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Biomedical subjects

J H Mayer

Publications and source records attributed to J H Mayer.

At least 19 recordsLinked to original sources

Reversal of deficits in axonal transport and nerve conduction velocity by treatment of streptozotocin-diabetic rats with myo-inositol.

This study examined the effects of myo-inositol treatment on the deficits of motor nerve conduction velocity and of axonal transport of choline acetyltransferase in rats with streptozotocin-induced diabetes. Motor nerve conduction velocity was measured in seven groups of male rats. Two groups formed nondiabetic controls; one survived for 3 and the other for 6 weeks, then motor nerve conduction velocity was again measured and the accumulation of choline acetyltransferase activity proximal to a 24-h sciatic nerve constriction was estimated. The other five groups were rendered diabetic and subjected to similar measurements. Two diabetic groups were untreated and survived 3 or 6 weeks. The other three groups received myo-inositol for 1, 2, and 3 weeks, respectively, commencing 21 days after induction of diabetes. These groups survived for 4, 5, or 6 weeks, respectively. In all groups surviving for longer than 3 weeks an interim measurement of motor nerve conduction velocity was made 21 days after the start of the experiment (immediately before onset of treatment in the treated groups). In these groups a third measurement was made on the day before death. At death, choline acetyltransferase accumulation was measured and the remainder of the sciatic nerves was assayed for sorbitol and myo-inositol. In the two untreated diabetic groups we found reduced motor nerve conduction velocity, a deficit in the accumulation of choline acetyltransferase proximal to the sciatic nerve constriction, and a marked build-up of nerve sorbitol and a depletion of nerve myo-inositol. All three treated groups showed a reversal of this myo-inositol depletion without a reduction in the nerve sorbitol content.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

An evaluation of a new patient compliance index using plasma propranolol levels.

Propranolol levels in plasma were studied in relation to dose prescribed in order to assess poor compliance with antihypertensive treatment. Fifty consecutive ambulatory patients (36-81 years) having hypertension, including 19 with azotemia, were investigated. Patient interviews using questionnaires and chart reviews were used to evaluate compliance. A composite Compliance Index was calculated for each patient. Individual oral doses of propranolol ranged from 20 to 160 mg. Subsequent plasma levels were determined by high performance liquid chromatography. Good correlation between last oral dose (mg) per body weight (kg) and log plasma propranolol levels were observed in patients whose compliance indices were above the mean for this sample (r = 0.74, p less than 0.01), when blood pressure control was satisfactory (r = 0.66) or excellent (r = 0.78), and when serum creatinines were greater than or equal to 1.4 (r = 0.76, p less than 0.001). Poor correlations between dose and propranolol levels suggest poor compliance with treatment.

Adult

Slow orthograde axonal transport of radiolabelled protein in sciatic motoneurones of rats with short-term experimental diabetes: effects of treatment with an aldose reductase inhibitor or myo-inositol.

This study examined the effect of streptozotocin diabetes of 5 weeks duration on the profile of slow orthogradely transported radiolabelled protein in rat sciatic motoneurones. The diabetic rats showed a retardation of the tail of the slow-component profile. This selective retardation was unaffected by treatment with an aldose reductase inhibitor, although this treatment reduced the accumulation of sorbitol and prevented the depletion of myo-inositol in the sciatic nerves of the treated diabetic rats. Other groups, treated with myo-inositol, had normal or elevated sciatic nerve myo-inositol levels in the presence of accumulated sorbitol. The axonal transport profiles from both control and diabetic myoinositol-treated groups gave normal tail velocities but an altered shape such that retardation of the tail of the profile may have been present in both. The study concludes that rats with 5 weeks streptozotocin diabetes show retardation of the velocity of the most slowly transported proteins in sciatic motoneurones, and that this defect is not linked to the polyol pathway.

Aldehyde Reductase

Prevention and reversal of defective axonal transport and motor nerve conduction velocity in rats with experimental diabetes by treatment with the aldose reductase inhibitor Sorbinil.

This investigation was designed to determine whether the aldose reductase inhibitor Sorbinil prevented the development of or reversed defects of nerve conduction and axonal transport in streptozotocin-diabetic rats. Untreated diabetes of either 3 or 6 wk duration caused a fall in sciatic motor nerve conduction velocity (MNCV) of 6-9 m/s (P less than 0.001) and significantly reduced the accumulation of axonally transported choline acetyltransferase activity against a 24-h sciatic nerve crush. These functional defects were associated with accumulation of sorbitol and depletion of myo-inositol in the sciatic nerve. Treatment with Sorbinil (25 mg/kg/day, p.o.) throughout the period of diabetes prevented the development of all these abnormalities in both 3- and 6-wk diabetic groups. In a second study, three groups of rats were subject to 3 wk untreated diabetes followed by Sorbinil treatment (as above) for 1, 2, or 3 wk to determine whether the abnormalities expected from 3 wk of untreated diabetes could be reversed. One week of treatment significantly elevated both MNCV and choline acetyltransferase accumulation (P less than 0.05). The longer treatments progressively ameliorated these defects such that the group that received Sorbinil for the second 3 wk of a 6-wk diabetic period gave values that were similar to controls and to diabetic rats that had been given Sorbinil throughout their diabetes. Sorbitol accumulation was markedly reduced by only 1 wk of Sorbinil treatment, but the normalization of myo-inositol levels required 2 wk of treatment. These findings indicate that Sorbinil treatment in diabetic rats prevented and reversed both Sorbitol accumulation and depletion of nerve myo-inositol in the sciatic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase

Prevention of defects of axonal transport and nerve conduction velocity by oral administration of myo-inositol or an aldose reductase inhibitor in streptozotocin-diabetic rats.

The effects of orally-administered myo-inositol have been compared with those of an aldose reductase inhibitor on acute neurological defects in experimentally diabetic rats. Three groups of streptozotocin-treated diabetic rats (50 mg/kg, IP) together with three groups of age-matched controls (saline, IP) were compared. One pair of groups (control and diabetic) were untreated for 3 weeks, another pair of groups received daily oral myo-inositol (667 mg/kg) and the third pair received an aldose reductase inhibitor (ICI 105 552; 50 mg . kg-1, day-1, orally). The untreated diabetic group showed statistically significant deficits in accumulation, proximal to 24 h sciatic nerve constrictions, of choline acetyltransferase activity by comparison with untreated controls (2.8 +/- 0.4 versus 5.1 +/- 0.4 nmol acetylcholine . h-1 . nerve-1; p less than 0.001). The untreated diabetic rats also showed a fall in motor nerve conduction velocity of 6.2 +/- 0.7 m/s which was statistically significant (p less than 0.001). Treatment of the diabetic group with myo-inositol prevented the development of both defects of axonal transport and conduction velocity; both measurements were similar to those of the myo-inositol treated control rats. Likewise the diabetic rats which received aldose reductase inhibitor showed prevention of both defects. Nerves from untreated diabetic rats showed marked sorbitol accumulation and a statistically significant reduction in myo-inositol content by comparison with the untreated controls (sorbitol, 1.56 +/- 0.22 versus 0.8 +/- 0.01 and myo-inositol, 1.47 +/- 0.10 versus 2.3 +/- 0.10 nmol/mg; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase

An examination of autonomic nervous function in genetically diabetic mice.

1 This study was designed to determine whether the autonomic innervation of the heart and vas deferens in genetically diabetic mice exhibited dysfunction similar to those seen in chemically diabetic animals and diabetic patients. 2 Diabetic mutant mice (outcrossed from the C57 BL/KS db/db strain) were compared with their non-diabetic litter-mates at age 20 to 22 weeks. Right and left atria and vasa deferentia were removed from freshly killed animals and subjected to nerve stimulation and treatment with noradrenaline (NA) or acetylcholine (ACh) in organ baths. 3 Right atria from diabetic animals were less responsive to noradrenergic nerve stimulation than control preparations but there was no such difference between the noradrenergic responses of left atria from the two groups of mice. Both atria were hypersensitive to exogenous NA. 4 Atria from diabetic mice responded to cholinergic nerve stimulation and exogenous ACh in a fashion similar to those of non-diabetic mice. Likewise in the responses of vasa deferentia to nerve stimulation were similar in the two groups. These findings are indicative of some autonomic nervous dysfunction characteristic, to an extent, of diabetes mellitus.

Animals

The regrowth of right atrial noradrenergic nerves after 6-hydroxydopamine in genetically diabetic mice; effects of insulin treatment.

1 This study examined the rate of repletion of right atrial noradrenaline levels after a single dose (100 mg/kg i.p.) of 6-hydroxydopamine (6-OH Da) in diabetic and non-diabetic mice of the C57 BL/KS db/db strain. 2 In mice which received no 6-OH Da there was no significant difference, in endogenous noradrenaline levels, between diabetic and non-diabetic animals. The depletion of noradrenaline 24 h after 6-OHDa was slightly more profound in the diabetic mice than in non-diabetic controls. Thereafter the rate of repletion of noradrenaline was more rapid in the diabetic group. 3 The normal noradrenaline content was reinstated in diabetic mice between 7 and 10 days after 6-OHDa. In the non-diabetic group levels similar to those found in untreated mie were not reinstated until 14 days after 6-OHDa. 4 Ten days after 6-OHDa right atria from diabetic mice were markedly more responsive to stimulation of the intramural noradrenergic nerves than were preparations from non-diabetic mice. 5 A group of diabetic mice was treated with insulin (10 m Units/g daily) for 6 weeks. The right atria from these animals, examined 10 days after 6-OHDa, were similar in their responses to noradrenergic nerve stimulation to the preparations from the non-diabetic mice. 6 All these groups of atria gave similar responses to exogenous noradrenaline. These findings indicate that regrowth of noradrenergic terminals after 6-OHDa was more rapid in diabetic mice than in either insulin-treated diabetic mice or non-diabetic mice.

Animals

Longitudinal study of cognitive abilities and academic achievement.

Assessment was made of the effectiveness of a battery of cognitive tests administered in kindergarten in the prediction of sixth grade achievement in reading comprehension, spelling, language usage, and arithmetic. Cognitive abilities included several factors of intelligence, visual perception and visual sequential memory, visual-motor integration, and auditory perception and auditory sequential memory. Measures of prior learning were also included. Subjects were 58 children in a suburban public school district. A criterion for predictive utility for correlation coefficients was established, and simple correlation coefficients for various kindergarten measures and sixth grade achievement ranged from the criterion of .35 to .69. In partial correlations with the effects of ability to understand ideas expressed in words removed, correlation coefficients for various cognitive measures and achievement tests ranged from the criterion of .35 to .63. Combinations of kindergarten measures having optimal multiple correlations with later school achievement generally approached or exceeded .70. These findings are discussed and suggestions are made for further research.

Achievement

Subclavian artery approach for insertion of intra-aortic balloon.

Subperiosteal clavicular resection for access to the subclavian artery is described. In those patients requiring intra-aortic balloon placement in the nonsurgical setting, such an approach provides a reasonably benign alternative when aortoiliac atherosclerosis prevents the usual retrograde femoral placement. Little morbidity or functional compromise is associated with clavicular wedge resections, and the anatomic availability of a large artery without the need for major surgical maneuvers in these gravely ill patients is a distinct advantage.

Aorta, Abdominal