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  • 1
    ISSN: 1432-0428
    Keywords: Diabetic neuropathy ; skin ; immunocytochemistry ; neuropeptides ; neurophysiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunocytochemistry for the general neuronal marker protein gene product 9.5 and four neuropeptides (calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide and neuropeptide Y) was performed on 20 skin biopsy specimens from 19 diabetic patients, age range 20–75 years, 17 Type 2 (non-insulin-dependent) and 3 Type 1 (insulin-dependent). Fifteen specimens were from the lower limb, 3 from the upper limb und 2 from the abdominal wall. Seven subjects had lower limb neurophysiological tests. All but one specimen showed reduced protein gene product 9.5 and neuropeptide immunoreactivity. Reduced protein gene product 9.5 and neuropeptide immunoreactivity was found in specimens taken from the abdominal wall and hand as well as those from the leg, and also in specimens from patients undergoing amputation for peripheral vascular disease. In general, the greater the number of abnormal neurophysiological tests, the greater the extent of neuronal abnormalities. Three patients with normal tests had abnormalities of dermal innervation. While these changes are also found in other axonal neuropathies, in the absence of other causes of peripheral nerve disease and of macrovascular disease, immunocytochemistry of skin biopsies may have a role in the assessment of diabetic neuropathy and its response to treatment.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Diabetic neuropathy ; small-fibre studies ; neuropeptides ; immunohistochemistry ; neurophysiology ; sudomotor function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Image-analysis was used to measure nerves immunoreactive to the general neuronal marker protein gene product 9.5 (PGP 9.5-IR) and the neuropeptides calcitonin gene-related peptide and vasoactive intestinal polypeptide in standardised leg skin biopsies of three age-matched groups of young subjects: non-diabetic (n=14), diabetic patients with normal small fibre function (“non-neuropathic”, (n=11) and diabetic patients with abnormal small fibre function (“neuropathic”, n=11). Depletion of nerves and neuropeptides was most marked in the epidermis, where calcitonin gene-related peptide-immunoreactivity was more frequently absent than PGP 9.5-IR in diabetic patients. Epidermal PGP 9.5-IR nerve area and counts were reduced in neuropathic compared with normal subjects (p〈0.001), as were epidermal calcitonin gene-related peptide nerve counts (p=0.003). Sweat gland PGP 9.5 and vasoactive intestinal polypeptide, which may be involved in sweat production, showed no diminution in diabetic patients (area: p=0.160, p=0.372 by ANOVA). Two diabetic patients showed elevated sweat gland PGP 9.5-IR and three had increased sweat gland vasoactive intestinal polypeptide; this may represent nerve proliferation. In local sweat tests, acetylcholine-stimulated sweat output was associated with increased immunoreactivity, while the sympathetic skin response showed inverse correlations with immunoreactivity. There were no consistent changes with other commonly-used neurophysiological tests. HbA1 correlated negatively with immunohistochemical measurements. Neuropeptide changes were seen in the absence of macro- and microvascular disease, and epidermal nerve depletion occurred in patients with normal thermal thresholds and cardiac autonomic function. Immunohistochemical measurement of cutaneous nerves in skin biopsies is a practical method for assessing peripheral small fibres in diabetes, and one which could be repeated in longitudinal studies.
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