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  • 1
    ISSN: 1432-0428
    Keywords: Diabetic neuropathy ; foot ulcers ; arteriovenous anastomoses ; venous oxygenation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Venous PO2 was measured in the feet and hands of four subject groups: 14 diabetics with neuropathy and foot ulceration; 12 diabetics with neuropathy but no ulceration; 11 diabetics with no evidence of microvascular complications; and 10 nondiabetic controls. Neither patients nor controls had clinical evidence of peripheral vascular disease. The mean venous PO2 in the feet of subjects with neuropathy and foot ulceration was significantly higher than in controls or the other two diabetic groups. Venous PO2 in the feet of the subjects with ulcers was also significantly higher than in their hands or in the hands of the other groups. These results provide further evidence of abnormal blood flow in the diabetic neuropathic foot and are compatible with arteriovenous shunting.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; peripheral neuropathy ; tissue oxygenation ; peripheral vascular disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Transcutaneous oxygen, laser Doppler flowmetry, peroneal nerve motor conduction velocity and skin temperature were assessed in both legs of 34 diabetic patients, who had a mean age of 41 (range 29–77) years, and diabetes duration of 21 (3–34) years. Transcutaneous oxygen significantly correlated with peroneal nerve motor conduction velocity (r=0.59 p〈0.001) and laser Doppler flowmetry (r=0.7 p〈0.001). Laser Doppler flowmetry correlated weakly with peroneal motor conduction velocity, (r=0.34 p〈0.05). In each patient the leg with the higher transcutaneous oxygen (mean 70.2±9.3 (SD) mmHg) had a significantly higher peroneal motor conduction velocity (45.3±7.1 vs 41.5± 6.3 m/s, p〈0.01), than the leg with the lower transcutaneous oxygen (61.0±11.9 mm Hg), though no difference in skin temperature was observed, 31.4±0.4 vs 31.1±0.5°C. We then assessed the potential for reversibility of conduction velocity deficits in ten non-diabetic patients, aged 59 (52–77) years, undergoing unilateral femoro-popliteal bypass, measuring transcutaneous oxygen, peroneal nerve motor conduction velocity and skin temperature pre- and 6 weeks post-surgery. In the control leg (unoperated) there was no significant change in transcutaneous oxygen (63.2±8.8 vs 63.0±4.6 mm Hg), peroneal nerve motor conduction velocity (45.1±7.8 vs 43.4±7.2 m/s) or skin temperature (30.8±1.3 vs 30.2±1.2°C) after surgery (all NS). In the operated leg, transcutaneous oxygen increased from 59.3±10.7 to 70.7±7.2 mm Hg (p〈0.01), and peroneal nerve motor conduction velocity from 42.6±6.1 to 46.7±3.2 m/s (p〈0.01), but skin temperature was unchanged 30.3±0.4 vs 30.4± 1.3°C (NS). These studies provide further evidence that peripheral nerve function is associated with tissue hypoxia and that improving tissue oxygenation can significantly improve nerve conduction over a short period of time.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Peripheral neuropathy ; peripheral vascular disease.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human diabetic peripheral neuropathy is believed to have, at least in part, a microvascular basis. This study was designed to examine the effects of restoration of arterial blood supply on peripheral nerve function in six non-insulin-dependent diabetic patients with peripheral occlusive vascular disease. In the revascularised legs, transcutaneous oxygen increased from a median 37.5 (28.5–45.7 interquartile range) mmHg to 55.5 (53.5–62.5) mmHg, p = 0.036, mean increase 20.2 (14.8–25.6, 95 % confidence intervals(CI)) mmHg. This was accompanied by a significant improvement in peroneal motor nerve conduction velocity from 31.7 (26.5–36.3) m/s to 33.5 (32.9–39.4) m/s, p = 0.04, mean increase 4.7 (1.7–7.7, 95 % CI) m/s. There was no significant change in transcutaneous oxygen or peroneal nerve motor conduction velocity in the contralateral control limbs. This improvement in conduction velocity with improved tissue oxygenation suggests that studies of agents which might indirectly bring about improvements in microvascular blood flow should be urgently considered. [Diabetologia (1995) 38: 1051–1054]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Peripheral neuropathy ; peripheral vascular disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human diabetic peripheral neuropathy is believed to have, at least in part, a microvascular basis. This study was designed to examine the effects of restoration of arterial blood supply on peripheral nerve function in six non-insulin-dependent diabetic patients with peripheral occlusive vascular disease. In the revascularised legs, transcutaneous oxygen increased from a median 37.5 (28.5–45.7 interquartile range) mmHg to 55.5 (53.5–62.5) mmHg, p=0.036, mean increase 20.2 (14.8–25.6, 95% confidence intervals(CI)) mmHg. This was accompanied by a significant improvement in peroneal motor nerve conduction velocity from 31.7 (26.5–36.3) m/s to 33.5 (32.9–39.4) m/s, p=0.04, mean increase 4.7 (1.7–7.7, 95% CI) m/s. There was no significant change in transcutaneous oxygen or peroneal nerve motor conduction velocity in the contralateral control limbs. This improvement in conduction velocity with improved tissue oxygenation suggests that studies of agents which might indirectly bring about improvements in microvascular blood flow should be urgently considered.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Nitric oxide ; NOS ; arginase ; foot ulcers ; diabetic neuropathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. l-arginine, an amino acid involved in wound healing, is metabolised by one of two pathways; nitric oxide synthase and arginase. If metabolised by nitric oxide synthase, this can result in tissue destruction, or matrix deposition if metabolised by arginase. The aim therefore was to investigate the role of these enzymes in the pathogenesis of diabetic foot ulcers. Methods. The activity, proteins by Western blot analysis and cellular distribution (using immunocytochemistry) of these enzymes were measured in diabetic foot ulcers, diabetic skin and normal skin. Results. Total and inducible nitric oxide synthase (p 〈 0.001) and endothelial nitric oxide synthase were increased in diabetic ulcers compared with diabetic and normal skin and were associated with increased plasma nitrite concentrations in diabetic ulcers (p 〈 0.05). Inducible nitric oxide synthase was the major isoform, with the macrophage being the predominant cellular source. Similarly arginase activity was increased (p 〈 0.01) in diabetic ulcers. The protein levels corroborated with the activity data, with the fibroblast being the major cellular source. The spatial and cellular distribution of the two enzyme systems was distinct. Transforming growth factor-beta1 was decreased in diabetic ulcers in comparison with diabetic skin and normal skin. Conclusion/interpretation. Increased nitric oxide synthase activity in diabetic foot ulcers may be responsible for the impaired healing in this disease. Furthermore, the increased activity of arginase could account for the characteristic callus formation around these ulcers. In addition, the lower concentrations of transforming growth factor-beta1 in diabetic ulcers may explain the raised concentrations of nitric oxide in this condition. [Diabetologia (1999) 42: 748–757]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Neurometer ; diabetic neuropathy ; vibration perception ; nerve conduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Neurometer is a variable constant current sine wave stimulator, and has recently been proposed as a simple non-invasive and quantitative measure of peripheral nerve function. The device is portable and battery operated; assessment of upper and lower extremities takes only a few min, in contrast to conventional assessment techniques. In order to assess its potential in the quantification of diabetic neuropathy, detection thresholds for constant current electric sine wave stimulation were measured at three different frequencies in different sites in 31 healthy control subjects and 90 diabetic patients with and without neuropathy. The device provides good discrimination between neuropathic and non-neuropathic groups (p〈0.001) and is quick and easy to use. Comparisons with results of conventional tests of nerve function show that high frequency detection thresholds correlate best with tests of large fibre function (r= 0.42–0.69, p〈0.001), and low frequency detection thresholds correlate with tests of small fibre function (r=0.34–0.46, p〈0.005). It is concluded that the device may be a simple and comprehensive way of assessing peripheral nerve function.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Diabetes ; neuropathy ; microangiopathy ; heterogeneity ; morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical, electrophysiological and ultrastractural morphometric observations were made in 5 diabetic non-neuropathic patients, 5 diabetic patients with mild neuropathy and 11 diabetic patients with severe neuropathy. Capillary abnormalities were assessed in simultaneous nerve, muscle and skin biopsies and compared with results from 6 age-matched, non-diabetic control subjects. Nerve capillaries demonstrated markedly greater pathology than skin and muscle capillaries. Endoneurial capillary density was significantly reduced in severely neuropathic diabetic patients (p〈0.01) when compared with control subjects. Capillary basement membrane (p〈0.002), endothelial cell (p〈0.003) and total diffusion barrier (endothelial cell, pericyte, basement membrane) (p〈0.001) thickness were significantly increased, and oxygen diffusing capacity was significantly reduced (p〈0.001) in the nerves of patients with severe diabetic neuropathy when compared to control subjects. Endothelial cell profile number and luminal perimeter were significantly increased in asymptomatic (p〈0.01), (p〈0.05) and severely neuropathic (p〈0.001), (p〈0.05) diabetic patients respectively. However, endothelial cell outer perimeter, a measure of capillary size, showed no significant increase in diabetic patients when compared with control subjects. An association was observed between neurophysiological and neuropathological measures of neuropathic severity. There was no significant correlation between the duration of diabetes and HbA1 levels with capillary pathology or with neuropathic severity. Very few abnormalities of muscle and skin correlated with neuropathic severity. However, all measures of nerve capillary pathology correlated significantly with neurophysiological and neuropathological measures of neuropathic severity.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; microangiopathy ; peripheral neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty diabetic patients with neuropathy underwent clinical and neurophysiological evaluation together with a detailed morphometric assessment of capillary pathology in endoneurial and epineurial microvascular beds of the sural nerve. Morphological data were compared with ten non-diabetic control subjects. There were no significant differences in control subjects between basement membrane area, endothelial cell area, endothelial cell profile number or luminal area of endoneurial when compared with epineurial capillaries. In contrast, when compared with epineurial capillaries, endoneurial capillaries from diabetic patients demonstrated a significant increase in basement membrane (p〈0.001) and endothelial cell (p〈0.001) area and a significant reduction in luminal area (p〈0.001). There was no significant difference in endothelial cell profile number between endoneurial and epineurial capillaries amongst diabetic patients. Previous studies have demonstrated a good correlation between the degree of microangiopathy and measures of neuropathic severity. In the present study increased endoneurial capillary basement membrane area was significantly related to reduced peroneal nerve conduction velocity (p〈0.001), myelinated fibre density (p〈0.001) and elevated vibration (p〈0.05) and thermal (p〈0.001) perception. Increased endothelial cell area and reduced luminal size were related to a reduced peroneal nerve conduction (p〈0.05, p〈0.01, respectively), reduced myelinated fibre density (p〈0.05, p〈0.01) and elevated thermal perception (p〈0.05, p〈0.001). Epineurial capillary basement membrane, endothelial cell and luminal area failed to relate to measures of neuropathic severity. This study has demonstrated more advanced microangiopathy and a more significant relationship to neuropathic severity in endoneurial compared with epineurial capillaries, thus providing further support for the role of microangiopathy in the pathogenesis of human diabetic neuropathy.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Medial arterial calcification ; neuropathy ; ankle pressure index ; toe pressure ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence and distribution of medial arterial calcification was assessed in the feet of four subject groups; 54 neuropathic diabetic patients with previous foot ulceration (U), median age 60.5 (50.5–67 interquartile range) years, duration of diabetes 19.5 (9.9–29.9) years; 40 neuropathic diabetic patients without a foot ulcer history (N), age 68 (62–73) years, duration of diabetes 14.0 (8.0–28.0) years; 43 non-neuropathic diabetic patients (NN), age 60.5 (52–68.5) years, duration of diabetes 14.0 (8.0–28.0) years and 50 non-diabetic control subjects, age 62.5 (53.7–70) years. A single radiologist graded medial arterial calcification as absent, mild or severe, at the ankle, hind-foot, mid-foot, metatarsals and toes on standardised plain lateral and antero-posterior foot radiographs taken by a single radiographer. Diabetes history, vibration perception threshold, ankle systolic pressure and serum creatinine were also assessed. Medial arterial calcification was significantly greater (total score 18 [3–31]) in neuropathic diabetic patients with previous ulceration (U vs N p〈0.01, U vs NN p〈0.001). Non-neuropathic diabetic patients did not have significantly higher arterial calcification scores than age-matched non-diabetic control subjects. Medial arterial calcification correlated with vibration perception threshold (r=0.35), duration of diabetes (r=0.32) and serum creatinine (r=0.41), (all p〈0.01). Logistic regression models showed vibration perception and duration of diabetes to predict the probability of any calcification. Serum creatinine level was added to predict severe calcification. Ordered categorical modelling confirmed that medial arterial calcification was significantly heavier at the ankle than the toes for all groups, odds ratio 4.35 (2.94–6.43, 95% confidence intervals), (p〈0.01). Ankle systolic pressure and ankle-brachial pressure index were significantly associated with degree of arterial calcification, r=0.40 and r=0.35, respectively, (both p〈0.01) in diabetic patients. However, arterial calcification was present in more than one-third of patients with an ankle-brachial pressure index of less than 1.0. In conclusion, although ankle pressures correlate with the degree of arterial calcification, medial arterial calcification may be present in patients with low ankle systolic pressures, which may be falsely elevated even at ‘normal’ values. This finding may provide a rationale for the use of toe rather than ankle pressure measurements in diabetic patients, particularly those with peripheral neuropathy, and this hypothesis should be directly tested in future studies.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; polymerase chain reaction ; diabetic nephropathy ; angiotensinogen ; angiotensin converting enzyme ; gene polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n=242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n=187); a geographically defined cohort of newly diagnosed diabetic patients (n=341); and IDDM patients with long duration of disease (〉15 years) and no evidence of overt nephropathy (n=166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p=0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p=0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.
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