Phenotypic heterogeneity of an adult form of adrenoleukodystrophy in monozygotic twins.

We describe genetically proven monozygotic twins with the adult form of adrenoleukodystrophy with significant phenotypic heterogeneity. Myeloneuropathy was common to both patients, but cognitive impairment and affective symptoms with extensive demyelination in the brain were prominent in the older twin, while adrenal insufficiency was predominant in the younger twin. The younger twin, however, exhibited affective symptoms similar to those displayed by his elder twin 10 years later. These findings suggest that nongenetic factors are important in determining the phenotypic variation of adrenoleukodystrophy gene.

[Autonomic dysfunction in vasculitic neuropathy--special reference to sudomotor function].

We examined autonomic functions in 14 patients with peripheral neuropathy caused by necrotizing vasculitis. These patients consisted of three allergic granulomatous angitis (Churg-Strauss syndrome, AGA), two systemic lupus erythematosus (SLE), two progressive systemic sclerosis (PSS), one mixed connective tissue disease (MCTD), one polyarteritis nodosa (PN) and five nonsystemic vasculitis. All of them were proven to have a vasculitis by sural nerve, muscle or skin biopsy. Sixteen age- and sex-matched healthy volunteers were also examined. Local sweating induced by intradermal injection of pilocarpine and nicotine (a concentration of 10(-4) g/dl, 0.1 ml) was measured with ventilated capsular method on the forearm and lower lateral leg at 23 degrees C of room temperature and 40% of relative humidity. Other autonomic functions including skin temperature at rest and after cold loading (15 degrees C, 6 minutes), variation in the R-R interval of heart beat (CV%), orthostatic hypotension and bladder dysfunction were also monitored. A decrease in sweat rate and recovery rate of skin temperature after cold-loading was seen more frequently in patients with necrotizing vasculitis than normal volunteers. Abnormality in the local sweat response against nicotine and pilocarpine was more frequently present in the involved area of somato-sensory and motor nerves as compared with those in the non-involved area. An occurrence of decrease in recovery rate of skin temperature after cold-loading also well correlated to the region of somato-sensory- and motor involvement. So far other autonomic dysfunction, only one patient had orthostatic hypotension, impotence and bladder dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

[Superior oblique myokymia--a case report and pathogenetic consideration].

A 30-year-old male visited us with complaints of dizziness and diplopia of abrupt onset in September, 1988. Neurological studies demonstrated paroxysmal rotatory to-and-fro oscillations of the left eye. There has been the same clinical episode at 25 years of age, lasting approximately 6 months. The characteristics of his ocular involuntary movement with the mild IVth cranial nerve paresis were as follows: quick, nonrhythmic, initially counterclockwise-rolling, more prominent in moving the left eye to the lower medial side, persisting for 1-10 seconds and rapidly repeated oscillations. When oscillations were prominent, he complained of faintness in addition to double vision. Except for the ocular signs, other neurological and laboratory examinations including cerebrospinal fluid, brain MRI and brain stem auditory evoked response, failed to disclose the precise location and nature of the lesion. Abnormal ocular movement was fluctuating for 4 months and gradually disappeared without any medication. In conclusion, the faintness could be considered to result from a lesion of reticular activating system adjacent to the IVth cranial nerve nucleus and its rostral (excitatory or inhibitory) supranuclei, and it suggests that a responsible lesion of the abnormal ocular movement is located at a region of the dorsomedial midbrain.

Plasma somatostatin-like immunoreactivity during the interdigestive period in the dog.

To study possible physiologic relationships between somatostatin and the gastric interdigestive contractions (GIC), gastric motor activity, and plasma somatostatin-like immunoreactivity (SLI) concentration were determined simultaneously in four conscious dogs, each of which was studied on two separate occasions. Plasma SLI level was highest during the GIC period and lowest 60 and 80 min after the cessation of the GIC; the mean difference in plasma SLI was 41 +/- 6 pg/ml. When synthetic motilin, a known stimulus of GIC, was infused at a physiologic rate during the period in which plasma SLI levels were low, SLI rose to approximately the same values observed during the contraction period and GIC similar to those that occur spontaneously were observed. When synthetic somatostatin, a known inhibitor of endogenous motilin release, was infused at a rate that raised the plasma SLI to approximately the levels observed during the contraction period (0.1 microgram/kg per h), the appearance of the subsequent GIC was significantly delayed. These results are consistent with a physiological role for somatostatin in the regulation of GIC in dogs and suggest an interrelationship between motilin and somatostatin.

Neural regulation of interdigestive motor activity in canine jejunum.

The hypothesis that extrinsic innervation of the small bowel provides pathways for initiation and coordinated propagation of the interdigestive migrating contractions (IMC) was reinvestigated in dogs. Motor activity was measured by chronically implanted force transducers. After a control study, 40-cm segments of the jejunum were extrinsically denervated. All IMC migrated distally through the extrinsically denervated segments. Thiry loops were then constructed from the extrinsically denervated segments, and continuity of the intestine was restored by end-to-end anastomosis. IMC proximal to the anastomosis did not migrate through the extrinsically denervated loop but migrated to sites across the anastomosis. In the extrinsically denervated loop, bands of strong contractions, quite similar to the IMC, occurred at the orad end of the loop independent of the IMC and propagated distally to the caudad end of the loop. The duration, frequency, and migrating velocity of these bands of contraction were different from those of IMC. These results suggest that extrinsic innervation is not essential for the initiation and orad sequential propagation of periodic motor activity like IMC, even when intrinsic innervation is discontinued.

[Effect of dopamine and its antagonists on contractile activity of the lower esophageal sphincter and the stomach (author's transl)].

Effect of dopamine and its antagonists, domperidone and metoclopramide (MCP), on contractile activity of the lower esophageal sphincter (LES) and the stomach was studied in 5 healthy conscious dogs. Contractile activity was measured by means of chronically implanted force transducers. Contractile activity of the LES and the stomach was completely inhibited by an intravenous infusion of dopamine (10, 20 and 40 micrograms/kg-min) during the digestive and interdigestive state. Domperidone, when administered alone (0.5, 1.0 and 2.0 mg/kg), had no effect on contractile activity of the LES and the stomach during the both periods. Though deprived of any noticeable effect on the digestive contractions, MCP (0.25, 0.5 and 1.0 mg/kg) abolished the interdigestive contractions and produced characteristic contractions. Domperidone restored postprandial and interdigestive contractions to their initial stage before dopamine administration in a dose-related fashion. Dopamine-induced inhibition was antagonized by MCP during the digestive state, however, MCP had no effect on the interdigestive contractions that had been inhibited by dopamine. Since domperidone has no activity upon normal contractions of the gastrointestinal tract, it may be assumed that if domperidone alone has some influence upon gut motor activity or any improvement in clinical symptoms is seen after domperidone, a disorder of the dopaminergic system could be strongly suggested.

Diurnal pH changes in duodenum of conscious dogs.

Continuous measurements of intraduodenal pH changes were made in five healthy conscious dogs by means of a miniature pH electrode inserted into the duodenum through a chronically implanted duodenal cannula. Gastric motor activity was also recorded simultaneously by means of a chronically implanted force transducer. When dogs were fed once a day with a measured volume of dog food, it was found that 24-h pH changes in the duodenal contents could be divided into three major periods: the weak acid period, the strong acid period, and alkaline period. The weak acid period lasted for 9.2 +/- 0.43 h after feeding with the duodenal pH ranging from 7.0 to 4.0. The weak acid period was gradually changed to the strong acid period in which the duodenal pH fluctuated widely from 8.0 to 1.0. This period lasted for 5.2 +/- 0.26 h. After the strong acid period, pH of the duodenum abruptly turned alkaline and remained between 7.0 and 8.3 until the next meal. These three periods of pH change are closely related to those of three different gastric motor patterns; the digestive, intermediate, and interdigestive patterns, respectively.

Regular and irregular cycles of interdigestive contractions in the stomach.

We have previously reported that during the interdigestive state repeated episodes of high-amplitude contractions interrupted by long-lasting motor quiescence were seen to occur regularly until the next meal in the dog. However, none of the dogs used in our laboratory showed such regular changes in gastric motor pattern all the time during the interdigestive state. In the present study, we measured plasma motilin concentrations and intraduodenal pH together with gastric motor activity in conscious dogs. It was found that as long as intraduodenal pH remained between 7.0 and 8.5 the regular occurrence of the interdigestive contractions was closely associated with increases in the plasma immunoreactive motilin (IRM) concentration. However, when intraduodenal pH became acid, there were no typical interdigestive contractions even though plasma IRM concentration was elevated. We consider that high-amplitude contractions like the interdigestive contractions could not be evoked in the acid-secreting stomach even if the plasma IRM concentration was elevated during the interdigestive state. Acid secretion during the fasted state, the cause of which is not known, seems to be one of the main factors in disturbing the regularity of the interdigestive motor pattern.

Interdigestive migrating contraction in short bowel dogs.

Extraluminal force transducers were chronically implanted onto the serosal surface of the gastrointestinal tract in dogs and the interdigestive migrating contractions (IMC) were studied in conscious dogs. When the IMC occurring periodically in the stomach reaches the distal ileum, the next IMC develops in the stomach. We therefore studied the effect of isolation or resection of the lower third of the small bowel on the periodic occurrence of IMC in the stomach. Transducers were sutured onto the antrum, the upper jejunum, the mid intestine and the terminal ileum. After control records on gastrointestinal motility were made for these dogs, the abdominal cavity was again opened to prepare a Thiry loop in the lower third of the small bowel. (isolation group) Next, the loop was removed (resection group) and gastrointestinal motility was recorded. In these groups, we 1) measured the time from the feeding to the initiation of the first IMC. 2) measured the time from the termination of one IMC to the termination of the next IMC. 3) measured the migrating time of the IMC. 4) and measured the duration of the IMC in the stomach. As a result, it was found that the time interval between the termination of one IMC in the stomach and the termination of the next was almost constant throughout all experiments. The migrating time of the IMC from the stomach to the terminal ileum in isolation and resection groups was slightly shortened. These findings indicate that the existence of the lower gut has no significant influence upon the regular periodic occurrence of the IMC in the stomach and the migrating time.

Changes in plasma motilin concentration and gastrointestinal contractile activity in conscious dogs.

Simultaneous measurement of plasma motilin concentration and gastrointestinal contractile activity was make in 12 healthy dogs. Plasma motilin concentration was measured by radioimmunoassay and gastrointestinal contractile activity was monitored by means of chronically implanted force transducers. During the interdigestive state, it was found that the plasma motilin concentration increased in complete accordance with the cyclical interdigestive contractions of the stomach. Furthermore, plasma motilin concentration was lowered by the ingestion of food, and it reamined low as long as the gastric motor activity was in the digestive pattern. Since, as reported previously the interdigestive contractions can be induced by tthe exogenous administration of motilin, we concluded that (1) motilin is released at constant intervals during the interdigestive state, and this release is suppressed by the ingestion of food; (2) motilin induces the interdigestive contractions of the stomach and duodenum; and (3) motilin is an interdigestive hormone and is the only known polypeptide hormone of the gut whose release is not induced by a meal.

Control of lower-esophageal-sphincter contractile activity by motilin in conscious dogs.

The effect of synthetic motilin on contractile activity in the lower esophageal sphincter (LES) and the stomach has been studied in 5 healthy dogs by means of chronically implanted strain gage force transducers. Motilin produced strong contractions in the LES and the stomach simultaneously after intravenous doses ranging from 0.3 to 2.7 microgram/kg hr, which were similar to the naturally occurring interdigestive contractions in the LES and the stomach. However, these contractions could be induced only in the interdigestive state; infusion of motilin into dogs in the digestive state brought about no significant effect on either the LES or the stomach. Motilin-induced contractions in the LES and the stomach were instantly abolished by ingestion of food. It is considered that the contractions induced by motilin are identical with the naturally occurring interdigestive contractions in the LES and these contractions are the most orad component of the interdigestive cyclic recurring caudad-moving bands of strong contractions in the dogs.

Characteristic motor activity of the gastrointestinal tract in fasted conscious dogs measured by implanted force transducers.

Gastrointestinal contractile actiivity from the gastric body to the terminal ileum in conscious dogs was continuously recorded for several weeks by means of chronically implanted strain-gage force transducers. It was found that the 24-hr changes in the gastrointestinal contractile activity consisted of the two different major patterns, the digestive and interdigestive patterns. In the interdigestive state, a cyclic, recurring, caudad-moving band of strong contractions starting in the stomach and the duodenum and traversing the entire length of the small intestine was observed. When one band of strong contractions reached the distal ileum, another developed in the stomach and the duodenum again and propagated in a caudad direction. Such recycling episodes interrupted by long-lasting quiescence repeatedly occurred until the next meal. These characteristic contractile activities observed in our dogs are identical with the interdigestive myoelectric complex of the stomach and the small bowel recently reported by Code and Marlett (5). Four sequential phases (I-IV) of the migrating myoelectric complex, defined in terms of action potential activity, seem to correspond to the resting (quiescence), preceding irregular contractions, strong contractions, and subsiding contractions observed in the present study, respectively. Function and control mechanism of the interdigestive contractile activity were discussed.