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Biomedical subjects

M C Robson

Publications and source records attributed to M C Robson.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides.

To better define thrombin-receptor interactions, we synthesized human thrombin peptides and identified binding-domain peptides that bind thrombin receptors and activate mitogenic signals (Glenn, K.C., G.H. Frost, J.S. Bergmann, and D.H. Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with a single topical application of thrombin receptor-activating peptide (TRAP-508) or human alpha-thrombin in saline enhances 7-d incisional breaking strength in normal rats up to 82% or 55% over saline-treated controls, respectively. Control wounds require approximately 11.5 d to achieve breaking strength equivalent to TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates healing, shifting the time course forward by up to 4.5 d. Histological comparisons at day 7 show more type I collagen, less evidence of prolonged inflammation, and an increase in number and maturity of capillaries in TRAP- and thrombin-treated incisions. Angiograms also show 50-65% more functional vascularization going across thrombin- and TRAP-treated surgical incisions. Thus, alpha-thrombin and thrombin peptides, such as those released following injury, appear to initiate or enhance signals required for neovascularization and wound healing. The ability to accelerate normal wound healing events with synthetic peptides representing receptor binding domains of human thrombin may offer new options for management of wound healing in man.

Amino Acid Sequence↗
PubMed1992

Making the burned hand functional.

The goal of treatment of the burned hand is to make the hand functional at the conclusion of treatment. Function should ideally include both fine pinch and power grip but will ultimately be determined by the individual patient's needs. At no time, however, can the care of the burned hand be performed in a vacuum, losing sight of the patient as a whole. It must also be remembered that the hand functions as part of the upper extremity. Full hand motion is useless if significant contractures of the elbow or axilla prevent the patient from positioning the hand so that this motion can be utilized. Rehabilitation must render the entire extremity functional. Thus, it becomes obvious that a team effort is mandatory. This usually will include the following individuals: physician, nurse, occupational therapist, physical therapist, vocational rehabilitation counselor, and social worker. A functional upper extremity means that the goal must be to return patients to their preburn vocations and avocations. A clear understanding of job requirements and work habits will allow realistic goals to be established. However, when the goal of optimal function cannot be reached, early retraining will help to obtain optimal rehabilitation.

Acute Disease↗
PubMed1991

Local infiltration of an angiogenic growth factor does not stimulate the delay phenomenon.

The role of angiogenesis in the delay phenomenon is unclear. In this study a potent angiogenic growth factor, basic fibroblast growth factor (bFGF) was used to ascertain the importance of angiogenesis in this phenomenon. bFGF (100 micrograms) was infiltrated beneath the panniculus carnosus on the dorsum of 50 rats. Another 50 rats received saline vehicle infiltration only. Ten days later a modified McFarlane flap (10 x 3 cm) was elevated and biopsies collected. Flap blood flow was determined by laser Doppler before and after elevation. The mean surviving length (Group I--71.3 +/- 4.6 mm and Group II--73.4 +/- 5.5 mm) and Doppler flow measurements were comparable between the two groups. Animals treated with bFGF showed marked perivascular changes and proliferation of fibroblasts, but no increase in the number or size of capillaries was seen. This lack of angiogenesis suggests pharmacologically mediated delay may require more than just an angiogenic stimulus.

Animals↗
PubMed1991

Effect of bFGF on the inhibition of contraction caused by bacteria.

Bacterial contamination of open wounds significantly inhibits wound contraction required in the healing process. Basic fibroblast growth factor (bFGF) has been shown to overcome contraction inhibition in wound-healing models impaired by diabetes or steroids. This study was designed to determine the effect of bFGF on wound contraction inhibition in an area contaminated with bacterial overgrowth. The topically applied bFGF reversed inhibition to wound contraction that normally occurs with bacterial contamination. This reversal does not appear to be due to increased collagen synthesis since bFGF has been shown to decrease collagen synthesis and the treated wounds showed no increase in breaking strength. The use of bFGF significantly decreased the number of days required for wound healing (P less than 0.01) despite active bacterial invasion and may be of value in the treatment of human contaminated wounds.

Animals↗
PubMed1991

Growth factors as wound healing agents.

Wound healing can no longer be considered a generic term: it is the summation of a complex series of processes beginning with coagulation and ending in remodelling. This review, therefore, summarizes the past year's advances in growth factor research according to the roles of the individual growth factors in the specific processes of the wound healing scheme.

Animals↗
PubMed1991

The effect of autogenous bone graft application on wound contamination.

A rat model was created in which contaminated wounds were closed in either the presence or absence of autogenous bone graft. The recipients of bone graft were divided into two groups--one receiving autogenous cancellous bone, the other receiving nonviable autogenous autoclaved cortical bone. Quantitative bacterial cultures were collected both at the time of wound closure and 2 weeks after closure. A significantly increased level of soft-tissue contamination was associated with wound closure in the presence of either type of bone graft, indicating an overall adverse effect on soft tissues. A critical level existed such that at initial bacterial contamination levels greater than 10(4) organisms/g tissue, final contamination levels were significantly elevated. With initial contamination levels less than 10(4) organisms/g tissue, however, final bacterial contamination levels were not significantly different. These results may help explain the different rates of infection that have been reported when delayed primary closure of open fractures is done in conjunction with autogenous bone graft.

Animals↗
PubMed1991

Class C firework injuries in a pediatric population.

Class C fireworks are those which can be readily purchased by the public. Between July 1971 and August 1988, 23 patients were admitted to our institution with firework injuries. Fourteen patients (60.9%) sustained injuries related to Class C fireworks. All patients were males with a mean age of 9.0 +/- 3.6 years, with a total body surface area (TBSA) burn of 18 +/- 20% with 10 +/- 15% being full thickness. Thirteen of the 14 patients required hospitalization. Five patients were admitted acutely and eight patients were referred to our institution at least 3 days postinjury. All patients required operative intervention in order to obtain wound closure. Patients admitted acutely showed a decrease in length of hospital stay and patient morbidity when compared to referral patients. Our data suggest that class C firework injuries, although small in terms of TBSA burned, result in full-thickness wounds that warrant aggressive surgical management.

Burns↗