Correction to: Electrocardiogram-based predictors for arrhythmia after spinal cord injury.

There is a typographical error in the formula presented for QTVI. While the formula was correctly applied to the data presented, the description of the formula has an incorrectly placed parenthesis. It should read.

Electrocardiogram-based predictors for arrhythmia after spinal cord injury.

PURPOSE: Individuals with spinal cord injury (SCI) have an increased risk of cardiac arrhythmias, particularly during autonomic dysreflexia (acute hypertensive episodes). This may be partly due to impaired autonomic control of the heart after SCI. The interval between the peak and end of the T-wave of the electrocardiograph (ECG) provides an index of transmural dispersion of repolarisation, a factor underlying the development of ventricular arrhythmias. Another ECG-based risk factor for ventricular arrhythmias is variability in the QT segment, the QT variability index (QTVI). Similarly, P-wave variability may be correlated with risk for atrial arrhythmias. We aimed to: (1) determine whether there are abnormalities in these parameters at rest in those with SCI; (2) determine correlations between these ECG parameters and severity of autonomic impairment after SCI. METHODS: ECG intervals were determined using customised software from a 15 min ECG recording (lead II) in 28 SCI subjects and 27 controls. Autonomic severity of SCI was determined from sympathetic skin responses, low frequency systolic blood pressure variability, and plasma noradrenaline levels. RESULTS: T(peak)-T(end) variability and QTVI were increased in those with autonomically complete SCI compared to controls. P-wave variability was increased in SCI individuals compared to controls, and was negatively correlated with plasma noradrenaline. CONCLUSION: The higher T(peak)-T(end) variability, QTVI and P-wave variability in individuals with SCI could be markers of severity of injury to cardiac autonomic (sympathetic) pathways after SCI, and may represent new risk assessment parameters for predisposition to cardiac arrhythmias in this population.

Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy.

Permeant cationic fluorescent probes are shown to be selectively accumulated by the mitochondria of living cells. Mitochondria-specific interaction of such molecules is apparently dependent on the high trans-membrane potential (inside negative) maintained by functional mitochondria. Dissipation of the mitochondrial trans-membrane and potential by ionophores or inhibitors of electron transport eliminates the selective mitochondrial association of these compounds. The application of such potential-dependent probes in conjunction with fluorescence microscopy allows the monitoring of mitochondrial membrane potential in individual living cells. Marked elevations in mitochondria-associated probe fluorescence have been observed in cells engaged in active movement. This approach to the analysis of mitochondrial membrane potential should be of value in future investigations of the control of energy metabolism and energy requirements of specific biological functions at the cellular level.

Purpura and bleeding due to calcium-channel blockers: an underestimated problem? Case reports and a pilot study.

BACKGROUND: Surgical bleeding and occasionally purpura due to calcium-channel blockers have been described. AIM: To present cases in whom purpura or internal bleeding due to calcium-channel blockers was a presenting feature, including one subject with drug-induced haematuria and haematospermia due to amlodipine and one with the Rumpel-Leede sign. Further support for a true association was sought in a pilot study using Hess testing to provoke purpuric skin lesions. METHODS: Four representative cases presenting due to purpura or bleeding are described, all of whom had an abnormal Hess test. A further 19 patients taking calcium-channel blockers and 13 control subjects were also tested. RESULTS: Of 19 patients on calcium-channel blockers, 16 had either abnormal Hess results (n = 13) or marked acral purpura (n = 3) after a Hess test procedure. A similar abnormal response, of milder degree, occurred in only 2 of 13 control subjects. CONCLUSIONS: The high frequency of purpura shown in this study, whether spontaneous or provoked, suggests that this is a pharmacological class effect rather than idiosyncratic. Purpura in patients taking these drugs may be a clue to diagnosis of internal or postsurgical bleeding. We conclude that purpura related to calcium-channel antagonists is probably underestimated, but further studies are needed to identify the mechanism by which this occurs.

Survey of patients' experiences after nail surgery.

Nail surgery is performed to aid diagnosis and treatment of nail disease. A survey was conducted to determine whether patients understood the nature and consequences of nail surgery at the time of consent and to ascertain the most important aspects of morbidity after the procedure. The results identified that most patients understood the nature of their surgery and the immediate postoperative limitations they would face. Pain was short-lived, with no patients requiring analgesics after 6 weeks. The most important finding from this survey was that sensory disturbance was recorded by a large proportion (47%; 29/62) of patients. Of these, 35% (22/62) recorded either complete or partial resolution by 6-12 months after surgery, but 11% (7/62) noted no improvement. This is a point that is not made clear in standard surgical texts. The significance of dysaesthesia of a fingertip must be considered when counselling a patient before surgery.

Assessment of the reliability of intubation and ease of use of the Cook Staged Extubation Set-an observational study.

The Staged Extubation Set has recently been introduced by Cook Medical for the management of difficult airway patients who potentially require reintubation; however, its reliability for intubation and ease of use is not reported in the literature. The set contains a wire and reintubation catheter with a central lumen for the wire and oxygenation if required. Reintubation is by a two-stage Seldinger-like technique. After induction of general anaesthesia, 23 low-risk elective surgical patients had the Staged Extubation Wire from the Cook set inserted into their trachea under direct laryngoscopy. The intubation was subsequently completed using the rest of the Staged Extubation Set as designed. Difficult intubation was simulated by intentionally decreasing the laryngeal view. Simulated reintubation failed in 8.3% and significant technical difficulty in simulated reintubation was noted in another 17.3% of intubation sequences. The latter represent probable failures in a clinical difficult reintubation setting. The mean time taken to intubate was 109 seconds. Using the Cook Staged Extubation Set may be inferior to using an airway exchange catheter for reintubation.

The inhibitory modulation of agonistic behavior in the rat brain: a review.

Neural regions which exercise an inhibitory influence on agonistic behavior are identified by the enhancement of agonistic behavior that follows their removal. The specific kinds of agonistic behaviors altered by each region are then examined. Increased reactivity to the experimenter and enhanced shock-induced fighting are produced by lesions of the region ventral to the anterior septum, the lateral septum, the medial hypothalamus, and the dorsal and median raphe nuclei. It is argued that the increased reactivity and shock-induced fighting correspond to an enhancement of defensive behavior. Mouse killing is induced by lesions of the anterior olfactory nucleus, the region ventral to the anterior septum, the lateral septum, the medial hypothalamus, the dorsal and median raphe nuclei, and the medial amygdala. Because the lesion-induced mouse killing is similar to that emitted by spontaneous mouse killers, it is argued that these regions normally exert an inhibitory control over predatory killing. The available evidence on social attack behavior has not convincingly identified regions exerting an inhibitory control over this dimension of behavior. Our conclusion is that separate brain systems exert an inhibitory control over defensive behavior, predatory killing, and social attack behavior. To a substantial extent, the regions modulating these behaviors appear to act independently of one another. The only neurotransmitter that is clearly active in these inhibitory systems is serotonin, and has only been directly implicated in the control of mouse killing by neurons originating in the dorsal and median raphe nuclei.

Neural systems and the inhibitory modulation of agonistic behavior: a comparison of mammalian species.

The olfactory bulb, lateral septum, medial accumbens, medial hypothalamus, dorsal and median raphe, and amygdala are known from experiments in rats to participate in the inhibitory modulation of defensiveness and predation but not social aggression. The present paper surveys the influence of these structures in the inhibitory control of these same dimensions of agonistic behavior in other species. The existing evidence suggests that lesions in the lateral septum, medial accumbens, medial hypothalamus, or the dorsal and median raphe (or PCPA-induced depletion or serotonin) induce hyperreactivity to the experimenter in mice, rats, cats, dogs, and humans in every instance where they have been tested with one exception. The exception is that lesions in the medial hypothalamus of mice do not induce heightened reactivity. The same lesions do not cause this dramatic increase in reactivity to the experimenter in gerbils, hamsters, guinea pigs, or rabbits but do heighten some other species typical patterns of defensiveness such as alarm calls and avoidance of contact with conspecifics. Lesions in these same areas in monkeys have not been observed to heighten defensive behaviors. Predatory killing or killing of young conspecifics has been observed in hamsters, mice, rats, and cats in every instance where they have been examined following lesions of the olfactory bulbs, lateral septum, medial accumbens, medial hypothalamus, or the dorsal and median raphe nuclei (or PCPA-induced depletion of serotonin). Social aggression has been decreased with these same lesions in each case where they have been examined except for septal lesions in hamsters which have been reported to heighten social aggression. Across species, the consistency with which lesions of the olfactory region, lateral septum, medial accumbens, medial hypothalamus, and dorsal and median raphe nuclei alter defensiveness and predation but not social aggression supports the inference that neural systems exist which subserve the inhibitory modulation of these dimensions of behavior. Finally, the evidence that the disruption of functioning within these structures in humans results in increased agonistic responses to environmental stimuli serves to further establish the important role of this neural circuitry in the normal inhibitory modulation of agonistic behavior in humans.

Aggression in humans: what is its biological foundation?

Although human aggression is frequently inferred to parallel aggression based on testosterone in nonprimate mammals, there is little concrete support for this position. High- and low-aggression individuals do not consistently differ in serum testosterone. Aggression does not change at puberty when testosterone levels increase. Aggression does not increase in hypogonadal males (or females) when exogenous testosterone is administered to support sexual activity. Similarly, there are no reports that aggression increases in hirsute females even though testosterone levels may rise to 200% above normal. Conversely, castration or antiandrogen administration to human males is not associated with a consistent decrease in aggression. Finally, changes in human aggression associated with neuropathology are not consistent with current knowledge of the neural basis of testosterone-dependent aggression. In contrast, human aggression does have a substantial number of features in common with defensive aggression seen in nonprimate mammals. It is present at all age levels, is displayed by both males and females, is directed at both males and females, and is not dependent on seasonal changes in hormone levels or experiential events such as sexual activity. As would be expected from current knowledge of the neural system controlling defensive aggression, aggression in humans increases with tumors in the medial hypothalamus and septal region, and with seizure activity in the amygdala. It decreases with lesions in the amygdala. The inference that human aggression has its roots in the defensive aggression of nonprimate mammals is in general agreement with evidence on the consistency of human aggressiveness over age, with similarities in male and female aggressiveness in laboratory studies, and with observations that some neurological disturbances contribute to criminal violence. This evidence suggests that human aggression has its biological roots in the defensive aggression of nonprimate mammals and not in hormone-dependent aggression based on testosterone.

Hormone-dependent aggression in male and female rats: experiential, hormonal, and neural foundations.

Hormone-dependent aggression in both male and female rats includes the distinctive behavioral characteristics of piloerection and lateral attack. In males the aggression is dependent on testicular testosterone and is commonly known as intermale aggression. In females, the aggression is most commonly observed as maternal aggression and is dependent on hormones whose identity is only beginning to emerge. The present review examines the experiential events which activate hormone-dependent aggression, the relation of the aggression to gonadal hormones, and the neural structures that participate in its modulation. In males and females, the aggression is activated by cohabitation with a conspecific of the opposite sex, by competitive experience, and by repeated exposure to unfamiliar conspecifics. In the female, the presence of pups also activates aggression. In both males and females, hormones are necessary for the full manifestation of the aggression. The essential hormone appears to be testosterone in males and a combination of testosterone and estradiol in females. The information available suggests the neural control systems for hormone-dependent aggression may be similar in males and females. It is argued that hormone-dependent aggression is behaviorally and biologically homologous in male and female rats.

Mouse killing induced by para-chlorophenylalanine injections or septal lesions but not olfactory bulb lesions is similar to that of food-deprived spontaneous killers.

Mouse killing induced by septal lesions, olfactory bulb lesions, or parachlorophenylalanine (PCPA) injections was compared with that of sated or food-deprived spontaneous mouse-killing rats in order to evaluate whether the experimentally induced killing corresponds to killing that occurs spontaneously, which tends to be viewed as predatory. On the first mouse kill, the intensity of the initial reaction to the mouse, the site of the initial attack, and the time required to kill by all groups were similar except that bulbectomized rats required longer to kill. Following the kill, only rats with septal lesions and bulbectomized rats bit the mouse significantly more than spontaneous killers. With the second mouse kill, there was an increase in the intensity of the response to the mouse and a decrease in attack latency by all groups except the bulbectomized rats and the nondeprived spontaneous killers. When presented with a freshly killed mouse, rats with septal lesions attacked with the greatest intensity, but PCPA-injected rats and food-deprived spontaneous killers also attacked more intensely than nondeprived killers. When presented with a wad of cotton or a block of wood, there was little or no response from the animals of all groups. It is argued that the mouse killing induced by septal lesions or PCPA injections may be due to an enhanced predatory tendency similar to that occurring in food-deprived spontaneous killers. In contrast, the mouse killing by bulbectomized rats cannot be inferred to be predatory because their attacks were of low intensity and involved repeated superficial bites rather than one or two well-directed forceful bites.

Whole body fatigue and critical power: a physiological interpretation.

Critical power (CP) is a fundamental concept describing fatigue and exhaustion. The main physiological determinant of CP is the ability to utilise oxygen. This in turn is dependent primarily on diffusion distance. During exercise, many different tissue systems must increase their metabolic demand. It is argued that each tissue system, such as cardiac, respiratory and leg muscles, has their own CP. Cardiac muscle has the greatest CP relative to its maximum power because it has the shortest diffusion distances. Respiratory muscle also has a substantially higher relative CP than leg muscle. The higher relative CPs of cardiac and respiratory muscle are due in part to the homeostatic functions these tissues provide. This built in protective design can be disrupted in certain conditions such as hypoxia. During high intensity exercise, fatigue and ensuing exhaustion will occur if any contributing physiological system functions above its CP.

Possible mechanisms of the anaerobic threshold. A review.

The anaerobic threshold consists of a lactate threshold and a ventilatory threshold. In some conditions there may actually be 2 ventilatory thresholds. Much of the work detailing the lactate threshold is strongly based on blood lactate concentration. Since, in most cases, blood lactate concentration does not reflect production in active skeletal muscle, inferences about the metabolic state of contracting muscle will not be valid based only on blood lactate concentration measurements. Numerous possible mechanisms may be postulated as generating a lactate threshold. However, it is very difficult to design a study to influence only one variable. One may ask, does reducing F1O2 cause an earlier occurrence of a lactate threshold during progressive exercise by reducing oxygen availability at the mitochondria? By stimulating catecholamine production? By shifting more blood flow away from tissues which remove lactate from the blood? Or by some other mechanism? Processes considered essential to the generation of a lactate threshold include: (a) substrate utilisation in which the ability of contracting muscle cells to oxidise fats reaches maximal power at lactate threshold; and (b) catecholaminergic stimulation, for without the presence of catecholamines it appears a lactate threshold cannot be generated. Other mechanisms discussed which probably enhance the lactate threshold, but are not considered essential initiators are: (a) oxygen limitation; (b) motor unit recruitment order; (c) lactate removal; (d) muscle temperature receptors; (e) metabolic stimulation; and (f) a threshold of lactate efflux. Some mechanisms reviewed which may induce or contribute to a ventilatory threshold are the effects of: (a) the carotid bodies; (b) respiratory mechanics; (c) temperature; and (d) skeletal muscle receptors. It is not yet possible to determine the hierarchy of effects essential for generating a ventilatory threshold. This may indicate that the central nervous system integrates a broad range of input signals in order to generate a non-linear increase in ventilation. Evidence indicates that the occurrence of the lactate threshold and the ventilatory threshold may be dissociated; sometimes the occurrence of the lactate threshold significantly precedes the ventilatory threshold and at other times the ventilatory threshold significantly precedes the lactate threshold. It is concluded that the 2 thresholds are not subserved by the same mechanism.

Aggression in the lactating female rat: the normal decline is not dependent on the physical development of the pups.

Female rats that had been assessed for aggression on two occasions during pregnancy were also assessed for aggressiveness toward an unfamiliar adult female on days 5, 12, and 19 of lactation. Each female had its litter of pups exchanged for another litter on days 10 and 17 following parturition. Half of the females received pups that were 2 days old. The other half received pups of the same age as those taken away. Aggression by females of the two groups declined at a similar rate during the period of lactation. Retrieval of a group of seven 6-day-old pups following the last aggression test was present in females whose litter had been replaced with 2-day-old pups but not in females whose litter had been replaced with same-age pups. Lactation was maintained in all females during the three weeks following parturition but declined to a level that was not sufficient to maintain growth following the normal 21 day lactation period. A single set of biological or stimulus variables does not maintain all aspects of maternal behavior. Physical and behavioral maturation of the pups does not appear responsible for the decline in maternal aggression during the final two weeks of lactation.

Aggression is attenuated by ovariectomy in pregnant female rats given progesterone and estradiol replacement to maintain pregnancy.

Female rats were tested for aggression toward an unfamiliar female conspecific 13 days following the beginning of cohabitation with a male. Forty-eight hours later, half of the females that displayed aggression were ovariectomized. To maintain pregnancy, they were also given Silastic implants of estradiol (1-mm tube) and progesterone (6 tubes, 30-mm long; Dow-Corning tubing #602-305) sufficient to maintain pregnancy but at lower levels than those normally present. Control females were given a sham ovariectomy and implanted with empty tubes. Each animal received a second aggression test at 48 h following surgery and a third test, 3 days following the second. Hormone implants successfully maintained pregnancy and supported the normal development of the pups. However, Ovariectomized females with hormone implants did not spontaneously give birth. Ovariectomized females displayed less aggression than their sham-ovariectomized counterparts at the second and third aggression tests. The difference was due to an increasing level of aggression by the control but not the experimental animals. These results are consistent with other evidence that circulating gonadal hormones influence the onset of maternal aggression in the female rat.

Medial hypothalamic lesions in the rat enhance reactivity and mouse killing but not social aggression.

In rats subjected to lesions of the medial hypothalamus, 8 of 11 animals became mouse killers and all manifested some degree of hyperreactivity to the experimenter. When introduced as intruders into a mixed sex colony group, the lesioned rats did not manifest piloerection nor did they emit flank attacks characteristic of social aggressive behavior. However, the lesioned animals did respond to the attacks of the resident male rats with significantly more counterattacks and biting than did sham-lesioned control rats. Spontaneous mouse killing rats also failed to show a level of social aggressive behavior significantly greater than that of sham-operated control rats, but the spontaneous mouse killers did kill rat pups in the colony groups. Alpha-male rats when introduced as an intruder into a colony group did exhibit piloerection and emit flank attacks characteristic of social aggressive behavior. These results demonstrate that the mouse killing and heightened reactivity associated with medial hypothalamic lesions do not represent an indiscriminant release of all forms of agonistic behavior.

Medial hypothalamic and medial accumbens lesions which induce mouse killing enhance biting and attacks on inanimate objects.

The response to a series of objects by rats with lesions of the medial hypothalamus or medial accumbens was compared to that of spontaneous killing rats and sham-lesioned nonkillers. When exposed sequentially to a piece of wood, a wad of cotton, or a freshly killed mouse, there were no differences in the intensity of the initial response toward the stimulus object by spontaneous mouse killing rats and lesioned animals that were later shown to kill mice. However, lesioned animals did spend more time biting these objects and were more likely than spontaneous killers to attack the objects if they were moved about by the experimenter. When allowed to kill mice, there were no differences in the intensity of the attack by spontaneous and lesion-induced killers but again the lesioned animals bit the prey more following the kill and were more likely to attack the dead prey when it was moved by the experimenter. Sham-lesioned nonkillers spent less time biting the stimulus objects than spontaneous killers and never attacked the objects when they were moved by the experimenter. It is argued that the killing of lesioned animals is homologous to that of spontaneous killers but that the lesioned animals exhibit most components of the predatory behavior to an exaggerated degree.

Rearing rats with mice prevents induction of mouse killing by lesions of the septum but not lesions of the medial hypothalamus or medial accumbens.

Rats which had been reared with mice and those which had not were subjected to lesions of the septum, medial accumbens, medial hypothalamus, or sham lesions. Forty-eight hours later all animals were presented with a mouse and the frequency of mouse killing recorded. In rats with lesions of the septum, the lesions induced killing only in those animals which had not been reared with mice. Rats with lesions of the medial accumbens or medial hypothalamus killed significantly more often than control animals even when they had been reared with mice. These results suggest that the septum, medial accumbens and medial hypothalamus subserve different functions in the inhibitory modulation of mouse killing behavior.

Aggression by a female rat cohabiting with a sterile male declines within 27 h following ovariectomy.

Females that had become aggressive as a result of cohabiting with a sterile male were ovariectomized and implanted with empty Silastic tubes. Control groups were either sham ovariectomized or ovariectomized and implanted with Silastic tubes providing replacement levels of estradiol and testosterone. Twenty-seven hours following surgery, all animals were tested for aggressiveness toward an unfamiliar female rat. The aggression of ovariectomized females without hormone replacement declined to a minimal level postoperatively and was significantly lower than that of sham-ovariectomized females or ovariectomized females with estradiol and testosterone replacement. Both sham-ovariectomized females and ovariectomized females given hormone replacement displayed a level of aggression close to that observed preoperatively. The aggression of a female rat cohabiting with a sterile male appears to be highly sensitive to the removal of gonadal hormones. This corresponds with observations made on pregnant females and contrasts with those made on lactating females.

Hormone-dependent aggression in the female rat: testosterone plus estradiol implants prevent the decline in aggression following ovariectomy.

Female rats were individually housed with a sterile male for the duration of the experiment. Beginning 7 to 10 weeks after the start of cohabitation, each female was tested for aggression toward an unfamiliar female at weekly intervals for 3 weeks. Females that displayed consistent and substantial aggression were given one of the following treatments: ovariectomy followed by both testosterone and estradiol implants, ovariectomy followed by 2 empty implants, or sham ovariectomy followed by 2 empty implants. The implants were subcutaneously placed hormone-filled Silastic capsules. They were expected to produce a serum testosterone concentration of 0.5 ng/ml and an estradiol concentration of 15 pg/ml. Postoperatively, the aggression of each female continued to be assessed on a weekly basis for 3 weeks. Ovariectomized females with hormone implants displayed a level of aggression postoperatively similar to that of sham-ovariectomized females and significantly greater than that of ovariectomized females with empty implants. These results, together with others, suggest that estradiol and testosterone act together to form the hormonal foundation of hormone-dependent aggression by females cohabiting with a sterile male.