days after footshock exposure. In addition, footshock exposure did not affect the preference for or consumption of a 0.05% saccharin solution on a long-term basis, although a decreased consumption of this solution was evident in S rats on day 1 postshock. These S rats showed an exaggerated immobility response to a sudden reduction in background noise level compared to C rats while placed in a novel environment on day 11 postshock. We conclude that the long-term effects of one short session of inescapable footshocks are not compatible with what is supposed to represent behavioural manifestations of depression in animals. It is argued that the common denominator of shock-induced long-lasting changes is increased behavioural defensiveness, which is more likely related to increased fear and/or anxiety.


Physiological and psychological differentiation of bidirectional baroreceptor carotid manipulation in humans. We investigated a phase-related-external-suction (PRES) method of bidirectional carotid stimulation which, unlike other methods, is not readily discriminable for direction (excitation vs. inhibition). Thirty-two subjects were first given 128 6-s PRES trials (64 each excitatory and inhibitory) which were signaled by two tones of differing frequency. There followed a 20-trial discrimination phase where subjects' task was to identify excitatory and inhibitory PRES trials (randomly presented) in terms of the two tone signals. Physiological (HR) discrimination was bidirectional (deceleration and acceleration for excitatory and inhibitory PRES trials, respectively), reflex-like (no habituation), but asymmetrical in magnitude (larger decelerations than accelerations), and topography (e.g., presence of a short latency deceleration). Group psychological discrimination was absent, although two subjects had a 100% hit rate on the discrimination test. There were, however, no systematic HR changes associated with these two subjects. Finally, the small-magnitude (2-3 bpm) physiological HR reflex was markedly augmented by what appeared to be a psychological, attentional factor. Accordingly, while the results indicated a dissociation between physiological and psychological differentiation, there was also evidence of a psychological factor (attention) influencing a physiologically induced reflex.


Individual aged rats are impaired on repeated reversal due to loss of different behavioral patterns. Aged rodents compared to young rodents are impaired in making repeated reversals and more variable in performance on many tasks. In the present study, a comparison of ten aged (21 months) and 10 young (3 months) Sprague-Dawley rats on a repeated spatial discrimination reversal water escape task revealed that the deficient and variable performance of the aged rats was due to the aged animals developing deficits in different behavioral patterns that were necessary to perform the task. Individual aged rats had deficits in inhibiting an unlearned first choice tendency (perseveration), repeating a first choice that lead to escape on the preceding trial (win-stay deficit) or inhibiting a first choice that lead to confinement and delayed escape on the preceding trial (lose-shift deficit). Because the aged animals were deficient on one or more of the necessary behavioral processes, as a group they were deficient on the repeated reversal task. However, because the aged rats differed on the specific behavioral process(es) on which they were deficient, when evaluated on any one process they were more variable than were the younger rats.


Behavioral response of rats with cortical lesions to cholinomimetics. This study examined the performance of cortically lesioned rats and their response to cholinomimetic agents in passive avoidance and water maze tasks. Lesions encompassing mainly the frontal and parietal cortices produce a deficit in a 5-day passive avoidance retention test. This deficit was attenuated by the intraperitoneal (IP) administration of muscarinic agonists or an anticholinesterase. In the Morris water maze task, lesioned vehicle-treated animals showed greater escape latency times when compared to their sham counterparts. Cholinomimetics, injected daily during acquisition, improved mean escape latency time on days 3 and 4 of testing. The performance of the various groups in a cued version of the water task did not differ. This work demonstrates that performance deficits arising from neocortical loss can be attenuated by cholinergic drugs.


Effects of haloperidol on the acquisition of a spatial learning task. The effects of systemic injections of the dopaminergic antagonist haloperidol on the acquisition of the Morris water maze with either a visible or an invisible platform (nonspatial vs. spatial learning) were investigated. An open field test was used for selecting a dosage (< or = 0.1 mg/kg), that (hardly) affected locomotor behaviour. Differential effects were found. At 0.1 mg/kg, haloperidol reduced locomotion in the open field, impaired acquisition in the Morris maze with a visible platform, and blocked escape onto an invisible one. Even though 0.07 mg/kg haloperidol reduced locomotion, both 0.04 and 0.07 mg/kg only impaired Morris maze performance in the spatial version. A large effect was found in the first trial of every day's training block. These results indicate that haloperidol at low doses can lead to a moderate but significant impairment of spatial learning. It is suggested that the effects found are related to the function of the striatal areas in cue- and noncue-directed behaviour.


Resetting of a feeding-entrainable circadian clock in the rat. Reentrainment of anticipatory activity (AA) after phase shifts of food access was studied in rats with lesions of the suprachiasmatic nuclei. Eight- or 10-h phase delays of feeding time resulted in delaying transients of AA. Twelve-h phase shifts and some 10-h phase advances resulted in rapid reentrainment (2-3 days) without visible transients. Most phase advances of 10 h resulted in delaying transients while 8-h advances induced transients with advancing and delaying components in a number of rats. Split transients were not prevented by advancing mealtime in 1-h steps. Phase shifts of food in multiple steps failed to accelerate delay shifts but retarded advance shifts. After the first 8-h phase delay shift, increased activity reappeared at the preshift phase of AA, simultaneously with anticipation of the phase-shifted meal time. The observation of split transients indicates that two or more circadian oscillators mediate entrainment to mealtime, and the reappearance of AA at a previously established phase suggest the possibility that this system has a memory of phase displacement.


Resetting of a circadian clock by food pulses. Rats with lesions of the suprachiasmatic nuclei were exposed to daily feeding until anticipatory activity (AA) developed. Meals were then phase advanced or delayed and presented for 1-4 consecutive days. The phase of the circadian pacemaker was assessed during probes of total food deprivation before or after 8 days of intervening ad lib feeding. One or two food pulses caused phase delays for one cycle but were insufficient to reset the feeding entrainable pacemaker. Complete or partial resetting to 6- or 9-h advances or delays was observed in some rats after three food pulses and in all rats after four food pulses. In some rats, phase shifts of meals appeared to induce both advancing and delaying transients, and two bouts of AA appeared during food-deprivation probes. This suggests that the feeding entrainable pacemaker consists of two or more oscillators which became uncoupled after phase shifts. The persistence of AA at the preshift phase observed after initial phase delays, concomitantly with AA to the phase shifted meals, also suggests the presence of a second oscillator.


The effect of neonatal capsaicin treatment on gustatory behavior in the albino rat. Small-diameter fibers present in gustatory peripheral nerves have historically been suspected of relaying information about the bitter quality of a taste stimulus. Neonatally injected capsaicin irreversibly destroys a proportion of unmyelinated C- and some A delta-fibers. Consummatory responses to increasing concentrations of quinine and other chemical solutions following neonatal capsaicin injection were compared to those of untreated and vehicle-injected control Sabra albino rats. Capsaicin-treated rats significantly increased their withdrawal thresholds to noxious, CO2 laser-generated heat pulses verifying treatment effectiveness. Furthermore, neonatal capsaicin treatment diminished sensitivity to pungent capsaicin solutions in mature rats. However, there were no group differences in quinine intake, suggesting that the full array of unmyelinated fibers associated with taste buds is not essential for the transmission of bitter taste. Capsaicin-treated animals showed a significant reduction in intake of normally highly preferred sodium chloride and sucrose concentrations. These results were probably not due to loss of peripheral unmyelinated afferent fibers per se, but rather to secondary central changes.


Ovariectomy does not attenuate aggression by primiparous lactating female rats. Nulliparous female hooded rats were allowed to cohabit with a sexually active male in a large living cage. Aggression toward an unfamiliar female was assessed during the second and third week of pregnancy. Within 12 to 24 h following parturition females were ovariectomized (n = 7) or sham-ovariectomized (n = 6) in a manner that balanced previous aggression scores. Aggression was assessed at 48 h following ovariectomy and at three weekly intervals thereafter. Ovariectomized and sham-ovariectomized females did not differ in the number of attacks, number of bites, duration of on-top, or frequency of piloerection on any test day following parturition. These results indicate that circulating levels of ovarian steroids do not influence the level of aggression by a primiparous lactating female toward an unfamiliar female conspecific.


Selective attention and the perceptual analysis of odor mixtures. Two psychophysical methods were used to investigate the capacity of humans to identify the constituents of odor mixtures consisting of up to six components. With one method subjects were required to identify all the components present in each stimulus; with the other, a selective attention procedure was used where subjects had to identify only one component at each trial. Little difference was found between the levels of identification obtained with both methods, reinforcing the finding that humans have great difficulty in identifying more than three components in an odor mixture and indicating that it is unlikely that olfactory adaptation influenced the identification process.


Antiserum to prolactin decreases rapid eye movement sleep (REM sleep) in the male rat. Previous reports suggest that blood-born prolactin (PRL) may selectively promote rapid eye movement sleep (REMS). To study the possible involvement of endogenous PRL in sleep regulation, rats were systemically injected with either antiserum to PRL or normal rabbit serum, and the sleep-wake activity was determined during the subsequent 12-h light cycle. The administration of normal rabbit serum in physiological saline did not alter sleep-wake activity compared to control recordings, whereas the PRL antiserum caused a modest and selective suppression in REMS. Immunoreactive PRL was eliminated from the serial plasma samples obtained between 6 to 11 h after the injection of the antiserum. Brain temperature was not affected by the antiserum. The results indicate that physiological pituitary PRL secretion has a slight REMS-promoting activity in the male rat. It is speculated that an increased release of pituitary PRL or the PRL-like substance previously demonstrated in the brain may significantly stimulate REMS.


NMDA lesions of lateral hypothalamus enhance the acquisition of schedule-induced polydipsia. Schedule-induced polydipsia (SIP) is affected by damage to various limbic structures that have connections with the lateral hypothalamus. The present experiment sought to determine whether or not SIP could be induced in rats bearing NMDA-induced lesions of the lateral hypothalamus. Following surgery, lesioned rats lost weight and were hypophagic and hypodipsic. Drinking, in response to systemic injection of hypertonic saline, was impaired in lesioned rats. Prior to testing for SIP, all rats were placed on a food-restriction regime to maintain body weight at 85% of normal. There was no statistically significant difference in mean body weight between lesioned and control groups before deprivation began, though lesioned rats were hypodipsic in their home cages. The lateral hypothalamic-lesioned rats acquired SIP significantly more rapidly than controls over the first six sessions, but over four following sessions no differences were present. The enhanced acquisition of SIP by lateral hypothalamic-lesioned rats cannot be accounted for by postoperative recovery of body weight or by hypodipsia in the home cage, neither of which correlated with SIP. It is suggested that the lateral hypothalamus has a role in cueing appropriate and inhibiting inappropriate behavior in conditions of motivational excitement. SIP is suggested to have two CNS components--one excitatory and one inhibitory.


The effects of wheel running, a light/dark cycle, and the instrumental cost of food on the intake of food in a closed economy. The effects of wheel running on the food intake of rats, and on the extent to which rats defend their daily food intake against increases in the instrumental cost of food, were studied in a closed economy. Rats lived in cages that were attached to running wheels. Within each cage, water was freely available and lever pressing was required for access to food; a fixed number of presses was required for the delivery of a single food pellet. All cages were located in an environmental chamber where a 12-h light/dark cycle was continuously maintained. During stage I, the entrance to each running wheel was blocked and two series (series 1 and 2) of progressively increasing fixed ratios (FRs) of presses per pellet were imposed. Each FR was used for a single day. During stage II, the entrance to each wheel was unblocked and wheel running and food intake were allowed to stabilize. During stage III, the running wheels remained available and the FR was again increased (series 3). In stage I, increases in the FR reduced food intake proportionally more rapidly during the light than during the dark, and this reduction in the light was greater during series 1 than series 2. During stage II, food intake was transiently reduced during the first week of access to running wheels, but recovered by the end of the second week. During stage III, increases in the FR again reduced food intake proportionally more rapidly during the light than during the dark. Wheel running did not affect the extent to which food intake was reduced within light and dark periods.(ABSTRACT TRUNCATED AT 250 WORDS)


Garlic in the ovine fetal environment.

Garlic in the ovine fetal environment. We investigated whether the odor of garlic can cross the placental barrier from the mother to the fetal environment. Samples of amniotic fluid, allantoic fluid, fetal blood, and maternal blood were collected 0, 50, 100, and 150 min after a pregnant ewe (approximately day 110 of gestation) was gavaged with 6 ml of Egyptian garlic oil. A panel of judges detected (p < 0.05) garlic odor in samples of allantoic fluid, fetal blood, and maternal blood collected 50, 100, and 150 min after the ewe was given garlic and in samples of amniotic fluid collected 100 min after treatment.


Lashley maze learning deficits in NZB mice. In a prior study we found excellent Lashley III maze learning in BXSB mice and poor learning in NZB mice, despite the fact that both strains are autoimmune and develop cortical ectopias. This prompted us to examine NZB Lashley maze performance in detail, including comparisons to other strains and attempts to improve performance by giving additional trials with or without additional intramaze visual cues. In conventional Lashley testing (10 trials), RF mice (non-autoimmune and nonectopic) and BXSBs performed well in the Lashley maze. They had high learning indices and few errors. NZB mice performed poorly, with low learning indices and many errors. Even with additional trials or additional trials plus intramaze cues, NZB performance remained poor. The number of backward and forward errors stayed high; learning indices were low. Since both BXSB and NZB mice develop autoimmune disorders and cortical ectopias, it is unlikely that differential Lashley performance is the result of the presence of these phenomena. NZB mice are known to have alterations in their hippocampal morphology, and this is a possible mediator of the Lashley deficit.


Description of a modular, low cost, eater meter for the study of feeding behavior and food preferences in fish. The eater meter described in this paper is especially designed for fish studies. It consists of three parts: the detector, the feeder, and the interface between the detector and the feeder. The detector is a rod that closed a circuit (by contact or through a magnetic detector) when stuck by a fish, the feeder is electric and can be of any commercial model, and the interface is a simple electronic device, or a computer. Some preliminary results obtained with rainbow trout, Oncorhynchus mykiss, are also presented in order to illustrate the uses of this modular eater meter for fish.


Lack of an order effect in brief contact taste tests with closely spaced test trials. The number of licks during 30-s exposures to a range of concentrations of sucrose, glucose, fructose, maltose, and Polycose were recorded. A complete series of concentrations of each carbohydrate was offered in ascending, descending, or random order with 30-s intertrial intervals. The order of presentation differed on different days. For sucrose, glucose, fructose, and maltose the number of licks in the 30-s periods was an increasing monotonic function of concentration regardless of the order of stimulus presentation. For Polycose, the lick rate-concentration function was an inverted U-shaped function of concentration with a peak on the 0.1 M to 0.2 M range. In all cases the rate of licking declined during the 30-s exposure period, suggesting the development of gustatory sensory adaptation. The results indicate that it is possible to obtain a rapid assessment of the taste sensitivity of the rat to a variety of carbohydrate solutions on a single day with very brief intertrial intervals.


Perinatal estradiol benzoate administration affects control of ventilation in adult male rats. One injection of estradiol benzoate (EB) (100 micrograms) or vehicle was administered to male rat pups 5 days after birth. Two months later ventilation, ventilatory responses to 7% carbon dioxide, and to 580 mg/kg aspartic acid (an agent used as a marker of sexually dimorphism in the control of ventilation) were evaluated and body weight, testes weight, and nose-anus length were measured in animals in each group. The EB-treated rats had similar tidal volumes, frequency of breathing, and minute ventilation as did control male rats. The ventilatory responses of EB-treated rats to hypercapnia were markedly less than those of control animals. Aspartic acid administration depressed ventilation in control animals, but had no effect on ventilation in EB-treated males. Body and testes weights, as well as nose-anus length, were less in EB-treated compared with control rats. However, when body weight was normalized by nose-anus length and testes weight was normalized by body weight, the values were comparable between the two groups. Thus, perinatal EB treatment of male rat pups results in small, hypogonadal adult animals whose ventilation in response to hypercapnia was diminished and whose response to aspartic acid was female-like relative to those of control rats.


Maudsley reactive and nonreactive rats in the forced swim test: comparison in fresh water and soiled water. Maudsley reactive (MR) and nonreactive (MNRA) and Sprague-Dawley (SD) male rats were tested for their immobility response in the forced swim test when the water was fresh or soiled by a rat of the same or other strain. For all strains, rats tested in soiled water were less immobile than rats in fresh water. The three strains did not differ as producers of soiling substance, but did differ in their response to it. The MR strain was least responsive, whereas the MNRA and SD did not differ from one another. These results support a previous study suggesting that MR rats are more immobile than MNRA rats in the forced swim test. The interpretation of these findings regarding the use of the Maudsley rat strains as an animal model for studying anxiety and/or depression is discussed.


The effect of odours on stimulated parotid salivary flow in humans. We have previously shown that smell has no effect on resting parotid salivary flow in humans. In this study we investigated the effect of two odours on unilateral parotid salivary flow stimulated by either mastication or mastication with gustation. Neither odour stimulated flow above that elicited by either mastication or mastication with gustation. Removing an odour by sealing the nares has been reported to reduce stimulated parotid salivary flow, suggesting that smell contributes to stimulated salivary flow. However, in the present study, sealing the nares with a nose clip caused a significant reduction in the saliva elicited by an odourless stimulus. Even placing the nose clip over the bridge of the nose without sealing the nares significantly reduced the salivary flow, suggesting that the nose clip itself causes a reduction in stimulated parotid salivary flow. In conclusion, smell has no effect on stimulated parotid salivary flow in humans.


Vasopressin prolongs behavioral and cardiac responses to mild stress in young but not in aged rats. In young male Wistar rats sudden silence superimposed on low intensity background noise evokes a relative decrease in heart rate. This bradycardia is accompanied by immobility behavior. In the present study, involving young (3 month), late-adult (14 month), aged (20 month), and senescent (25 month) rats the magnitude of the stress-induced bradycardia shows an age-related reduction while the behavioral immobility response remained unchanged during the process of aging. Arginine-8-vasopressin (AVP, 6 micrograms/kg SC) administered 60 min prior to the experiment led to a prolonged behavioral and cardiac stress response in young and late-adult rats, but not in aged and senescent animals. The peripheral and central mechanisms possibly involved in the failure of systemically applied AVP to improve bradycardiac stress responses in aged rats are discussed.


Behavioral thermoregulation in mice inoculated with influenza virus. Mice housed at 30 degrees C and inoculated with a mouse-adapted influenza virus show a fall in body temperature (Tb) and a decrease in food intake to almost 0 grams per day. This study tested whether the fall in Tb could be accounted for by the decreased food intake and whether the fall in Tb was due to a decrease of thermoregulatory set point or to an inability to maintain Tb at set point level. The fall in Tb of influenza-infected mice was greater than that of food-deprived mice. When food deprived, mice given access to a thermal gradient increased their preference for warmer areas in the gradient and, as a result, Tb did not fall as much as Tb of starved mice not given access to a thermal gradient. When infected with influenza virus, mice given a thermal gradient decreased Tb less and at a slower rate than mice not given a gradient. However, this fall in Tb of influenza-infected mice was greater than that of food-deprived mice given a thermal gradient. Mice given a thermal gradient increased their preference for the warmer temperatures after inoculation; this returned to preinoculation preference for cooler temperatures during the later days of infection despite a continuous fall in Tb. Influenza-infected mice given a thermal gradient survived significantly fewer days than infected mice not given a thermal gradient. We conclude that the influenza-induced fall of Tb in mice cannot be explained solely by the decrease in food intake, and is partially due to a decrease in thermoregulatory set point.


An anorectic agent from adipose tissue of overfed rats: effects on feeding behavior. Parabiosis and blood-transfer studies with rodents suggest the existence of humoral factors capable of affecting energy balance. The nature and origin of these factors is undetermined. Aqueous extracts of adipose tissue from overfed rats significantly reduce food intake when administered intraperitoneally (IP) or intracerebroventricularly (ICV). We term the agent(s) responsible for this effect adipose satiety factor (ASF). A single IP dose of ASF, equivalent to 44 mg crude protein, suppresses cumulative food intake for over 12 h. ASF, prepared using a combination of adipose tissue from obese Zucker rats and overfed rats, is more potent per unit of protein than ASF prepared exclusively using adipose tissue from overfed rats. A single ICV dose of this hybrid preparation, equivalent to 14.6 micrograms of crude protein, suppresses cumulative food intake by 40% for up to 48 h. By ultrafiltration, the molecular weight associated with maximal ASF activity is between 30 and 100 kilodaltons (kDa). The behavioral specificity of ASF-induced anorexia is demonstrated using meal pattern, taste aversion, and differential starvation paradigms.


Unilateral but not bilateral olfactory bulbectomy inhibits body weight gain in hamsters. The relation of the olfactory bulbs and photoperiod to the regulation of body weight was studied in male golden hamsters. Animals underwent sham operation, bilateral olfactory bulbectomy, or unilateral bulbectomy. They were left on long photoperiod for 5 weeks and then were transferred to short photoperiod for 11 weeks. The unilaterally olfactory bulbectomized hamsters gained less weight on long or short photoperiod than the sham operated group, while the bilaterally bulbectomized hamsters gained at least as much weight as the sham group. Thus, we report the novel finding that unilateral but not bilateral olfactory bulbectomy reduces body weight gain in male golden hamsters.


Food intake and body temperature responses of rats to recombinant human interleukin-1 beta and a tripeptide interleukin-1 beta antagonist. Food intake and body temperature are two of many factors affected by IL-1 beta, a cytokine which is produced in response to tissue injury and inflammatory processes. In the present experiment, a tripeptide IL-1 beta antagonist which blocked IL-1 beta-induced hyperalgesia was tested for the ability to block IL-1 beta-induced effects on food intake and body temperature. Food intake was decreased 4-22 h after intraperitoneal (IP) administration of 1.25, 1.88, or 2.50 micrograms IL-1 beta/rat, and 0-22 h food intake was decreased by 1.88 and 2.50 micrograms IL-1 beta/rat. The effect of 1.25 micrograms IL-1 beta/rat on food intake measured 4 and 22 h after (IP) injection was blocked by coadministration of 5 mg tripeptide IL-1 beta antagonist. However, 25 mg tripeptide IL-1 beta antagonist/rat plus 1.25 micrograms IL-1 beta/rat decreased 0-22 h food intake more than IL-1 beta alone. Administration (IP) of 1.25 micrograms IL-1 beta/rat increased body temperature 1 degrees C 4 h later, and 5 and 25 mg tripeptide IL-1 beta antagonist/rat blocked this increase. Although food intake remained decreased after IL-1 beta administration alone or with 25 mg tripeptide IL-1 beta antagonist/rat for 22 h, body temperature returned to normal under these conditions. Thus, a tripeptide IL-1 beta antagonist shown to block IL-1 beta-induced hyperalgesia also blocked food intake and body temperature responses to IL-1 beta, although the effective doses of IL-1 beta and the tripeptide IL-1 beta antagonist differ by 4,000-fold when both are administered peripherally.


Effects of adrenal steroid agonists on food intake and macronutrient selection. These experiments tested the effects of subcutaneous (SC) and paraventricular nucleus (PVN) administration of the steroid receptor agonists, corticosterone (CORT), aldosterone (ALDO), RU28362, and dexamethasone (DEX), on food intake and macronutrient selection during the first h of the dark feeding period in the rat. Results indicate that CORT and the selective type II receptor agonist RU28362 specifically stimulate carbohydrate ingestion after SC or PVN administration, while DEX has no effect on feeding. This selective effect of SC CORT on carbohydrate ingestion is dose dependent, seen at doses ranging from 0.125 to 2.0 mg/kg. Moreover, the stimulatory effects of CORT and RU28362 on carbohydrate intake are observed in ADX rats but not in sham rats. This is in contrast to SC and PVN administration of the type I receptor agonist ALDO, which specifically enhances fat ingestion in both sham and ADX rats. These results, with both peripheral and central steroid administration, reveal selective effects of type I and type II receptor stimulation on fat and carbohydrate intake, respectively.


Acute, but not chronic, exercise lowers the body weight set-point in male rats. The influence of muscular training on overall energy balance and body weight is not clear. A group of male rats was trained to feed every day from 1000 to 1200. Then the intersect of regression line of food hoarded during meal time vs. body weight with the X-axis was measured. Finally, the rats were trained to run 1 h every day on a motor-driven treadmill. When the training took place in the morning, just before the hoarding session, the mean intersect was significantly lowered from control (497 +/- 18 g to 433 +/- 9 g). When the training took place in the afternoon, after the hoarding session, the mean intersect was not significantly different (504 +/- 21 g) from control. Food intake during the hoarding sessions was affected neither by body weight changes nor by muscular exercise. These results suggest that the set-point for body weight regulation is acutely lowered just after muscular exercise, but is not influenced by chronic training.


Effects of body weight loss and taste on VMH-LH electrical activity of rats. Electrical responses of ventromedial (VMH) and lateral (LH) hypothalamus to graded decrease in body weight and to taste were recorded from a conscious rat with chronically implanted macroelectrodes. Graded reduction in body weight was correlated with gradual increase in LH activity and reciprocal decrease in VMH activity, both of which were stable and specific to each gradation in body weight. On gustation of any test solution, basal activity was temporarily altered, if any. On sweet taste of calorically rich sucrose, VMH activity was enhanced and LH showed decrease. But on sweet taste of calorically inert saccharin, VMH activity was increased, though a reciprocal decrease in LH was not shown. Contrastingly, both bitter taste and salt taste caused increased LH activity but no change in VMH activity. Enhanced VMH activity correlated with sweet taste may be due to activation of VMH glucoreceptors. LH activation correlated with bitter and salt taste is a likely response of two distinct groups of LH units; one responding to salt taste and the other to bitter aversive taste.


Long-term regulation of pancreatic B-cell responsiveness to D-glucose by food availability, feeding schedule, and diet composition. The immediate metabolic, cationic, and secretory response of the insulin-producing B-cell to D-glucose is regulated, in a delayed or long-term manner, by nutritional factors such as food availability, feeding schedule, or diet composition. The B-cell keeps the memory of these nutritional manipulations so that the corresponding changes in its responsiveness to D-glucose can be documented in vitro in isolated pancreatic islets. The results of experiments conducted in starved rats, in animals exposed to an altered feeding schedule, and in rats given free access to a high-carbohydrate, high-protein, or high-lipid, as distinct from balanced, diet all suggest that a sufficient prandial hyperglycemia is essential for maintenance of an optimal metabolic and secretory behavior of the islet B-cell in response to a rise in D-glucose concentration.


Further characterization of cortical polarization-induced motor behavior in rabbits. Anodal direct currents of 1 or 10 microA were unilaterally applied for 30 min once a day to the premotor area of the cerebral cortex in rabbits, in which the current application was repeated 10 times at intervals of 2-3 days. Peripheral motor behavior was observed during and after each polarization trial, and was compared with that before polarization. The motor manifestations were classified into two types: gentle flexion of either forelimb and struggle with violent movement of forelimbs. Flexion of the forelimb contralateral to the polarized cortical side was clearly increased by polarization at an intensity of 1 microA, but not at 10 microA. Forelimb struggle of both sides decreased only when 10 microA was applied. These results suggest that the passage of 1 microA current activates the polarized local area of the cortex, while 10 microA has an inhibitory effect on cortical activity.


Chronic dietary choline enrichment affects DRL responding of old, but not of adult CPBB rats. Using adult (11-month-old) and aged (22-month-old) inbred female CPBB rats, we tested the hypothesis that chronic dietary choline supplementation affects timing behavior. The rats had received choline chloride in their tap water for about 9 months before they acquired responding on a differential reinforcement of low-rate schedule with a critical delay of 8 s (DRL-8"). One retention session and two extinction sessions were given 4 weeks after the end of acquisition. The treatment had no effect on the timing behavior of the adult rats. Choline-treated old animals made more perservation errors, i.e., responses with interresponse times (IRTs) < 2 s, than the untreated old control rats. Even after correction for burst responses, the frequency of short IRTs was higher in the treated than in the control group, indicating that choline supplementation slightly impaired timing behavior. The mechanisms underlying the action of supplemented choline are still unknown.


Ethological categorization of adult rat motor behavior in an open field. From 100 rats observed during 1 h, elementary behavioral units were identified, characterized, and behavioral boundaries were established. From this, two main categories were established and named a) basic body postures, and b) posture-associated moving actions. Four subcategories concerning posture-associated moving actions were 1) body-directed actions; 2) actions of interaction with the environment; 3) moving actions without locomotion; and 4) displacement actions with locomotion. This ethological characterization in an open field could be applied to the study of motor effect induced by experimental manipulation of the brain function, at maturity.


An improved method for carotid artery infusion without vessel occlusion. This is an simple, non-time-consuming and advantageous procedure for catheterization and drug administration in thin arteries of small animals. The cannulation method consists of implanting polyimide-coated silica capillary tubing. To avoid vascular tear during puncture, the tubing tip is beveled. The cannula is stuck to the wall of the artery without artery ligation, using a small drop of a fast cyanoacrylate adhesive. The surgical procedure can be completed in 15 min and has the following properties: 1) it is wise but not indispensable to perfuse a solution continually through the cannula; 2) the dead volume is low and drugs may be injected in a very low solution volume; 3) it is not necessary to close the lumen of the vessel during catheterization; 4) the drug solution may be perfused into a normal bloodstream and thus its kinetic behavior is not modified by undesired cul-de-sac effects presented after artery ligation.


Cryptolepis sanguinolenta: antimuscarinic properties of cryptolepine and the alkaloid fraction at M1, M2 and M3 receptors. From an ethanol extract of the roots of Cryptolepis sanguinolenia the alkaloid fraction and its main constituent cryptolepine were isolated by partitioning at pH 11 and column chromatography using silica gel and chloroform/methanol as eluent. Cryptolepine was identified mainly by EI-MS and 1H/13C-NMR spectroscopy. Cryptolepine (3-30 microM) and the alkaloid fraction of Cryptolepis sanguinolenta (3-10 micrograms/ml) antagonized muscarinic effects at M1 receptors in rabbit vas deferens, M2 receptors in guinea-pig atria, and M3 receptors in guinea-pig ileum. The experiments, using N-methylatropine as reference drug, showed a significant antimuscarinic activity for both cryptolepine and the alkaloid fraction, but no appreciable receptor subtype selectivity (pA2 = 5.00-5.73). Cryptolepine was determined as the antimuscarinic principle of Cryptolepis sanguinolenta. At higher concentrations both materials displayed negative inotropic effects.


Effect of Gomisin A (TJN-101) on liver regeneration. We studied the effect of TJN-101, a lignan component of Schisandra fruits (Schisandrae fructus), on liver regeneration after partial hepatectomy. TJN-101 was given orally to male Wistar rats 30 min before partial hepatectomy. The mitotic index and the level of DNA synthesis increased after partial hepatectomy and their increase was significantly enhanced by TJN-101. Ornithine decarboxylase (ODC) activity increased in the early stages of liver regeneration and it was also significantly enhanced by TJN-101. Besides, TJN-101 enhanced the increase in hepatic putrescine. These results suggest that TJN-101 stimulates liver regeneration after partial hepatectomy by enhancing ODC activity, which is an important biochemical event in the early stages of liver regeneration.


Structure and hepatoprotective activity of a biflavonoid from Canarium manii. Canarium manii (Burseraceae) was chemically investigated and the presence of the biflavonoid agathisflavone is reported for the first time from this plant. Pharmacologically, this biflavonoid in doses 50.0 mg and 100.0 mg given orally exhibited dose-dependent hepatoprotective activity against experimentally-induced carbon tetrachloride-hepatotoxicity in rats and mice.


Analgesic and anti-inflammatory effects of Ranunculus japonicus extract. The analgesic and anti-inflammatory effects of Ranunculus japonicus extract after parenteral administration were determined in several animal models. The extract inhibited the mice writhing responses caused by acetic acid and raised the pain thresholds of mice in the hot-plate test. The extract also inhibited the paw edema of rats induced by carrageenin, ear swelling of mice caused by xylene, mice vascular permeability increase induced by acetic acid, and granuloma formation in rats.


Histamine release inhibition activity of bisbenzylisoquinoline alkaloids. Eleven examples of bisbenzylisoquinoline alkaloids (head-to-head; 10, head-to-tail; 1) and one half molecule type (N-methylcoclaurine), were tested by in vitro histamine release inhibition assay. The order of the potency of the inhibitory effect was ranked thus: homoaromoline, aromoline, isotetrandrine, cepharanthine, fangchinoline, obaberine, and tetrandrine. The following substances, cepharanoline, berbamine, oxyacanthine, and cycleanine (head-to-tail structure) had no inhibitory effect. N-Methylcoclaurine showed an inhibitory effect comparable to that of fangchinoline.


Effect of "Rosa Canina" infusion and magnesium on the urinary risk factors of calcium oxalate urolithiasis. The effects on the calcium oxalate urolithiasis urinary risk factors of "Rosa Canina", in herb infusion form, and magnesium chloride have been studied using female Wistar rats under balanced dietary conditions. No significant effects on the volume of liquids drunk or on creatinine, phosphate, and oxalate urinary concentrations and excretions were observed. The herb infusion did not cause any diuretic effect. Calciuria decreased and citraturia increased when taking the herb infusion, and vice versa when taking magnesium chloride. Magnesium chloride decreased the urinary pH value, but this effect was not observed when magnesium chloride was administered with herb infusion. In conclusion, the same beneficial effects of the studied infusion herb on calcium oxalate urolithiasis urinary risk factors can be clearly detected. An interesting fact is that it seems that some possible effects depend on dietary components, thus, i.e., an increase in the urinary pH was only detected when the intake of the herb infusion was studied in a magnesium chloride-supplemented diet.


Hypoglycemic activity of olive leaf.

Hypoglycemic activity of olive leaf. The hypoglycemic activity of olive leaf was studied. Maximum hypoglycemic activity was obtained from samples collected in the winter months, especially in February. One of the compounds responsible for this activity was oleuropeoside, which showed activity at a dose of 16 mg/kg. This compound also demonstrated antidiabetic activity in animals with alloxan-induced diabetes. The hypoglycemic activity of this compound may result from two mechanisms: (a) potentiation of glucose-induced insulin release, and (b) increased peripheral uptake of glucose.


Immunostimulant activity of Picroliv, the iridoid glycoside fraction of Picrorhiza kurroa, and its protective action against Leishmania donovani infection in hamsters. Picroliv, a standardised fraction from root and rhizome of Picrorhiza kurroa, consisting of iridoid glycosides and shown to be responsible for its hepatoprotective activity, was studied for immunostimulant activity. Oral administration of Picroliv (10 mg/kg x 7 days) in mice prior to immunization with sheep red blood cells (SRBC) resulted in a significant increase in haemagglutinating antibody (HA) titre, plaque forming cells (PFC), and delayed hypersensitivity (DTH) response to SRBC. Picroliv enhanced the non-specific immune response characterized by an increase in macrophage migration index (MMI), [14C]-glucosamine uptake, phagocytosis of [14C]-leucine labelled Escherichia coli, chemiluminescence of peritoneal macrophages, and higher uptake of [3H]-thymidine in the lymphocytes of treated mice. It also induced a high degree of protection in golden hamsters against challenge infection with Leishmania donovani promastigotes.


Effects of three compounds extracted from Morinda lucida on Plasmodium falciparum. The effects of three compounds, digitolutein (1), rubiadin 1-methyl ether (2) and damnacanthal (3) extracted from the stem bark and the roots of Morinda lucida Benth. on the growth of Plasmodium falciparum in vitro were investigated. The number of parasites (schizonts) decreased significantly in a dose-dependent manner, and 100% of inhibition was obtained with 30 to 40 micrograms of each compound tested. The IC50 values were calculated.


Inhibitory effect of tannic acid sulfate and related sulfates on infectivity, cytopathic effect, and giant cell formation of human immunodeficiency virus. The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human immunodeficiency virus [HIV (HTLV-III/LAV)]. In this report, we synthesized sulfated plant polyphenols such as tannic acid sulfate, rutin sulfate, ellagic acid sulfate, (-)-epicatechin sulfate, and (-)-epigallocatechin 3-gallate sulfate, and examined the in vitro inhibitory effect on HIV infection using human T-cell lymphotropic virus type-I-carrying MT-4 cells, which are extremely susceptible to HIV infection. Of the compounds tested, tannic acid sulfate was the most effective and had low cytotoxicity. Tannic acid sulfate completely inhibited the cytopathic effect of HIV and the HIV-specific antigen expression in MT-4 cells at the concentration of 6 micrograms/ml. In addition, this sulfate inhibited giant cell formation in coculture at the concentration of 5 micrograms/ml.


In vitro antimalarial activity and chloroquine potentiating action of two bisbenzylisoquinoline enantiomer alkaloids isolated from Strychnopsis thouarsii and Spirospermum penduliflorum. The bisbenzylisoquinolines 7-O-demethyltetrandrine and limacine, respectively, isolated from Strychnopsis thouarsii Baill. and Spirospermum penduliflorum Thou. were evaluated for their intrinsic antimalarial activity in vitro and chloroquine potentiating action against the chloroquine-resistant Plasmodium falciparum FCM 29 originating from Cameroon. They both showed significant antiplasmodial potency in vitro with very similar IC50 values of respectively, 740 nM and 789 nM (IC50 = 214 nM for chloroquine used as standard drug), which demonstrated that the stereochemistry of the C-1 and C-1' configuration likely plays a role in the chloroquine potentiating effect of these drugs. If confirmed in vivo, these results may account for the traditional use of the two plants as antimalarials and adjuvant to chloroquine in Madagascan folklore remedies.


Antihepatotoxic C-glycosylflavones from the leaves of Allophyllus edulis var. edulis and gracilis. From the leaves of Allophyllus edulis var. edulis and Allophyllus edulis var. gracilis nine C-glycosylflavones have been isolated and identified as schaftoside (8), vicenin-2 (9), lucenin-2 (10), isovitexin 2"-O-rhamnoside (11), cerarvensin 2"-O-rhamnoside (12), vitexin 2"-O-rhamnoside (13), isoorientin 2"-O-rhamnoside (15), orientin 2"-O-rhamnoside (16) and saponarin (17). In addition, gallic acid (2), the phenol C-glycosides bergenin (3) and 11-O-galloylbergenin (4), three flavonol 3-O-rhamnosides and a new C-glycosylflavone identified as mollupentin 2"-O-rhamnoside (14) were obtained from the leaves of Allophyllus edulis var. edulis. Their structures were elucidated on the basis of chemical and spectral data. For the first time the C-glycosylflavones were found to have remarkable anti-hepatotoxic activities against CCl4 and galactosamine cytotoxicity in primary cultured rat hepatocytes. Structure-activity relationships are discussed.


Cajucarinolide and isocajucarinolide: anti-inflammatory diterpenes from Croton cajucara. Cajucarinolide and isocajucarinolide, two new clerodane diterpenes, have been isolated from the cortices of Croton cajucara (Euphorbiaceae). These compounds possess anti-inflammatory activity and inhibit bee venom phospholipase A2 in vitro.


[Clinical study of correlation pre-senile, senile depressive state with silent cerebral infarction--MRI findings and its distribution]. We examined the relationship between the pre-senile/senile depressive state and silent cerebral infarction using MRI. The subjects studied were 56 patients 50 years of age or older with a depressive state who underwent MRI and who were hospitalized and treated at the Department of Psychiatry or the Department of Neurology of Hiroshima Prefectural Hospital. We made a diagnosis of depression in patients who fulfilled the criteria of DSM-III-R for major depression. Patients in whom apoplectic attacks had occurred, or who had local neurologic symptoms or a history of evident cerebrovascular disorders, were not included in the study. Silent cerebral infarction was observed with pre-senile onset in 60.3% of patients with a pre-senile depressive state, and the complication rate was significantly higher than for cases with juvenile onset (20%). For patients with a senile depressive state, the complication of silent cerebral infarction was found in 53.6% of cases of pre-senile onset and in 100% of cases of senile onset. These rates were remarkably higher than the age-related complication rate of silent cerebral infarction in normal persons reported hitherto, we therefore suspect that nearly half of patients with depressive state of pre-senile onset and most of patients with that of senile onset might have an organic-depressive state complicated by silent cerebral infarction. Both perforating-type infarcts and cortical-type infarcts were found, suggesting that infarct-related foci of depressive states were polyphyletic. When we divided the depressive states complicated by cerebral infarction into 2 subtypes, those complicated by a perforating-type infarct and those by a cortical-type infarct, and compared the 2 types, we found possible differences in clinical symptoms and course between the subtypes. These differences seem worthy of further study. Among cortical-type lesions, parietal lesions were predominant, followed by frontal and then temporal lesions in incidence. There were significantly more left frontal lesions than right frontal lesions. Infarcts of both the parietal lobe and left frontal lobe may be related to the depressive state. Compared with cases not complicated by cerebral infarction, those with perforating- and mixed-type cerebral infarction were complicated with PVH significantly more frequently, similarity in risk factors and pathology between perforating-type cerebral infarction and PVH was suggested by these results.


[Changes of pupil size in brain death patients]. The representative criteria of brain death in Japan is Takeuchi Criteria (Koseisho Criteria), which is the definition of irreversible loss of brain function (functional brain death). The 3rd item of that criteria is "fixed pupil" and pupil size more than 4 mm. The 4th item is loss of the brain nerve reflexes including the light reflex. Three cases of brain death by whole brain destruction (organic brain death) who showed slow changes of pupil size were reported. Except fixed pupil, one case fulfilled Takeuchi Criteria. Other two cases fulfilled all items of Takeuchi Criteria, showing the same pupil size accidentally at the first and the second judgements. But, they changed their pupil size slowly and continuously after the examinations, showing tendencies toward mydriasis and/or miosis, repeatedly. They never decreased their pupil size less than 4 mm. The changes of pupil size were so slow that we could recognize them only after several hours or several days, and they were quite different from the light reflex. They did not receive any influences from turnover of day and night, darkness of the room, dopamine, etc. For the changes of pupil size were observed in the cases of organic brain death, it was elucidated that they were not due to the brain nerve activity. Then, it was considered that the changes of pupil size in the cases of functional brain death should be the same phenomena, because brain nerve function was lost.(ABSTRACT TRUNCATED AT 250 WORDS)


Elevated frontal cerebral blood flow in Gilles de la Tourette syndrome: a 99Tcm-HMPAO SPECT study. Case reports, numerous brain imaging studies, and certain disease states suggest that the orbital frontal cortex and the striatum are dysfunctional in obsessive-compulsive disorder (OCD). Interest has also grown recently concerning the genetic, neuroanatomic, and clinical links between OCD, chronic motor tics, and Gilles de la Tourette Syndrome (GTS). To test the hypothesis of possible orbito-frontal/basal ganglia dysfunction in GTS, similar to OCD, we studied 20 unmedicated GTS subjects, 10 of whom also had comorbid OCD (GTS/OCD), and 8 control subjects. The subjects were examined with high-resolution single photon emission computed tomography (SPECT) and the labeled regional cerebral blood flow (rCBF) ligand technetium-99m-d,l-hexamethyl-propylene amine oxime (99Tcm-HMPAO). As a group, GTS subjects showed significantly elevated right frontal/visual cortex activity (mean = 0.879, SD = 0.107) compared with control subjects (mean = 0.798, SD = 0.049). A subanalysis comparing simple GTS versus GTS with comorbid OCD failed to reveal significant differences in regional flow.


Leukoencephalopathy and major depression: a preliminary report. The comparative prevalence of leukoencephalopathic changes in 119 young and old inpatients and outpatients with major depression was examined. Patients underwent magnetic resonance imaging (MRI) examinations with T1- and T2-weighted pulse sequences. Leukoencephalopathic changes were uncommon in depressed patients and medical control subjects younger than 45 years of age. Such changes were, however, seen in approximately 44% of older depressed patients and 30% of elderly medical control subjects.


Reliability of drawing regions of interest for positron emission tomographic data. We determined interrater reliability for two raters who independently used a standard protocol to draw regions of interest (ROIs) on F-18 fluorodeoxyglucose positron emission tomographic data acquired from eight patients with mild to moderate memory impairment. Intraclass correlation coefficients for region sizes (total pixel number) varied among anatomical ROIs (RIs from 0.324 to 0.935). However, correlations calculated from relative metabolic rates (normalized average counts) were consistently high (RI > or = 0.954). The raters also showed high agreement for region recognition on each image plan (kappa = 0.978). These results suggest that rater disagreements in ROI margins have minimal impact on average count densities used to calculate metabolic rates.


A comparison of xenon-133 and xenon-127 for the determination of regional cerebral blood flow measured by dynamic SPECT. Phantom studies and cerebral blood flow (CBF) measurements in 11 normal subjects at rest were performed by single photon emission tomography (SPECT) with Xe-133 (16 mm full-width at half-maximum [FWHM] collimation) and Xe-127 (16 mm, 12 mm, and 9 mm FWHM collimation). The phantom results clearly illustrated the feasibility of Xe-127 studies and the advantage of Xe-127 over Xe-133 for equivalent patient dose exposures. CBF values obtained with Xe-127 were comparable to those of Xe-133 for the 16 mm collimator, although higher flow values were found with the better resolution, probably because of reduced partial volume effects. The correlations between the various groups of examinations were high, except for the Xe-133 and Xe-127 16 mm collimator groups. Xe-127 allows a considerable increase in the resolution of the images, while exposing the patient to a lower radiation dose. Potential limitations because of higher energy penetrating photons from Xe-127 were not observed in this specially shielded equipment.


Exploratory statistical methods, with applications to psychiatric research. This article introduces statistical methods for describing and summarizing the results of studies and introduces statistical principles that will guide the psychiatric researcher in the evaluation and interpretation of clinical research. We discuss relatively easy-to-use and informal methods for describing and comparing data. Our aim is to develop methods for investigating relationships among variables, to learn about the effect of one variable upon another. Once we have observed an apparent relationship between variables, an important question to be addressed is whether or not this observed relationship is causal in the sense that a change in one variable causes a changes in the other. We discuss and illustrate principles related to the evaluation of the nature of the association among variables. Throughout the article, principles and methods will be illustrated by examples and case studies based on data sets primarily from the psychiatric research literature.


Striatal dopamine metabolism is differentially affected by insulin according to the genotype in Zucker rats: a microdialysis study. The genetically obese Zucker rat presents several abnormalities related to insulin and brain monoamines, which may play a role in its impaired regulation of food intake and body weight. In a previous study, the possible insulin-monoamine interplay was investigated by measuring brain monoamine and metabolite levels in the three genotypes of the Zucker strain. In addition to the expected results, insulin had a particular effect on striatal dopamine (DA) release, regardless of ponderal status and genotype. We further investigated this point in the present study, using the brain microdialysis technique in the striatum. Lean homozygous Fa-Fa rats responded as expected to insulin with regard to striatal DA release, with increases in DA and 3-methoxy-tyramine levels and decreases in dihydroxyphenylacetic acid and homovanillic acid. Lean heterozygous Fa-fa rats showed a very specific response profile, with decreases in all dopaminergic parameters, suggestive of an effect on DA synthesis rather than DA release. This further emphasizes the marked differences between homozygous and heterozygous lean rats. The obese fa-fa rats clearly fell into two populations. The first showed a profile of response to insulin similar to that of the lean Fa-fa rats, in keeping with the disturbances related to the "fa" gene. The second showed an increase in all the dopaminergic parameters. This pattern of response was, however, different from that of the Fa-Fa rats. These opposing responses in the two obese populations did not reflect differences in the blood glucose response to insulin. One explanation is that 16 wk may be a critical transition period in the development of genetic obesity, with regard to brain monoamine disturbances and the response to insulin.


Cortisol response during different anxiogenic challenges in panic disorder patients. The present study assessed the relation of cortisol response to anxiogenic reactivity during intravenous lactate infusion and oral fenfluramine in 12 panic disorder (PD) patients who responded positively to both challenges and in eight non-reactive control subjects. There was no significant cortisol response difference between the PD patients and the controls during lactate infusion, but there was s significant difference at 120 min during the fenfluramine challenge. These findings are consistent with the possibility that these challenges stimulate different neurobiologic mechanisms and that fenfluramine-precipitated anxiety is more akin to anticipatory or generalized anxiety than to true panic anxiety.


Cortisol levels and vigilance in eating disorder patients. Elevated plasma levels of cortisol, as well as deficits in cognitive processes such as attention, have been observed in patients with eating disorders. The association between plasma cortisol and performance in vigilance task was studied in 17 patients with bulimia nervosa or anorexia nervosa during the acute phase of their eating disorder. In comparison to normal young women, the patients had a significantly lower hit rate in a discrimination task and showed an impaired perceptual sensitivity index. They also displayed significantly longer reaction times to hits, but not to false alarms. Cortisol levels of the patients were significantly higher than those of the normal controls. When patients were divided according to their median cortisol level, the patients with higher levels performed significantly more poorly than did the patients with lower levels. In the total patient sample, cortisol levels showed a significant negative correlation with hit-rate (r = -.54) and a significant positive correlation with reaction time to hits (r = .70). Other clinical characteristics were not related to cognitive performance. These results suggest a possible role of cortisol in the development of attentional deficits in eating disorder patients.


Effects of estrogen on memory function in surgically menopausal women. The effects of estrogen (E) on memory were assessed in 19 women who required a hysterectomy and bilateral oophorectomy for benign disease. Blood samples were drawn and memory tests were administered before surgery and again after 2 mo of postoperative treatment consisting of either monthly E or placebo (PL) injections. Scores on the immediate and delayed recall of paired-associates stayed at the same level in E-treated women, whereas they decreased significantly pre- to post-operatively in the PL-treated subjects. In the immediate recall of paragraphs, the scores of those given E improved postoperatively compared to baseline; scores remained unchanged in the PL group. No hormonal effects were apparent on the immediate or delayed recall of visual material, delayed recall of paragraphs, or digit span scores. These findings suggest that variations in specific aspects of memory function may occur in surgically menopausal women coincident with changes in plasma estrone and estradiol levels.


Variations in memory function and sex steroid hormones across the menstrual cycle. Memory, mood, and hormone levels were measured in 25 women during the menstrual and luteal phases of their cycles. Significantly lower visual memory (delayed recall) scores were found during the menstrual phase compared to the luteal phase. No phase differences were found on mood measures or on other memory measures including digit span, paired-associate learning, immediate recall of visual material, and immediate or delayed paragraph recall. The visual memory decrease was most prominent in approximately one-half of the sample and was significantly correlated with plasma progesterone in the luteal phase. For all subjects, paragraph recall scores were negatively correlated with free testosterone levels, whereas paired-associate learning was positively correlated with estradiol levels in the luteal phase. These results suggest that changes in memory test performance may be associated with sex steroid levels, particularly in some subgroups of women.


Neuroendocrine aspects of primary endogenous depression: XII. Receiver operating characteristic and kappa analyses of serum and urine cortisol measures in patients and matched controls. The majority of studies investigating the diagnostic utility of hypothalamo-pituitary-adrenal (HPA) axis measures in major depression have focused on the dexamethasone (DEX) suppression test (DST). The DST correlates well, but imperfectly, with other measures of HPA activity. Fewer studies have considered the ability of basal cortisol measures to discriminate depressives from non-depressed patients or normal subjects. We used receiver operating characteristic (ROC) analysis to examine the mean 24-hr serum cortisol concentration, our benchmark of basal HPA axis activity, compared to smaller segments of the 24-hr cortisol profile, post-DEX serum cortisol values, and pre- and post-DEX 24-hr urinary free cortisol (UFC) levels in 40 primary endogenous major depressives compared to 40 matched normal control subjects. No statistically significant differences in ROC curves were found between mean 24-hr cortisol and the other cortisol measures. The mean 24-hr, 1300h-1600h, 1600h-1900h, and 16-hr post-DEX serum cortisol concentrations and the post-DEX UFC level all appeared to be comparable estimators of HPA activity. The single 2300h pre-DEX serum cortisol concentration and the pre-DEX 24-hr UFC level performed notably poorer than did the other measures. We additionally calculated kappa statistics to determine the optimally sensitive and specific discriminators of the cortisol measures between the depressives and the normal controls. The 2300h post-DEX serum cortisol measure was optimally sensitive, and the 1500h post-DEX serum cortisol was optimally specific. The 0700h, 1500h, and 2300h post-DEX serum cortisols were very close together as the optimally efficient measures (best combination of sensitivity and specificity).


The effect of haloperidol on aldosterone secretion. Haloperidol (0.02 mg/kg, intravenous) did not stimulate aldosterone secretion in six normal controls or in six schizophrenic subjects. This is contrary to our hypothesis, which was based on the finding that peripheral D2 receptor antagonists stimulate aldosterone secretion, including haloperidol in rats and chlorpromazine in man. We speculated that a different dose of haloperidol would stimulate aldosterone in man. As expected, prolactin release was markedly stimulated in both groups of subjects, but no difference was found between groups.


Relapse-precipitating life events and feelings in patients with inflammatory bowel disease. This study examined whether life event stress under general or more specific conditions (fear of separation, feeling of being under pressure, feeling of being caught between two quarreling parties, separation experiences) contribute to the aggravation of inflammatory bowel disease (IBD). Firstly, 51 patients with ulcerative colitis, 57 patients with Crohn's disease, and 60 controls were compared in terms of these variables. In addition, the IBD patients filled out questionnaires asking for life events, the specific psychological conditions mentioned above, and their symptoms every 3 months for 1 year after the first measurement. Patients with Crohn's disease and patients with ulcerative colitis reported a lower amount of life event stress than members of the control group, but listed more feelings of being under pressure. Within group comparisons between patients in relapse and patients in remission, as well as comparisons between patients with recently increased disease activity and patients without increased disease activity did not yield clear results. We conclude that the variables in question have little influence on the beginning of a relapse.


Chronic fatigue syndromes in clinical practice. Chronic fatigue is a common and difficult challenge in clinical practice. The majority of patients with this chief complaint have treatable mood or anxiety disorders, complicated by a tendency toward somatization. A minority of patients suffer from sleep disorders, endocrinologic abnormalities, or chronic inflammatory conditions. Prolonged recovery after viral infections is only rarely the cause of chronic fatigue. Specific pharmacologic interventions and cognitive-behavioral therapy are effective in an environment that is sensitive to the patient's interpretation of symptoms and avoids unproven medical investigations and therapies.


The measurement of quality of life through the content analysis of verbal behavior. The 'quality of life' is a construct which many researchers are attempting to measure by means of self-rating procedures and by ratings from external observers. Another method of measuring this construct includes features of both the self-report method and the external observer rating method, and by doing so it minimizes some of the measurement errors inherent in the separate methods; this third method involves the content analysis of verbal behavior. This latter method preserves the reliability and validity of the scales that have been developed and tested for content analysis, while preserving the meanings intended by the subjects who are being assessed on this dimension, which meanings are often obscured or lost through self-report and ratings scales. A group of Content Scales especially applicable to assess the quality of life are reviewed and examples of their applicability are given. A discussion is provided dealing with special problems involving the assessment of this dimension, including cross-cultural issues and other factors that need consideration with respect to generalizability of the findings.


Sick-role susceptibility. A commentary on the contemporary data base (1989-1991) and classification system. A brief review of the historical and current status of the 'sick-role' concept is followed by an extensive literature survey of 526 articles published on the sick role since 1989. The commentary discusses measurement and research issues and then examined the areas of enquiry and trends from a biological, psychological, social and cultural perspective. Questions are raised about the significance of the data base from the view-point of classification and treatment. A descriptive and therapeutic model is proposed.


Alexithymia--state and trait.

Alexithymia--state and trait. Alexithymia is conceptualized as both affect-deficit disorder and continuous personality variable. Two-hundred-sixty-four adolescents were surveyed using (1) a core symptom questionnaire for alexithymic state; (2) the Toronto Alexithymia Scale (TAS), and (3) the Solacing Methods Questionnaire. Three percent were positive for core symptoms and used significantly fewer solacers than matched controls (p = 0.048); the affect-deficit disorder hypothesis is supported. Twenty-three percent were TAS-positive suggesting the need for a trait measure. However, only one of the 8 core symptom subjects was TAS-positive raising a question about the sensitivity of the TAS to the extreme cases on which the alexithymia concept is based. While 62.5% of the matched controls reported using memories for solace, none of the core symptom subjects did; one of the alexithymic's central problems may consist in finding psychological as opposed to action-oriented and physical comfort.


Effects of group psychosocial intervention on coronary risk factors. The purpose of this study was to investigate whether a psychosocial intervention approach aimed at resolving psychological conflicts could reduce the severity of risk factors for post-acute myocardial infarction patients. Twenty-three patients with a recent myocardial infarction participated in a group psychosocial intervention program which lasted 1 year. Twenty other patients with recent myocardial infarction served as controls. Patients form both groups had regular clinical and laboratory follow-up as well as medication. Mean values for seven risk factors of coronary heart disease (smoking, S; body weight, W; serum cholesterol, C; triglycerides, T; systolic and diastolic blood pressure, SBP, DBP; serum uric acid, U) were compared between the two groups in the 1st, 3rd, 6th and 12th months of the follow-up. The maximal mean improvements of the study versus the control group were as follows: W: -2.82 vs. -1.05 kg; C: -56.04 vs. -6.25 mg/dl; T: -20.61 vs. -2.4 mg/dl; U: -0.57 vs. -0.9 mg/dl; S at 1 year -55.5 vs. -10%. It is concluded that group psychosocial intervention with post-acute myocardial infarction patients considerably reduces some coronary-disease risk factors.


Immunotherapy of immune-mediated diseases. Owing to advances in knowledge of the basic mechanisms of the immune response, pathogenetic mechanisms in animal models of human disease and genetic and pathogenetic processes in human disease itself, it is now possible not only to speculate on but to apply novel immunotherapeutic treatments to immune-mediated human diseases. Some of these regimens have already shown therapeutic promise but in order to assess their effectiveness, optimum mode of administration and possible short- and long-term side-effects, multicentre controlled clinical trials are clearly required. Such work is already underway.


Spectrum of hospital-acquired acute renal failure in the developing countries--Chandigarh study. The spectrum of hospital-acquired acute renal failure in the developing countries has not been documented. We undertook a prospective study to define the causes and outcome of hospital acquired acute renal failure as seen at a referral center in North India. Over a one year period, all patients who developed acute elevation in serum creatinine during the hospital stay were studied. One hundred and ninety of 29,503 admitted patients (0.64 per cent) satisfied the criteria for entering into the study. Nephrotoxic drugs (29 per cent), decreased renal perfusion (21 per cent), major surgery (18 per cent) and septicaemia (17 per cent) were the most frequent causes. Acute renal failure was non-oliguric in 52 per cent of patients. Non-oliguric patients had significantly fewer episodes of hyperkalaemia, neurological abnormalities, metabolic acidosis and gastrointestinal bleeding. They required fewer episodes of dialysis (p < 0.001) and had a significantly lower mortality (p < 0.001) compared to the oliguric patients. Other poor prognostic factors included severity of renal insufficiency, high baseline serum creatinine and presence of multiorgan failure. The present study shows that the spectrum of hospital-acquired acute renal failure in the developing countries is quite similar to that of technologically advanced countries, although the pattern of community acquired acute renal failure is vastly different.


Anorexia nervosa as a compulsive behaviour disease. A number of anorexic young women develop bulimia, a condition in which binge eating is driven so intensely they cannot resist it. Although this drive has the character of a compulsion the patients do not as a rule suffer from obsessional-compulsive neurosis. A questionnaire was developed and used to determine whether similar compulsive drives manifest themselves in restricting anorexics and whether there are compulsive features resembling patients with compulsive personality disorder (as described in DSM-III) in eating disorders. A total of 162 patients were studied, comprising 42 controls, 30 depressed patients, 34 non-bingeing anorexics, 28 bingeing anorexics and 28 compulsive patients. The questionnaire was shown to be a stable instrument and, on the compulsion scale, the anorexics, bulimics and compulsive patients all scored very highly (mean +/- S.E.; 32.1 +/- 1.9, 35.8 +/- 1.9, 28.0 +/- 2.2, respectively) compared to the controls (13.1 +/- 1.1, p < 0.005). The compulsive patients did not have anorexia-type eating disorders. It was concluded that many of the factors which underlie compulsive personality disorder are present in primary eating disorders and the compulsive nature of anorexia could not be ignored when treatment was considered. The difference between compulsive behaviour and addiction is discussed in the light of the failure of long-term naloxone infusion to cure severe anorexia, even though some patients had dramatic weight gains associated with the antilipolytic action of naloxone.


The ventilatory cost of exercise compared in chronic heart failure and chronic renal anaemia. The cardiorespiratory responses to maximal treadmill exercise were compared in matched groups of patients with chronic renal anaemia or treated chronic heart failure, and in normal controls. Exercise capacity was similarly reduced in both patient groups compared to normal controls, the raised respiratory exchange ratio at peak exercise implying anaerobic metabolism due to limited oxygen delivery in heart failure and limited oxygen carrying capacity in anaemia. Minute ventilation (VE) was related linearly to minute CO2 production (VCO2) in all subjects (each r > 0.92) from all three groups. The slope of the VE/VCO2 relationship was normal in anaemia but steeper in heart failure, reflecting ventilation/perfusion mismatching in chronic heart failure.


Outcome of pregnancy in an Oxford-Cardiff cohort of women with previous bacteriuria. To investigate the influence of asymptomatic bacteriuria in childhood on subsequent pregnancy, we reviewed the outcome of 139 pregnancies in 88 women who were first identified during a programme of screening schoolgirls for asymptomatic bacteriuria carried out between 1970-1972. Data were analysed for the following groups: 50 pregnancies in 28 women with known renal scars (group 1); 16 pregnancies in 14 women with normal kidneys and reflux (group 2); 73 pregnancies in 46 women with normal urinary tracts (group 3); 139 healthy controls. Women in group 1 had a 3.3-fold increased relative risk of hypertension (p < 0.01) and a 7.6-fold increased risk of pre-eclampsia (p < 0.05) compared to controls, and a higher rate of obstetric interventions, including emergency caesarean section. Women in groups 2 and 3 appeared to carry a slightly increased risk of hypertension during the last trimester (RR = 1.8) but there were no significant differences in this or the incidence of pre-eclampsia or mode of delivery. Bacteriuria was more prevalent in all index groups compared to controls (37 per cent vs. 8 per cent, p < 0.01) and included four cases of acute pyelonephritis in in the study group. Fetal outcome was satisfactory in all cases. These results suggest that women with renal scars are at risk of hypertension and pre-eclampsia during pregnancy but that modern obstetric care minimizes these risks.


Successful treatment of bone marrow failure in Gaucher's disease with low-dose modified glucocerebrosidase. We report the beneficial effects of enzyme replacement therapy with mannose-terminated human glucocerebrosidase ('Ceredase') in a patient suffering from transfusion-dependent bone marrow failure due to Gaucher's disease. Treatment with low-dose enzyme infusions, given twice weekly, rapidly reversed the haematopoietic failure and incapacitating skeletal disease. It appears likely that prior splenectomy favourably influenced the response to this therapy.


Haematological manifestations of primary Sjögren's syndrome: a clinicopathological study. Clinically significant cytopenias are thought to be uncommon in primary Sjögren's syndrome: only a few cases have been reported in the literature. Over a 3-year period we identified haematological abnormalities in 11 of 27 patients with Sjögren's syndrome. Six patients had a positive direct antiglobulin test, including one patient with all the features of autoimmune haemolytic anaemia and two others with some features of this condition. Four patients had immune thrombocytopenia and two patients had myelodysplastic syndrome. Neutropenia was noted in two patients, one patient had aplastic anaemia and one had pure red cell aplasia. Haematological disorders were found to be common in patients with Sjögren's syndrome (40 per cent). Accordingly, we suggest that patients with immune cytopenia(s) should be screened for Sjögren's syndrome using sensitive assays for anti-SS.A and anti-SS.B antibodies, and that patients with Sjögren's syndrome should be periodically monitored, with a full blood count to rule out any haematological abnormality.


Snoring increases the risk of stroke and adversely affects prognosis. In a case-controlled study we recruited 400 patients admitted to hospital with stroke and 400 community controls matched for age, gender and family practitioner. Snoring history was obtained from 326 patients and 345 controls. Odds ratio for admission to hospital with stroke was 3.2 (95 per cent confidence intervals 2.3-4.4) for regular snorers against those who did not snore regularly. This risk was independent for age, gender and other risk factors for stroke. Snoring did not increase the chances of stroke during sleep. Level of consciousness was reduced more frequently in snorers (p = 0.0003). As the frequency of snoring increased so did the mortality to 6 months (p = 0.0006). Snoring is an important risk factor for stroke and adversely affects the prognosis in patients admitted to hospital with stroke.


Yersinia-related arthritis in the United Kingdom. A report of 12 cases and review of the literature. Reactive arthritis following infection with Yersinia is endemic in Scandinavian countries; the prevalence is low in the UK, however. We have reviewed the literature pertaining to Yersinia-related reactive arthritis in the UK and describe 12 patients who presented over a 3-year period with an asymmetrical seronegative polyarthropathy and serological evidence of recent Yersinia infection. Five patients recalled having a diarrhoeal illness prior to the onset of the arthropathy. None had a prior history of psoriasis, inflammatory bowel disease or ankylosing spondylitis. A history of urethral discharge was elicited from one patient. Extra-articular manifestations were seen in three patients (iritis in two, erythema nodosum in another). Four patients developed chronic joint disease after periods of 4, 6, 8, and 18 months, respectively. The prevalence of Yersinia-related arthritis in the UK may be higher than previously thought.


Postural fall in blood pressure in the elderly in relation to drug treatment and other lifestyle factors. In a study of 843 independent-living men and women aged between 60 and 87 in Perth, Western Australia, stepwise multiple regression, after correction for initial levels of systolic blood pressure, showed that postural fall in systolic blood pressure was positively related to alcohol intake of more than 20 ml/day, the use of sleeping tablets and higher levels of anxiety on the Spielberger state-trait scale, and negatively related to body mass index. Postural fall in blood pressure was not significantly related to treatment for hypertension, age, sex, patterns of usual physical activity, tea or coffee drinking, or the diagnosis of diabetes mellitus. This analysis is the first to examine the relationship between lifestyle factors and the magnitude of the fall in systolic blood pressure on standing after adjustment for the association between the change in a variable and its initial level. Our analysis suggests the need for further study of the possible role of lifestyle factors such as the use of sleeping tablets and alcohol in postural hypotension in the elderly.


Asymptomatic thrombocytopenia developing during pregnancy (gestational thrombocytopenia)--a clinical study. During pregnancy some women develop unexplained thrombocytopenia (gestational thrombocytopenia). Previous studies have detected abnormal platelet antibodies, suggesting an autoimmune aetiology. To determine whether gestational thrombocytopenia is associated with increased maternal bleeding or adversely affects the fetus, 31 pregnant women with asymptomatic thrombocytopenia were compared with 12 women with thrombocytopenia associated with pre-eclampsia and 34 normal pregnant controls. There was no increase in maternal bleeding in those with asymptomatic thrombocytopenia compared with the normal controls, but pre-eclamptic women experienced more bleeding (mean difference 181 ml, 95 per cent confidence limits 50-312 ml, p < 0.01). There was no difference in the mean weights of the babies or placenta, nor in the APGAR scores between infants born to controls and those with asymptomatic thrombocytopenia. Cord blood platelet levels were measured in 26 women with asymptomatic thrombocytopenia and were normal in 25 and mildly reduced in one. Thus measures used for the treatment and delivery of pregnancies complicated by autoimmune thrombocytopenia are not indicated in gestational thrombocytopenia. Pregnant women should not be considered thrombocytopenic unless the platelet count has fallen below 120 x 10(9)/l.


A clinical study of type 2 neurofibromatosis. The clinical features, age at onset of symptoms and survival of 150 patients with type 2 neurofibromatosis were studied. The mean age at onset was 21.57 years (n = 110) and no patients presented after 55 years of age. Patients presented with symptoms attributable to vestibular schwannomas (acoustic neuroma), cranial meningiomas and spinal tumours. In 100 patients studied personally by the authors 44 per cent presented with deafness and this was unilateral in the majority (35/44). Deafness was accompanied by tinnitus in a further 10 per cent and muscle weakness or wasting was the first symptom in 12 per cent. Less common presenting symptoms were seizures (8 per cent), vertigo (8 per cent) numbness and tingling (2 per cent) and blindness (1 per cent). Eleven patients were diagnosed asymptomatically through screening. Café au lait spots occurred in 43 per cent (n = 43) but only one case had six. Skin tumours were detected in 68 per cent (68/100) and 38 per cent (34/90) had an identifiable lens opacity or cataract. The mean age at death in 40 cases was 36.25 years and all but one death was a result of a complication of neurofibromatosis. There are marked inter-family differences in disease severity and tumour susceptibility.


Clinico-pathological correlations and long-term follow-up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulonephritis Registry. The Medical Research Council's Glomerulonephritis Registry was used to study clinicopathological correlations and renal survival in patients with IgA nephropathy reported between 1978 and 1985. IgA nephropathy was the histological diagnosis in 9.3 per cent of all renal biopsies reported to the registry during this period, and in 18.1 per cent of those with a primary glomerulonephritis. The 10-year cumulative renal survival rate accounting for censored data (Kaplan-Meier) was 83.3 per cent. Univariate analysis of survival curves (log-rank test) found the following parameters to be significantly correlated with poor renal survival: serum creatinine > 120 mumol/l (p < 0.001), hypertension (p < 0.001), serum albumin < 40 g/l (p < 0.005), proteinuria > 1 g (p < 0.025), age > 30 years (p < 0.025), and focal mesangial proliferation (p < 0.05). There was no significant difference in renal survival between males and females. Multivariate analysis (Cox's proportional hazards model) revealed that only a serum creatinine of > 120 mumol/l and a serum albumin of < 40 g/l were independently predictive of outcome. These findings indicate marked similarities between the UK experience of IgA nephropathy and the published European experience. IgA nephropathy is not a benign condition in the UK and patients with impaired renal function and/or those with a reduced serum albumin are significantly more likely to progress to end-stage renal failure within 10 years.


Obstructive left ventricular hypertrophy. Reversibility of outflow tract obstruction by drug therapy. We report the cases of four patients with secondary left ventricular hypertrophy (three due to hypertension and one to aortic stenosis) in whom Doppler echocardiography showed dynamic left ventricular outflow tract obstruction and marked impairment of diastolic filling. Each patient derived marked symptomatic benefit from treatment with either a beta-blocker (atenolol) or calcium antagonist (verapamil). Repeat Doppler studies in three patients revealed a substantial improvement in systolic and diastolic flow abnormalities. Ventricular outflow tract obstruction should be recognized as occurring in a subgroup of patients with secondary left ventricular hypertrophy, and its presence should be sought by Doppler echocardiography before embarking on therapy. Negatively inotropic or positively lusitropic agents such as beta-blockers and rate-limiting calcium antagonists appear to be logical therapy for this condition.


An epidemiological and clinical investigation of pulmonary function and respiratory symptoms in patients with rheumatoid arthritis. Several studies have investigated lung function in patients with rheumatoid arthritis but have reached different conclusions. The main discrepancy has been between airways disease reported in 38-65 per cent of patients and interstitial pulmonary disease reported in 30-41 per cent. These variable results have probably arisen because specific lung disorders have often been diagnosed on the basis of non-specific tests of lung function which, when considered in isolation, are subject to different interpretations. We adopted a combined epidemiological and clinical approach to investigate lung function and respiratory symptoms in patients with rheumatoid arthritis. Epidemiological data showed that rheumatoid arthritis is associated with a mild restrictive lung defect with reductions in mean FEV1 and FVC of 0.26 l and 0.29 l respectively and a normal FEV1/FVC ratio. The reduction in mean maximum mid-expiratory flow rate of 0.34 l/s could be explained on the basis of lung restriction and there was no evidence of widespread airways dysfunction other than that which could be explained by cigarette smoking. The clinical study showed that abnormal lung function tests in individual patients were caused by a heterogeneous group of conditions which are frequently caused, or exacerbated, by cigarette smoking. Cigarette smoking, and not the rheumatoid process, was the most frequent cause of abnormal lung function in rheumatoid arthritis.


Normal levels of lipoproteins including lipoprotein(a) after liver-heart transplantation in a patient with homozygous familial hypercholesterolaemia. A 33-year-old female with severe diffuse coronary artery disease and left ventricular outflow tract obstruction secondary to homozygous familial hypercholesterolaemia underwent liver and heart transplantation. During a post-operative follow-up period of 13 months, apart from one episode of cardiac rejection at 3 weeks, she has remained well and without evidence of accelerated coronary disease on angiography. By 3 months after transplantation serum total cholesterol, low density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) levels had decreased and apolipoprotein A-I and high density lipoprotein cholesterol levels had increased, all to within the normal range. These changes were accompanied by marked regression of xanthomata and were maintained at 13 months. Liver transplantation provides an effective means of correcting serum lipids in patients with homozygous familial hypercholesterolaemia and is an important adjunct to cardiac transplantation.


Dietary management of patients with familial hypercholesterolaemia treated with simvastatin. The effect of diet on plasma lipids and lipoproteins was examined in 19 patients with familial hypercholesterolaemia treated with the HMGCoA reductase inhibitor, simvastatin. The study was a randomized double-blind cross-over trial of two diets: a low fat diet and a higher fat diet, and was performed to determine whether ongoing attention to diet is necessary for patients receiving this drug for the treatment of familial hypercholesterolaemia. Plasma cholesterol concentration was 6.5 per cent lower on the low fat diet than on the high fat diet. The difference was within the range predicted by the Jacobs modification of the Keys formula from the reported intake on the two diets. The fall on the low fat diet was principally accounted for by a reduction in low density lipoprotein cholesterol, although high density lipoprotein cholesterol and apolipoprotein A1 also fell. Patients taking HMGCoA reductase inhibitors for the treatment of familial hypercholesterolaemia respond to changes in dietary fat intake. They are thus likely to achieve further reduction in their coronary heart disease risk, and should remain on a low saturated fat low cholesterol diet even when taking these powerful lipid lowering drugs.