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At this moment, pressure ulcer risk assessment is dominated by subjective measures and does not predict pressure ulcer development satisfactorily. Objective measures are, therefore, needed for an early detection of these ulcers. The current in vitro study evaluates cytokines and chemokines [interleukin 1alpha (IL-1alpha), interleukin 1 receptor antagonist (IL-1RA), tumor necrosis factor alpha (TNF-alpha) and interleukin 8 (CXCL8/IL-8)] as early markers for mechanically-induced epidermal damage. Various degrees of epidermal damage were induced by subjecting commercially available epidermal equivalents (EpiDerm) to increasing pressures (0, 50, 75, 100, 150, and 200 mmHg) for 24 h, using a loading device. At the end of the loading experiment, tissue damage was assessed by histological examination and by evaluation of the cell membrane integrity. Cytokines and chemokines were determined in the culture supernatant. Sustained epidermal loading resulted in an increased release of IL-1alpha, IL-1RA, TNF-alpha and CXCL8/IL-8. This was first observed at 75 mmHg, when the tissue was only slightly damaged. Swollen cells, vacuoles, necrosis and affected cell membranes were observed at pressures higher than 75 mmHg. Furthermore, at 150 and 200 mmHg, the cells in the lower part of the epidermis were severely compressed. In conclusion, IL-1alpha, IL-1RA, TNF-alpha and CXCL8/IL-8 are released in vitro as a result of sustained mechanical loading of the epidermis. The first increase in cytokines and chemokines was observed when the epidermal tissue was only slightly damaged. Therefore, these cytokines and chemokines are potential markers for the objective, early detection of mechanically-induced skin damage, such as pressure ulcers.

Pressure ulcers develop due to morphological and biochemical changes triggered by the combined effects of mechanical deformation, ischemia, and reperfusion that occur during extended periods of immobility. The goal of this study was to test the effectiveness of a novel electrical stimulation technique in the prevention of deep tissue injury (DTI). We propose that contractions elicited by intermittent electrical stimulation (IES) in muscles subjected to constant pressure would induce periodic relief in internal pressure; additionally, each contraction would also restore blood flow to the tissue. The application of constant pressure to the quadriceps muscles of rats generated a DTI that affected 60 +/- 15% of the compressed muscle as assessed by magnetic resonance imaging. In contrast, in the groups of rats that received IES at 10- and 5-min intervals, DTI of the muscle was limited to 16 +/- 16 and 25 +/- 13%, respectively. Injury to the muscle was corroborated by histology. In an experiment with a human volunteer, compression of the buttocks reduced the oxygenation level of the muscles by approximately 4%; after IES, oxygenation levels increased by approximately 6% beyond baseline. Concurrently, the surface pressure profiles of the loaded muscles were redistributed and the high-pressure points were reduced during each IES-induced contraction. The results of this study indicate that IES significantly reduces the amount of DTI by increasing the oxygen available to the tissue and by modifying the pressure profiles of the loaded muscles. This presents a promising technique for the prevention of pressure ulcers in immobilized and/or insensate individuals.

Background: Our study investigated nutritional status, body composition, and resting energy expenditure (REE) in elderly patients with advanced-stage pressure sores (PS), in addition to researching any hypermetabolic condition and its relationship with PS size., Methods: The study involved 52 institutionalized bedridden elderly women (aged 83.7 +/- 6.3 years), divided into two groups: 23 with advanced-stage (stage 3 and 4) PS and 29 without PS. Albumin, prealbumin, and retinol-binding protein were measured in all patients, and fat-free mass (FFM) and fat mass (FM) were obtained by dual-energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry and predicted with the Harris-Benedict formula. PS area and volume were also measured., Results: The elderly women with and without PS were comparable in age, FFM, and FM. Mean albumin, prealbumin, and retinol-binding protein values were lower in cases with PS. Unadjusted mean REE was significantly higher in patients with PS (1212.3 +/- 236.7 vs 1085.5 +/- 161.3 kcal/d; p <.05), even after adjusting for FFM or expressed per kilogram of body weight (25.8 +/- 6.7 vs 21.1 +/- 4.0 kcal/d/kg; p <.01). Hypermetabolism, i.e., a measured REE > 110% of the predicted REE, was seen in 74% of patients with PS and 38% of controls. The difference between measured and predicted REE (DeltaREE) correlated with PS volume (r = 0.58; p <.01), but not with area., Conclusion: Advanced-stage PS in elderly women are associated with a hypermetabolic state that is influenced by the volume of the PS.

There is growing interest in the relationship of hyaluronan and inflammation in a number of physiologic processes including wound healing. The objective of this study was to make a quantitative comparison of inflammation and hyaluronan expression in human normal healing open wounds and in pressure ulcers. Using an open dermal wound model, myeloperoxidase activity was found to peak at day 3. Hyaluronan levels showed a bimodal distribution with transient peaks occurring on days 1 and 7. Mean levels of myeloperoxidase activity in pressure ulcers were significantly higher than at any time in the acute wounds, whereas hyaluronan levels were significantly lower than at any time in the acute wounds. Levels of hyaluronidase activity increased slightly in the postwound period. Hyaluronidase activity in pressure ulcers was significantly elevated compared with the acute wounds. These results suggest a role for increased enzymatic degradation of hyaluronan as a function of inflammation during wound repair. This is the first reported quantitative examination of hyaluronan expression in human acute dermal wounds and in chronic pressure ulcers.

Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs. In this study we investigated the role of oxidative damage in PUs and the probable beneficial effect of beta-glucan treatment against this damage. beta-glucan is known to have immunomodulatory effects. Experiments were carried on Wistar albino rats. PU was induced by applying magnets over steel plates that were implanted under the skin, to compress the skin and cause ischemia where removing the magnets cause reperfusion of the tissue. Within the first 12 h, rats were subjected to 5 cycles of ischemia/reperfusion (I/R), followed by 12 h ischemia. This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, beta-glucan was either applied locally (25 mg/kg) as an ointment on skin, or administered orally (50 mg/kg) as a gavage. At the end of the experimental periods, tissue samples (skin, liver, kidney, lung, stomach, and ileum) were taken for the measurement of malondialdehyde (MDA)--an index of lipid peroxidation--and glutathione (GSH)--a key antioxidant--levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase activity, while collagen contents were measured for the evaluation of tissue fibrosis. Skin tissues were also examined microscopically. Liver and kidney functions were assayed in serum samples. Local treatment with beta-glucan inhibited the increase in MDA and MPO levels and the decrease in GSH in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, BUN, ALT, AST, LDH and collagen levels in PU group were prevented by beta-glucan treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU group. Tissue injury was decreased especially in the locally treated group. Thus, supplementing geriatric and neurologically impaired patients with adjuvant therapy of beta-glucan may have some benefits for successful therapy and improving quality of life.

We investigated the distribution of moxifloxacin in the interstitial space of normal and infected subcutaneous tissue in patients with spinal cord injury and decubitus ulcers using in vivo microdialysis. Drug concentrations achieved in serum, saliva, normal and infected tissues showed approximately parallel time profiles. The interstitial tissue fluids reached bactericidal levels for common bacteria found in infected skin lesions. Our findings suggest that moxifloxacin exhibits good and similar penetration into the interstitial space fluid in normal subcutaneous tissue and infected decubitus ulcers in patients with spinal cord injury.

Objective: Pressure-induced vasodilation (PIV) allows skin blood flow to increase in response to locally applied pressure and may be protective against pressure ulcers. We previously showed that PIV was absent in 1-week diabetic mice exhibiting no neuropathy. Our aim was to determine whether the diabetes-induced PIV alteration could be prevented., Methods and Results: Diabetic mice received no treatment or a daily treatment with either sorbinil, alagebrium or alpha-lipoic acid (LPA) for 1 week. Laser Doppler flowmetry was used to evaluate PIV as well as endothelium-dependent vasodilation following iontophoretic delivery of acetylcholine (ACh). The effect of each treatment on oxidative stress was examined by plasma 8-isoprostane assay. LPA was the sole treatment to prevent both PIV and ACh vasodilation alterations, with a significant reduction of oxidative stress in diabetic mice. Both PIV and ACh-vasodilation were abolished in LPA-treated diabetic mice following injection of Nomega-nitro-L-arginine (p<0.05). In contrast, alagebrium and sorbinil prevented neither diabetes-induced PIV abolition nor endothelial alteration., Conclusions: LPA treatment significantly reduced the oxidative stress and was able to preserve endothelial nitric oxide availability in the cutaneous microcirculation and then to preserve the PIV response in diabetic mice. LPA treatment could play a key role in limiting the risk of pressure-induced cutaneous ulcer during diabetes.

Objective: We investigated the relation between oxidative stress and the occurrence of the acute-phase response with serum ascorbic acid and alpha-tocopherol levels in patients with pressure sores., Methods: The following groups of patients were studied: 1) those who had patients with pressure sores, 2) those who had pneumonia, and 3) those who did not develop pressure sores or any type of infection (control). Concentrations of total proteins, albumin, creatinine, iron, ferritin, transferrin, C-reactive protein, alpha1-acid glycoprotein, total iron-binding capacity, ascorbic acid, alpha-tocopherol, and malondialdehyde were measured during the first days of hospitalization., Results: Albumin concentrations were significantly lower (P < 0.05) and C-reactive protein concentrations were significantly higher (P < 0.05) in patients with pressure sores compared with controls. Concentrations of ascorbic acid and alpha-tocopherol were significantly decreased (P < 0.05) in patients who had pressure sores or infection, whereas malondialdehyde concentrations were significantly increased (P < 0.05) compared with control patients. Five of 11 patients (55.56%) with pressure sores and 10 of 12 patients (83.33%) with pneumonia presented serum ascorbic acid concentrations below the reference value (34 to 91 micromol/L). Concentrations of ascorbic acid and alpha-tocopherol versus malondialdehyde were significantly correlated in the three patient groups (r = -0.44, P < 0.05; r = -0.55, P < 0.01, respectively)., Conclusion: Patients with pressure sores and acute infection present a systemic inflammatory response accompanied by an increase in lipid peroxidation that is associated with decreased serum ascorbic acid and alpha-tocopherol levels, suggesting that these patients may be at risk for important nutritional deficiencies.

Objectives: To estimate energy requirements in diseased elderly patients with pressure ulcers (PUs)., Design: Open, case-control study., Setting: University Hospital of Angers (France)., Participants: Twenty-nine patients with PUs (Norton index risk=14.3+/-3.3) and 27 controls hospitalized for various diseases (Norton=13.9+/-3.3)., Measurements: Energy requirements were estimated using measured resting metabolic rate (RMR) and multiplied by 1.26 and 1.5 to range between minimal World Health Organization (WHO) requirements and those of adults undergoing light physical activity. Energy intakes were estimated using 3-day food weight records. Measured RMR was compared with the prediction equations of Harris-Benedict, WHO, and Schofield., Results: Measured RMR did not differ between the two groups (P=.48), and was not related to grade or size of the PUs. The WHO equation (82 kcal/d, P=.006) and the Schofield formula (57 kcal/d, P=.05) slightly underestimated calculated RMR, but the Harris-Benedict equation (40 kcal/d, P=.13) accurately estimated it. Energy requirements therefore ranged between 1,536+/-340 kcal/d and 1,828+/-405 kcal/d, (25-30 kcal/kg body weight per day). Energy intake was lower than energy requirements by 176 to 479 kcal/d., Conclusion: Diseased elderly patients with PUs do not have greater energy expenditure, with their requirements suggested to range between 25 and 30 kcal/kg body weight per day. Malnutrition within this population is most likely the result of low energy intake.

In a 16-patient study, cultured fibroblast populations from normal skin were able to replicate an average of 14.8 +/- 2.2 times before becoming senescent, while fibroblast populations from the ulcer bed reached the end of their replicative life span after 7.2 +/- 1.9 population doublings (p= 0.001). Fibroblast populations from 10 of 16 pressure ulcers became senescent after fewer than five population doublings, whereas when populations of fibroblasts from adjacent normal skin were studied, only 2 of 16 became senescent within this same time period. In addition, only an occasional fibroblast from normal skin stained positively for senescence-associated beta-galactosidase compared to approximately 50% of equally aged ulcer bed fibroblasts (p = 0.0060). Senescent ulcer bed fibroblasts secreted significantly more plasmin than early passage ulcer bed fibroblasts (p= 0.0237), nearly six times as much plasmin as early passage normal skin fibroblasts (p < 0.0001), three and a half times the level of normal skin fibroblasts of the same age (11.52 +/- 4.58 microg/mg protein; p= 0.0003), and more than one and a half times the level of senescent normal skin fibroblasts (p= 0.0525). Senescent pressure ulcer fibroblasts generated significantly more plasminogen activator inhibitor-1 (1179.27 +/- 25.37 ng/mg protein) than normal skin fibroblasts of the same age (132.16 +/- 16.20 ng/mg protein; p = 0.0357). Also, senescent ulcer bed fibroblasts produced higher levels of transforming growth factor-beta1, but these were not significantly different from senescent normal skin fibroblasts. Although senescent ulcer fibroblasts produce elevated levels of plasminogen activator inhibitor-1 and transforming growth factor-beta1, the ratio of these factors to plasmin levels suggests that this may have little influence on extracellular matrix synthesis or maintenance in the chronic wound. These data show that cultured fibroblasts from most patient pressure ulcers profile a wound environment that is associated with an increasing population of senescent fibroblasts; however, factors within the chronic wound environment that promote cellular senescence remain unclear. We have proposed that a prolonged inflammatory response may be a contributing factor to the chronic wound condition.

Background: The plasminogen activation system represents a potent mechanism of extracellular proteolysis and is an essential component of normal wound healing. It has also been implicated in the pathogenesis of chronic, nonhealing ulcers. Traditionally, urokinase-type plasminogen activator (uPA) has been associated with pericellular proteolytic activity involved in tissue remodelling processes, and tissue-type plasminogen activator (tPA) mainly with intravascular fibrinolysis., Objectives: The present study was conducted to characterize the spatial distribution of the various plasminogen activation system components in chronic ulcers and acute, well-granulating wounds., Methods: The expression of uPA, tPA, urokinase receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and vitronectin was investigated by immunohistochemical staining, in addition to uPA, tPA and PAI-1 expression by in-situ hybridization, in samples from eight chronic venous ulcers, five decubitus ulcers, five well-granulating acute wounds and five normal skin samples., Results: In chronic venous leg ulcers tPA mRNA was detected in basal and suprabasal keratinocytes at the leading wound edge, while in well-granulating wounds and in decubitus ulcers tPA mRNA was expressed only in a few keratinocytes. However, tPA was widely expressed in fibroblast- and macrophage-like cells in the stroma of well-granulating wounds, while less tPA was detected in the granulation tissue of chronic ulcers. tPA mRNA and protein were localized in the superficial granular layers in normal skin. Although no qualitative differences in expression of uPA, PAI-1 or uPAR in the wound edge keratinocytes in chronic ulcers vs. normally granulating wounds were found, their expressions were more pronounced in the granulation tissue of well-granulating wounds., Conclusions: These results suggest that in poorly healing venous leg ulcers, the pattern of tPA expression is altered in keratinocytes at the leading edge of the wound, and the patterns of tPA, uPA and PAI-1 expression are altered in the granulation tissue.

Although it is well recognized that pressure-induced ischemia initiates the formation of pressure ulcers, the many complex mechanisms responsible for the pathogenesis of these ulcers remain poorly understood. It has been reported that chronic ulcers contain an elevated level of proteolytic enzymes, especially neutrophil-derived matrix metalloproteinase-8 and elastase. This evidence suggests that neutrophils are a major component in the pathogenesis of chronic pressure ulcers. Therefore, this study characterized the cellular components of chronic pressure ulcers. Three-millimeter biopsies (6 mm deep) from granulation tissue in pressure ulcers were obtained from 11 patients. A total of 14 biopsies were obtained from these 11 patients for analysis. A portion of each specimen was fixed in formalin for routine histology. Other portions of biopsies were frozen for analysis of myeloperoxidase activity. In addition, cells on the surfaces of the ulcers were collected by lavage for histologic characterization. Routine histologic analysis of all 14 biopsies of the pressure ulcers showed regions near the surface of each that contained dense neutrophil infiltration associated with edema and apparent marked matrix dissociation. In the deeper regions there was an increased density of blood vessels, and many contained rounded endothelial cells surrounded by migrating neutrophils. Cells collected by lavage from the ulcer surface were prepared by Cytospin and found to be greater than 95% neutrophils with occasional large macrophages actively phagocytosing depleted neutrophils. In addition, there was a significant correlation of myeloperoxidase activity with actual neutrophil counts in the ulcer biopsies further confirming the dense presence of neutrophils. These studies directly show that there is extensive neutrophil infiltration in chronic pressure ulcer granulation tissue. Furthermore, the persistence of neutrophils and their destructive enzymes appears responsible for the extensive matrix dissociation and thus contributes to the chronicity of these ulcers.

Chronic decubital lesions have a limited potential to heal. Evidence suggests that a lack of local revascularization is involved in this aetiology. The present study investigated the expression of one of the most important angiogenic factors, the vascular endothelial growth factor (VEGF), in different regions of sacral chronic decubital lesions and in normal skin by immunohistochemical, biochemical, molecular, and cell biology methods. To elucidate some of the factors responsible for the induction of VEGF in chronic skin ulcers, cultured fibroblasts were exposed to hypoxia and/or growth factors. In the central part (zone I) of chronic ulcers and in normal skin, immunostaining for VEGF remained largely negative. However, VEGF could be immunostained in cells in the granulation tissue adjacent to central necrosis (zone II). VEGF receptor 2 (VEGFR-2; KDR) could also be identified in microvessels. High VEGF levels were present in homogenates from granulation tissue by enzyme-linked immunosorbent assay (ELISA) and western blot experiments: low concentrations were found in areas of central necrosis and negligible amounts were present in normal skin. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that only the splice variants VEGF(121) and VEGF(165) were expressed. In cultured fibroblasts, hypoxia or platelet-derived growth factor (PDGF) raised VEGF production. The angiogenic peptide VEGF is present in all zones of chronic decubital ulcers. Its strong expression within the adjacent granulation tissue supports the view that there is no deficiency of VEGF. VEGF may be involved in the healing process of chronic skin lesions, but it seems that loss of another factor may be responsible for the poor healing response., (Copyright 2003 John Wiley & Sons, Ltd.)

The relatively modern concept of wound-bed preparation draws together elements of current practice, including various methods of 'maintenance debridement' and the use of antibiotics and antiseptic agents, to speed up healing of chronic wounds.

Objective: To measure resting energy expenditure (REE) in a group of people with postacute paraplegia, quantify the impact of asymptomatic bacteriuria and pressure sore(s) on patients' metabolic rate, and estimate the adequacy of patients' nutritional intakes to preserve patients' protein levels., Material and Methods: Ten males with post-acute paraplegia aged 42.1+/-18.7 years. We evaluated: height, body mass index (BMI), resting energy expenditure (REE), total daily calorie requirement (E), 24-h urine creatinine excretion (Cru), creatinine index (CI), and nitrogen balance (NB)., Results: Subjects with paraplegia showed high erythrocyte sedimentation rates. As a group, they had normal resting calorie consumption when REE was normalized for unit of urine creatinine (REE/Cru), it was higher in patients than in controls. Six of the 10 patients had a low calorie intake: of these only three had a negative nitrogen balance., Conclusion: In conclusion, the resting energy expenditure of the subjects with significant bacteriuria and pressure sore(s) of 23.7 kcal/kg/day suggests that a large portion of patients may have an inadequate calorie protein intake to preserve their nutritional status. The clinical significance of this study is that 28.5 kcal/kg/day may be the lower calorie threshold to meet the metabolic demands of people with apyretic paraplegia with bacteriuria and pressure sore(s).

Evidence for age-related effects on wound healing have been derived for the most part from empirical observations without adjustment for confounders other than age. Age-related changes in the structure and function of the skin do occur. Some of these changes result from chronic solar radiation exposure rather than chronological age per se. The tensile strength of wounds, accumulation of wound healing factors and rate of wound closure have all been examined in relation to chronological aging. However, the clinical impact of these changes in acute wound healing appears to be small. Poor healing in chronic wounds is more often related to comorbid conditions rather than age alone. Since the majority of these chronic wounds occur in elderly populations, this has contributed to the conclusion that aging itself may influence healing. Progress in understanding the role that growth factors play in wound healing and the ability to synthesise adequate quantities of these factors for clinical use has led to clinical trials evaluating their use in wound healing. The results of these studies, with the possible exception of those in diabetic wounds, have been disappointing. Insight into the wound healing process indicates that growth factors interact during wound healing in a sequential and orderly process. Improved wound healing may require different clinical designs or the use of these factors in a precisely timed sequential administration.

In the present study, Langerhans' cells (LCs) in the sacral epidermis, 8-10 cm from lesions of patients (mean age 71 years) with decubital ulcers, were compared ultrastructurally and morphometrically with those in the patients' own normal epidermis from the upper leg, before and after supplementation with 50 mg/day elementary zinc (in the form of a 220-mg tablet of Avazinc, administered once daily) for four months. Zinc intake resulted in from 80% to full healing of the decubital ulcers in the patients studied. The percentages of LCs were low in both perilesional sacral epidermis (2.07 +/- 0.71%) and in control leg epidermis (2.71 +/- 1.38%) before zinc supplementation and also afterward (2.12 +/- 0.16% and 2.59 +/- 0.88%, respectively). LCs demonstrated a more dendritic morphology after zinc supplementation: 68.15 +/- 9.28% and 77.0 +/- 3.45% of sacral and of control leg epidermal LCs, respectively, had dendrites before, and 91.52 +/- 3.43% and 84.15 +/- 3.64% of sacral and of control leg epidermal LCs, respectively, had dendrites after zinc supplementation. The LC section area in the sacral epidermis near the lesion as well as in the control leg epidermis and the number of LC granules in LC sections were not affected by zinc supplementation. The higher percentage of LCs having dendrites in the epidermis of patients with decubital ulcers after zinc supplementation may indicate that these LCs are in a more motile state, which might affect the healing process of the lesions.

Alternating-pressure air mattresses (APAMs) are used increasingly for the prevention and treatment of pressure sores. Laboratory evaluation techniques have centred largely on interface pressure (IP) measurement, typically analysing discrete maximum and minimum levels, or average pressure. However, since pressure relief varies with time, a time-based analysis technique has been developed for performance assessment. IP was recorded continuously, and the duration of pressures below three thresholds (30, 20 and 10 mmHg) was calculated automatically using a computerized rig. Fifteen healthy volunteers were used to evaluate the pressure-relieving characteristics of four APAMs, including one overlay. Results indicated significant differences (P < 0.001) between products when durations below the 20 and 10 mmHg thresholds were analysed, showing that some devices were only capable of momentarily relieving pressure. Maximum contact pressures on the sacrum were significantly lower (P < 0.0001) on devices whose inflation pressure was adjusted according to subject's body mass. This technique could assist in the selection of alternating or dynamic surfaces of any description with further clinical validation.

The effect of alternating current (AC) and direct current (DC) stimulation was studied on experimental pressure ulcer healing in a new monoplegic pig model. The study was conducted in 30 healthy young Hanford minipigs. The rate of wound healing, histology, vascularization, collagen formation, microbiology, perfusion, and the mechanical strength of the healed wounds were studied. Normal pigskin was compared to denervated control and denervated AC and DC stimulated healed skin. Hind limb denervation was by right unilateral extradural rhizotomies from the L2 to S1 nerve roots. Reproducible uniformly controlled Stage III or higher tissue ulcers were created. When compared to the control wounds, both the AC and DC stimulated wounds showed reduced healing time and increased perfusion in the early phases of healing. DC stimulation reduced the wound area more rapidly than AC, but AC stimulation reduced the wound volume more rapidly than DC. The electrical stimulation did not reduce the strength of the healing wounds below those of the nonstimulated controls. The applied current appears to orient new collagen formation even in the absence of neural influences.

The purpose of this article is to refine and advance the theory that tissue perfusion is the key concept in the development and delayed healing of pressure ulcers. The person likely to have (be at risk for) pressure ulcers is at greater risk for inadequate tissue perfusion generally and specifically at pressure points. Accordingly, the tissue perfusion theory of pressure ulcer development states that the factors that contribute to inadequate tissue perfusion should be used to predict (identify risk factors for) pressure ulcer development and delayed healing. Factors influencing a person's adequacy of tissue perfusion need to be assessed to identify risk for pressure ulcers. In addition, adequate tissue perfusion needs to be maintained to provide for healing of such wounds. Current beliefs about the causes and prevention of pressure ulcers are described. Physiologic components of the tissue perfusion theory are discussed: cellular exchange of nutrients and wastes, autoregulation of blood flow at the cellular level, and regulatory mechanisms that affect tissue perfusion when it is significantly compromised. The North American Nursing Diagnosis Association (NANDA) framework is used to classify or group examples of common pathophysiologic, treatment-related, situational, and maturational factors. Implications for research, practice, and education also are discussed.

Based on a review of the literature related to the prediction and prevention of pressure sores, a conceptual scheme on pressure sores in introduced. The article highlights the four elements of the scheme: pressure, shearing force, tissue tolerance for pressure and tissue tolerance for oxygen. Factors influencing pressure and shearing forces, the pressure distribution capacity of tissue, the oxygen need of tissue and oxygen supply to tissue are discussed.

Aims: To assess the viability of soft tissues in elderly patients subjected to prolonged support pressures., Design: measurements were performed on the soft tissues of patients undergoing surgery for fracture of the proximal femur., Methods: 10 subjects, mean age 84 years, participated. Transcutaneous gas tensions were continuously monitored in an area adjacent to the contralateral greater trochanter, which was loaded with an external applicator. Subcutaneous interstitial pressures using a slit catheter were also measured., Results: Transcutaneous oxygen partial pressure fell in some patients to critically low levels, defined as below 2.7 kPa (20 mmHg), whilst they were subjected to normal interface pressures on the operating table. Transcutaneous partial carbon dioxide pressures rarely rose above 8.0 kPa (60 mmHg). The measured interstitial pressures could lead to local occlusion of skin microvessels., Conclusions: This study confirms that tissue viability could be compromised in elderly patients undergoing surgical procedures. The methods employed may be of value in assessing support surfaces in the operating theatre to reduce the incidence of pressure sores in this high-risk patient group.

The aim of this study was to use transcutaneous oxygen pressure (tcpO2) measurements to evaluate the efficacy of a solution containing hyper-oxygenated fatty acid esters in the prevention of pressure sores in 28 patients at high risk of developing sores. Statistical analysis indicates a significant difference between tcpO2 values during pressure exertion before and after application of the product (p = 0.014). Oxygen pressure values decreased significantly when the patient applied pressure to the sacral area before the test product was applied whereas no difference in oxygen pressure values was noted after application of the test product.

This article examines the application of a simple technique for the collection of sweat to the investigation of tissue metabolites in 11 debilitated subjects attending a rehabilitation unit. It is applicable to subjects with a range of clinical conditions. Sweat was collected at the sacrum with the subjects either seated in a wheelchair or lying in bed, which was representative of their usual daily routine. The tissues could be loaded during sweat collection by sacral support in either of these positions. Collections were made for about 10 hours and interface pressures were recorded on at least two occasions. After the prescribed period, the sweat pads were removed and a quantitative analysis of a range of metabolites was performed. Metabolite concentrations may reflect local tissue viability and responses to loading. In unloaded tissues the metabolite concentrations were similar to those observed in nondisabled subjects in an earlier study. During prolonged loading at relatively low levels of pressure, there was elevation in the levels of some metabolites; for example 39 and 28% increases for lactate and urea respectively. Successive measurements on an individual over a period of months showed variations, which were small compared to those observed in either groups of nondisabled or debilitated subjects. These observations suggest that the technique may be best applied in clinical practice to monitor sequential changes in individual subjects.

We studied the relationship between decubitus ulcers and changes in skin blood flow with respect to the presence or absence of a decompression medium. We also studied the relationship between decubitus ulcers and the results of biochemical tests that reflect nutritional status. Two groups of inpatients with decubitus ulcers in areas other than the sacral region were studied: One used cloth diapers and the other used paper diapers. Skin blood flow was measured with a laser Doppler blood flowmeter and a sheet of polyurethane (decompression medium) in the sacral region. Data were also obtained from patients with and without decubitus ulcers, and whose levels of albumin, total cholesterol, and triglyceride for three months were known. When the decompression medium was used, skin blood flow changed significantly after body position was changed in the patients who used paper diapers. Nutritional analyses showed significant differences in the levels of albumin and total cholesterol between patients with and without decubitus ulcers. The levels of albumin and total cholesterol were lower in the patients with decubitus ulcers than in those without decubitus ulcers. Because the cloth diapers acted as a compression factor, even an externally applied decompression medium did not suppress the reductions in skin blood flow.

Health individuals with quadriplegia generally have a reduced metabolic rate. However, individuals with quadriplegia who develop pressure ulcers may have an elevated metabolic rate. In this study, energy expenditure in 16 individuals with quadriplegia and pressure ulcers (PU-QUAD) was compared to the energy expenditure in 16 individuals with quadriplegia but no pressure ulcers (NPU-QUAD) and 16 healthy non-spinal cord injured subjects (controls). Resting energy expenditure (REE) was measured by indirect calorimetry. Both measured REE (t(30) = 2.38, p = 0.24) and percent predicted REE (t(30) = 3.23, p = .003) were significantly higher in subjects with quadriplegia and pressure ulcers compared with subjects with quadriplegia but no pressure ulcers. On average, REE in the PU-QUAD subjects was nearly equal to the absolute energy expenditure of healthy non-spinal cord injured controls. To ensure optimal care of patients with quadriplegia and pressure ulcers, quantification of energy expenditure with provision of adequate caloric intake is recommended.

Heat shock protein 70 (hsp 70) is an important member of the heat shock protein family, which is induced by different forms of stress. We attempted to find out if hsp 70 is also involved in wound healing, which likewise resembles a stress situation for cells too. Therefore we collected tissue samples from well healing and chronic human wound tissue. We used Northern- and Western-blot analysis to study the expression of hsp 70. At the protein level we found a strong correlation between well healing wounds and high expression of hsp 70, whereas chronic wounds showed no or weak expression. Interestingly hsp 70 mRNA did not show this significant correlation, displaying a variant expression pattern in the same kind of wound tissue, possibly due to unknown posttranscriptional regulating step, which has to be investigated in further studies. To localize hsp 70 mRNA and protein was used insitu hybridization and immunohistochemistry. Both displayed an overexpression in endothelial cells of capillary vessels.

Objective: To determine the overall effect of paraplegia and pressure sores on resting metabolic rate., Design: Unblinded, case-control study using a convenience sample., Setting: Hospital primary care setting., Patients: Fourteen individuals with paraplegia and pressure sores (PS-Para), 24 with paraplegia in good health (NPS-Para), and 23 non-spinal cord injury (SCI) controls., Main Outcome Measures: The planned outcome measures consisted of resting metabolic rate, percent of predicted resting metabolic rate, resting metabolic rate per kilogram body weight, and resting metabolic rate per meter squared body surface area. Post hoc analyses were used to identify the effect of completeness of lesion, smoking, and pressure sores on percent of predicted resting metabolic rate and resting metabolic rate per kilogram body weight., Results: Percent of predicted resting metabolic rate and resting metabolic rate per kilogram body weight were significantly higher in the PS-Para group than in the NPS-Para or control groups (115% +/- 4% vs 100% +/- 2% or 107% +/- 2%, p < .05) and (25.9 +/- 1.2 vs 21.4 +/- 0.6 or 22.5 +/- 0.4 kcal/kg, p < .05, respectively). The resting metabolic rate per meter squared body surface area was significantly higher in the PS-Para group than in NPS-Para group (973 +/- 39 vs 874 +/- 20kcal/m2, p < .05). In the PS-Para group, current smokers had significantly higher resting metabolic rate per kilogram body weight than nonsmokers (27.3 +/- 1.7 vs 24.0 +/- 1.4kcal/kg, p < .01). Controlling for the effects of smoking in a multiple regression model, those in the PS-Para group had significantly (p < .001) greater percent of predicted resting metabolic rate and resting metabolic rate per kilogram body weight than those in the NPS-Para group., Conclusions: These findings indicate that individuals with SCI may have a decreased percent of predicted resting metabolic rate and those with pressure sores may have a hypermetabolic state. This hypermetabolic state is significantly higher than that resulting from smoking. Because ordinary prediction equations for energy expenditure may not be accurate when applied to subjects with paraplegia and pressure sores, quantification of energy needs by indirect calorimetry is recommended.

This is a review of the literature on air-fluidized beds and nutrition with an emphasis on patients with pressure ulcers. Studies suggest that the warm, dry environment of the air-fluidized bed may affect nutritional status. Patients maintained on air-fluidized beds have increased fluid losses and decreased urinary nitrogen losses. While the evidence suggests that air-fluidized beds may reduce protein catabolism, further and lengthier metabolic studies are needed. Clinicians should continue to provide high levels of energy and protein for patients with pressure ulcers on air-fluidized beds.

A straightforward technique was developed for sweat collection applicable to tissues subjected to external load without introducing distortion of underlying tissues, and for analysis of six metabolites in the collected sweat. Chloride was measured colorimetrically and lactate, urea and urate by enzymatic methods on a centrifugal analyser. Sodium and potassium were measured by flame photometry. The methods showed good precision, recovery and linearity. To assess the technique sweat was collected: (i) from the sacrum, ischium, forearm and calf in healthy individuals at 32 degrees C for 1 h; (ii) from the sacrum of healthy subjects at ambient temperature for 9 h; (iii) at ambient temperature from the sacrum of a patient with a history of pressure sores. Sweat rates were greater at the sacrum and ischium than the calf or forearm. There were differences in the concentrations of lactate and urea between sites but these were smaller when expressed as amount secreted. Sweat rates were significantly lower in groups (ii) and (iii), but sweat could be collected reliably. This technique has potential clinical application to the investigation of susceptibility to pressure sores.

Exogenously applied transforming growth factor-beta (TGF-beta) isoforms enhance wound healing processes in animal models; however, little is known about the expression of endogenous TGF-beta s and TGF-beta receptors in intact human skin or during wound healing. The present study has revealed several unexpected findings by means of in situ hybridization and immunohistology techniques. In humans, TGF-beta 3 is constitutively expressed in the epidermis of intact skin and in that of acute and chronic wounds--a pattern of expression closely mirrored by the TGF-beta type II receptor. Although not detected in intact skin, TGF-beta 1 mRNA expression was observed in the regenerating epidermis of acute (thermal) wounds but was not found in chronic decubital (pressure) wounds. TGF-beta 2 mRNA expression was not detected in the epidermis of any human skin or wound biopsies. From these findings we suggest that constitutive expression of TGF-beta 3 is important for maintenance of epidermal differentiation and that an induction of TGF-beta 1 expression is essential for re-epithelialization of human skin wounds. Lack of TGF-beta 1 expression in chronic pressure wounds may be associated with their protracted healing tendencies.

Background and Design: Pulsed low-intensity direct current (300 to 600 microA) has been used in a double-blind placebo multicenter study in the treatment of stage II and stage III chronic decubitus ulcers., Results: Seventy-four ulcers were treated in four centers. Forty-three patients were selected for the experimental group, and 31 control subjects used the sham instrument (placebo group). In the treated group, 25 ulcers (58%) healed in 8 weeks, whereas in the placebo group, only one ulcer (3%) healed and most ulcers increased in size. Statistical analysis, based on surface area and ulcer depth before and after treatment, showed that low-intensity direct current had a significant influence on the healing rates for these ulcers (P < .0001). Experiments with guinea pigs (n = 10) showed that pulsed low-intensity direct current caused a rapid calcium flux in the epidermis., Conclusions: Pulsed low-intensity direct current represents a useful approach for the treatment of stage II and stage III chronic decubitus ulcers by increasing the healing rate. The growth of fibroblasts and keratinocytes may be enhanced by pulsed low-intensity direct current due to changes in calcium homeostasis.

Pressure sores are a common occurrence in immobilized patients. They increase morbidity and mortality and impede rehabilitation. Antibiotics are routinely used to assist in effecting a cure when infection is present. Nevertheless, for patients with spinal cord injuries (SCI), strategies for effective therapy with antibiotics based on measurement of concentrations in tissue and pharmacokinetic behavior in extravascular spaces do not exist. By analyzing the concentration-time profile and protein binding of amikacin in the interstitial fluid (IF) in contact with pressure sores, we found that the disposition of amikacin in the tissue contiguous with pressure sores appears to be governed by simultaneous first-order and capacity-limited pharmacokinetic behavior. Amikacin disposition in IF proceeded without a simple relationship to amikacin concentrations in serum, and the time course in IF was not accurately simulated by linear models of amikacin pharmacokinetic behavior. Total amikacin clearance estimated from a pharmacokinetic model using simultaneous first-order and nonlinear intercompartmental transfer of amikacin was not significantly different from clearance calculated by us in a prior study of amikacin pharmacokinetic behavior in patients with SCI. In patients with SCI, optimal use of amikacin in the treatment of infected pressure sores is contingent upon accurate characterization of the pharmacokinetic behavior of this aminoglycoside in serum and in the IF in contact with these lesions. Only methods which quantitate amikacin concentration and protein binding in IF and incorporate a model that can simultaneously simulate nonlinear and linear disposition processes should be relied upon to influence therapeutic decision making.

Arachidonic acid metabolites have been implicated as mediators of progressive dermal ischemia. Decubitus ulcer formation results from chronic mechanical pressure on the skin which results in a diminished blood supply to the skin and underlying tissues. To evaluate the role of thromboxanes in pressure wounds, we measured TxB2, a stable metabolite of TxA2, in spontaneously occurring pressure wounds on Greyhound dogs. In pressure wounds in which the skin was showing early signs of pressure necrosis but was still intact, elevated TxB2 concentrations were found in healthy appearing tissues immediately adjacent to the pressure wounds, in the inner edge of the wounds, and in the center of the wounds. Significantly greater TxB2 concentrations (P less than 0.05) were found in the center of the intact wounds versus the TxB2 concentrations in the inner edge of the wounds or in healthy appearing tissues adjacent to the wounds. In pressure wounds in which the center of the wound had ulcerated or had an eschar, elevated TxB2 concentrations were found in tissues in the inner edge of the wounds and in healthy appearing tissues immediately adjacent to the pressure wounds. These results demonstrate the occurrence of elevated thromboxane concentrations in and around spontaneously occurring pressure wounds.

Ultrastructural, enzyme histochemical and immunohistochemical studies were performed on tissue obtained from eight cases of malignant fibrous histiocytoma (MFH) and five cases of sacral decubitus ulcer. The MFH was composed of two major tumour cell types: fibroblast-like and histiocyte-like cells. Both cell types demonstrated abundant branching, fragmented rough endoplasmic reticulum (rER), many free ribosomes, occasional small mitochondria, an oval, elliptical or irregularly shaped nucleus with one or two prominent nucleoli and often a few dense bodies. However, pseudopodial projections, multivesicular bodies and phagosomes, common histiocyte organelles, were not seen. With little difference between cases or selection sites, the MFH cells reacted to acid phosphatase (AcP) and alpha-naphtyl butyrate esterase (ANBE) by enzyme histochemistry and with ferritin (Fer), alpha 1-antitrypsin (AT), alpha 1-antichymotrypsin (ACT), fibronectin (FN), HLA-DR, HLA-DP, Leu 10 and OKT 9 in immunohistochemical studies. MFH tumour cells did not immunostain with monocyte/macrophage markers (Leu M1, Leu M3, Mo 1, Mo 2 and Macrophage) although non-neoplastic histiocytes did react to these markers. In addition, granulation tissue, such as that found in sacral decubitus ulcers, was examined and the existence of a specific cell type called the "fibrohistiocytoid (FH) cell" was documented. The FH cell was short, spindle shaped and elliptical. Ultrastructurally, it had fragmented rER distributed in a branching pattern, dispersed free ribosomes, small mitochondria and a few dense bodies, but lacked diverse fused lysosomes and distinct pseudopodial cytoplasmic extensions. The FH cells reacted with AcP, alkaline phosphatase and ANBE but not with peroxidase using enzyme histochemistry and with Fer, AT, ACT, FN, HLA-DR, HLA-DP, Leu 10 and OKT 9 but not with monocyte/macrophage markers, C3d receptor, C3bi receptor in immunohistochemical studies. The FH cells had morphological, enzyme histochemical and immunohistochemical characteristics intermediate between fibroblasts and histiocytes. Similarities between MFH cells and the FH cells seen in chronic inflammation are discussed.

Cultured epidermal cells of explants from decubitus ulcer edges showed significant (P less than 0.05) decreased maximal growth rate (range, 1.3-15.6%) and decreased area of outgrowth per explant (mean and SD, 1.6 +/- 1.7 mm2) when compared with explants obtained 4-5 cm distant from the ulcer edge (range, 46.7-68.8% and 4.6 +/- 2.7 mm2, respectively) and from healthy skin (range, 78.8-93.3% and 6.6 +/- 1.2 mm2, respectively). In contrast, epidermal cells in biopsies from the ulcer edge were significantly (P less than 0.05) more prevalent (range, 1.9-48.2%) as compared with biopsies of healthy skin (range, 3.1-5.1%). Therefore, the decreased growth rate and decreased area of outgrowth may be caused by a defective migration potential rather than an impaired mitotic activity. The latter seems to be normal, as demonstrated by the histomorphometry, which indicates the in vivo situation. Decreased migration potential of epidermal cells could explain the clinically observed protracted epithelialization of decubitus ulcers.

Much emphasis has been placed on the measurement of physical parameters at the body support interface in order to detect and moderate conditions which could result in pressure damage to soft tissues. Major difficulties are encountered both in the design of instrumentation and interpretation of the data collected. Metabolic processes in sweat glands that control sweat secretion have been shown to be sensitive to applied pressure, producing sweating rate suppression and changes in sweat NaCl concentration. In this study, we have demonstrated the feasibility of measuring lactate concentration in sweat collected locally using an electrochemical stimulation technique (iontophoresis of pilocarpine nitrate). Elevated levels of sweat lactate concentration during local tissue indentation were detected in a group of able-bodied subjects. Upon removal of the indentor, however, levels of sweat lactate returned to normal.