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Biomedical subjects

P Low

Publications and source records attributed to P Low.

At least 19 recordsLinked to original sources

The North American Multiple System Atrophy Study Group.

The North American Multiple System Atrophy Study Group involves investigators in 12 US medical centers funded by a grant from the National Institutes of Health. The objectives are to examine the environmental and genetic risk factors for MSA; elucidate pathogenic mechanisms underlying the disorder; and refine evaluations used for assessment. During its first year, the group enrolled 87 patients, implemented four cores, and initiated four scientific projects. Most patients among the 87 had parkinsonian features, which frequently began asymmetrically and remained asymmetrical; one-third responded to levodopa and many developed levodopa complications; almost two-thirds of the patients had cerebellar dysfunction, of these 90% had ataxia; urinary incontinence occurred commonly, and sleep disorders affected most. The investigators studied the effects of oxidative and nitrative stress upon the formation of alpha-synuclein inclusions; generated transgenic models of alpha-synuclein accumulation that recapitulate several behavioral and neuropathological features of MSA; and compared the severity of the autonomic features of MSA, Parkinson's disease and dementia with Lewy bodies.

Animals↗

Assay for Rab geranylgeranyltransferase using size exclusion chromatography.

A simple chromatographic assay for Rab geranylgeranyltransferase (Rab GGTase) has been developed. The method involves separation of the reaction mixture on a Sephadex G-25 superfine minicolumn. Addition of 2-propanol to the assay results in substantial (approximately 90%) decline of formation of noncovalent lipid-protein complexes, increasing reproducibility and reliability of the method. The activity of Rab prenyltransferase was measured in crude and partially purified enzyme preparations from wheat seedlings; measurements for several other plants and rat brain cytosol fractions are also presented. This method can be routinely applied to evaluate the activity of different protein prenyltransferases.

Alkyl and Aryl Transferases↗

Evidence-based design: the ACOEM Practice Guidelines Dissemination Project.

A steering committee and investigators from the American College of Occupational and Environmental Medicine (ACOEM) designed and carried out the ACOEM Practice Guidelines Dissemination Project to encourage adoption of the ACOEM Occupational Medicine Practice Guidelines. The project also involved research on guideline acceptance as well as potential improvements and additions to the guidelines. To increase guideline adoption and use in improving the appropriateness and consistency of practice and case management, the design was based on existing research on guideline format, education, and adoption efforts. This article summarizes that information and the needs assessment done prior to case-based guidelines training. Other articles in this issue report on guideline adoption and use and the results of the market research on the ACOEM guidelines.

Diffusion of Innovation↗

Acceptance and self-reported use of national occupational medicine practice guidelines.

The authors conducted a survey to ascertain post-training attitudes and self-reported use of the American College of Occupational and Environmental Medicine occupational medicine practice guidelines. Trainees were surveyed 3 to 4 months after completing a case-based practice ACOEM occupational practice guidelines seminar. Of 96 physician respondents, 95% reported that the guidelines improved their practice in some manner. Fifty-two percent of physicians thought that guideline use decreased medical costs. Seventy-one percent reported that their care complied with the guidelines in 70% or more of their cases; however, "actually considering the guidelines in particular cases" was reported by only 47%. Discussion of cases was frequent (92%) and involved physicians, patients, and other health care providers. We concluded that physicians' attitudes toward the guidelines are positive and that reported compliance is high. Guidelines are discussed frequently.

Attitude of Health Personnel↗

Beliefs about and use of occupational medicine practice guidelines by case managers and insurance adjusters.

Workers' compensation case managers and adjusters have increased their use of practice guidelines recently, partly in response to state regulations. However, informally reported rates of use are not as high as desired for the best managed care practices and the greatest reductions in lost work time. Although there are several studies of physicians' use of guidelines, there are few if any studies about case managers' and adjusters' beliefs about, and utilization of, either general medical or occupational medical practice guidelines. Information about attitudes, beliefs about practice guidelines, and actual use should help developers make the guidelines more usable and bring about more effective interaction among case managers, adjusters, treating physicians, and other health professionals. This article reports on pre- and post-training surveys of a cohort of case managers and adjusters who participated in a case-based guideline training course. It then compares their responses to those of the physicians whose cases they might manage.

Case Management↗

Suggested improvements in practice guidelines: market research to support clinical quality improvement.

The American College of Occupational and Environmental Medicine's Practice Guideline Dissemination Project included market research to better understand the wants and needs of physicians, case managers, and insurance adjusters who used the guidelines. We used structured and open-ended survey questions and focus groups administered to a cohort of physicians, adjusters, and case managers trained as part of the project. Respondents were generally satisfied with the format and contents of the guidelines. They requested additional material on case management and facilitation of effective treatment and return to work by other health professionals. They also suggested a variety of formats to improve the accessibility of the guidelines. The suggestions may be used in new product development or for guideline revisions.

Attitude of Health Personnel↗

[Consensus on the diagnosis of multi-system atrophy].

We report the results of a consensus conference on the diagnosis of multiple system atrophy. We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible multiple system atrophy requires one criterion plus two features from separate domains. The diagnosis of probable multiple system atrophy requires the criterion for autonomic failure/urinary dysfunction plus poor levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite multiple system atrophy requires pathological confirmation.

Diagnosis, Differential↗

Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology.

We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poor levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.

Antiparkinson Agents↗

The fate and possible role of arylphorin during the metamorphosis of Mamestra brassicae.

1. Arylphorin, one of the storage proteins has been isolated from the hemolymph of Mamestra brassicae. 2. It has been established that Mamestra arylphorin is the most similar to manducin from among the known storage proteins of other species. 3. A rabbit polyclonal antibody has been developed against arylphorin, and its concentration changes have been determined quantitatively by ELISA in the hemolymph and fat body from the 1st day of the last larval instar to the 3rd day of the imago stage. 4. Histological sections were made on each day during the investigated period and it was shown by immunohistochemical methods that the main quantity of arylphorin was accumulated in the storage protein granules of the fat body and it could be detected even in the imaginal fat body. 5. The uptake of arylphorin by the fat body is induced by 20-hydroxyecdysone. 6. During differentiation of the imaginal cuticle arylphorin is incorporated first in the epidermal cells and it is built in the endocuticular layer of the integument thereafter.

Animals↗

Chronic hypoxia induces selective maldevelopment of peripheral myelin in rat.

To determine the morphologic effect of chronic hypoxia on peripheral nerve development, four-week-old rats were placed in a 10% O2 environment for ten weeks and compared with controls. Light microscopic morphometric analysis of hind limb nerves of hypoxic as compared to control nerves showed at statistically significant levels, a) smaller total fascicular areas, b) smaller median diameters, c) fiber spectra with peaks at smaller diameters, d) fewer large myelinated fibers per nerve, e) larger fiber density, f) smaller myelin areas. On average myelin areas, relative to axon size, were smaller in oxygen-deprived than in control rats. Also myelin spiral length and the number of myelin lamellae relative to axon area were smaller. These findings suggest that hypoxia retards myelinated fiber diameter and especially myelin development.

Animals↗

Slow axonal transport in experimental hypoxia and in neuropathy induced by p-bromophenylacetylurea.

The slow axonal transport of proteins radiolabeled by incorporation of [35S]methionine was studied in motor nerves of rats subjected to chronic hypoxia. The conditions involved exposure to an atmosphere of 8-10% oxygen for periods of 3, 5, or 10 weeks. An experimentally verified computer model predicted a drop in mean endoneurial oxygen tension from 30.5 to 19 mm Hg, despite a measured increase in circulating hemoglobin from 16 to 22 g%. Nerve conduction velocity was unaffected during the early stages of hypoxia. After 10 weeks of hypoxia, conduction velocity still appeared normal in the sciatic nerve but was reduced in the caudal nerve by 2.5-4.5 m/s. At no time, however, was there evidence of impaired slow axonal transport, which proceeded with a mean velocity between 1 and 2 mm/day. Another set of experiments was performed to evaluate slow axonal transport in motor nerves of rats with peripheral neuropathy induced by the toxicant, p-bromophenylacetylurea. The results suggested a lower transport velocity in rats showing total hind-limb paralysis as compared with rats showing only mild to moderate motor dysfunction. The difference, however, could have reflected accelerated transport in mild neuropathy. In our view, the observations in experimental hypoxia- and toxicant-induced neuropathy are noteworthy for the resistance of slow transport to perturbation of the neuronal environment.

Animals↗

Somatic and autonomic function in progressive autonomic failure and multiple system atrophy.

We studied 62 consecutive patients with progressive autonomic failure (PAF) or multiple system atrophy (MSA) (26 PAF; 36 MSA). Patients were well matched in age (67 vs 66 years), duration (39 vs 36 months), and severity of autonomic failure (median values for PAF and MSA). Peripheral somatic neuropathy occurred in 2 patients with PAF and 7 patients with MSA. Postganglionic sudomotor and vasomotor functions were studied using the quantitative sudomotor axon reflex test and supine plasma norepinephrine. The extent and severity of autonomic failure were assessed by the thermoregulatory sweat test, by heart rate responses to deep breathing and the Valsalva maneuver, and by blood pressure recordings. Severe and widespread anhidrosis was found in both PAF and MSA patients. Postganglionic sudomotor failure occurred at the forearm in 50% each of PAF and MSA patients and at the foot in 69% and 66% of PAF and MSA patients, respectively. However, postganglionic sudomotor function was preserved in some patients with anhidrosis on thermoregulatory sweat test, indicating a preganglionic lesion. Vagal abnormalities were found in 77% and 81% of PAF and MSA patients. Supine plasma free norepinephrine values were significantly reduced in PAF (p less than 0.001), but not in MSA, patients. Standing plasma norepinephrine values were reduced in both PAF (p less than 0.001) and MSA (p less than 0.001) patients. We conclude the following: (1) PAF is characterized by combined postganglionic sudomotor and adrenergic failure. (2) MSA is associated with a similar frequency of postganglionic sudomotor failure, but postganglionic adrenergic denervation was uncommon. (3) Preganglionic neuron is also involved in both disorders, but more severely in MSA. (4) Somatic neuropathy may occur.

Adolescent↗

Spatial pattern of nerve fiber abnormality indicative of pathologic mechanism.

Estimates of the number, density, and size distribution of myelinated fibers at selected levels of roots, spinal tracts, and sampled levels of peripheral nerves may be used in the detection and characterization of alterations of motor, sensory, and autonomic neurons and their axons with development, aging and disease. Use of imaging techniques, now available, increases the reliability, versatility, and speed of such analysis. In this study, the authors evaluated the spatial pattern of fibers in sampled frames and contour areas of transverse sections of nerve fascicles, utilizing, the coefficient of variation and index of dispersion (ID), the latter extensively employed by plant ecologists. The ID was used for recognization of increased, normal, or decreased variability of density within fascicles, between fascicles, and between nerves in health and in various experimental neuropathies. In addition, various morphometric measurements were made in transverse sections at defined levels along the hind limb nerves of rats in acute and chronic ischemia, after rhizotomy and in galactose neuropathy. These stereomorphometric studies, emphasizing the number, size, shape, and spatial pattern of fibers, revealed differences among experimental neuropathies and may be found to be helpful in the characterization and prediction of pathologic mechanisms in neuropathies of unknown cause. Specifically, these approaches could be used for study of whether fiber loss in human diabetic neuropathy is multifocal and determination of the levels of such losses.

Acute Disease↗

The Mayo Clinic experience with plasma exchange in chronic inflammatory-demyelinating polyneuropathy (CIDP).

Fourteen patients with static or progressive CIDP with a neurologic disability score (NDS) greater than or equal to 50 were entered into a double-blind, stratified, 3-week trial of twice-weekly plasma exchange or sham plasma exchange. The end-points evaluated included the NDS, computer assisted sensory examination of the foot, and various attributes of nerve conduction of motor and sensory fibers of limb nerves. Of the 7 patients receiving plasma exchange, 4 improved by more than 10 points on the NDS (45, 32, 11, and 24 points) while 3 remained unchanged (2, -2, and -3 points). One patient, who did not appear to respond to either sham or plasma exchange, improved (100 points) with a 3 month alternate day course of prednisone. Of the 7 patients on sham exchange, 3 improved by more than 10 points (26, 15, and 16), 3 remained unchanged (-5, 4, and 8) and 1 was not able to complete the study due to cardiac tamponade. This preliminary trial will end with acquisition of 30 patients. It is too early to draw any conclusion from these studies other than that the double-blind study employed here is feasible and should provide information on the efficacy of plasma exchange in CIDP if its effect is prompt and large. The improvement which may be seen in the sham group appears to suggest that studies of efficacy require a double-blind design.

Adult↗