Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031117 (peripheral neuropathy)
 10,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Healthy skin is protected from pressure-induced ischemic damage because of the presence of pressure-induced vasodilation (PIV). PIV relies on small sensory nerve fibers and endothelial function. Since aging alters both nervous and vascular functions, we hypothesized that PIV is altered with aging. We compared PIV in non-neuropathic and neuropathic older subjects (60-75 years) with that of young subjects (20-35 years). Laser Doppler flowmetry was used to evaluate the cutaneous responses to local pressure application, acetylcholine, and local heating. Quantitative sensory tests were used to evaluate sensory-nerve-fiber function. The non-neuropathic older subjects had an impaired PIV (12+/-7% increase in blood flow with pressure) compared with young subjects (62+/-4%, P<0.001). In the presence of peripheral neuropathy, the older subjects were totally deprived of PIV, leading to early pressure-induced cutaneous ischemia (-31+/-10%, P<0.001). This inability of the skin to adapt to localized pressure in older subjects is related to the severity of the sensory-fiber dysfunction rather than to endothelial dysfunction, which was comparable between the non-neuropathic (141+/-19% increased blood flow with acetylcholine, P<0.05) and neuropathic older subjects (145+/-28% increase, P<0.05) compared with young subjects (234+/-25% increase).
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PMID:Aging-associated sensory neuropathy alters pressure-induced vasodilation in humans. 2014 44

The diabetic foot syndrome (DFS) is one of the most significant complications of diabetes mellitus and frequently leads to amputation of the affected extremity. Cardiovascular mortality and morbidity of affected patients are still high and healed ulcers often recur. The pathogenesis of DFS is complex, clinical presentation is variable and management requires early expert assessment. Interventions should be directed towards infection, peripheral ischemia and pressure relief caused by peripheral neuropathy and limited joint mobility. Treatment includes wound clean-up, stage-oriented local wound management and the appropriate treatment of bacterial infection. Useful preventive measures are blood glucose control training of diabetics, regular foot care and the provision of appropriate footwear.
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PMID:[Diabetic foot syndrome from the perspective of angiology and diabetology]. 1994 39

Maintenance of the foot at 90 degrees to the lower leg following posterior calf lengthening or to prevent an equinus contracture in situations in which splint, cast, or external fixation is deemed inappropriate is a challenge. The author presents an observational case series involving 9 extra-articular ankle stabilizations performed in 9 consecutive patients. Each patient underwent his or her index surgery followed by percutaneous placement of 2 smooth 2.8-mm or larger diameter Steinmann pins extra-articular to the ankle joint. There were 6 men and 3 women with a mean age of 56.1 years (range, 31-73 years). Five patients had diabetes with peripheral neuropathy, 2 had critical limb ischemia, 1 had alcohol-induced neuropathy, 1 had lupus, and 1 was an active smoker. Eight patients had posterior calf lengthening, and 1 had open metatarsal fractures with severe soft-tissue disruption with an inability to use splint immobilization. Three patients had a transmetatarsal amputation, 2 patients had Chopart amputations, 2 patients had forefoot plastic surgery reconstructive procedures, 1 had a complex Charcot reconstruction, and 1 had a splittibialis anterior tendon transfer. Extra-articular ankle stabilization fixation was retained for a mean of 5.5 weeks (range, 2-10 weeks). Mean follow-up was 12 months (range, 1-17 months). All extra-articular stabilization procedures were deemed successful. When properly performed, extra-articular stabilization to maintain the foot at 90 degrees to the lower leg represents a safe, simple, reliable, and minimally invasive technique useful in situations in which traditional splint or cast immobilization is not possible and when external fixation is deemed inappropriate.
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PMID:Extra-articular ankle stabilization: a case series. 2050 12

Peripheral neuropathy remains a major chronic complication of diabetes mellitus. Its pathogenesis mainly involves chronic glucose toxicity and nerve ischemia. Preclinical studies have shown that cilostazol, a reversible selective inhibitor of phosphodiesterase-3A with antiplatelet, antithrombotic, and vasodilatory properties, exerts beneficial effects on nerve function in experimental diabetes. Clinical data, however, is sparse. Two recent randomized placebo-controlled clinical trials showed that cilostazol did not improve diabetic neuropathy in humans. Hence, more data is needed to confirm or refute the poor clinical efficacy of cilostazol. Importantly, future studies should include larger patient series, provide longer follow-up data, and employ more accurate diagnostic tools.
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PMID:Cilostazol in diabetic neuropathy: premature farewell or new beginning? 2151 79

Although historically used for the treatment of anemia, erythropoietin (EPO) has emerged as a neurotrophic and neuroprotective agent in different conditions of neuronal damage (traumatic brain injury, ischemia, spinal cord compression, peripheral neuropathy, retinal damage, epilepsy, Parkinson's Disease, among others). Nonetheless, EPO's therapeutic application is limited due to its hematological side-effects. With the aim of obtaining EPO derivatives resembling the hormone isolated from cells and tissues of neural origin, a novel combination of less acidic EPO glycoforms -designated as neuroepoetin (rhNEPO)- was purified to homogeneity from the supernatant of a CHO-producing cell line by a four-step chromatographic procedure. This simple and single process allowed us to prepare two EPO derivatives with distinct therapeutic expectations: the hematopoietic version and a minimally hematopoietic, but mainly in vitro cytoprotective, alternative. Further biological characterization showed that the in vivo erythropoietic activity of rhNEPO was 25-times lower than that of rhEPO. Interestingly, using different in vitro cytoprotective assays we found that this molecule exerts cytoprotection equivalent to, or better than, that of rhEPO in cells of neural phenotype. Furthermore, despite its shorter plasma half-life, rhNEPO was rapidly absorbed and promptly detected in the cerebrospinal fluid after intravenous administration in rats (5 min postinjection, in comparison with 30 min for rhEPO). Therefore, our results support the study of neuroepoetin as a potential drug for the treatment of neurological diseases, combining high cytoprotective activity with reduced hematological side-effects.
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PMID:Isolation and characterization of a subset of erythropoietin glycoforms with cytoprotective but minimal erythropoietic activity. 2160 41

Diabetes mellitus with peripheral sensory neuropathy frequently results in forefoot ulceration. Ulceration at the first ray level tends to be recalcitrant to local wound care modalities and off-loading techniques. If healing does occur, ulcer recurrence is common. When infection develops, partial first ray amputation in an effort to preserve maximum foot length is often performed. However, the survivorship of partial first ray amputations in this patient population and associated re-amputation rate remain unknown. Therefore, in an effort to determine the actual re-amputation rate following any form of partial first ray amputation in patients with diabetes mellitus and peripheral neuropathy, the authors conducted a systematic review. Only studies involving any form of partial first ray amputation associated with diabetes mellitus and peripheral sensory neuropathy but without critical limb ischemia were included. Our search yielded a total of 24 references with 5 (20.8%) meeting our inclusion criteria involving 435 partial first ray amputations. The weighted mean age of patients was 59 years and the weighted mean follow-up was 26 months. The initial amputation level included the proximal phalanx base 167 (38.4%) times; first metatarsal head resection 96 (22.1%) times; first metatarsal-phalangeal joint disarticulation 53 (12.2%) times; first metatarsal mid-shaft 39 (9%) times; hallux fillet flap 32 (7.4%) times; first metatarsal base 29 (6.7%) times; and partial hallux 19 (4.4%) times. The incidence of re-amputation was 19.8% (86/435). The end stage, most proximal level, following re-amputation was an additional digit 32 (37.2%) times; transmetatarsal 28 (32.6%) times; below-knee 25 (29.1%) times; and LisFranc 1 (1.2%) time. The results of our systematic review reveal that one out of every five patients undergoing any version of a partial first ray amputation will eventually require more proximal re-amputation. These results reveal that partial first ray amputation for patients with diabetes and peripheral sensory neuropathy may not represent a durable, functional, or predictable foot-sparing amputation and that a more proximal amputation, such as a balanced transmetatarsal amputation, as the index amputation may be more beneficial to the patient. However, this remains a matter for conjecture due to the limited data available and, therefore, additional prospective investigations are warranted.
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PMID:Incidence of re-amputation following partial first ray amputation associated with diabetes mellitus and peripheral sensory neuropathy: a systematic review. 2239 32

Schwann cells exhibit a high degree of plasticity in adult peripheral nerves after mechanical injury; they have, therefore, been implicated in promoting nerve regeneration. However, Schwann cell behavior after ischemic injury has not yet been elucidated. To determine how Schwann cell plasticity may contribute to recovery from ischemic neuropathy, we used a rat model in which ischemia was induced in the tibial nerve by a 5-hour occlusion of the supplying arteries. Proliferation of immature Schwann cells that emerged in the injured nerve was evaluated by double immunostaining for the p75 neurotrophin receptor and proliferating cell nuclear antigen. The number of proliferating cell nuclear antigen/p75 neurotrophin receptor double-positive cells increased significantly in 1 to 2 weeks after ischemia and subsequently decreased by 4 weeks. During this time, the postmitotic Schwann cells differentiated into mature cells, as demonstrated with bromodeoxyuridine incorporation, which facilitated axon guidance and subsequent axon remyelination. These results suggest the emergence and proliferation of immature Schwann cells that contribute to nerve regeneration after ischemic injury. The manipulation of this population of proliferating immature Schwann cells may be a useful strategy for treating ischemic peripheral neuropathy.
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PMID:Proliferating immature Schwann cells contribute to nerve regeneration after ischemic peripheral nerve injury. 2258 87

131 HA-TTR patients from a single referral centre presented at onset five major clinical syndromes: (1) the typical "Portuguese variant" axonal polyneuropathy with dissociated (syringomyelic like) sensory loss and autonomic dysfunction; (2) bilateral carpal tunnel syndrome; (3) restless leg syndrome with impotence and unexplained loss of weight; (4) pure motor neuropathy without autonomic abnormalities; (5) recurrent small brain or spinal cord ischemia or haemorrhages with leptomeningeal amyloid deposition (and late superficial siderosis of the central nervous system) and vitreous deposits. Some patients in our population presented a "pseudodemyelinating" onset of the somatic neuropathy, as well as atypical motor neuropathy simulating lower motor neuron disease. The five syndromes can overlap in advanced stages of the disease. Genetic screening of HA-TTR could be worthwhile in any idiopathic progressive axonal peripheral neuropathy, as well as in drug resistant demyelinating sensory-motor neuropathy or in pure motor neuropathy, when multi-organ involvement is present.
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PMID:Genotypic and phenotypic correlation in an Italian population of hereditary amyloidosis TTR-related (HA-TTR): clinical and neurophysiological aids to diagnosis and some reflections on misdiagnosis. 2262 Sep 67

Diabetic neuropathy includes damage to neurons, Schwann cells and blood vessels. Rodent models of diabetes do not adequately replicate all pathological features of diabetic neuropathy, particularly Schwann cell damage. We, therefore, tested the hypothesis that combining hypertension, a risk factor for neuropathy in diabetic patients, with insulin-deficient diabetes produces a more pertinent model of peripheral neuropathy. Behavioral, physiological and structural indices of neuropathy were measured for up to 6 months in spontaneously hypertensive and age-matched normotensive rats with or without concurrent streptozotocin-induced diabetes. Hypertensive rats developed nerve ischemia, thermal hyperalgesia, nerve conduction slowing and axonal atrophy. Thinly myelinated fibers with supernumerary Schwann cells indicative of cycles of demyelination and remyelination were also identified along with reduced nerve levels of myelin basic protein. Similar disorders were noted in streptozotocin-diabetic rats, except that thinly myelinated fibers were not observed and expression of myelin basic protein was normal. Superimposing diabetes on hypertension compounded disorders of nerve blood flow, conduction slowing and axonal atrophy and increased the incidence of thinly myelinated fibers. Rats with combined insulinopenia, hyperglycemia and hypertension provide a model for diabetic neuropathy that offers an opportunity to study mechanisms of Schwann cell pathology and suggests that hypertension may contribute to the etiology of diabetic neuropathy.
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PMID:Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats. 2279 Dec 95

Efficacy of ischemic preconditioning is decreased in animal models of type 2 diabetes mellitus while the responses in humans with diabetes are contradictory. It is unknown whether attenuation is related to decreased release of a mediating humoral cardioprotective factor or reduced ability to respond in the target tissue. The aim of the present study was to investigate the release and effect of a circulating cardioprotective factor in type 2 diabetes mellitus patients. Blood samples were drawn from nine non-diabetic subjects, eight diabetic patients without peripheral neuropathy, and eight diabetic patients with peripheral neuropathy before (control) and after a remote ischemic preconditioning (rIPC) stimulus. Blood samples were dialyzed against Krebs-Henseleit buffer and the cardioprotective effects of the dialysates were tested in rabbit hearts mounted on a Langendorff model and subjected to 30-min global ischemia and 120-min reperfusion. rIPC dialysate from non-diabetic and diabetic subjects without peripheral neuropathy reduced infarct size and improved hemodynamic recovery compared to control dialysate from non-diabetic and diabetic subjects. However, in the subgroup of diabetic patients with neuropathy the cardioprotective effect was attenuated. These findings indicate that the release mechanism involves neural pathways.
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PMID:Release of a humoral circulating cardioprotective factor by remote ischemic preconditioning is dependent on preserved neural pathways in diabetic patients. 2282 47


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