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Biomedical subjects

E M Burgess

Publications and source records attributed to E M Burgess.

At least 19 recordsLinked to original sources

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

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

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

Transcutaneous oxygen tension as a predictor of success after an amputation.

We measured local transcutaneous oxygen tension at the foot and proximal and distal to the knee in 162 patients who then had 206 amputations. When the values for oxygen tension at the foot and distal to the knee were compared with the success or failure of healing after an amputation of the foot or distal to the knee, respectively, a clearly increasing probability of failure was correlated with decreasing transcutaneous oxygen tension. However, even at a tension of zero the probability of failure was not 100 per cent. The results were similar for diabetic and non-diabetic patients. Preoperative values for transcutaneous oxygen tension were a much more consistent predictor of success or failure of healing after an amputation of the foot or distal to the knee than were measurements of systolic blood pressure at the ankle, but neither was predictive of the outcome after an above-the-knee amputation.

Amputation, Surgical

Reliability of transcutaneous oxygen tension (TcPO2) measurements in elderly normal subjects.

This study was conducted to evaluate the reliability of TcPO2 measurements in a well characterized group of 10 elderly normal subjects with an age distribution typical for the population with peripheral vascular disease (PVD) and amputation. The TcPO2 values were obtained on three separate occasions at 2-week intervals at seven anatomic sites commonly measured in patients with PVD. The TcPO2 values were comparable to those previously reported for similar sites in normal elderly subjects. Measurement to measurement variation averaged 1.1 kPa (8 mmHg) for a coefficient of variation (CV) of 14.4%. Confidence intervals ranging from 2.1 kPa (16 mmHg) above a single TcPO2 value to 2.1 kPa (16 mmHg) below were necessary to contain the true value 95% of the time. While TcPO2 measurement is assuming an important role in the evaluation of disease states in both paediatric and adult medicine, our observations emphasize the importance of using such measurements as an adjunct in clinical decision making and not basing such decisions on a single TcPO2 value alone. The size of the confidence intervals can be reduced substantially for a given site by taking the mean of two or more TcPO2 measurements taken at separate times.

Aged

Factors relating to the sensory acuity of limbs with peripheral vascular insufficiency.

We examined several possible causes for the high incidence of poor sensory acuity in the limbs of 176 patients with moderate to severe peripheral vascular insufficiency. We investigated the relationships of diabetes, alcoholism, and smoking, as well as the severity of peripheral vascular disease, to the integrity of basic sensory modalities such as two-point discrimination and perception of light touch. The presence or absence of diabetes exerted the strongest effect on peripheral sensation. In patients who did not have diabetes, sensation in the limbs was most strongly affected by whether the patient was an alcoholic. Smoking did not have a significant effect on limb sensation. Among nondiabetic, nonalcoholic patients, there was a weak residual effect related to the severity of the peripheral vascular insufficiency. Even among these patients, however, systemic factors predominated in determining the loss of sensation. We also examined the extent to which loss of sensation might be related to the development of ulcers. Among patients who were not diabetic, there was a highly significant relationship between loss of sensation and the presence of limb ulceration. Surprisingly, however, there was no discernable relationship between the presence of ulcers in diabetic patients and the degree of loss of peripheral sensation. This result suggests that a large percentage of ulcers seen in diabetic patients are not of neurogenic origin.

Adult

The road ahead.

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Artificial Limbs

Transcutaneous oxygen tension measurements on limbs of diabetic and nondiabetic patients with peripheral vascular disease.

We measured transcutaneous oxygen tension (TcPo2) at a skin temperature of 44 degrees C on 319 limbs in an approximately equal number of nondiabetic and diabetic patients with peripheral vascular disease. Measurements were made above the knee, below the knee (BK), and on the dorsum of the foot. Nondiabetic limbs with leg/foot (the lesser of BK or foot) TcPo2 values below 20 mm Hg were significantly more likely to have ulcers, to have rest pain, or to require an amputation on the limb as compared with limbs with leg/foot TcPo2 values above 20 mm Hg. Patients with more severe symptoms had significantly reduced limb TcPo2 values, and these values were lower at more distal measurement sites. Generally, these results were similar in diabetic and nondiabetic patients without limb ulceration; however, the diabetic patients were more likely to have ulcers in the presence of high limb TcPo2. This observation suggests that ulceration in a substantial proportion of the diabetic patients may have resulted from factors other than insufficient cutaneous tissue oxygen delivery.

Aged

The effect of exercise upon cutaneous oxygen delivery in the extremities of patients with claudication and in a human laboratory model of claudication.

Transcutaneous PO2 measurements have been shown previously to reflect local cutaneous oxygen delivery in patients with severe peripheral arterial insufficiency. In the present studies, transcutaneous PO2 measurements indicated that exercise of the involved extremity lowered cutaneous oxygen delivery in patients with moderate peripheral arterial insufficiency (claudication). These exercise-related changes in transcutaneous PO2 were reproduced in a human laboratory model of claudication. The pattern of change in transcutaneous PO2 observed in this model during and after exercise correlated closely with the pattern of change in mean systemic blood pressure during the same time period.

Ankle

Contralateral limb and patient survival after leg amputation.

Fifty-three patients who required amputation for ischemic disease of the legs were evaluated actuarially. The incidence of subsequent contralateral amputation and the length of patient survival were found to be nearly identical to incidence rates reported during the 1960s. The diffuse end-stage nature of the atherosclerotic process which led to the initial amputation in both time periods accounted for the similarity. Operative mortality decreased from more than 10 percent to 1.5 percent, presumably because of improved cardiovascular support and early rehabilitation.

Adult

Amputations.

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Amputation, Surgical