Avascular necrosis of bone after cardiac transplantation. Prevalence and relationship to administration and dosage of steroids.

We studied the relationship of the administration and dosage of steroids to the development of avascular necrosis of bone in 168 patients who had had a heart transplantation (156 patients) or a heart and lung transplantation (twelve patients). One hundred and forty-one of the patients were male and twenty-seven were female. The average age was forty-five years (range, seven to sixty-six years). The average duration of follow-up was forty months (range, twelve to eighty months). Avascular necrosis developed in five patients (3 per cent). The femoral head was involved in three patients (bilaterally in two and unilaterally in one), the medial femoral condyle was involved bilaterally in one, and several sites were involved in the fifth patient. The avascular necrosis was diagnosed an average of five months (range, two to eleven months) after the transplantation. In order to evaluate the influence of the dosage of the steroids on the development of avascular necrosis of bone, the doses of prednisone and Solu-Medrol (methylprednisolone) at one week, one month, six months, and one year after the transplantation were calculated for each patient. There was no association between the cumulative dose of prednisone and the development of avascular necrosis. There was, however, a strong statistical association (p = 0.005), as determined with pooled two-tailed variance analysis, between the cumulative dose of Solu-Medrol administered in the first month after the transplantation and the development of avascular necrosis.

Avascular necrosis superimposed on Legg-Calvé-Perthes disease in a cardiac transplant patient.

The pathogenesis of both Legg-Calvé-Perthes disease (LCPD) and avascular necrosis (AVN) remains controversial. Evidence suggests, however, that both conditions are produced by vascular compromise in the femoral head. A patient with a previous history of LCPD at age eight subsequently developed AVN at age 46 after having a cardiac transplant for ischemic cardiomyopathy. A review of the past ten years' literature disclosed no reports of similar cases.

Intra-habenular injection of 6-hydroxydopamine produces impaired acquisition of DRL operant behavior.

The anatomical connections of the habenula complex indicate it provides a relay between limbic forebrain and midbrain. Somewhat paradoxically, consequences of nonspecific lesion of the habenula are ambiguous with little change in basic response evident within simple behavioral paradigms. However, the potential functional importance for this relay has more recently been indicated by the demonstration of deficits in the ability of lesioned animals to alter behavior appropriate to both internal and external stimuli in more demanding behavioral tasks. Doubts concerning the importance of the habenula remain because of the large number of descending fibers of passage through the habenula. To provide more substantive evidence, 6-hydroxydopamine was injected into the habenula of rats to provide more limited lesion of catecholaminergic terminals. Animals were subsequently trained on an operant DRL 20-s schedule for which deficits have been reported following nonspecific lesion of the habenula. Lesioned animals showed a tendency to overrespond and were significantly less efficient on the schedule with decreased number of reinforcements received relative to controls. While the neurotoxic lesion procedure used does not differentiate noradrenergic and dopaminergic damage, the importance of intact catecholaminergic systems within the habenula for effective DRL acquisition is consistent with the suggested importance of the habenula for feedback regulation of dopamine within the ventral tegmental area through ascending dopamine fibers to the habenula.

Increased immobility in an automated forced swimming test following lesion of the habenula in rats: absence of evidence for a contribution from motor impairment.

The effects of lesions of the habenula on responses during a forced swimming test (FST) were examined. Active behavior, documented by turns on a drum immersed in a water tank, were reduced in lesioned rats. Lesioned rats also demonstrated an inability to escape from the water by climbing onto the drum when it was locked in position at the end of the test. There was a tendency for lesioned rats to show more activity in open-field tests either after the FST or independent of such prior testing. Lesioned rats showed no motor or postural abnormalities and were able to maintain position for longer than controls during a rotating rod test. Collectively, the results are compatible with the suggestion that lesions of the habenula impair the ability to change motor strategies under stress but indicate such failures may not be ascribed to gross motor impairment.

Effort and stress influence the effect of lesion of the habenula complex in one-way active avoidance learning.

Previous studies which have examined the effects of lesions of the habenula on active avoidance learning have not provided unambiguous support for response deficits. Moreover, interpretation of early studies is confounded by large lesions which damaged adjacent structures. We report the effects of smaller circumscribed lesions of the habenula complex on a simple one-way active avoidance paradigm in three separate experiments in which the required operant was a step or jump onto an elevated platform. In the first study involving avoidance of shock of low intensity (0.5 mA) with an average long intertrial interval of 8 minutes, lesioned animals were not significantly different from sham operated controls. However, in following experiments in which stress levels were increased by raising the shock intensity and reducing the intertrial-interval, or in which the operant was made considerably more demanding by raising the height the animals had to jump to make an avoidance response, there were large lesion induced deficits in avoidance responding. The absence of significant differences between lesioned and sham operated controls in escape latencies suggested no lesion induced impairment of the response to the shock. It is suggested that the data not only support an effect of habenular lesions on active avoidance learning but also are consistent with a previous suggestion that the functional effects of lesion of the habenula on behaviour are effected through changes in dopaminergic function.

A failure to support cross-sensitization between effects of apomorphine and lesions of the habenula nucleus.

An interchangeability between the effects of stress and psychostimulants has been reported. The possible common physiological effects of lesions of the habenula, stress and psychostimulant administration of activation of ascending dopamine systems suggested examination of a cross-sensitization between lesions of the habenula and psychostimulant administration. Lesions of the habenula were found to increase baseline activity but there were no significant changes in response to apomorphine in either various categories of stereotypy or locomotor response. Lesioned rats and controls both demonstrated similar dose and time-related effects in various response measures. Although not significant, certain results suggested that changes tended to be in the direction opposite to that of the suggested sensitization. The results are contrasted with previous supporting data and discussed in terms of the potentially diverse manner in which habenular manipulation and psychostimulants may influence dopaminergic activity and subsequent behaviour.