Evidence of partial protection against foot-and-mouth disease in cattle immunized with a recombinant adenovirus vector expressing the precursor polypeptide (P1) of foot-and-mouth disease virus capsid proteins. (1/110)

A recombinant live vector vaccine was produced by insertion of cDNA encoding the structural proteins (P1) of foot-and-mouth disease virus (FMDV) into a replication-competent human adenovirus type 5 vaccine strain (Ad5 wt). Groups of cattle (n = 3) were immunized twice, by the subcutaneous and/or intranasal routes, with either the Ad5 wt vaccine or with the recombinant FMDV Ad5-P1 vaccine. All animals were challenged by intranasal instillation of FMDV 4 weeks after the second immunizations. In the absence of a detectable antibody response to FMDV, significant protection against viral challenge was seen in all of the animals immunized twice by the subcutaneous route with the recombinant vaccine. The observed partial protection against clinical disease was not associated with a reduction in titre of persistent FMDV infections in the oropharynx of challenged cattle.  (+info)

Incidence, outcomes, and cost of foot ulcers in patients with diabetes. (2/110)

OBJECTIVE: To determine the incidence of foot ulcers in a large cohort of patients with diabetes, the risk of developing serious complications after diagnosis, and the attributable cost of care compared with that in patients without foot ulcers. RESEARCH DESIGN AND METHODS: Retrospective cohort study of patients with diabetes in a large staff-model health maintenance organization from 1993 to 1995. Patients with diabetes were identified by algorithm using administrative, laboratory, and pharmacy records. The data were used to calculate incidence of foot ulcers, risk of osteomyelitis, amputation, and death after diagnosis of foot ulcer, and attributable costs in foot ulcer patients compared with patients without foot ulcers. RESULTS: Among 8,905 patients identified with type 1 or type 2 diabetes, 514 developed a foot ulcer over 3 years of observation (cumulative incidence 5.8%). On or after the time of diagnosis, 77 (15%) patients developed osteomyelitis and 80 (15.6%) required amputation. Survival at 3 years was 72% for the foot ulcer patients versus 87% for a group of age- and sex-matched diabetic patients without foot ulcers (P < 0.001). The attributable cost for a 40- to 65-year-old male with a new foot ulcer was $27,987 for the 2 years after diagnosis. CONCLUSIONS: The incidence of foot ulcers in this cohort of patients with diabetes was nearly 2.0% per year. For those who developed ulcers, morbidity, mortality, and excess care costs were substantial compared with those for patients without foot ulcers. The results appear to support the value of foot-ulcer prevention programs for patients with diabetes.  (+info)

Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. (3/110)

OBJECTIVE: To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings. RESEARCH DESIGN AND METHODS: The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed. RESULTS: From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in > 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and < 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot. CONCLUSIONS: The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes.  (+info)

Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers. (4/110)

OBJECTIVE: To identify risk factors for lower-extremity amputation (LEA) in individuals with diabetes and to estimate the incidence of LEA. RESEARCH DESIGN AND METHODS: This is a prospective study of 776 U.S. veterans in a general medicine clinic in Seattle, Washington. The outcome was first LEA during follow-up. Potential risk factors evaluated in proportional hazards models included, among others, peripheral vascular disease (PVD), sensory neuropathy, former LEA, foot deformities and ulcers, diabetes duration and treatment, and hyperglycemia. RESULTS: Associated with an increased risk for LEA were PVD defined as transcutaneous oxygen < or = 50 mmHg (relative risk [RR] = 3.0, 95% CI 1.3-7.1), insensitivity to monofilament testing (RR = 2.9, odds ratio = 1.1-7.8), lower-extremity ulcers (RR = 2.5, CI 1.1-5.4), former LEA, and treatment with insulin when controlling for duration of diabetes and other factors in the model. PVD defined as absent or diminished lower-extremity pulses or an ankle arm index < or = 0.8 was also associated with a significantly higher risk of LEA in separate models. Foot ulcers were associated with an increased ipsilateral risk of amputation. The age-adjusted incidence among men only for LEA standardized to the 1991 U.S. male diabetic population was 11.3/1,000 patient-years. CONCLUSIONS: This prospective study shows that peripheral sensory neuropathy, PVD, foot ulcers (particularly if they appear on the same side as the eventual LEA), former amputation, and treatment with insulin are independent risk factors for LEA in patients with diabetes.  (+info)

A prospective study of risk factors for diabetic foot ulcer. The Seattle Diabetic Foot Study. (5/110)

OBJECTIVE: Little prospective research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents. We prospectively studied the effects of diabetes characteristics, foot deformity, behavioral factors, and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs. RESEARCH DESIGN AND METHODS: Eligible subjects included all diabetic enrollees of a general internal medicine clinic without foot ulcer, of whom 83% agreed to participate. Baseline assessment included history and lower-limb physical examination, tests for sensory and autonomic neuropathy, and measurements of macro- and microvascular perfusion in the foot. Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal, with a mean follow-up of 3.7 years. RESULTS: Using stepwise Cox regression analysis, the following factors were independently related to foot ulcer risk: foot insensitivity to the 5.07 monofilament (relative risk [95% CI]) 2.2 (1.5-3.1), past history of amputation 2.8 (1.8-4.3) or foot ulcer 1.6 (1.2-2.3), insulin use 1.6 (1.1-2.2), Charcot deformity 3.5 (1.2-9.9), 15 mmHg higher dorsal foot transcutaneous PO2 0.8 (0.7-0.9), 20 kg higher body weight 1.2 (1.1-1.4), 0.3 higher ankle-arm index 0.8 (0.7-1.0), poor vision 1.9 (1.4-2.6), and 13 mmHg orthostatic blood pressure fall 1.2 (1.1-1.5). Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups. Unrelated to foot ulcer risk in multivariate models were diabetes duration and type, race, smoking status, diabetes education, joint mobility, hallux blood pressure, and other foot deformities. CONCLUSIONS: Certain foot deformities, reduced skin oxygenation and foot perfusion, poor vision, greater body mass, and both sensory and autonomic neuropathy independently influence foot ulcer risk, thereby providing support for a multifactorial etiology for diabetic foot ulceration.  (+info)

Microcirculatory investigations to determine the effect of spinal cord stimulation for critical leg ischemia: the Dutch multicenter randomized controlled trial. (6/110)

PURPOSE: Patients with non-reconstructable critical limb ischemia generally undergo medical treatment only to prevent or postpone amputation. There is some evidence that spinal cord stimulation (SCS) stimulates ischemic wound healing. Thus, this could benefit limb survival through improved skin perfusion. We investigated the effect of SCS versus conservative treatment on skin microcirculation in relation to treatment outcome in patients with non-reconstructable critical limb ischemia. METHODS: Standard medical treatment plus SCS was compared with only standard medical treatment in a multicenter randomized controlled trial comprised of 120 patients with surgically non-reconstructable chronic rest pain or ulceration. We investigated skin microcirculation by means of capillary microscopy, laser Doppler perfusion, and transcutaneous oxygen measurements in the foot. The microcirculatory status just before treatment was classified in three categories (poor, intermediate, and good) and was related to limb survival after a minimum follow-up period of 18 months. RESULTS: Clinical parameters, peripheral blood pressures, and limb survival rates showed no significant differences between the SCS and standard groups during the follow-up period. In both treatment groups, amputation frequency after 18 months was high in patients with an initially poor microcirculatory skin perfusion (SCS 80% vs standard treatment 71%; NS) and low in those with a good skin perfusion (29% vs 11 %, respectively; NS). In patients with an intermediate skin microcirculation amputation, frequency was twice as low in patients additionally treated with SCS as in the standard treatment group (48% vs 24%; P =.08). In these patients, microcirculatory reactive hyperemia during the follow-up period reduced in the standard group but not in the SCS group (P <.01). CONCLUSION: Selection on the basis of the initial microcirculatory skin perfusion identifies patients in whom SCS can improve local skin perfusion and limb survival.  (+info)

Efficacy of dorsal pedal artery bypass in limb salvage for ischemic heel ulcers. (7/110)

PURPOSE: Although pedal artery bypass has been established as an effective and durable limb salvage procedure, the utility of these bypass grafts in limb salvage, specifically for the difficult problem of heel ulceration, remains undefined. METHODS: We retrospectively reviewed 432 pedal bypass grafts placed for indications of ischemic gangrene or ulceration isolated to either the forefoot (n = 336) or heel (n = 96). Lesion-healing rates and life-table analysis of survival, patency, and limb salvage were compared for forefoot versus heel lesions. Preoperative angiograms were reviewed to evaluate the influence of an intact pedal arch on heel lesion healing. RESULTS: Complete healing rates for forefoot and heel lesions were similar (90.5% vs 86.5%, P =.26), with comparable rates of major lower extremity amputation (9.8% vs 9.3%, P =.87). Time to complete healing in the heel lesion group ranged from 13 to 716 days, with a mean of 139 days. Preoperative angiography demonstrated an intact pedal arch in 48.8% of the patients with heel lesions. Healing and graft patency rates in these patients with heel lesions were independent of the presence of an intact arch, with healing rates of 90.2% and 83.7% (P =.38) and 2-year patency rates of 73.4% and 67.0% in complete and incomplete pedal arches, respectively. Comparison of 5-year primary and secondary patency rates between the forefoot and heel lesion groups were essentially identical, with primary rates of 56.9% versus 62.1% (P =.57) and secondary rates of 67.2% versus 60.3% (P =.50), respectively. CONCLUSION: Bypass grafts to the dorsalis pedis artery provide substantial perfusion to the posterior foot such that the resulting limb salvage and healing rates for revascularized heel lesions is excellent and comparable with those observed for ischemic forefoot pathology.  (+info)

A case of bilateral heel ulcers associated with hydroxyurea therapy for chronic myelogenous leukemia. (8/110)

Bilateral heel skin ulcers developed in a 50-year-old male in the chronic phase of chronic myelogenous leukemia who had been receiving hydroxyurea (HU) therapy for 3 years. Histological examination showed perivascular lymphocytic inflammation without vasculitis. After interruption of HU administration, the heel ulcers were completely resolved within 2 months. The clinical course strongly suggested that the heel ulcers were induced by long-term HU therapy.  (+info)