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  • 11
    ISSN: 1432-0533
    Keywords: Key words Spontaneous diabetes ; Peripheral ; neuropathy ; Perineurium ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Structural abnormalities of the perineurium from six spontaneously diabetic dogs (diabetes duration 4–8 years and six control animals were quantified using detailed electron microscopic morphometric methods on superficial peroneal nerve biopsy specimens. Total perineurial sheath thickness (μm) was significantly increased in diabetic (8.8 ± 0.6) compared to control animals (6.2 ± 0.3) (P 〈 0.02). This was attributed to a significant increase in the mean perineurial lamellar width in diabetic (0.49 ± 0.03) compared to control (0.40 ± 0.01) (P 〈 0.04) animals. The number of lamellae also showed a non-significant increase in diabetic animals (7.8 ± 0.4) compared to controls (6.9 ± 0.13) (P 〈 0.06). There was no change in the mean interlamellar space in diabetic (0.7 ± 0.05) compared to control (0.6 ± 0.06) (P = 0.15) animals. The total interlamellar space was increased in diabetic (5.7 ± 0.5) compared to control (4.1 ± 0.36) (P 〈 0.04) animals. The perineurial cell basement membrane thickness (nm) was significantly increased in diabetic (126.9 ± 9.8) compared to control (62.8 ± 6.1) (P 〈 0.005) animals. The current study has demonstrated significant abnormalities of the perineurium in the spontaneously diabetic dog, which may have relevance to the pathogenesis of diabetic neuropathy.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-0533
    Keywords: Diabetic neuropathy ; Axonal regeneration ; Nerve growth factor receptors ; Schwann cells ; Basal lamina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Observations were made on myelinated fibre regeneration in diabetic sensory polyneuropathy assessed in sural nerve biopsy specimens. These confirmed that regenerative clusters initially develop within abnormally persistent Schwann cell basal laminal tubes. The number of regenerating fibres, identified by light microscopy, was found to decline in proportion to the reduction in total myelinated fibre density. The relative number of regenerating fibres was significantly greater in patients with insulin-dependent as compared with those with non-insulin-dependent diabetes after correction for age. There was a slight negative correlation between the relative proportion of regenerating fibres and age, but this was not statistically significant. The progressive reduction in the number of regenerating fibres with declining total fibre density indicates that axonal regeneration fails with advancing neuropathy. The production of nerve growth factor (NGF) and NGF receptors by denervated Schwann cells is likely to be important for axonal regeneration. To investigate whether the failure of axonal regeneration could be related to a lack of NGF receptor production by Schwann cells, we examined the expression of p75 NGF receptors by Büngner bands immunocytochemically. In comparison with other types of peripheral neuropathy, p75 NGF receptor expression appeared to take place normally. It is concluded that failure of axonal regeneration constitutes an important component in diabetic neuropathy. Its explanation requires further investigation.
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1432-0428
    Keywords: Diabetes ; neuropathy ; hypoxia ; ischaemia ; ischaemia resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Resistance to ischaemic conduction failure is a recognised but unexplained property of diabetic peripheral nerve. We have studied matched groups of control, diabetic, and non-diabetic hypoxic subjects (hypoxia: arterial oxygen tension ⩽ 60 mm Hg (8 kPa) on at least one occasion and secondary to chronic lung disease). Similar resistance to ischaemia was seen in the hypoxic and diabetic groups compared with control subjects (p〈0.001). The degree of resistance correlated with arterial oxygen tension at the time of testing (r = 0.72, p〈0.01). In all individuals with acute exacerbations of hypoxia, the resistance to ischaemia was normalised with improvement of respiratory function (p〈0.02). These results are compatible with the hypothesis that endoneurial hypoxia may be a factor in the pathogenesis of diabetic neuropathy.
    Type of Medium: Electronic Resource
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  • 14
    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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  • 15
    ISSN: 1432-0428
    Keywords: Hypoxia ; diabetes ; neuropathy ; microangiopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical and neurophysiological studies were conducted in 47 patients with chronic obstructive airways disease and compared with 46 age-matched control subjects. Symptomatic neuropathy was reported in 13% and ankle jerks were absent in 45% of hypoxic patients. Peroneal and median nerve conduction velocities and median and sural sensory nerve amplitudes were significantly reduced in hypoxic patients (p〈0.01). Six hypoxic patients underwent biopsy of the sural nerve, soleus muscle and overlying skin. Nerve glucose, sorbitol, fructose and myo-inositol concentrations were normal. Detailed light and electronrmicroscopy revealed both nerve fibre and microvascular pathology. Segmental demyelination (32%) and unmyelinated fibre degeneration were found to be prominent lesions. The sural nerve perineurium was thickened due to an increase in the number of perineurial lamellae and an increase in intraperineurial space. Basement membrane thickening was observed in capillaries of nerve, muscle and skin. Endothelial cell hyperplasia and hypertrophy were observed in nerve and muscle capillaries but not in skin capillaries. In conclusion, this study has provided neurological, neurophysiological and neuropathological evidence of a neuropathy in hypoxic patients with chronic obstructive airways disease. These findings may be of relevance to some aspects of the aetiology of human diabetic neuropathy.
    Type of Medium: Electronic Resource
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  • 16
    ISSN: 1432-0428
    Keywords: Keywords Diabetes mellitus ; autonomic neuropathy ; diabetic neuropathy ; diabetic nephropathy ; gustatory sweating.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The treatment of gustatory sweating in diabetes mellitus is usually with oral anti-cholinergic drugs, but these frequently lead to unacceptable side effects. Glycopyrrolate is an anti-muscarinic agent that can be applied topically and is efficacious in gustatory sweating occurring in other conditions. In a double-blind placebo-controlled crossover study, we assessed the value of glycopyrrolate in 13 diabetic patients with gustatory sweating. Sweating was measured by a sweat challenge, and diaries recorded by the patients throughout the 2 weeks of each treatment period. Compared to placebo, glycopyrrolate reduced the sweat response to a challenge by 82 % (p 〈 0.01). The frequency of episodes of gustatory sweating during the treatment period was also reduced by 51 % (p 〈 0.01), with a nearly 100 % reduction in the frequency of episodes of severe sweating (p 〈 0.01). In conclusion, topically applied glycopyrrolate is a very effective treatment in reducing both the severity and frequency of diabetic gustatory sweating. [Diabetologia (1997) 40: 299–301]
    Type of Medium: Electronic Resource
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  • 17
    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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  • 18
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; factor VIII ; ketoacidosis ; endothelial damage ; factor VIII multimers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Factor VIII-related antigen and von Willebrand factor are synthesised by and released from vascular endothelium. Acute increases in the plasma concentration of these proteins may reflect endothelial cell damage. We have thus measured the plasma concentration of factor VIII-related antigen and von Willebrand factor, together with procoagulant factor VIII, during the course of acute diabetic ketoacidosis in seven patients. In addition, evidence for qualitative changes in the factor VIII complex was sought. Plasma factor VIII-related antigen and von Willebrand factor were markedly increased (plasma factor VIII-related antigen at presentation, median 2.75 U/ml; von Willebrand factor 2.95 U/ml) and returned toward normal with clinical and biochemical resolution (plasma factor VIII-related antigen at clinical recovery, median 1.80 U/ml; von Willebrand factor 2.05 U/ml). Plasma procoagulant factor VIII followed a similar pattern, but levels were less elevated (plasma procoagulant factor VIII, at presentation, median 1.6U/ml; at clinical recovery, 1.2U/ml). Crossed immunoelectrophoresis and sodium dodecyl sulphate-acrylamide electrophoresis with autoradiographic identification of multimeric structure revealed no evidence of structurally abnormal factor VIII-related antigen in diabetic ketoacidosis. However, an extra peak on crossed immunoelectrophoresis (“pre-peak”) was a feature in the acute phase ketoacidotic plasma in six subjects, and may represent aggregated factor VIII. Changes in plasma factor VIII are a feature of diabetic ketoacidosis and, whilst not specific to this condition, may be the result of endothelial cell damage.
    Type of Medium: Electronic Resource
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  • 19
    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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  • 20
    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.
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