Wound healing and tissue repair of the surgical amputation of limbs.
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Amputation, Surgical↗
Biomedical subjects
E M Burgess
Publications and source records attributed to E M Burgess.
Design and pilot testing of the DVA/Seattle Footwear System for diabetic patients with foot insensitivity.
Clinical epidemiology studies suggest the majority of lower limb amputations were preceded by a minor traumatic event, often footwear-related, and lower limb ulcers. To reduce foot trauma and ulcers, the diabetic patient with foot insensitivity has unique footwear needs. To address these needs for patients not requiring custom shoes, the DVA/Seattle Footwear System was developed. The six components of this system include: 1) a specially designed shoe last based on the geometry of the diabetic foot and research findings on foot regions at highest risk of ulceration, 2) a depth-inlay shoe, "Custom Stride by PRS," designed to be paired with either a custom-fabricated cork insole or a preformed polyurethane insole, 3) a laser digitizing system that captures 3-D plantar foot contours, 4) DVA/Seattle ShapeMaker software adaptation for modifying plantar surface contours and applying free-form and template modifications to increase or relieve loading, 5) software that translates files into code used by a milling machine to define the cutting path and carve cork blockers into custom insoles, and 6) a preformed polyurethane insole thicker than a typical insole to accommodate the extra volume and the interior dimensions of the shoe. A 6-month pilot cross-over trial of 24 diabetic male veterans without prior foot ulcers was conducted to determine the feasibility of producing, and the safety of wearing, these depthinlay shoes and both types of insoles. During the first 4 weeks, patients were assigned to the study shoes and one type of insole. During the next 4 weeks, they wore the other type of insole, and during the final 4 months, they chose which pair of insoles to wear with the study shoes. Over 150 person-months of footwear observation revealed no breaks in the cutaneous barrier with use of either cork or polyurethane insoles and the study shoes. Patient compliance with the footwear was 88%. Patients were highly satisfied with the appearance, stability, and comfort of the shoes and the comfort of both types of insole. However, 75% of the patients noted that the study shoes felt heavier than their customary shoes. Further research is needed to determine the long-term effectiveness of footwear in prevention of foot ulcers in the population at highest risk for diabetic reulceration and amputation.
Aged↗
Molecular similarity from atomic electrostatic multipole comparisons. Application to anti-HIV drugs.
A procedure is presented for the rapid calculation of the similarity between a pair of molecules based on atomic electrostatic multipole comparison. The multipoles are derived from semiempirical SCF wave functions, and the results obtained compare favorably with ab initio results. The method is illustrated by correlating the similarity and anti-HIV-1 activity of a series of azo compounds. Some generalizations are presented on the structure-activity relationships which are based on the atomic multipole distribution in the azo compounds.
Antiviral Agents↗
A model for the study of wounds in normal elderly adults and patients with peripheral vascular disease or diabetes mellitus.
The purpose of the study was to test the hypothesis that significant delays in cutaneous wound healing could be demonstrated using standard wounds and high quality histological methods in patients with severe peripheral vascular disease (PVD) and/or diabetes mellitus (DM) compared to healthy elderly controls. Additionally, we proposed that standard wounds on the arms of elderly controls would heal more rapidly than comparable wounds on the legs. In order to test these hypotheses we developed and characterized a partial thickness wound model which could be used safely in human subjects. The study population consisted of 25 elderly normal volunteers, 17 patients with PVD, and 24 patients with DM. Standard wounds were created using a Simplate II bleeding-time device. A total of 309 wounds ranging in age from 1 to 25 days were determined to be suitable for analysis. A global index of wound maturity was developed based on selected epidermal and dermal events of repair which could be scored histologically. The superficial component (within 0.1 mm of the epidermis) and deep components of dermal wounds were analyzed separately. Simultaneously created arm and leg wounds were studied in 15 of the elderly controls. Transcutaneous partial pressure of oxygen (TcPO2) measurements were used to estimate the severity of cutaneous ischemia. Data analysis revealed that the most striking differences observed were in dermal events of repair. Control wounds were more mature than dermal wounds from patients with PVD (P < 0.05). A significant reduction in the number of neutrophils and macrophages (P < 0.05) was demonstrated in 7-day-old wounds of patients with PVD compared to controls. Patients with DM showed a similar trend of reduced wound maturity but it did not reach statistical significance. Wounds created in skin with TcPO2 > 20 were more mature than wounds with TcPO2 < or = 20 (P < 0.05) and arm wounds were more mature than leg wounds (P < 0.01). The most significant difference noted in this wound model was that the superficial compartment of dermal wounds was significantly more mature than the deep compartment (P < 0.001). Good agreement was observed between two independent scorers of wound histology and no complications were noted in either patients or controls when using this human wound model. We conclude that the model described allows evaluation of both epidermal and dermal events of repair with relative safety even in patients with PVD and DM.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
Novel quinone antiproliferative inhibitors of phosphatidylinositol-3-kinase.
The inhibition of phosphatidylinositol-3-kinase (PtdIns-3-kinase), protein kinase C and c-Src protein tyrosine kinase by a series of halogenated naphthoquinones and quinoline quinones related to the plant-derived naphthoquinones juglone and methyljuglone, which inhibit protein kinase C, has been investigated. Some of the compounds inhibited PtdIns-3-kinase at micromolar concentrations and below. PtdIns-3-kinase inhibition was time dependent and could be prevented by endogenous thiol. The compounds were only weak inhibitors of PtdIns-4-kinase. Some of the compounds inhibited protein kinase C, but c-Src protein tyrosine kinase was only weakly inhibited. In intact cells, PtdIns-3-kinase was only partly inhibited by concentrations of the halogenated quinones that inhibited cell growth. Some halogenated quinones showed in vivo antitumor activity without accompanying toxicity, while methyljuglone was without in vivo antitumor activity. Halogenated quinones may have multiple biochemical effects in the cell that could contribute to their cytotoxic and antitumor effects. Inhibition of PtdIns-3-kinase by the halogenated quinones may provide a lead for the development of more potent and specific inhibitors.
Breast Neoplasms↗
Synthesis of 2-methyl-(Z)-4-(phenylimino)naphth[2,3-d]oxazol-9-one , a monoimine quinone with selective cytotoxicity toward cancer cells.
A regio and stereospecific synthesis of 2-methyl-(Z)-4-(phenylimino)naphth[2,3-d]oxazol-9-one (1) was achieved by using titanium tetrachloride in methylene chloride in the preparation of the imine. The regiochemistry was assigned by single-crystal X-ray analysis. In vitro tests showed that this diastereomer is selectively active for some solid cancer tumors.
Antineoplastic Agents↗
Achilles tendon tenodesis to prevent heel pad migration in the Syme's amputation.
In an attempt to prevent migration of the heel pad, 11 patients underwent a combined Syme's amputation and Achilles tendon tenodesis between December 1989 and April 1992. Ten patients healed the Syme's amputation, and one patient failed to heal the surgical wounds and required a below-knee amputation. In all 10 successful Syme's cases, the heel pad has remained stable with no migration, and no skin breakdown at an average follow-up of 18.5 months. Published series of Syme's amputations report that the incidence of heel pad migration is between 7.5% and 45%, and occurs primarily in the post-operative or early rehabilitation stage. We believe that tenodesis of the Achilles tendon is a technically easy addition to the Syme's amputation, that it keeps tension off of the incision during healing, and that it prevents migration of the heel pad.
Achilles Tendon↗
Clinical and laboratory study of amputation surgery and rehabilitation.
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Amputation, Surgical↗
Automated fabrication of mobility aids: review of the AFMA process and VA/Seattle ShapeMaker software design.
Computer-aided design and manufacture of prosthetic and orthotic devices has recently moved out of the laboratory into clinical use. The Department of Veterans Affairs Rehabilitation Research and Development Service has directed coordinated evaluation and development projects of this emerging technology under the name: Automated Fabrication of Mobility Aids or AFMA. One of the major results of the effort was the creation of mobility aid design software (ShapeMaker) concurrent with AFMA clinical testing of preexisting systems and development efforts. In order to provide a foundation for future discussions regarding AFMA, this paper provides a descriptive review of the AFMA processes and a review of the conceptual basis for the ShapeMaker AFMA software development.
Artificial Limbs↗
Inhibition of porcine pancreatic elastase by 7-substituted 4-chloro-3-ethoxyisocoumarins: structural characteristics of modeled noncovalent complexes relate to the measured inhibition kinetics.
Kinetic measurements for the inhibition of porcine pancreatic elastase by 7-substituted 4-chloro-3-ethoxyisocoumarins were performed. To obtain possible explanations for the kinetic results, structures resulting from energy minimizations of inhibitor-enzyme complex structures where each inhibitor was initially positioned in 64 locations within the active site were obtained. In keeping with solution NMR studies, a positive-charged His-57 was employed. The number of low energy complex structures with Ser-195 O gamma-inhibitor benzoyl ester carbonyl carbon distances < or = 2.9 A, Ser-195 O gamma-inhibitor benzoyl ester carbonyl carbon-inhibitor benzoyl ester carbonyl oxygen angles > 91 degrees, and the inhibitor in the oxyanion hole exhibits a direct linear relationship to ln(Ki/k3). The proportion of those structures that show 7-substituent H-bonding between the inhibitor and porcine pancreatic elastase exhibits a direct relationship to k3. Assuming a direct linear relationship to ln(k3) and k3, finer differences in k3 than are experimentally observed are expected. The relationship with k3 and that with Ki/k3 are shown to be useful tools for the design of more potent 7-substituted 4-chloro-3-ethoxyisocoumarins. A novel inhibitor of this class (4-chloro-3-ethoxy-7-[(2-methyl-2- butylcarbamoyl)amino]isocoumarin) expected to be more potent is synthesized and tested. Its potency within experimental error is as predicted. Although the relationship observed with Ki/k3 involves only a twofold increase in Ki/k3 (a statistically significant increase), results with the novel inhibitor show the relationship to be valid over a four- to fivefold increase.
Amino Acid Sequence↗
Clinical measurement of normal and shear stresses on a trans-tibial stump: characteristics of wave-form shapes during walking.
Stresses on the surface of a stump within a prosthetic socket during walking can potentially traumatize stump tissues. To gain insight into stresses and design parameters that affect them, normal and shear interface stresses were measured on three unilateral trans-tibial amputee subjects during walking trials. During stance phase repeated characteristics in wave-form shapes from different subjects were apparent. They included "loading delays", "high frequency events (HFE's)", "first peaks", "valleys", "second peaks", and "push-off". Characteristics did not necessarily occur at the same time from one step to the next but their timings matched well with events in shank force and moment data which were collected simultaneously. For "plantarflexion" and "dorsiflexion" alignment changes, the above wave-form characteristics were still present but their timings within the stance phase changed. The physical meaning and relevance of the characteristics to stump tissue mechanics are discussed.
Adaptation, Physiological↗
Effect of FK 506 and donor-specific blood transfusion on the rat composite tissue limb allograft and the mechanism of long-term graft survival.
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Animals↗
Michaelis complexes of porcine pancreatic elastase with 7-[(alkylcarbamoyl)amino]-4-chloro-3-ethoxyisocoumarins: translational sampling of inhibitor position and kinetic measurements.
A step leading to the formation of the covalent complexes between porcine pancreatic elastase (PPE) and 7-[(alkylcarbamoyl)amino]-4-chloro-3-ethoxyisocoumarins (alkylHNCO-EICs) is the formation of the noncovalent Michaelis complex. No average structures are available for the Michaelis complexes of PPE with alkylHNCO-EICs. We present the results of an initial step in obtaining these structures and have determined kinetic constants as well. The kinetic results indicate that formation of the Michaelis complex is what differentiates the effectiveness of these inhibitors in inactivating PPE. The structural and kinetic results together suggest that the structure of the Michaelis complex is necessary for the design of potent alkylHNCO-EIC inhibitors of PPE. Two novel alkylHNCO-EICs are predicted to be the best inhibitors of this series. An alternate mechanism for serine protease inhibition is also proposed. Evidence for, and studies that may add support to, the hypothesized mechanism are discussed.
Animals↗
Interface shear stresses during ambulation with a below-knee prosthetic limb.
Shear stresses on a residual limb in a prosthetic socket are considered clinically to contribute to tissue breakdown in below-knee amputees. When applied simultaneously with normal stresses, they can cause injury within the skin or can generate an abrasion on the surface. To gain insight into shear stresses and parameters that affect them, interface stresses were recorded on below-knee amputee subjects during walking trials. On the tibial flares, resultant shear ranged from 5.6 kPa to 39.0 kPa, while on the posterior surface it ranged from 5.0 kPa to 40.7 kPa. During stance phase, anterior resultant shears on a socket were directed toward the apex while posterior resultant shears were directed downward approximately perpendicular to the ground. Waveform shapes were usually double-peaked, with the first peak at 25% to 40% into stance phase and the second peak at 65% to 85% into stance. Application of these results to residual limb tissue mechanics and prosthetic design is discussed.
Adult↗
Automated fabrication of mobility aids (AFMA): below-knee CASD/CAM testing and evaluation program results.
In 1988 the Department of Veterans Affairs Rehabilitation Research and Development Service, under the directorship of Margaret J. Giannini, M.D., began a nationally directed computer-aided design and computer-aided manufacturing (CAD/CAM) research program for the Automated Fabrication of Mobility Aids (AFMA). Under this program CAD/CAM research and development centers were established at the Prosthetics Research Study in Seattle, WA; at Northwestern University and the VA Lakeside Medical Center in Chicago, IL; and at the VA Medical Center and New York University Medical Center in New York, NY. These three centers conducted a collaborative program: (a) to introduce CAD/CAM technologies to prosthetists, physicians, therapists, and rehabilitation health care professionals in the United States; (b) to evaluate the feasibility of using CAD/CAM systems in clinical prosthetics settings; (c) to test and evaluate the University College London-Bioengineering Center's and the University of British Columbia-Medical Engineering Resource Unit's respective systems for the computer-aided design and computer-aided manufacture of prosthetic sockets (CASD/CAM) for below-knee amputees; and, (d) to obtain quantitative data for refinement of the CASD/CAM systems tested, and for the development of new, enhanced, more efficacious, and expedient systems.
Adult↗
Synergistic effect of FK 506 and donor-specific blood transfusion on rat skin but not on composite tissue (limb) allograft survival.
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Animals↗
Pathways to diabetic limb amputation. Basis for prevention.
We defined the causal pathways responsible for 80 consecutive initial lower-extremity amputations to an extremity in diabetic patients at the Seattle Veterans Affairs Medical Center over a 30-mo interval from 1984 to 1987. Causal pathways, either unitary or composed of various combinations of seven potential causes (i.e., ischemia, infection, neuropathy, faulty wound healing, minor trauma, cutaneous ulceration, gangrene), were determined empirically after a synthesis by the investigators of various objective and subjective data. Estimates of the proportion of amputations that could be ascribed to each component cause were calculated. Twenty-three unique causal pathways to diabetic limb amputation were identified. Eight frequent constellations of component causes resulted in 73% of the amputations. Most pathways were composed of multiple causes, with only critical ischemia from acute arterial occlusions responsible for amputations as a singular cause. The causal sequence of minor trauma, cutaneous ulceration, and wound-healing failure applied to 72% of the amputations, often with the additional association of infection and gangrene. We specified precise criteria in the definition of causal pathway to permit estimation of the cumulative proportion of amputations due to various causes. Forty-six percent of the amputations were attributed to ischemia, 59% to infection, 61% to neuropathy, 81% to faulty wound healing, 84% to ulceration, 55% to gangrene, and 81% to initial minor trauma. An identifiable and potentially preventable pivotal event, in most cases an episode involving minor trauma that caused cutaneous injury, preceded 69 to 80 amputations. Defining causal pathways that predispose to diabetic limb amputation suggests practical interventions that may be effective in preventing diabetic limb loss.
Adult↗