Abstract: BACKGROUND: Long-term patients with diabetes and peripheral neuropathy show altered foot biomechanics and abnormal foot loading. This study aimed at assessing muscle performance and ankle mobility in such patients under controlled conditions. METHODS: Forty six long-term diabetes patients with (DN) and without (D) peripheral neuropathy, and 21 controls (C) were examined. Lower leg muscle performance and ankle mobility were assessed by means of a dedicated equipment, with the patient seated and the examined limb unloaded. 3D active ranges of motion and moments of force were recorded, the latter during maximal isometric contractions, with the foot blocked in different positions. RESULTS: All patients showed reduced ankle mobility. In the sagittal and transversal planes reduction vs C was 11% and 20% for D, 20% and 21% for DN, respectively.Dorsal-flexing moments were significantly reduced in all patients and foot positions, the highest reduction being 28% for D and 37% for DN. Reductions of plantar-flexing moments were in the range 12-15% for D (only with the foot blocked in neutral and in dorsal-flexed position), and in the range 10-24% for DN. In all patients, reductions in the frontal and transversal planes ranged 14-41%. CONCLUSION: The investigation revealed ankle functional impairments in patients with diabetes, with or without neuropathy, thus suggesting that other mechanisms besides neuropathy might contribute to alter foot-ankle biomechanics. Such impairments may then play a role in the development of abnormal gait and in the onset of plantar ulcers.
Abstract: AIMS: To determine current management and to identify patient-related factors and barriers that influence management strategies in diabetic foot disease. METHODS: The Eurodiale Study is a prospective cohort study of 1232 consecutive individuals presenting with a new diabetic foot ulcer in 14 centres across Europe. We determined the use of management strategies: referral, use of offloading, vascular imaging and revascularization. RESULTS: Twenty-seven percent of the patients had been treated for > 3 months before referral to a foot clinic. This varied considerably between countries (6-55%). At study entry, 77% of the patients had no or inadequate offloading. During follow-up, casting was used in 35% (0-68%) of the plantar fore- or midfoot ulcers. Predictors of use of casting were male gender, large ulcer size and being employed. Vascular imaging was performed in 56% (14-86%) of patients with severe limb ischaemia; revascularization was performed in 43%. Predictors of use of vascular imaging were the presence of infection and ischaemic rest pain. CONCLUSION: Treatment of many patients is not in line with current guidelines and there are large differences between countries and centres. Our data suggest that current guidelines are too general and that healthcare organizational barriers and personal beliefs result in underuse of recommended therapies. Action should be undertaken to overcome these barriers and to guarantee the delivery of optimal care for the many individuals with diabetic foot disease.
Abstract: AIMS/HYPOTHESIS: Outcome data on individuals with diabetic foot ulcers are scarce, especially in those with peripheral arterial disease (PAD). We therefore examined the clinical characteristics that best predict poor outcome in a large population of diabetic foot ulcer patients and examined whether such predictors differ between patients with and without PAD. METHODS: Analyses were conducted within the EURODIALE Study, a prospective cohort study of 1,088 diabetic foot ulcer patients across 14 centres in Europe. Multiple logistic regression modelling was used to identify independent predictors of outcome (i.e. non-healing of the foot ulcer). RESULTS: After 1 year of follow-up, 23% of the patients had not healed. Independent baseline predictors of non-healing in the whole study population were older age, male sex, heart failure, the inability to stand or walk without help, end-stage renal disease, larger ulcer size, peripheral neuropathy and PAD. When analyses were performed according to PAD status, infection emerged as a specific predictor of non-healing in PAD patients only. CONCLUSIONS/INTERPRETATION: Predictors of healing differ between patients with and without PAD, suggesting that diabetic foot ulcers with or without concomitant PAD should be defined as two separate disease states. The observed negative impact of infection on healing that was confined to patients with PAD needs further investigation.
Abstract: AIMS/HYPOTHESIS: The aim of the present study was to investigate resource utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in resource utilisation between individuals with or without peripheral arterial disease (PAD) and/or infection. METHODS: Data on resource utilisation were collected prospectively in a European multicentre study. Data on 1,088 patients were available for the analysis of resource use, and data on 821 patients were included in the costing analysis. Costs were calculated for each patient by multiplying the country-specific direct and indirect unit costs by the number of resources used from inclusion into the study up to a defined endpoint. Country-specific costs were converted into purchasing power standards. RESULTS: Resource use and costs varied between outcome groups and between disease severity groups. The highest costs per patient were for hospitalisation, antibiotics, amputations and other surgery. All types of resource utilisation and costs increased with the severity of disease. The total cost per patient was more than four times higher for patients with infection and PAD at inclusion than for patients in the least severe group, who had neither. CONCLUSIONS/INTERPRETATION: Important differences in resource use and costs were found between different patient groups. The costs are highest for individuals with both peripheral arterial disease and infection, and these are mainly related to substantial costs for hospitalisation. In view of the magnitude of the costs associated with in-hospital stay, reducing the number and duration of hospital admissions seems an attractive option to decrease costs in diabetic foot disease.
Abstract: High-mobility group box 1 (HMGB1) protein is a multifunctional cytokine involved in inflammatory responses and tissue repair. In this study, it was examined whether HMGB1 plays a role in skin wound repair both in normoglycemic and diabetic mice. HMGB1 was detected in the nucleus of skin cells, and accumulated in the cytoplasm of epidermal cells in the wounded skin. Diabetic human and mouse skin showed more reduced HMGB1 levels than their normoglycemic counterparts. Topical application of HMGB1 to the wounds of diabetic mice enhanced arteriole density, granulation tissue deposition, and accelerated wound healing. In contrast, HMGB1 had no effect in normoglycemic mouse skin wounds, where endogenous HMGB1 levels may be adequate for optimal wound closure. Accordingly, inhibition of endogenous HMGB1 impaired wound healing in normal mice but had no effect in diabetic mice. Finally, HMGB1 had a chemotactic effect on skin fibroblasts and keratinoyctes in vitro. In conclusion, lower HMGB1 levels in diabetic skin may play an important role in impaired wound healing and this defect may be overcome by the topical application of HMGB1.
Abstract: This article describes the rationale and protocol of a large data collection study in patients with new diabetic foot ulcers by the Eurodiale study group, a consortium of centers of expertise in the field of diabetic foot disease within Europe. This study is a multicenter, observational, prospective data collection study. Its main aim is to determine the major factors determining clinical outcome and outcome in terms of health-related quality of life and health care consumption. Between September 1, 2003, and October 1, 2004, in 14 European centers, all consecutive patients with diabetes and a new foot ulcer were included in the study and followed until the end point or for a maximum of 1 year. End points were healing of the foot, major amputation, or death. Data were collected on patient, foot, and ulcer characteristics and on diagnostic and management procedures. Furthermore, data were collected on health care organization, quality of life, and resource use. A total of 1232 patients were included in the study. Sixty-three percent of the patients were referred by their general practitioner or were self-referrals. Twenty-seven percent of the patients were admitted at the time of inclusion; 1088 patients were followed until the end point. "Optimal Organization of Health Care in Diabetic Foot Disease" is one of the first large multicenter studies in the field of diabetic foot disease on clinical presentation, clinical outcome, quality of life, resource utilization, and health care organization and their interrelationships. These data will provide us with new insights that enable us to improve care for these patients and guide the development of new studies in this area. The results of this study are the subject of a separate presentation.
Abstract: AIMS/HYPOTHESIS: Large clinical studies describing the typical clinical presentation of diabetic foot ulcers are limited and most studies were performed in single centres with the possibility of selection of specific subgroups. The aim of this study was to investigate the characteristics of diabetic patients with a foot ulcer in 14 European hospitals in ten countries. METHODS: The study population included 1,229 consecutive patients presenting with a new foot ulcer between 1 September 2003 and 1 October 2004. Standardised data on patient characteristics, as well as foot and ulcer characteristics, were obtained. Foot disease was categorised into four stages according to the presence or absence of peripheral arterial disease (PAD) and infection: A: PAD -, infection -; B: PAD -, infection +; C: PAD +, infection -; D: PAD +, infection +. RESULTS: PAD was diagnosed in 49% of the subjects, infection in 58%. The majority of ulcers (52%) were located on the non-plantar surface of the foot. With regard to severity, 24% had stage A, 27% had stage B, 18% had stage C and 31% had stage D foot disease. Patients in the latter group had a distinct profile: they were older, had more non-plantar ulcers, greater tissue loss and more serious comorbidity. CONCLUSIONS/INTERPRETATION: According to our results in this European cohort, the severity of diabetic foot ulcers at presentation is greater than previously reported, as one-third had both PAD and infection. Non-plantar foot ulcers were more common than plantar ulcers, especially in patients with severe disease, and serious comorbidity increased significantly with increasing severity of foot disease. Further research is needed to obtain insight into the clinical outcome of these patients.
Abstract: OBJECTIVE: To validate nerve-axon reflex-related vasodilatation as an objective method to evaluate C-nociceptive fibre function by comparing it with the standard diagnostic criteria. METHODS: Neuropathy was evaluated in 41 patients with diabetes (26 men and 15 women) without peripheral vascular disease by assessing the Neuropathy Symptom Score, the Neuropathy Disability Score (NDS), the vibration perception threshold (VPT), the heat detection threshold (HDT), nerve conduction parameters and standard cardiovascular tests. The neurovascular response to 1% acetylcholine (Ach) iontophoresis was measured at the forearm and at both feet by laser flowmetry. An age-matched and sex-matched control group of 10 healthy people was also included. RESULTS: Significant correlations were observed between the neurovascular response at the foot and HDT (r(s) = -0.658; p<0.0001), NDS (r(s) = -0.665; p<0.0001), VPT (r(s) = -0.548; p = 0.0005), tibial nerve conduction velocity (r(s) = 0.631; p = 0.0002), sural nerve amplitude (r(s) = 0.581; p = 0.0002) and autonomic function tests. According to the NDS, in patients with diabetes who had mild, moderate or severe neuropathy, a significantly lower neurovascular response was seen at the foot than in patients without neuropathy and controls. A neurovascular response <50% was found to be highly sensitive (90%), with a good specificity (74%), in identifying patients with diabetic neuropathy. CONCLUSION: Small-fibre dysfunction can be diagnosed reliably with neurovascular response assessment. This response is already reduced in the early stages of peripheral neuropathy, supporting the hypothesis that small-fibre impairment is an early event in the natural history of diabetic neuropathy.
Abstract: Foot problems are common causes of disability in diabetic patients with as many as 25% expected to develop severe foot or leg problems during their lifetimes. Although skin ulceration is the most frequent problem, bones may also be involved in two different clinical conditions: osteomyelitis and Charcot osteoarthropathy. Osteomyelitis causes complications in up to one third of diabetic foot infections and is due to direct contamination from a soft-tissue ulcer. Osteoarthropathy Charcot foot is a chronic and progressive disease of the bone and joints. Both osteomyelitis and Charcot joint are conditions with an increased risk of lower limb amputation, both may have a successful outcome when recognized and treated in the early stages. The major diagnostic difficulty is in distinguishing bone infection (osteomyelitis) from non-infectious neuropathic bony disorders as in osteoarthropathy Charcot foot. An additional difficulty is found when a bone infection superimposes a Charcot osteopathy. This condition, which can be clinically suspected when foot ulceration appears in Charcot foot, needs to be diagnosed because it implies a different therapeutic strategy. This article aims to summarize both these two clinical conditions and give indications to make a timely and correct diagnosis.
Abstract: AIM: The aim of this study was to examine foot function in the presence of diabetes-induced alterations of the anatomical and biomechanical unit formed by the Achilles tendon, plantar fascia and metatarso-phalangeal joints. More specifically, we focused on the Windlass mechanism, the physiological mechanism which entails stiffening of the foot during propulsion. METHODS: Sixty-one diabetic patients, with or without neuropathy, and 21 healthy volunteers were recruited. The thickness of Achilles tendon and plantar fascia was measured by ultrasound. The main biomechanical parameters of foot-floor interaction during gait were acquired by means of dedicated platforms. The range of motion of the 1st metatarso-phalangeal joint was measured passively. RESULTS: The plantar fascia (PF) and Achilles tendon (AT) were significantly thickened in diabetic patients [control subjects: PF 2.0+/-0.5 mm, AT 4.0+/-0.5 mm; diabetic patients without neuropathy: PF 2.9+/-1.2 mm (P=0.002), AT 4.6+/-1.0 mm (P=0.016); diabetic patients with neuropathy: PF 3.0+/-0.8 mm (P<0.0001), AT 4.9+/-1.7 mm (P=0.026)]. Joint mobility was significantly reduced [control subjects: 100.0+/-10.0 degrees; diabetic patients without neuropathy: 54.0+/-29.4 degrees (P<0.0001); diabetic patients with neuropathy: 54.9+/-17.2 degrees (P<0.0001)]. Loading times and force integrals under the heel and the metatarsals increased [metatarsal loading time (% stance phase): control subjects 88.2+/-4.1%; diabetic patients without neuropathy 90.1+/-4.7% (P=0.146); diabetic patients with neuropathy 91.7+/-6.6% (P=0.048)]. CONCLUSIONS: Increased thickness of Achilles tendon and plantar fascia, more evident in the presence of neuropathy, may contribute to an overall increase of tensile force and to the occurrence of an early Windlass mechanism, maintained throughout the whole gait cycle. This might play a significant role in the overall alteration of the biomechanics of the foot-ankle complex.
Abstract: AIM: To evaluate the prevalence of peripheral arterial disease (PAD) with the ankle-brachial index (ABI) in newly diagnosed Type 2 diabetic subjects. METHODS: Between autumn 2002 and spring 2003, 2559 newly diagnosed Type 2 diabetic subjects (about 15% of the cases/year in Italy) were enrolled in 265 diabetology centres. Family history of diabetes, smoking, height, weight, waistline, fasting glycaemia, glycosylated haemoglobin, total and HDL-cholesterol and triglyceride values were collected. Claudication, cyanosis, cold foot, foot hair anomalies, skin thinning and femoral, popliteal, posterior tibial and dorsalis pedis pulses were assessed. The ABI was measured with a portable Doppler continuous-wave instrument. RESULTS: An ABI < 0.9 was found in 539 (21.1%) patients. Claudication was present in 187 (7.3%). Femoral pulse was absent in 218 (8.5%), popliteal in 316 (12.3%), tibial in 563 (22.0%) and dorsalis pedis in 578 (22.6%). Foot cyanosis was observed in 88 (3.4%), cold foot in 359 (13.9%), skin thinning in 468 (18.3%) and hair anomalies in 857 (33.5%). Multivariate analysis of the variables associated with ABI < 0.9 in the univariate analysis confirmed the independent role of age [relative risk (RR) 1.02, P < 0.001, confidence interval (CI) 1.01, 1.04], claudication (RR 4.53, P < 0.001, CI 2.97, 6.93), absence of tibial pulse (RR 3.45, P < or = 0.001. CI 2.54, 4.68) and pedis pulse (RR 1.96, P < or = 0.001, CI 1.4, 2.68). CONCLUSIONS: PAD, as represented by ABI < 0.9, is common in newly diagnosed Type 2 diabetic patients.
Abstract: OBJECTIVE: To monitor transcutaneous oxygen tension (TcPO2) after percutaneous transluminal angioplasty (PTA) in diabetic patients with ischaemic foot ulcers. RESEARCH DESIGN AND METHODS: Twenty-three diabetic patients with ischaemic foot ulcers who underwent successful revascularization by PTA (SR group) were retrospectively selected. Twenty diabetic patients who underwent unsuccessful revascularization (UR group) were also included. Transcutaneous oxygen tension was measured at the dorsum of the foot before and 1 (+/- 1), 7 (+/- 1), 14 (+/- 1), 21 (+/- 1) and 28 (+/- 1) days after the surgical procedure. RESULTS: After PTA, TcPO2 progressively improved in the SR group, reaching its peak 4 weeks after angioplasty. A concomitant decrease of cutaneous carbon dioxide tension (TcPCO2) was also observed immediately after PTA which reached the lowest levels 3 weeks later. In the UR group, TcPO2 showed a slight improvement immediately after PTA but remained stable throughout the observation, while TcPCO2 levels did not change. Finally, the percentage of SR patients with a TcPO2 > or = 30 mmHg was 38.5% 1 week after PTA, while it increased to 75% 3 weeks later. CONCLUSION: Transcutaneous oxygen tension monitoring showed that after successful revascularization it takes 3-4 weeks for cutaneous oxygenation to improve and reach the optimal levels for wound healing. Transcutaneous carbon dioxide tension monitoring may be more useful to identify the negative outcome of a revascularization procedure. Our findings suggest that, when the surgical approach can be delayed, the best timing to perform a more aggressive debridement or minor amputations is 3-4 weeks after successful revascularization.
Abstract: BACKGROUND: The diabetic foot often undergoes abnormal plantar pressures, changing in walking strategy, ulcerative processes. The present study focuses on the effects that diabetes-induced alterations of Achilles tendon, plantar fascia and first metatarso-phalangeal joint-both anatomical and functional-may have on foot loading. METHODS: Sixty-one diabetic patients, with or without neuropathy, and 21 healthy volunteers were recruited. Thickness of Achilles tendon and plantar fascia was measured by ultrasound. Flexion-extension of the first metatarso-phalangeal joint was measured passively. Main biomechanic parameters of foot-floor interaction during gait were acquired and related to the above measurements. FINDINGS: Plantar fascia and Achilles tendon were significantly (P<0.05) thicker in diabetics than in controls; mean values (SD) for controls, diabetics without and with neuropathy were 2.0 mm (0.5), 2.9 mm (1.2) and 3.0 mm (0.8) for plantar fascia, respectively, and 4.0 mm (0.5), 4.6 mm (1.0) and 4.9 mm (1.7) for Achilles tendon, respectively. Flexion-extension of the first metatarso-phalangeal joint was significantly (P<0.05) smaller in diabetics than in controls; mean values (SD) for controls, diabetics without and with neuropathy were 100.0 degrees (10.0), 54.0 degrees (29.4) and 54.9 degrees (17.2), respectively. The increase in the vertical force under the metatarsals was strongly related (R=0.83, explained variance=70.1%) to the changes in the three above parameters. INTERPRETATION: Thickening of plantar fascia and Achilles tendon in diabetics, more evident in the presence of neuropathy, concurs to develop a rigid foot, which poorly absorbs shock during landing (performs the physiological impact force absorption during landing). More generally, an overall alteration of the foot-ankle complex motion likely occurs throughout the whole gait cycle, which partly explains the abnormal loading under the forefoot.
Abstract: Magnetic resonance (MR) imaging has improved the possibility of evaluating musculoskeletal structures thus gaining an important role in the diagnosis and treatment of foot and ankle pathologies. In this review, the normal and pathological images of the ankle and foot obtained using MR techniques are presented and discussed. The high soft-tissue contrast resolution and the multiplanar sections of MRI allow the imaging of contiguous tissues where small contrast differences exist, such as ligamentous and tendinous injuries or impingement syndromes. The spatial resolution with high sensitivity for bone signal changes offers an early detection of osseous abnormalities such as stress fractures or osteonecrosis. Here it is specified possibilities and limitations of MRI in the diabetic foot: this technique is superior to nuclear medicine and computed tomography (CT), however it is unable to distinguish between neuro arthropathy and infection.
Abstract: AIM: To evaluate the effect of local anesthesia on the skin vasodilation induced by the iontophoresis of sodium nitroprusside and heating. METHODS: Skin vascular reactivity, in response to iontophoresis of sodium nitroprusside (SNP), was evaluated at the forearm and foot in 13 neuropathic diabetic (DN) and 11 nonneuropathic diabetic (D) patients and 9 healthy, nondiabetic subjects who served as controls (C). The direct (DI) and nerve axon reflex-related (N-V) vasodilation were measured by using two single-point laser Doppler probes. The vasodilation in response to local warming was also assessed. A topical anesthetic was applied on the contralateral forearm and foot and all the measurements were repeated. RESULTS: Dermal anesthesia resulted in a reduction of the direct vasodilation to SNP at the forearm [C: 58.1 +/- 16, D: 60.6 +/- 11%, and DN: 48.3 +/- 37% (postanesthesia percentage of reduction; mean +/- SEM), P<0.01] and at the foot in all three groups (D: 38.5 +/- 12%, P<0.01; C: 27.2 +/- 14% and DN: 11.3 +/- 17.5%, P=NS). The N-V related vasodilation was very low before and did not change after local anesthesia. The postanesthesia hyperemic response to warming was significantly reduced at low temperatures but did not change at 44 degrees C. CONCLUSION: The sodium nitroprusside-related vasodilation is reduced after local anesthesia in a similar way in healthy subjects and diabetic patients with and without neuropathy. The response to heating is also reduced at low temperatures. This indicates a stabilizing effect of local anesthesia on the smooth muscle cell.
Abstract: OBJECTIVE: To evaluate the role of the C-nociceptive nerve fibers in nerve axon reflex-related vasodilation. METHODS: Skin vascular reactivity, in response to iontophoresis of acetylcholine and sodium nitroprusside, was evaluated at both the forearm and the foot levels in 13 diabetic neuropathic (DN),11 nonneuropathic (D), and 9 healthy control (C) subjects. The total and nerve axon reflex-related vasodilation were measured by two single-point laser probes. A topical anesthetic was applied on the contralateral forearm and foot, and all the measurements were repeated. RESULTS: Dermal anesthesia resulted in a reduction of the nerve axon reflex-related vasodilation at the forearm in all three groups (C 70.7 +/- 12%, D 59.7 +/- 7%, and DN 73.5 +/- 14%; percentage of reduction over preanesthesia response, mean +/- SEM; p < 0.001) and at the foot in the two nonneuropathic groups (C 74 +/- 10% and D 68.9 +/- 9%; p < 0.001 versus before anesthesia). This reduction was absent at the foot of the neuropathic patients (DN -4 +/- 21%; p = NS versus before anesthesia). A correlation was found between the nerve axon reflex-related response and measurements of nerve function (neuropathy disability score, r = -0.425, p < 0.017; vibration perception threshold, r = -0.527, p < 0.002; Semmes-Weinstein monofilament perception, r = -0.619, p < 0.001). CONCLUSION: The nerve axon reflex-related vasodilation is directly related to the function of the C-nociceptive fibers and is significantly associated with other nerve function measurements. As this is an objective measurement, it has the potential to be used as an alternative to currently employed techniques to evaluate small-fiber function.
Abstract: OBJECTIVES: Secondary to peripheral neuropathy, plantar hyperpressure is a proven risk factor for foot ulceration. But limited joint mobility (LJM) and soft tissue abnormalities may also contribute. The aim of this study was to evaluate the relationships among thickness of plantar fascia, mobility of the metatarso-phalangeal joint, and forces expressed under the metatarsal heads. RESEARCH DESIGN AND METHODS: We evaluated 61 diabetic patients: 27 without neuropathy (D group), 19 with neuropathy (DN group), and 15 with previous neuropathic foot ulceration (DNPU group). We also examined 21 control subjects (C). Ultrasound evaluation was performed with a high resolution 8- to 10-MHz linear array (Toshiba Tosbee SSA 240). The foot loading pattern was evaluated with a piezo-dynamometric platform. First metatarso-phalangeal joint mobility was assessed with a mechanic goniometer. RESULTS: Diabetic patients presented increased thickness of plantar fascia (D 2.9 +/- 1.2 mm, DN 3.0 +/- 0.8 mm, DNPU 3.1 +/- 1.0 mm, and C 2.0 +/- 0.5.mm; P < 0.05), and significantly reduced motion range at the metatarso-phalangeal joint (D 54.0 +/- 29.4 degrees, DN 54.9 +/- 17.2 degrees, DNPU 46.8 +/- 20.7 degrees, and C 100.0 +/- 10.0 degrees; P < 0.05). The evaluation of foot-floor interaction under the metatarsal heads showed increased vertical forces in DN and DNPU and increased medio-lateral forces in DNPU. An inverse correlation was found between the thickness of plantar fascia and metatarso-phalangeal joint mobility (r = -0.53). The thickness of plantar fascia was directly correlated with vertical forces under the metatarsal heads (r = 0.52). CONCLUSIONS: In diabetic patients, soft tissue involvement may contribute to the increase of vertical forces under the metatarsal heads. Changes in the structure of plantar fascia may also influence the mobility of the first metatarso-phalangeal joint.
Abstract: The application of tissue engineering technology to wound healing has resulted in the development of a number of "living skin equivalents." These have become a viable option in the treatment of chronic, nonhealing wounds. Such wounds present a major cost burden as well as increased morbidity and mortality. Unique among skin tissue engineering technology is the TissueTech autograft system, as it incorporates an autologous dermal substitute-Hyalograft 3D-and an autologous epidermal replacement, Laserskin autograft. Each includes a matrix of a hyaluronic acid ester to promote cellular migration and graft take.
Abstract: OBJECTIVE: Diabetic neuropathic patients show a peculiar loading pattern of the foot, which led us to hypothesize that a substantial modification exists in their deambulatory strategy. The aim of the present study was to support this hypothesis by quantifying the changes of the loading patterns and by monitoring the excursion of center of pressure (COP) during gait. RESEARCH DESIGN AND METHODS: -A total of 21 healthy volunteers (C) and 61 diabetic patients were evaluated: 27 diabetic subjects without neuropathy (D), 19 with neuropathy (DN), and 15 with previous neuropathic ulcer (DPU). A piezo-dynamometric platform was used to record the foot-to-floor interaction by measuring loading time and the instantaneous COP position during the stance phase of gait. RESULTS: Loading time was significantly longer in neuropathic patients than in control subjects (DPU: 816.8 +/- 150 ms; DN: 828.6 +/- 152 ms; D: 766.5 +/- 89.9 ms; C: 723.7 +/- 65.7 ms; P < 0.05). COP excursion along the medio-lateral axis of the foot clearly decreased from C to DPU groups (C: 6.41 +/- 0.1 cm; D: 4.88 +/- 0.2 cm; DN: 4.57 +/- 0.1 cm; DPU: 3.36 +/- 0.1 cm; P < 0.05) as well as COP excursion along the longitudinal axis for the DPU group only (C: 26.6 +/- 1 cm; D: 26.9 +/- 1 cm; DN: 27.2 +/- 1 cm; DPU: 24.2 +/- 1 cm; P < 0.05). COP integrals were significantly reduced for all pathological classes (DPU: 14.2 +/- 8 cm(2); DN: 25.8 +/- 6 cm(2); D: 27.7 +/- 3 cm(2); C: 38.6 +/- 6 cm(2); P < 0.05). CONCLUSIONS: The accurate quantification of loading patterns and of COP excursions and integrals highlights changes of foot-to-floor interaction in diabetic neuropathic patients. The decreased medio-lateral and longitudinal COP excursions and corresponding changes of loading times and patterns support our hypothesis that a change in the walking strategy of diabetic patients with peripheral neuropathy does occur.
Abstract: We assessed saccadic eye movements (SEM) and the visual evoked potentials (VEP) with the aim to evaluate whether a correlation exist between SEM and visual pathways function, in insulin-dependent diabetes mellitus (IDDM) patients. In IDDM patients we observed significantly longer SEM latency, while SEM velocity and accuracy were similar to those of the controls; VEP showed a significant delay of the latencies and significant reduction of the amplitudes in IDDM patients no relationship between SEM and VEP parameters were found. In conclusion SEM latency delay suggest an impairment of the saccadic eye movement system, while impaired VEP may be ascribed to a dysfunction of the visual pathways. The lack of correlation between VEP impairment and SEM latency delay suggests that in our IDDM patients the delay of saccadic latency could be ascribed to a difuse neuronal problem exceeding the visual pathways disfunction.
Abstract: OBJECTIVES: The role of tangential stress in neuropathic foot ulceration is yet unknown. The aim of this study was to investigate the tangential forces developed during gait by the whole foot and by selected subareas of it, namely the heel, the metatarsals and the hallux. METHODS: 61 diabetic patients have been evaluated: 27 without neuropathy, 19 with neuropathy and 15 with previous neuropathic ulcer. The patients were compared with 21 healthy volunteers. A piezo-dynamometric platform was used to measure the three components of the ground reaction force under the total foot and the selected subareas. RESULTS: A significant reduction was observed for the forward peak and the backward peak of the anteroposterior ground reaction force component measured under the whole foot. Patients with previous neuropathic ulcer showed a significant increase of the mediolateral stress under the metatarsals. CONCLUSIONS: Tangential stress is altered in diabetic neuropathic patients; the increased mediolateral component suggests that tangential stress could have a role in the high risk of recurrence observed in patients with previous ulceration. RELEVANCE: To assess the effectiveness of a non-invasive methodology for the estimation and the monitoring of significant alterations of the tangential stress with the increase of neuropathy.
Abstract: Persons with type 1 diabetes show electrophysiological abnormalities of the visual system which are revealed by methods such as flash electroretinogram (FERG), oscillatory potentials (OPs), pattern electroretinogram (PERG), focal electroretinogram (focal ERG), visual evoked potentials (VEP) in basal condition and after photostress. This review reports the changes in electrophysiological responses of the different structures composing the visual system observed in persons with type 1 diabetes before the development of the overt clinical retinopathy. In persons with type 1 diabetes without retinopathy (IDD), the earlier abnormal electrophysiological responses are recorded from the innermost retinal layers and postretinal visual pathways, as suggested by impaired PERGs and delayed retinocortical time (RCT). These are observed in IDD persons with a disease duration shorter than 6 months. Further electrophysiological changes are recorded from the macula (abnormal focal ERG and VEP after photostress) in IDD persons with disease duration greater than 1 year. Additional electrophysiological changes are recorded from the middle and outer retinal layers (impaired FERG and OPs) in IDD persons with a disease duration greater than 10 years. All the electrophysiological tests show a greater degree of abnormal responses in persons with type 1 diabetes when a background retinopathy is present.
Abstract: OBJECTIVES: Visual evoked potentials (VEPs) show abnormal responses in newly-diagnosed insulin-dependent diabetic (IDDM) patients. Electrophysiological methods allow one to dissect and explore different structures contributing to neural conduction in the visual pathways. The aim of our work was to assess whether the VEP abnormalities are due to impaired function of the retinal layers and/or a delayed conduction in the postretinal visual pathways. METHODS: Simultaneous recordings of VEP and pattern-electroretinogram (PERG) were performed at two intervals (at entry of the study and after 3 months) in 14 newly-diagnosed IDDM patients (age: 24.8+/-6.8 years; duration of disease: 3+/-1.5 months), and in 14 age-matched control subjects. RESULTS: In comparison with control subjects, IDDM patients showed: VEP P100 latencies significantly delayed (P < 0.01), a significant impairment of all PERG parameters (P < 0.01) and retinocortical time (RCT, difference between VEP P100 and PERG P50 latencies) and latency window (LW, difference between VEP N75 and PERG P50 latencies) also significantly increased (P < 0.01). All electrophysiological parameters were not significantly changed when retested after 3 months. No correlations were found between VEP P100 latency, RCT, LW and PERG parameters. CONCLUSIONS: Impaired PERG indicates an involvement of the innermost retinal layers; increased values of RCT and LW represent an index of delayed neural conduction in the postretinal visual pathways. Therefore two sources, one retinal (impaired PERG) and one postretinal (delayed RCT and LW), may independently contribute in to the abnormal responses of VEP observed in newly-diagnosed IDDM patients. Three months of relatively-stable metabolic control have not normalized the VEP and PERG impairment.
Abstract: We have analysed the results of surgical treatment for microcarcinoma of the thyroid (MCT). In sixteen patient clinical and follow-up data were retrospectively evaluated during a 35.1-month follow-up. Thyroid hyperfunctional state us was present in two subjects. A single nodule was detected by echotomography in 11 patients, while multinodular diffuse goitre was revealed in 3 patients. In the last two subjects, thyroid gland appeared completely normal at ultrasonography, despite laterocervical lymph node metastases. Fine-needle aspiration biopsy was performed in 6 patients and its diagnostic accuracy was high (83,3%). MCT was classified as "incidental" in 12 patients and "occult" in the remaining 4 patients. Eight subjects underwent total thyroidectomy and 8 hemithyroidectomy plus isthmectomy. No postoperative complications were recorded. In 10 patients MCT histotype was papillar adenocarcinoma, in 5 was follicular adenocarcinoma and in the remaining case it was medullary carcinoma. Goitre was associated in 75% of the cases. Only in a patient disease progressed to death because of hematogenous metastases. In conclusion, we believe that incidental MCT is a low-grade malignancy with a benign biological behaviour. Occult MCT is a potentially lethal disease. We did not observe differences in the long-term results between different surgical treatments of MCT.
Abstract: OBJECTIVE: To evaluate the contribution of central neuropathy on postural impairment observed in diabetic patients with peripheral neuropathy. RESEARCH DESIGN AND METHODS: Central sensory and motor nervous propagation, nerve conduction velocity, and static posturography were assessed in the following age-matched subjects: 7 IDDM patients with peripheral neuropathy (group DN), 18 IDDM patients without peripheral neuropathy (group D), and 31 control subjects (group C). Somatosensory-evoked potentials (SEPs) during tibial nerve stimulation were recorded, and the spine-to-scalp sensory central conduction time (SCCT) was evaluated. Motor-evoked potentials (MEPs) were recorded from leg muscles during magnetic transcranial brain stimulation, and the scalp-to-spine motor central conduction time (MCCT) was evaluated. The following posturographic parameters were calculated from the statokinesigram: trace length, trace surface, velocity of body sway with its standard deviation, and VFY (a parameter derived from the velocity variance and the anteroposterior mean position of the body). RESULTS: SCCT was significantly higher in the DN group than in the C and D groups (P < 0.001). MCCT was similar in all groups. Posturographic parameters were all significantly impaired in the DN group (P < 0.01). While posturographic parameters showed a direct relationship with some parameters of peripheral nerve conduction, no correlations were observed with SEP and MEP central conduction time. These results were also confirmed by logistic regression, which indicates peripheral neuropathy as the only implicating factor in postural instability (odds ratio 0.22, 95% CI 0.07-0.75) after data reduction by means of factor analysis. CONCLUSIONS: Although diabetic patients with peripheral neuropathy show a delay in central sensory conduction, postural instability may be fully explained by the presence of peripheral neuropathy.
Abstract: Various electrophysiological tests have been employed to reveal functional abnormalities at different levels of the visual system in insulin-dependent diabetic (IDDM) patients. The aim of our work was to assess, with a comprehensive neurophysiological protocol evaluating the retinal, macular and visual pathways functions, whether and when such electrophysiological abnormalities do appear in IDDM patients free of any fluorangiographic sign of retinopathy with various disease duration. Flash-electroretinogram (ERG), oscillatory potentials (OPs), pattern-electroretinogram (PERG), and visual evoked potentials (VEPs) in basal condition and after photostress were assessed in 12 control subjects (C) and 42 aged-matched IDDM patients without clinical retinopathy (DR-) divided, on the basis of the disease duration, into 4 groups (1-5, 6-10, 11-15, 16-20 years). In addition another age-matched group of IDDM patients with a background retinopathy (DR+; n = 12; duration of disease 18 +/- 49 years) was evaluated. In all IDDM DR-patients PERG and VEP were significantly impaired. In addition, groups 11-15 and 16-20 years displayed impaired OPs. All electrophysiological parameters were further impaired in DR+ patients. In conclusion, retinal, macular and visual pathways functions are differently impaired in IDDM (DR-) patients with different disease duration. Electrophysiological impairment starts in the nervous conduction of the visual pathways with an early involvement, goes on in the innermost retinal layers and in the macula and ends in the middle and outer retinal layers.
Abstract: OBJECTIVE: To evaluate the influence of diabetic peripheral neuropathy on postural strategy. RESEARCH DESIGN AND METHODS: Static posturography and nerve conduction velocity were performed in the following age-matched subjects: 10 IDDM patients with peripheral neuropathy, 23 IDDM patients without peripheral neuropathy, and 21 control subjects. All subjects with signs or symptoms of postural instability were excluded from the study. The following posturographic parameters were drawn: 1) velocity of body sway, expressed as mean velocity and average of the SDs, 2) VFY, the parameter derived from the velocity variance and the anteroposterior mean position of the body (this parameter monitors the postural strategy pursued by the subject), and 3) fast Fourier transformation on the x (FFTX) and y (FFTY) planes, spectral analysis of the frequencies of body oscillation on frontal (x) and anteroposterior (y) planes. RESULTS: Mean velocity and its SD were higher in IDDM patients with peripheral neuropathy than in control subjects and IDDM patients without peripheral neuropathy (P < 0.001). VFY was increased in IDDM patients with peripheral neuropathy versus control subjects and IDDM patients without peripheral neuropathy (P < 0.01). A direct relationship was found between parameters of posturography and some parameters of nerve conduction tests. CONCLUSIONS: Diabetic patients with peripheral neuropathy demonstrate a shift from physiological ankle control to hip postural control as monitored by specific posturography analysis.
Abstract: OBJECTIVE: To evaluate the efficacy of manufactured shoes specially designed for diabetic patients (Podiabetes by Buratto Italy) to prevent relapses of foot ulcerations. RESEARCH DESIGN AND METHODS: A prospective multicenter randomized follow-up study of patients with previous foot ulcerations was conducted. Patients were alternatively assigned to wear either their own shoes (control group, C; n = 36) or therapeutic shoes (Podiabetes group, P; n = 33). The number of ulcer relapses was recorded during 1-year follow-up. RESULTS: Both C and P groups had similar risk factors for foot ulceration (i.e., previous foot ulceration, mean vibratory perception threshold > 25 mV). After 1 year, the foot ulcer relapses were significantly lower in P than in C (27.7 vs. 58.3%; P = 0.009; odds ratio 0.26 [0.2-1.54]). In a multiple regression analysis, the use of therapeutic shoes was negatively associated with foot ulcer relapses (coefficient of variation = -0.315; 95% confidence interval = -0.54 to -0.08; P = 0.009). CONCLUSIONS: The use of specially designed shoes is effective in preventing relapses in diabetic patients with previous ulceration.
Abstract: Electrophysiological tests (electroretinogram, oscillatory potentials, visual evoked potentials, in the basal condition and after photostress) reveal an abnormal function of the visual system in insulin-dependent diabetic (IDDM) patients. The aim of our work was to assess whether electrophysiological abnormalities in visual function exist in newly-diagnosed diabetic patients free of any fluorangiographic signs of retinopathy. Ten control subjects (age 28.7 +/- 2.44 years) and then IDDM patients (age 25.2 +/- 6.78 years; disease duration 5.3 +/- 3.5 months) in stable metabolic control (HbA1C 7.5 +/- 1.1%) were evaluated. Flash-electroretinograms and oscillatory potentials were similar in both groups. Visual evoked potentials (VEP) recorded under basal conditions showed that P100 latency was significantly increased in the diabetic patients compared to control subjects (p < 0.01), while N75-P100 amplitude was similar in both groups. The recovery time of VEP after photostress was equivalent in diabetic patients and control subjects. The impaired basal VEPs suggest an early involvement of the nervous conduction in the optic nerve. However, the preserved flash-electroretinogram and the normal recovery time after photostress indicate that a short disease duration does not induce physiopathological changes in the outer retinal layers or in the macular function.
Abstract: OBJECTIVE--To evaluate the influence of peripheral neuropathy on body sway assessed by posturography. RESEARCH DESIGN AND METHODS--The age-matched study subjects included 10 insulin-dependent diabetes mellitus (IDDM) patients with peripheral neuropathy (DN), 23 IDDM patients without peripheral neuropathy (D) according to the San Antonio Consensus Conference guidelines, and 21 control subjects (C). All subjects with symptoms and/or clinical signs of postural instability were excluded from the study. RESULTS--The trace surface was significantly larger in the DN than in the C and D groups (P < 0.05), and the trace length was longer in the DN than in the C and D groups (P < 0.01). Mean velocity was faster in the DN than in the other two groups (P < 0.001). A direct relationship was found between the parameters of posturography and some parameters of the nerve conduction velocity. CONCLUSIONS--Diabetic patients with peripheral neuropathy demonstrate a relative deficit in their ability to maintain posture. Posturography allows an early disclosure of the failure of postural control.
Abstract: Visual evoked potentials (VEPs) were assessed under basal conditions and after photostress in normal control subjects, in insulin-dependent diabetic patients with retinopathy (IDDPWR) and in insulin-dependent diabetic patients without retinopathy (IDDP). The VEPs recorded under basal conditions showed a P100 latency significantly higher in IDDP and IDDP-WR eyes than in control eyes and in IDDPWR than in IDDP eyes (P < 0.01). N75-P100 amplitude was significantly lower in IDDP and IDDPWR eyes than in control eyes (P < 0.01). No difference was recorded in the N75-P100 amplitudes between IDDP and IDDPWR eyes. In all eyes, the VEPs recorded after photostress showed an increase in latency and a decrease in amplitude. In both IDDPWR eyes and IDDP eyes VEPs recorded at 20, 40 and 60 s after photostress showed higher mean increments in P100 latency than in C control eyes, and IDDPWR eyes showed higher mean increments in P100 latency than IDDP eyes (IDDP vs control P < 0.01, IDDPWR vs control P < 0.01, IDDPWR vs IDDP P < 0.017). The mean reductions in amplitude observed at 20, 40 and 60 s after photostress in IDDP and IDDPWR eyes were lower than in control eyes (IDDP vs control P = 0.01, IDDPWR vs control P < 0.01, IDDPWR vs IDDP P < 0.01). VEPs were superimposable on the basal VEP (recovery time) at 73.9 s in control eyes, at 88.17 s in IDDP eyes and at 113.3 s in IDDPWR eyes. VEPs after photostress in IDDP patients with normal visual acuity and no fluorangiographic signs of retinopathy may show multiple modifications. This may indicate the presence of an early functional deficiency of the central retinal layers.
Abstract: Although the St Vincent declaration calls for common European action in order to reduce major amputations, the differences in the incidence of foot problems and the prevalence of risk factors has not been fully investigated. We have examined the risk factors for foot ulceration and amputation in 278 consecutive patients (mean age 50.4 years, range 18-79 years) attending outpatient clinics of four teaching hospitals: Athens, Manchester, Rome, and Antwerp. There were no differences in age, weight or sex among the four groups but the percentage of patients with Type 1 diabetes was higher in Rome and Antwerp. Patients in Rome and Antwerp also had a longer duration of diabetes compared to Athens and Manchester. Mean vibration perception threshold was similar in all groups. No differences were found in the number of patients with moderate or severe clinical neuropathy (neuropathy disability score > 5), severe sensory loss (VPT > 25 V), and limited joint mobility. Symptomatic peripheral vascular disease was more frequent in Antwerp (p < 0.05) compared to the other three centres and foot ulceration in Rome compared to Manchester (p < 0.05). The number of smokers or ex-smokers and the average alcohol consumption were similar in all centres. We conclude that, despite a few differences mainly in Type 1 diabetic patients, there are no major differences in the risk factors for foot ulceration and that, therefore, similar strategies for the prevention of foot problems may be equally successful in different European countries.
Abstract: OBJECTIVE--To assess the influence of autonomic neuropathy on toe blood pressure (TBP), a parameter used currently as an ischemic index. RESEARCH DESIGN AND METHODS--The age-matched study subjects included 20 non-insulin-dependent diabetes mellitus (NIDDM) patients with autonomic neuropathy (DN) and 10 NIDDM patients without autonomic neuropathy (D), assessed by standard cardiovascular tests and galvanic skin response, and 8 control subjects (C). None of the subjects had peripheral vascular disease (PVD) (ankle/brachial index 0.9-1.1. RESULTS--The TBP and toe/brachial index (TBI) were significantly lower in DN than in C and D (P < 0.01). The saturation index (SI), the ratio between foot venous and arterial partial pressure of oxygen (PO2), was significantly higher in DN than in C and D (P < 0.05). An inverse relationship was found between TBI and SI (r = 0.554, P = 0.001). CONCLUSIONS--The autonomic nervous system directly influences peripheral circulation. In diabetic patients without PVD, a failure of sympathetic fibers caused by autonomic neuropathy could lead to a reduction of TBP. Therefore, TBP cannot be used as an ischemic index in diabetic patients.
Abstract: Transcutaneous oxygen tension is a useful method with which to assess the functional status of skin blood flow. The reduced values observed in diabetic patients have been interpreted as a consequence of peripheral vascular disease. However, diabetic patients show lower transcutaneous oxygen tension values than control subjects with equivalent degrees of peripheral vascular disease, suggesting that additional factors are involved. Since the autonomic nervous system influences peripheral circulation, we studied the relationship between autonomic neuropathy and foot transcutaneous oxymetry in non-insulin-dependent diabetic (NIDDM) patients without peripheral vascular disease. The following age-matched patients were selected and evaluated: control subjects, C, (n = 20), NIDDM patients without autonomic neuropathy, D, (n = 16) and with autonomic neuropathy, DN, (n = 20). All diabetic patients showed lower transcutaneous oxygen tension values than control subjects, while no differences were observed between the diabetic patients with and without autonomic neuropathy. In addition the saturation index that increases in the presence of autonomic neuropathy does not correlate with foot TcPO2. In conclusion autonomic neuropathy does not influence foot TcPO2 and therefore it is unlikely that it contributes to development of foot lesions during induction of foot skin ischaemia.
Abstract: Inhibitors of HMG-CoA reductase are new safe and effective cholesterol-lowering agents. Elevation of alanine-amino transferase (ALT) and aspartate-amino transferase (AST) has been described in a few cases and a myopathy with elevation of creatinine kinase (CK) has been reported rarely. The inhibition of HMG-CoA reductase affects also the biosynthesis of ubiquinone (CoQ10). We studied two groups of five healthy volunteers treated with 20 mg/day of pravastatin (Squibb, Italy) or simvastatin (MSD) for a month. Then we treated 30 hypercholesterolemic patients in a double-blind controlled study with pravastatin, simvastatin (20 mg/day), or placebo for 3 months. At the beginning, and 3 months thereafter we measured plasma total cholesterol, CoQ10, ALT, AST, CK, and other parameters (urea, creatinine, uric acid, total bilirubin, gamma GT, total protein). Significant changes in the healthy volunteer group were detected for total cholesterol and CoQ10 levels, which underwent about a 40% reduction after the treatment. The same extent of reduction, compared with placebo was measured in hypercholesterolemic patients treated with pravastatin or simvastatin. Our data show that the treatment with HMG-CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage.
Abstract: We examined the effect of three distinct depolarizing conditions on [3H]ACh release from cardiac postganglionic parasympathetic neurons in age-matched controls and insulin-treated STZ-induced diabetic rats to determine whether alterations in neurotransmitter release were present in the diabetic group. The effect of TTX, which exerts a use- and voltage-dependent block of sodium channels, was examined on the release of ACh stimulated by SRIF14 (preferentially acts at the cell body). We also studied the effect of STZ-induced diabetes on [3H]ACh release by the relatively site-specific depolarizing agent VT (preferentially acts at the axon) and high potassium (non-site-specific). Basal, SRIF14-(10(-7) M), VT-(10(-4) M), and K+ (100 mM)-stimulated [3H]ACh release was similar in control and STZ-induced diabetic animals. However, in STZ-induced diabetic but not control rats, SRIF14-induced [3H]ACh release was resistant to TTX (2 x 10(-7) M). In addition, the response to submaximal K+ (25 mM) stimulation was greater in STZ-induced diabetic compared with control animals. Treatment with insulin corrected these abnormalities. These data indicate that in the acute STZ-induced diabetic rat, SRIF14-, VT-, and high K(+)-evoked release of ACH is not impaired, which suggests that the mechanisms associated with ACh storage and release in postganglionic cardiac parasympathetic neurons are not affected in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: We have quantitatively assessed the percentage of lower limb arterio-venous (a-v) shunting using a radioisotopic technique and correlated it with autonomic neuropathy evaluated by cardiovascular tests. We have studied three groups of diabetic patients: Group A, 12 non-neuropathic subjects without foot lesions; Group B, 12 neuropathic subjects without foot lesions; Group C, 12 neuropathic subjects with recurrent foot ulcers. Shunting was higher in Group C (10.4 +/- 2.7%) than in Group B (6.8 +/- 2.3%, P less than 0.01) and Group A (3.8 +/- 1.2%, P less than 0.001). Shunts in Group B were higher than in Group A (P less than 0.05). All the tests exploring autonomic function were more impaired in Groups B and C than in Group A, with no difference between Groups B and C. A direct correlation was found between a-v shunting and the following cardiovascular tests: postural hypotension (PH) (r = 0.41, P less than 0.02), sustained handgrip (SH) (r = 0.56, P less than 0.001), deep breathing (DB) (r = 0.40, P less than 0.005) and lying to standing (LS) (r = 0.44, P less than 0.01). A positive correlation was also found between a-v shunts and duration of the disease (r = 0.62, P less than 0.001). Arterio-venous shunting was found to be directly related to autonomic neuropathy even if the higher shunting found in the patients with foot ulcers was not related to a higher degree of autonomic involvement; in addition, this group of patients was characterized by having a more advanced sensory and motor neuropathy. In conclusion, autonomic neuropathy, through its influence on a-v shunts, may play a role in the pathogenesis of diabetic foot, but peripheral neuropathy probably plays a key role in conditioning the development of the overt clinical manifestations of diabetic foot.
Abstract: Autonomic neuropathy is a common complication of diabetes. In this study we evaluated autonomic neuropathy by determining somatostatin (S-14)-evoked acetylcholine (Ach) release from postsynaptic parasympathetic fibers in the atria of controls (C) and streptozotocin diabetic rats (STZ-D), with and without tetrodotoxin (TTX). The release induced by S-14 did not differ in C and STZ-D. TTX blocked S-14 induced Ach in C but failed in STZ-D. TTX resistance in STZ-D may be explained by variations of membrane potential in nerve fibers.
Abstract: Among the numerous techniques used to measure body composition, this study utilised anthropometric methods (weight, height, circumference and skin folds) and impedance measurement (measurement of bioelectric impedance). Results from the two methods were compared in order to assess whether BMI parameters and the waist/hips ratio (WHR) influenced this correlation. One hundred and eighty patients (133 F, 47 M) were included in the study. Patients were divided into groups according to the degree of obesity expressed as BMI and WHR. Body composition was evaluated using anthropometric methods (according to Garrow Webster, Durnin-Womersley, modified Durnin-Womersley and Jackson-Pollock) and impedance measurement in which resistive bioelectric impedance is measured using a tetrapolar technique. A good correlation was generally observed in the female population between impedance assessment and anthropometric methods, and this correlation was not influenced by either BMI or WHR. In the male group, on the other hand, the correlation between the two methods was limited by BMI greater than 30 and WHR greater than 1. In conclusion, impedance measurement and plicometric methods are generally compatible, but areas of uncertainty arise in the male population with BMI greater than 30 and WHR greater than 1.
Abstract: Previous reports of somatostatin's atropine-sensitive negative inotropic effect on cardiac function prompted the present studies to characterize the molecular forms and actions of somatostatin in the canine heart. Radioimmunoassay of cardiac extracts revealed concentrations of somatostatin-like immunoreactivity ranging from 0.50 +/- 0.13 pmol/g tissue (means +/- SE, n = 6) in the pulmonary artery to 0.78 +/- 0.23 pmol/g tissue in the right ventricle. On gel filtration of the extracts, two major molecular forms of somatostatin-like immunoreactivity were elicited, the predominant one coeluting with somatostatin-14 and a minor peak corresponding to somatostatin-28. Experiments performed with slices of atrial septum indicated that somatostatin-14 (10(-10) to 10(-7) M) stimulated the release of acetylcholine in a dose-dependent manner. This action of somatostatin-14 was additive with K+-evoked acetylcholine release, unaffected by hexamethonium, and blocked by tetrodotoxin, suggesting mediation via a nonnicotinic postganglionic neural pathway. Our studies lead us to conclude that somatostatin may function as a neurotransmitter in the heart, which exerts its negative inotropic action by promoting the release of acetylcholine.
Abstract: Over a period of 4 years, 20 patients suffering from severe forms of psoriasis (erythrodermic, sub-erythrodermic, resistant generalized forms and/or forms associated with acute arthropathy) were treated with 96 h of continuous i.v. infusion of somatostatin (Stilamin, Serono) diluted in D5W at 250 micrograms/h. In addition to the usual blood chemistry parameters, circadian levels of growth hormone (GH) and epidermal growth factor (EGF) were measured before, during, and after therapy. Approximately 2-3 weeks after termination of therapy, erythrodermic and suberythrodermic symptoms had disappeared. In some patients, a few lesions of psoriasis vulgaris remained, although they were much less severe. Remission of acute arthropathy was impressive. Blood chemistry parameters were unchanged after therapy. Circadian levels of GH and EGF, normal before therapy, were significantly decreased after therapy. The infusion was well-tolerated. Infusion rates of greater than 250 micrograms/h caused only some complaints of abdominal pain, nausea, and vomiting. During the 4 years, erythrodermic symptoms reappeared only in seven patients, three of whom were also arthropathic. After 6-8 months, they underwent a second course of somatostatin therapy with good results. The other patients are still able to control their disease with tar-based products alone or with low-dose 8-methoxypsoralen + UVA (PUVA) or UV therapy. The arthropathic patients control their symptoms with periodic low-dose nonsteroidal antiinflammatory drug therapy.
Abstract: The present study was undertaken in order to establish the significance of glucagon in glucose intolerance in liver cirrhosis. The plasma glucose response to an oral glucose load (75 g) was determined in 10 control subjects and in 10 cirrhotic patients, after infusions of: glucagon (3 ng.kg-1.min-1) or saline (154 mmol/l); somatostatin (SRIH) (500 micrograms/h); and SRIH plus glucagon (3 ng.kg-1.min-1). Glucagon infusion did not impair glucose tolerance, neither in normal subjects nor in patients with cirrhosis. On the other hand, in both groups glucose tolerance was impaired by SRIH infusion, presumably owing to an absolute insulin deficiency. Both in normal subjects and in cirrhotic patients, SRIH plus glucagon infusion further impaired glucose tolerance, presumably as a result of excess glucagon and concomitant insulin deficiency. In conclusion, our data show that hyperglucagonemia is not an important factor in the development of the glucose intolerance in patients with hepatic cirrhosis.
Abstract: The rate at which somatostatin appears in the circulation after subcutaneous bolus injection and continuous administration by pump was determined in normal subjects by serial radioimmunoassays of immunoreactive somatostatin. Following a single subcutaneous injection of 250 micrograms, the somatostatin peak in plasma appeared after 5 min and had only a transient effect on insulin levels. During continuous administration, somatostatin reached levels able to reduce significantly insulin and glucagon. Somatostatin plasma levels exerting biological effects were observed during the subcutaneous administration of the peptide.
Abstract: Somatostatin has been proposed as a regulatory peptide of nutrient entry and fuel homeostasis because of its ability to inhibit the release of substances involved in food digestion and metabolism. The aim of the study was to evaluate the somatostatin response to a test meal in type I diabetics at the clinical onset of the disease and after two months of intensive insulin therapy. Normal subjects and diabetics in good metabolic control showed a characteristic biphasic somatostatin rise after a test meal; this response was lacking in diabetics at the onset of the disease. The response of somatostatin to a mixed meal in normals confirms its involvement in nutrient digestion and metabolism. The lacking somatostatin response in newly diagnosed type I diabetics might be related to deficient GIP response to the test meal or to other factors such as the insulinopenia or metabolic derangement characteristic of the clinical onset of the disease.
Abstract: Experimental and clinical studies suggest that somatostatin, a regulatory peptide widely distributed in human tissues may have electrophysiologic effects. We studied a group of 14 patients who underwent a complete electrophysiologic study for different rhythm disturbances. Somatostatin significantly increased the spontaneous cycle length, the atrial and atrioventricular nodal effective refractory periods, and the Wenckebach cycle length. The AH and HV intervals during sinus rhythm remained unchanged. The effectiveness of somatostatin to interrupt paroxysmal supraventricular tachycardias was assessed in 18 patients. Termination was obtained in 15 (82.5%). Our results show that somatostatin has a significant electrophysiologic effect on the human heart, and confirm its clinical effectiveness in some arrhythmias.
Abstract: Haematic concentrations of catecholamines were found to be higher in cirrhotic patients with ascites, than cirrhotic patients without ascites and controls. In compensated and decompensated cirrhosis, different forms of sympathetic nervous activity were observed. The high catecholamine values in cirrhotic patients and the activation of the renin angiotensin-aldosterone system suggest the use of beta-blockers to reduce sodium-water retention.
Abstract: The recent demonstration that intravenous administration of somatostatin, an ubiquitous peptide-like substance, may interrupt paroxysmal supraventricular tachycardia in man has disclosed new perspectives in the assessment of the mechanisms of neuro-humoral cardiac regulation in normal and pathologic conditions. Prospective studies on normal subjects and diabetics with and without autonomic cardiac neuropathy, helped in giving an outlook on the mechanism by which somatostatin acts on the human heart. This substance exerts in vivo a powerful chronotropic and dromotropic influence on sinoatrial and A-V node cells both in normals and diabetics with and without autonomic cardiac neuropathy. This influence is blocked by preventive administration of atropine or atropine plus metoprolol (intrinsic heart rate). Since somatostatin-like-substances have been found in cholinergic postganglionic neurons of the cardiac vagus of some animals, the demonstrated "vagomimetic" action of somatostatin on human cardiac cells seems to support the hypothesis that also the human heart may contain vagal somatostatinergic neurons with modulatory function on the heart rate and rhythm. Present observations disclose new perspectives in the pathophysiology and therapy of cardiac arrhythmias.
Abstract: We report a case of ankylosing spondylitis associated with hairy cell leukemia. This is the second observed case (I3) of ankylosing spondylitis with a B-type lymphoproliferative disorder which allows us to make some observations about the pathogenesis of these rare diseases.
Abstract: Monoclonal gammopathy has rarely been reported in ankylosing spondylitis. We observed a patient with ankylosing spondylitis and monoclonal gammopathy with no signs of malignancy, chronic infections or amyloidosis. This association may show some possible pathogenetic mechanisms involved in these two different diseases of still uncertain etiology.
