Biomedical subjects

M C Robson

Publications and source records attributed to M C Robson.

At least 55 records · Page 3Linked to original sources

PubMed1995

Extension of the life span of pressure ulcer fibroblasts with recombinant human interleukin-1 beta.

Recombinant human interleukin-1 beta (rhuIL-1 beta) was investigated in a randomized, blinded placebo-controlled trial to evaluate its effect on the healing of chronic pressure ulcers. The influence of this topically applied cytokine to 26 pressure ulcer patients was correlated with tissue culture and electron microscopic evaluation. Cellular replication studies showed that low (0.01 micrograms/cm2/day) and medium (0.1 micrograms/cm2/day) concentrations of rhuIL-1 beta were not effective in extending replication in pressure ulcer fibroblasts, in vitro. Tissue culture measurements from pressure ulcer biopsies demonstrated that, after 29 days of a high level of rhuIL-1 beta treatment (1.0 micrograms/cm2/day), the cytokine was effective in extending the ability of pressure ulcer fibroblasts to replicate. Tissue culture and electron microscopy suggested that, although rhuIL-1 beta promoted increases in fibroblast numbers, the primary effect appeared to be development of the extracellular matrix. The possible direct and indirect influences of rhuIL-1 beta therapy on pressure ulcers are discussed.

Cell Survival↗

PubMed1994

In vivo ovine flap model to evaluate surgical infection and tissue necrosis.

Although the inciting causes and the end results of soft tissue infection are well described, we have not achieved a quantitative methodistic description of the sequence of events in between. The following study presents an isolated in vivo model which will allow specific manipulations and quantifications of the events of integumentary infection. Pedicle flaps were raised on the buttock of the adult range ewe and it was multiply inoculated with Staphylococcus aureus, and followed for 96 hr. This pedicle contains not only a well-defined artery, vein, and nerve, but also a well-developed efferent lymphatic vessel. In addition, the distal portion of the flap is primarily supplied by a musculocutaneous arterial perforator, making the distal flap a watershed area. Anatomic, radiologic, and vital stain injection studies confirmed these results. The sheep model was found to be superior to the pig model both in terms of its anatomy (the addition of an efferent lymphatic vessel) as well as the disposition of the sheep which was more compliant than that of the pig. We believe that this flap will allow multiple manipulations and provide an in vivo isolated system to study the pathobiology of soft tissue infection.

Animals↗

PubMed1994

Cytoprotection of human dermal fibroblasts against silver sulfadiazine using recombinant growth factors.

Topical antimicrobial agents, silver sulfadiazine (SSD) and mafenide acetate (MA), have been associated with delayed wound healing. Previous in vitro studies with human dermal fibroblasts (HDF) have shown progressive cellular cytotoxicity with increasing concentrations of SSD and MA. However, preexposure of HDF to epidermal growth factor, basic fibroblast growth factor, or platelet-derived growth factor has resulted in cytoprotection of HDF against 0.01 and 0.03% concentrations of SSD as determined by phase-contrast microscopy (PCM), hemocytometer cell counts, and total cellular protein content. PCM, however, showed slower destruction of HDF at the 0.05% concentration of SSD. These data suggest that cells activated by growth factors either take up less SSD or are more resistant to the direct cytotoxic effects of this drug.

Epidermal Growth Factor↗

PubMed1994

Definitions and guidelines for assessment of wounds and evaluation of healing.

Chronic wounds represent a worldwide problem. For laboratory and clinical research to adequately address this problem, a common language needs to exist. This language should include a system of wound classification, a lexicon of wound descriptors, and a description of the processes that are likely to affect wound healing and would healing end points. The report that follows defines wound, acute wound, chronic wound, healing and forms of healing, wound assessment, wound extent, wound burden, and wound severity. The utility of these definitions is demonstrated as they relate to the healing of a skin wound, but these definitions are broadly applicable to all wounds.

Journal Article↗

PubMed1994

Safety and effect of topical recombinant human interleukin-1beta in the management of pressure sores.

Interleukin-1beta is produced by numerous cell types including monocytes and fibroblasts. It has been shown to stimulate multiple cell types including fibroblasts, keratinocytes, endothelial cells, neutrophils, macrophages, and lymphocytes. Previously, interleukin-1beta was shown to accelerate healing in partial-thickness and full-thickness wounds in animals and was also shown to be safe when applied topically in Phase I human trials. Therefore a prospectively randomized, blind, placebo-controlled trial was performed with patients with chronic pressure ulcers. Doses of interleukin-1beta of .01 microg, .10 microg, and 1.0 microg per square centimeter did not show acceleration of healing of the pressure ulcers. Therefore use of recombinant human interleukin-1beta in this study was safe but, at the dose levels tested, did not result in improvement in the healing ratio.

Journal Article↗

PubMed1994

Determination of endogenous cytokines in chronic wounds.

OBJECTIVE: This study objectively characterized the microenvironment of indolent, chronic wounds by developing a method by which minute quantities of cytokines could be extracted from chronic wounds and separately identified. SUMMARY BACKGROUND DATA: Recombinant DNA technology and the ability to clone compounds such as cytokines allow new management schemes for the treatment of acute and chronic wounds. Before treatment with an exogenous cytokine is started, it would be helpful to know the endogenous level of that cytokine in the wound. Although various methods of extracting cytokines from acute wounds have been reported, no techniques have existed to reliably measure endogenous levels of cytokines in chronic wounds. METHODS: Porous, inert hydrophilic dextranomer beads were tested for their ability to absorb or adsorb protein and cytokines in vitro with either albumin or albumin laced with various known amounts of cytokines, and then from chronic human pressure ulcers. The Bradford protein assay was used to determine protein levels. Enzyme-linked immunosorbent assay (ELISA) techniques were used to determine levels of platelet-derived growth factor (PDGF)-AB, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and transforming growth factor-Beta (TGF-beta) extracted by the beads. RESULTS: Between 88% and 98% of known amounts of albumin could be recovered. Similarly, more than 90% of the laced cytokines could be recovered. In 20 grade III/IV pressure ulcers, although protein concentrations were remarkably similar, endogenous levels of cytokine growth factors varied tremendously. Platelet-derived growth factor-AB ranged from 49 to 867 pg/mL; bFGF from 47 to 697 pg/mL; and EGF from nondetectable to 247.5 pg/mL. TGF-B was not detected in 17 of the 20 pressure ulcers. CONCLUSIONS: This new technique appears useful for measuring endogenous levels of cytokines. Levels of cytokines found in these chronic wounds are much lower than those reported from acute wounds. The marked variation found among the 20 wounds may help to explain the differences reported in recent wound healing trials with exogenous cytokines.

Chronic Disease↗

PubMed1994

Definitions and guidelines for assessment of wounds and evaluation of healing.

BACKGROUND: Chronic wounds represent a worldwide problem. For laboratory and clinical research to adequately address this problem, a common language needs to exist. OBSERVATION: This language should include a system of wound classification, a lexicon of wound descriptors, and a description of the processes that are likely to affect wound healing and wound healing end points. CONCLUSIONS: The report that follows defines wound, acute wound, chronic wound, healing and forms of healing, wound assessment, wound extent, wound burden, and wound severity. The utility of these definitions is demonstrated as they relate to the healing of a skin wound, but these definitions are broadly applicable to all wounds.

Acute Disease↗

PubMed1993

Reconstructive management of patients with greater than 80 per cent TBSA burns.

With improving acute burn care, greater numbers of patients are surviving large burns. Meshed skin grafts or cultured epithelial autografts are often required to achieve rapid wound closure, even in areas such as the hands or face. This, plus the lack of suitable donor tissue for reconstruction, is mandating a change in reconstructive principles. Twenty-eight patients surviving > or = 80 per cent TBSA full skin thickness burns were evaluated using two specially devised instruments (Inventory of Potential Reconstructive Needs; Donor Tissue Surveillance). A total of 564 reconstructive needs were identified in the 28 patients, an average of 20.1 per patient. There were 265 defects in the head and neck, 143 in the upper extremities, and 156 in the torso/lower extremities. The injured anatomical units most frequently identified were the hand (74), trunk (60), nose/nasolabial fold (48), mouth (46), ankle/foot (42), neck (31) and check (28). The Donor Tissue Surveillance form revealed that the necessary donor tissue was frequently not available, and when available, was often of poor quality. These facts require a different set of priorities for reconstruction of the massively burned patient. No longer can a simple stepwise plan of active function, passive function, and aesthetic needs be followed. The patient and family desires must be combined with a realistic outlook by the entire burn team to determine the most judicious and efficient use of available donor tissue to meet the reconstructive needs.

Burns↗

PubMed1993

Application of basic fibroblast growth factor may reverse diabetic wound healing impairment.

This study examines the effect of application of basic fibroblast growth factor (bFGF) on the wound healing impairment seen in streptozotocin-induced diabetic (SD) rats compared with control nondiabetic (NL) animals. Under general anesthesia, a 6-cm dorsal incision was made through the skin and panniculus carnosus. Both the NL and SD wounds were injected with 0.1 ml of one of the following three solutions: saline, vehicle, and 10 micrograms of bFGF. The wounds were closed with interrupted sutures of 4-0 nylon. The animals were returned to their cages and sacrificed at 7, 10, 14, or 21 days later. Breaking strength of the wound was analyzed by using an Instron Tensiometer 4201 to assay for relative collagen maturation. Data among groups were compared using an analysis of variance. At 7 and 10 days, all NL wounds were stronger than all SD wounds. By 14 days there was no statistically significant difference in breaking strength between the bFGF-SD wounds and all subgroups of NL wounds. The bFGF-SD subgroup was statistically significantly stronger than the saline-SD (p < 0.02) and vehicle-SD (p < 0.01) wounds. At 21 days the bFGF-SD wounds were statistically significantly stronger than the vehicle-SD wounds to a confidence level of p < 0.001. These findings indicate that application of bFGF may reverse the impairment seen in diabetic wound healing.

Animals↗

PubMed1993

Inhibition of wound contraction by topical antimicrobials.

Spontaneous wound healing occurs partly by wound contraction, a process that requires intact functioning fibroblasts, and collagen production. Disruption of fibroblasts by the topical antimicrobials, silver sulfadiazine and mafenide acetate has been demonstrated in vitro. An acute rat wound model was used to show that wound contraction in vivo is significantly impeded by silver sulfadiazine and mafenide acetate.

Administration, Topical↗

PubMed1993

Surface area measurement of pressure sores using wound molds and computerized imaging.

OBJECTIVE: To develop a method to measure wound surface area. DESIGN: Validity study. SETTING: Inpatient service. PARTICIPANTS: Four patients with decubitus ulcers. MEASUREMENTS: A new imaging process estimating wound surface area and volume by NMR spectroscopy of a mold of the pressure ulcer and a comparison measurement of volume of the mold by water displacement. Measurements made serially totalled 17. RESULTS: Measurement of the volume of the mold by the computer system correlated strongly with measurement of the volume by water displacement. Surface area of the pressure sore mold correlated strongly with volume of the mold raised to the two-thirds power. CONCLUSIONS: It is possible for the first time to measure surface area of decubitus ulcers. This may provide a way of determining accurately the dose of newly proposed topical treatments.

Colloids↗

PubMed1992

Platelet-derived growth factor BB for the treatment of chronic pressure ulcers.

A randomised, phase I/II, double-blind, placebo-controlled study was designed to assess the effect of topically applied recombinant human BB homodimeric platelet-derived growth factor (rPDGF-BB) on healing of chronic pressure ulcers. Twenty patients were randomly allocated daily treatment for 28 days with 1, 10, or 100 micrograms/ml rPDGF-BB (0.01, 0.1, or 1.0 micrograms per cm2 ulcer area) or placebo. Patients treated with 100 micrograms/ml rPDGF-BB showed a greater healing response than the placebo group, but the lower doses had little effect. After 28 days, ulcers treated with 100 micrograms/ml rPDGF-BB were smaller than those treated with placebo (mean [SE] volume 6.4 [4.0] vs 21.8 [5.6]% of day 0 volume). There were no toxic effects. These preliminary findings suggest that rPDGF-BB is a potent wound-healing agent in soft tissue.

Administration, Topical↗

PubMed1992

Altered cytokine production in black patients with keloids.

The treatment of keloids in black patients remains a medical dilemma. Previous studies have focused on primary alterations in the metabolism of fibroblasts as the key in the etiology of this condition. Yet alterations in the production of various cytokines which may alter fibroblast responses secondarily have received little attention. Twelve black patients with clinical and histological diagnosis of keloids and eight black control volunteers were studied. Peripheral blood mononuclear-cell (PBMC) fractions from both groups were assayed for production of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), alpha-interferon (IFN-alpha), beta-interferon (IFN-beta), gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and tumor necrosis factor-beta (TNF-beta). The production of IFN-alpha, IFN-gamma, and TNF-beta were markedly depressed in keloid patients compared to normal controls. However, IL-1 and IL-2 production was not significantly different between the two groups. In contradistinction, keloid patients produce greater amounts of IL-6, TNF-alpha, and IFN-beta. Altered levels of immunoregulatory cytokines may play a significant role in the net increase in collagen which characterizes keloid formation.

Black People↗

PubMed1992

Differential inhibition of human basal keratinocyte growth to silver sulfadiazine and mafenide acetate.

The impact of topical antimicrobial agents on improving the survival of patients with major thermal injuries is significant. However, the effects of these agents on cells responsible for wound healing has only recently received attention. Fresh human basal keratinocytes were grown in serum-free modified MCDB 153 medium under standard tissue culture conditions. Cells were subsequently exposed to concentrations of silver sulfadiazine and mafenide acetate as low as 1/100 of that used clinically over a period of 5-7 days. Cellular responses documented with hemocytometer cells counts, cellular protein assays, phase-contrast microscopy, and transmission electron microscopy show only severe toxicity to mafenide acetate. Such data imply that inhibition of wound epithelialization is greater with the use of mafenide acetate than with the use of silver sulfadiazine.

Cell Count↗

PubMed1992

A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers.

Chronic wounds such as venous stasis ulcers have become a socioeconomic problem. Even with successful initial management, the recurrence rate approaches 70%. With the advent of new wound healing agents, nonoperative attempts to heal these wounds appear indicated. This study reports a prospective randomized evaluator-blinded trial comparing two potential wound healing agents to an inert vehicle placebo. Eighty-six evaluable patients completed the trial. Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo. There was no difference between the latter two treatments. Silver sulfadiazine has been shown to allow keratinocyte replication and to have antiinflammatory properties. In this trial its antibacterial action was not used since all ulcers had comparable bacterial levels (less than or equal to 10(5)/gm of tissue) before treatment. These results suggest that the silver sulfadiazine cream used in this study may facilitate healing in wounds healing largely by the process of epithelialization.

Adult↗

PubMed1992

Recombinant human platelet-derived growth factor-BB for the treatment of chronic pressure ulcers.

A randomized phase I/II double-blind, placebo-controlled study was designed to evaluate 1, 10, and 100 micrograms/ml (0.01, 0.1, and 1.0 micrograms/cm2) recombinant human BB homodimeric platelet-derived growth factor (rPDGF-BB) applied topically to chronic pressure ulcers for 28 days. Twenty patients were enrolled and completed the trial. No toxicities were associated with rPDGF-BB treatment. Patients treated with 100 micrograms/ml of rPDGF-BB had a pronounced healing response compared with placebo-treated patients. By day 29, ulcers treated with 100 micrograms/ml of rPDGF-BB were smaller in remaining size compared with those of placebo-treated patients when the following specific parameters were measured: percentage of initial depth (14.1 +/- 7.4 vs. 34.9 +/- 6.7) and percentage of initial volume (6.4 +/- 4.0 vs. 21.8 +/- 5.6). Histological analyses of biopsies revealed active wound healing processes in all groups with no disruption in the normal healing sequence in rPDGF-BB-treated wounds. The results of this small, descriptive study suggest rPDGF-BB is a potent vulnerary agent for accelerating soft-tissue repair, warranting further study.

Administration, Topical↗

PubMed1992

The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores.

The first randomized, blinded, placebo-controlled human trials of recombinant basic fibroblast growth factor (bFGF) for pressure sore treatment were performed. Three different concentrations of bFGF in five dosing schedules were tested for safety using hematology, serum chemistries, urinalysis, absorption, antibody formation, and signs of toxicity. Efficacy was evaluated by wound volumes, histology, and photography. No toxicity, significant serum absorption, or antibody formation occurred. In six of eight subgroups, there was a trend toward efficacy with bFGF treatment. When all subgroups were combined, comparison of the slopes of the regression curves of volume decrease over initial pressure sore volume demonstrated a greater healing effect for the bFGF-treated patients (p < 0.05). Histologically, bFGF-treated wound sections demonstrated increased fibroblasts and capillaries. More patients treated with bFGF achieved > 70% wound closure (p < 0.05). Blinded observers were able to distinguish differences in visual wound improvement between bFGF and placebo groups. These data suggest that bFGF may be effective in the treatment of chronic wounds.

Administration, Topical↗

PubMed1992

The effect of denervation on soft-tissue infection pathophysiology.

Pressure is the sine qua non in the etiology of pressure sores; however, ischemia, denervation, edema, and infection also have been implicated. The role of denervation in tissue infection was studied in an isolated in vivo ovine flap model. Twenty-six adult ewes, divided into three groups, had 29 island pedicle flaps raised on their buttocks. In group I, the cutaneous nerve remained intact, while group II had its nerve divided acutely. Group III had prolonged denervation, where the nerve was divided 7 days before flap elevation. All flaps received intradermal inoculations of 10(7) Staphylococcus aureus. Ninety-six hours later, quantitative bacteriology showed counts of 10(7), 10(7), and 10(9) colony-forming units (CFU) per gram of tissue in groups I, II, and III, respectively. Septic foci were larger in group III, and there was a significant increase in tissue edema between groups I and III. A 25-fold increase in bacterial counts seen in the prolonged denervation group may help explain why neurologically injured patients are more susceptible to infection and pressure ulcerations.

Abscess↗