Hippocampal α7-nicotinic cholinergic receptors modulate memory reconsolidation: a potential strategy for recovery from amnesia.

When subjects are exposed to new learning experiences, the novel information could be acquired and eventually stored through memory consolidation process. The exposure of mice to a novel experience (a hole-board) after being trained in an inhibitory avoidance apparatus is followed by impaired performance of the avoidance memory in subsequent tests. The same impairing effect is produced when mice are exposed to the novel environment after the reactivation of the avoidance memory. This interfering effect is due to impaired consolidation or reconsolidation of the avoidance memory. The administration of the α7-nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8 µg/hippocampus) immediately after the inhibitory avoidance memory reactivation, allowed memory recovery. This effect of Ch was time-dependent, and retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the effects on performance are not due to non-specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by new learning is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change whether a memory will be expressed in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia.

Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation.

It is widely known that pre-training systemic administration of the muscarinic antagonist scopolamine (SCP) (0.5mg/kg, i.p.) leads to anterograde memory impairment in retention tests. The administration of the α(7)-nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8µg/hippocampus) immediately after memory reactivation allowed recovery from scopolamine-induced memory impairment. This effect of Ch was time-dependent, and retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the performance effects are not due to non-specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by low doses of SCP is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change memory expression in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia.

Memory consolidation and reconsolidation of an inhibitory avoidance task in mice: effects of a new different learning task.

CF-1 male mice were trained in an inhibitory avoidance task using a high footshock (1.2mA, 50Hz, 1 s) in order to reduce the influence of extinction on retention performance. A single session of 5 min exposure to a hole-board (nose-poke behavior), either immediately after training or the first retention test (memory reactivation) impaired retention performance over two consecutive days. The effects were time-dependent since they were not observed when the exposure to the hole-board was delayed 3 h. When mice were habituated to the hole-board (5 min/day, 5 days), and then trained in an inhibitory avoidance task, the immediately post-training or memory reactivation exposure to the hole-board did not modify retention performance over two consecutive days. The effects of the post-reactivation acute exposure to the hole-board were long-lasting (21 days). Reinstatement was not observed in our experimental conditions. The non-spontaneous recovery of retention performance over 21-days and the lack of reinstatement, suggest that the impairment of retention performance observed was not probably due to a deficit in memory retrieval. These findings suggest that the exposure to a potential new learning situation impairs not only memory consolidation but also memory reconsolidation of the original learning task.

Memory reconsolidation of an inhibitory avoidance task in mice involves cytosolic ERK2 bidirectional modulation.

Reconsolidation has been defined as the process of memory stabilization after retrieval involving, among others, gene expression regulation and post-translational modifications. Many of these mechanisms are shared with memory consolidation. Here, we studied hippocampal ERK participation on memory reconsolidation of an inhibitory avoidance task in CF-1 mice. We found a retrieval-induced cytosolic ERK2 activation in the hippocampus (HIP) 15 min after memory reactivation, and an inhibition at 45 min. PD098059, a MEK1/2 (MAPK/ERK kinase) inhibitor, administered in the HIP immediately after retrieval impaired memory in a dose-dependent fashion. However, infusions of the highest dose of PD098059 performed 40 min after retrieval enhanced memory in mice trained with a weaker footshock. These results suggest for the first time that ERK2 is involved in memory reconsolidation in a biphasic fashion. Furthermore, the inhibition of ERK could either impair or enhance mice performance depending on ERK state of activation.

Hippocampal dynamics of synaptic NF-kappa B during inhibitory avoidance long-term memory consolidation in mice.

Since the discovery that long-term memory is dependent on protein synthesis, several transcription factors have been found to participate in the transcriptional activity needed for its consolidation. Among them, NF-kappa B is a constitutive transcription factor whose nuclear activity has proven to be necessary for the consolidation of inhibitory avoidance in mice. This transcription factor has a wide distribution in the nervous system, with a well-reported presence in dendrites and synaptic terminals. Here we report changes in synaptosomal NF-kappa B localization and activity, during long-term memory consolidation. Activity comparison of synaptosomal and nuclear NF-kappa B, indicates different dynamics for both localizations. In this study we identify two pools of synaptosomal NF-kappa B, one obtained with the synaptoplasm (free fraction) and the second bound to the synaptosomal membranes. During the early steps of consolidation the first pool is activated, as the membrane associated transcription factor fraction increases and concomitantly the free fraction decreases. These results suggest that the activation of synaptic NF-kappa B and its translocation to membranes are part of the consolidation of long-term memory in mice.

A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis.

We attempted to define the role of subtle changes in the normal-appearing white matter (NAWM) in the development of disability in multiple sclerosis (MS). Twenty-seven clinically definite MS patients with either relapsing-remitting or chronic-progressive courses and 10 sex- and age-matched controls entered the study. For each patient and control, we studied two NAWM areas in the frontal lobe with magnetization transfer imaging (MTI). For patients, we also calculated the MT ratios (MTRs) for three contiguous areas of NAWM progressively further from "isolated" lesions visible on conventional MRI. Frontal NAWM in MS patients had lower mean MTRs than the frontal white matter of the controls (p = 0.02). MTRs in the NAWM adjacent to isolated lesions increased with distance from them to the cortical gray matter (p = 0.04). This pattern was typical for patients with chronic-progressive MS whose MTRs in the first two regions of NAWM adjacent to lesions were lower than those of the same regions of patients with relapsing-remitting MS. This study confirms that there are alterations in the NAWM of MS patients and suggests that such changes might be relevant to the disability in MS.

Memory consolidation and reconsolidation of an inhibitory avoidance response in mice: effects of i.c.v. injections of hemicholinium-3.

The immediate post-training i.c.v. administration of hemicholinium-3 (HC-3) (1 microg), a specific inhibitor of the high-affinity choline uptake (HACU) in brain cholinergic neurons, impaired retention test performance of a one-trial step-through inhibitory avoidance response in adult male CF-1 mice. The effect was observed in mice that received a footshock (0.8 mA, 50 Hz, 1 s) on the learning trial, and not only 48 h after training, but also 7 days after it. After the completion of the retention test at each of the training-test interval that were studied, the HACU in the hippocampus of HC-3-treated mice was not significantly different from that of saline-injected (1 microl) control groups. Mice that were over-reinforced (1.2 mA, 50 Hz, 1 s) on the learning trial, exhibited a high retention performance 48 h after training. The immediate i.c.v. injection of HC-3 (1 microg) after the retention test, that is, after memory reactivation, significantly impaired retention performance over 4 consecutive days, whereas the saline-injected control group shown a slight, but significant performance decrease only at the last retention test. Retention performance was unchanged in HC-3-treated mice not undergoing memory reactivation session. These results, taken together, indicate that HC-3, not only impaired consolidation, but also reconsolidation of an inhibitory avoidance task in mice, suggesting a critical participation of central cholinergic mechanisms in both memory processes.

Selective brain noradrenaline depletion induced by the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP 4) does not prevent the memory facilitation induced by a muscarinic agonist in mice.

These experiments investigated the effects of central noradrenaline (NA) depletion and its interaction with cholinergic and dopaminergic mechanisms upon retention of a passive-avoidance response in mice. The NA selective neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP 4) (50 mg/kg IP, 7 days) was injected into mice to produce depletion of NA in frontal cortex, hypothalamus, cerebellum, midbrain and brain stem without any significant change in dopamine (DA) levels in frontal cortex, striatum, hypothalamus and midbrain. Depletion of brain NA produced by DSP 4 was significantly but not completely prevented by the NA uptake inhibitor desmethylimipramine (DMI) (10 mg/kg IP, 30 min before DSP 4 injection). Despite the marked NA depletion, DSP 4 neither impaired the retention of a passive-avoidance response in mice nor prevented the enhancement of retention of this response induced by the central muscarinic agonist oxotremorine (OTM) (0.05 mg/kg IP, immediately after training. This lack of effect of DSP 4 on retention was prevented neither by DMI nor by the serotonin uptake inhibitor fluoxetine (5 mg/kg IP, 30 min before DSP 4 injection). The enhancement of retention induced by OTM in the groups of mice injected with either water or DSP 4 was prevented by atropine (0.5 mg/kg IP, 20 min before training) but not by methylatropine in the same experimental conditions. This suggests that both in controls and DSP 4-pretreated mice, the primary effect of OTM is due to an interaction with muscarinic brain receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Memory facilitation with posttrial injection of oxotremorine and physostigmine in mice.

The immediate posttrial injection of oxotremorine (0.125, 0.250 and 0.500 muMol/kg i.p.) and equimolecular doses of physostigmine can facilitate the retention of a passive avoidance response in mice. Injections given 10 min after training also significantly facilitate retention, but injections given 30 or 120 min after training do not affect retention. These findings suggest an action of oxotremorine and physostigmine on mechanisms involved in memory storage. The enhanced retention produced by oxotremorine and physostigmine was blocked by pretreatment with atropine (2 muMol/kg, 20 min, i.p.) but was not affected by methylatropine (2 muMol/kg, 20 min, i.p.). The retention was not modified by posttrial injection of metoxotremorine (0.25 muMol/kg i.p.) or neostigmine (0.250 muMol/kg i.p.), quaternary analogs of oxotremorine and physostigmine, respectively. The results suggest a central action of both cholinergic agents attributable to an activation of muscarinic brain receptors.

Brain catecholamines modifications. The effects on memory facilitation induced by oxotremorine in mice.

the immediate posttrial injection of oxotremorine (0.250 mu Mol/kg, IP) can facilitate the retention of a passive-avoidance response in mice. After the administration of alfa-methyl-p-tyrosine methylester (alpha-MPT) by intracerebroventricular injection at doses that had no effect on retention (100 microgram, 10 microliter, 60 min before trial), the immediate posttrial injection of oxotremorine did not enhance retention. The employed dose of alpha-MPT reduced brain levels of norepinephrine by about 40% and those of dopamine by about 25%. Pretreatment with nialamide (30 mg/kg, 20h IP), which prevents the catecholamine depletion induced by alpha-MPT, counteracted the effects depletion induced by alpha-MPT, counteracted the effects of alpha-MPT on the actions of oxotremorine on retention. These results suggest a participation of brain catecholamines on the actions of oxotremorine on retention and a possible interaction of cholinergic neurons with catecholaminergic system in memory processes.

Possible cholinergic-dopaminergic link in memory facilitation induced by oxotremorine in mice.

The immediate post-trial injection of the centrally active muscarinic agonist oxotremorine (0.025, 0.050 and 0.100 mg/kg, IP) can facilitate the retention of a passive-avoidance response in mice, as indicated by performance on a retention test 24 h later. Injections given 10 min after training also significantly facilitated retention, but given 120 min after training did not affect retention. These findings suggest an action of oxotremorine on memory mechanisms. The enhanced retention was neither the result of a punishing effect of oxotremorine nor of a nonspecific proactive pharmacological action of the drug. The memory facilitation produced by oxotremorine (0.050 mg/kg, IP) was not antagonized by pretreatment with phentolamine (10 mg/kg, 30 min, IP), phenoxybenzamine (10 mg/kg, 120 min, IP) or piperoxane (20 mg/kg, 30 min, IP). The alpha-noradrenergic blocking agents had no effect by themselves. On the other hand, the immediate post-trial injection of oxotremorine (0.050 mg/kg, IP) did not enhance retention when mice were pretreated with haloperidol (0.5 mg/kg, 120 min, IP). Haloperidol injected either before training or before the retention test did not alter performance during the retention test. This suggests that haloperidol impairs neither acquisition of the avoidance response nor its retrieval. Thus, it is probable that haloperidol pretreatment impaired oxotremorine-induced memory facilitation. We suggest a possible participation of brain catecholamines in memory facilitation induced by oxotremorine in mice.

A spinal cord MRI study of benign and secondary progressive multiple sclerosis.

This study was performed to achieve a better definition of the nature of the disability in multiple sclerosis (MS). Axial spinal cord magnetic resonance imaging (MRI) at C5 was obtained in 15 patients with benign MS, 17 patients with secondary progressive MS and 10 healthy controls. Patients with secondary progressive MS had smaller spinal cord cross-sectional area (P = 0.01) and transverse diameter (P = 0.006) than patients with benign MS. The degree of disability was inversely correlated with both the cross-sectional area (r = -0.6, P = 0.0018) and transverse diameter (r = -0.5, P = 0.0032) of the cord. Spinal cord atrophy was found in 7 (41%) patients with secondary progressive MS and in 2 (13%) with benign MS. These findings suggest that destructive pathology within MS lesions might play a relevant role in the development of disability in MS.

Memory improving actions of gabapentin in mice: possible involvement of central muscarinic cholinergic mechanism.

Male CF-1 mice were tested 48 h after training on a one trial step-through inhibitory avoidance task. Immediately post-training, intraperitoneal (i.p.) injections of the antiepileptic gabapentin (1-(aminomethyl) cyclohexaneacetic acid) (GBP, 10 mg/kg) enhanced retention performance. The effect was prevented by atropine, a central muscarinic cholinergic receptor antagonist (0.5 mg/kg, i.p.) administered after training but 10 min prior to GBP treatment. In contrast, neither methylatropine (0.5 mg/kg, i.p.), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training GBP on retention performance. Low subeffective doses of the central acting anticholinesterase physostigmine (35 mg/kg, i.p.) administered immediately after training, and GBP (5 mg/kg, i.p.), given 10 min after training, significantly enhanced retention performance. The effects of GBP (5 mg/kg, i.p.) were not influenced by the peripherally acting anticholinesterase neostigmine (150 mg/kg, i.p.). Considered together, these findings suggest a disinhibitory action of GBP on the activity of central muscarinic cholinergic mechanisms that are involved in memory consolidation.

Gabapentin, an antiepileptic drug, improves memory storage in mice.

Male CF-1 mice were tested 48 h after training in a one-trial step-through inhibitory avoidance task. Immediately post-training i.p. injections of the antiepileptic drug gabapentin (1-aminomethyl cyclohexaneacetic acid) (GBP; 5, 10, 50, and 100 mg/kg) induced a dose-dependent enhancement of retention performance. Gabapentin did not affect response latencies in mice not given the footshock on the training trial, indicating that the actions of GBP on retention were not due to non-specific proactive effects on response latencies. The effects of GBP (10 mg/kg) were time-dependent, and the administration of GBP (10 mg/kg) 30 min before training also enhanced retention performance. However, the administration of GBP (10 mg/kg) 30 min prior to the retention test did not modify retention latencies of mice that had received either saline or GBP (10 mg/kg) immediately after training. Altogether, the results suggest that GBP influences retention by modulating time-dependent processes involved in memory storage, although the mechanism(s) of this action remain to be established.

Acute transverse myelopathy: spinal and cranial MR study with clinical follow-up.

PURPOSE: To evaluate the contribution of MR in determining the cause of acute transverse myelopathy, to determine the frequency and types of the intracranial lesions detectable on MR at the onset of the disease, and to monitor clinical and MR evolution of the disease. METHODS: Spinal and cranial MR images were obtained for 30 patients with acute transverse myelopathy. Gadopentetate dimeglumine was administered in 10 patients. Mean follow-up time was 18 months. RESULTS: Spinal cord MR findings were abnormal in 14 of 30 patients. The abnormal MR can be divided into group A, in which one segment was involved (8 patients), and group B, in which more than one segment was involved (6 patients). In both groups there were 2 patients with enhancing lesions. Enhancement was less homogeneous in the group B patients. Enhancement did not change with increased length of lesion. At follow-up, the diagnostic categories of the patients were multiple sclerosis (8 patients), encephalomyelitis (1 patient), viral myelitis (3 patients), and myelopathy of unknown cause (18 patients). After the episode of acute transverse myelopathy, in 4 of 8 patients in group A and in 4 of 5 patients with normal spinal MR but abnormal brain MR findings clinical signs of multiple sclerosis developed. In no patients in group B did multiple sclerosis develop. The final diagnoses for the 4 patients with gadolinium-enhancing spinal lesions were myelopathy of unknown cause (2 patients), multiple sclerosis (1 patient), and viral myelitis (1 patient). CONCLUSION: MR contributed to establishing the diagnosis in 40% of our cases.

Intraobserver and interobserver variability in schemes for estimating volume of brain lesions on MR images in multiple sclerosis.

PURPOSE: Our goal was to evaluate the intraobserver and interobserver reproducibility of measurements of brain lesion load in multiple sclerosis (MS) by using two proposed acquisition schemes. METHODS: Three-millimeter-thick conventional spin-echo (CSE) and fast fluid-attenuated inversion-recovery (FLAIR) sequences were obtained and the lesions segmented using a semiautomated technique based on local thresholding to calculate intraobserver and interobserver reproducibility. These were compared with images obtained from two separate MR units in which 5-mm CSE sequences were obtained and segmented by using the local thresholding technique and also by manual outlining. RESULTS: The intraobserver coefficient of variation was 4.0% (95% confidence interval [CI], 3.0% to 4.5%) for the 5-mm CSE sequence measured with manual outlining, 3.1% (95% CI, 2.5% to 3.2%) and 5.1% (95% CI, 4.1% to 5.6%) for the two sets of 5-mm CSE sequences measured using the local thresholding technique, 5.7% (95% CI, 3.9% to 6.6%) for the 3-mm CSE sequence, and 2.6% (95% CI, 2.1% to 2.7%) for the fast FLAIR sequence. The interobserver coefficient of variation was 7.1% (95% CI, 4.9% to 8.7%) and 8.3% (95% CI, 6.4% to 9.6%) for the two sets of 5-mm CSE sequences, 7.3% (95% CI, 4.7% to 9.1%) for the 3-mm CSE sequence, and 2.9% (95% CI, 2.3% to 3.3%) for the fast FLAIR sequence. The intraobserver and interobserver reproducibility of measurements obtained with the fast FLAIR technique was significantly better than those obtained with the other techniques. CONCLUSIONS: Our data indicate that the intraobserver and interobserver variability in quantifying MS lesions can be reduced significantly with the use of fast FLAIR sequences, while no significant improvement is gained by reducing the section thickness from 5 mm to 3 mm.

Effects of 6-hydroxydopamine Treatment at birth on the submaxillary gland of the rat.

Six and 18 months after neonatal administration of 6-hydroxy-dopamine or surgical sympathetic denervation the submaxillary gland of the rat showed a marked depletion of noradrenaline stores. Six months afer removal of the superior cervical ganglion the gland's endogenous noradrenaline was lowered to 0.032 +/- 0.004 mug/g while after neonatal 6-hydroxydopamine the values were 0.228 +/- 0.023 mug/g (controls 2.145 +/- 0.382 mug/g). Eighteen months after either type of sympathetic denervation the neurotransmitter was still depleted. In rats treated with 6-hydroxydopamine the sailagogue effect of injected noradrenaline was potentiated 2.7-fold while the potentiation of the effect of noradrenaline was 3.6 times after surgical denervation. The magnitude of the supersensitivity developed to isoprenaline did not differ between both types of denervation. No supersensitivity to the cholinomimetic agent, methacholine, was observed. Cocaine administration or removal of the superior cervical ganglion slightly increased the supersensivity to noradrenaline in rats treated with 6-hydroxydopamine. Eighteen months after surgical or chemical denervation, the activity of choline-acetyl-transferase in the submaxillary gland was increased by about 50%. Of the respiratory enzymes studied, sussinic dehydrogenase, fumarase and cytochrome oxidase, the activity of only the latter was markedly reduced by a chronic sympathetic denervation. From the results obtained it is concluded that neonatal treatment with 6-hydroxy-dopamine causes a permanent and almost complete sympathectomy of the submaxillary gland of the rat.

The enhancement of retention performance induced by picrotoxin in mice may be mediated through a release of endogenous vasopressin.

Male Swiss mice were tested 48h after training in a one-trial step-through inhibitory avoidance task. Immediately post-training i.p. injection of the GABA antagonist picrotoxin (0.3-3.0mg/kg), at nonconvulsive doses, induced a dose-dependent modification of retention performance. The lower doses of picrotoxin (0.1-1.0mg/kg) enhanced retention, whereas the highest dose (3.0mg/kg) impaired retention. Picrotoxin did not affect response latencies in mice not given the footshock on the training trial, indicating that the actions of picrotoxin on retention performance were not due to nonspecific proactive effects on response latencies. The enhancing effects of picrotoxin (1.0mg/kg) on retention were time-dependent, which suggests that picrotoxin enhanced storage of recently acquired information. The enhancement of retention induced by picrotoxin (1.0mg/kg) was prevented by the vasopressin receptor antagonist, AAVP (0.01µg/kg, s.c.) administered immediately after training, but prior to picrotoxin treatment. This dose of AAVP did not affect retention by itself, either under the standard experimental conditions, or in mice trained with a high footshock. Low subeffective doses of picrotoxin (0.1mg/kg, s.c.) administered immediately after training, and hypertonic saline (1ml of 0.5M NaCl, i.p.), given 10min after training, interacted to improve retention. Considered together, these findings suggest that the better retention performance induced by post-training administration of picrotoxin could result, at least in part, from an endogenous release of vasopressin.

Partially saturated fluid attenuated inversion recovery (FLAIR) sequences in multiple sclerosis: comparison with fully relaxed FLAIR and conventional spin-echo.

Fluid attenuated inversion recovery (FLAIR) sequences produce selective cerebrospinal fluid (CSF) suppression by employing a very long inversion time (TI). We used the FLAIR sequence to study patients with multiple sclerosis (MS) at 0.6 T. So far, a very long TR (and long acquisition time) has been used in a fully relaxed (FR-FLAIR) system. To speed up the FLAIR sequences, we used a shorter TR, and demonstrated that complete CSF suppression can be maintained with partial saturation (PS-FLAIR) by reducing TI at the same time. The introduction of partial saturation, however, reduced the contrast between lesions and normal appearing white matter (NAWM). Suboptimal CSF suppression therefore had to be accepted to maintain sufficient lesion to NAWM contrast. Using a TE of 60 ms, the PS-FLAIR and FR-FLAIR performed equally well in the detection of MS-lesions, although the former provided poorer CSF suppression. Both FLAIR sequences, however, provided poorer constrast between lesions and NAWM compared to conventional spin-echo sequences. Although the long acquisition time of the FLAIR sequence can be reduced by using partial saturation, complete CSF suppression and good lesion to NAWM contrast are incompatible at short TRs. Using a TE of 60 ms, conventional spin-echo sequences detect more lesions and provide better contrast between lesions and NAWM than FLAIR sequences in MS patients.

Prevention and early diagnosis of cancer in the rectal stump of ulcerative colitis patients after colectomy and topical treatment.

Ulcerative colitis with malignant degeneration and dysplasia can be a precancerous lesion. Therefore, it is necessary to prevent or, at least to diagnose as early as possible any development toward neoplasia in the colon or rectum of the colitis patients. The only reliable guide for a risk of malignant tissue degeneration is dysplasia of the mucosa. A group of 31 patients was studied after total colectomy with ileorectal anastomosis and subsequent topical treatment with enemas containing sulphasalazine and corticosteroids. Two of these patients had mild rectal dysplasia before surgery, seen in a biopsy specimen obtained endoscopically. All the patients were followed for a long time after surgery, with endoscopy and microscopic and ultrastructural observation of rectal biopsy material taken from different sites in the mucosa, both from areas that looked dysplastic by endoscopy and from those that appeared normal. The two patients with presurgical dysplasia, when examined later, one 12 months and one 18 months after surgery, had no rectal dysplasia; the mucosal covering was moderately complete and the anastomosis was functioning. It is considered that to prevent development of cancer in the rectal stump, colectomy should always be followed by regular topical treatment and there should be a check-up at short intervals for early diagnosis of any premalignant areas that might develop. Regression of such lesion was observed to lesser degrees after continuous treatment with the topical medication.