Skin & Aging’s sister journal Wounds is the nation’s leading wound care research journal, and it’s the major source of current research, treatment methodology, and current protocol in the field of wound care. In addition, this journal is the standard reference tool of those healthcare professionals who are leaders in establishing wound care programs and treatment centers both nationally and internationally.
This month, we bring you the top 10 selections from the whole body of research published in Wounds in 2006.
Dermatologist and wound care expert, Dr. Robert Kirsner, who is a Section Editor for Wounds and an Editorial Advisory Board member for Skin & Aging, selected the following research findings as the most relevant to dermatology. Read on for synopses of these wound care findings and for Dr. Kirsner’s commentary regarding the relevance of each selection.
1. Sexual Healing
Wounds in the elderly tend to heal more slowly than those in younger people. It’s not entirely clear why, but researchers have been exploring a possible explanation: the effects of sex hormones on tissue repair.
A review of the animal and human data by Boston University investigators suggests that while estrogen and testosterone do play important roles in wound healing, they work at cross-purposes.
Estrogen, especially topically, seems to be generally beneficial for wound healing in both women and men, according to the report, by Desiree May Oh, M.D., and Tania J. Phillips, M.D. Studies in animals and humans suggest that the hormone can reduce collagen loss, promote skin elasticity, mollify inflammation and stimulate other physiologic changes valuable for healing.
Systemic estrogen may also help. A U.K. study found that post-menopausal women who underwent estrogen replacement therapy developed fewer pressure and venous ulcers than their peers who did not use the drugs.
Testosterone, on the other hand, may be less salubrious for wounds. One study found that the wounds of men with higher testosterone levels healed more slowly than those of men with lower concentrations of the hormone. Like other androgens, testosterone is known to enhance inflammation. These substances may interact adversely with Smad3, which mediates TGF-ß function and has been shown to slow healing.
“Since most of the data has been gathered from animal studies,” the authors write, “it will be of great importance to conduct more studies on human subjects.” Ultimately, they add, the research could have “special utility for the geriatric population and post-menopausal women, a high percentage of whom are at risk for chronic wounds.”
The study appeared in the January 2006 issue of Wounds and was funded by ConvaTec Wound Therapies.
2. Gold Standard for Silver Dressings?
The various brands of silver dressings appear to affect fibroblast function differently, producing changes in cell viability that may have clinically significant implications for wound healing, U.K. researchers have found.
Christine A. Cochrane, Ph.D., of the University of Liverpool, and her colleagues analyzed the in vitro effects of seven silver dressings — Aquacel Ag, Acticoat Absorbent, Silvercel, Contreet Foam, PolyMem Silver, SilvaSorb and Urgotul S.Ag — on fibroblast behavior. They exposed cells in a dish to the dressings for four days, measuring fibroblast contraction every 24 hours and performing trypan blue exclusion assays to determine cell viability.
The dressings produced minimal changes on collagen cell contraction. However, three — Acticoat, Contreet and SilvaSorb — led to sharp drops in cell viability, with a death rate greater than 80%, according to the investigators. Aquacel, Silvercel, PolyMem and Urgotul S.Ag were “least detrimental to cells” in the study, they write.
The researchers suggest that the variability observed with different silver dressings reflects both the active ingredient and the “physiochemical properties of the different dressings.” The results, they add, “have provided further evidence that dressing selection should not be based on one particular attribute but … on the overall characteristics of a dressing, such as its antimicrobial, fluid handling, physical, and chemical properties.”
A report on the findings appeared in the February 2006 issue of Wounds.
3. Scar Tissue Model May Aid Keloid Studies
Treatment of excessive scarring such as keloids and hypertrophic lesions is a significant problem for clinicians. But lack of a solid understanding of how heavy scars form has effectively relegated therapy to the realm of the empirical. Now, California researchers have developed a rabbit model of elevated scarring that could improve the prospects for better treatments for the condition.
The model relies on three proteins: platelet-derived growth factor-BB (PDGF-BB), transforming growth factor-b1 (TFG-b1), and basic fibroblast growth factor (FGF-2). Dan-Ling Gu, M.D., and colleagues at Canji Inc. in San Diego, injected the growth factors into the margins of ear lesions they’d made in New Zealand white rabbits.
Compared to control wounds injected with saline, bovine serum albumin or nothing at all, scars on the animals that received growth factors grew significantly larger and did so in a dose-dependent manner, according to the researchers. “Wounds treated with the highest dose of PDGF-BB displayed the thickest elevated scar formation,” they write. (See Figure 1 below.) (Interestingly, they add, wounds treated with albumin also produced elevated scars at day 14 compared to saline-treated wounds.)
“The mechanism of actions of these growth factors in the rabbit ear excessive scar model is unknown, and additional factors may also contribute to human excessive scar formation,” the researchers continue. “This improved model might still provide a useful tool for evaluation of newly produced anti-scarring agents.”
The findings appeared in the March 2006 issue of Wounds.
4. Does Homocysteine Hinder Wound Healing?
Homocysteine gets the most attention for its role in cardiovascular disease, but a new study suggests that the substance may be a “stealth” agent in suppressing wound repair.
The study, by Joseph V. Boykin Jr., M.D., Ph.D., of HCA Retreat Hospital Wound Healing Center in Richmond, VA, and Chris Baylis, Ph.D., of the University of Florida in Gainesville, included 12 patients with non-healing lower-extremity wounds. The researchers found a statistically significant correlation (P<0.05) between higher blood levels of homocysteine and delayed wound healing. Elevated homocysteine was also linked to lower nitric oxide bioactivity.
Tests of other patients found elevated homocysteine levels in half of those with chronic non-healing wounds, 63% of those with diabetic, neuropathic ulcers and nearly 47% of non-diabetics with chronic venous stasis ulcers.
Furthermore, researchers showed in one patient that lowering homocysteine levels — with a regimen of L-methylfolate, pyridoxal 5’-phosphate, and methylcobalamin — restored healthy wound repair. (See Figures 2 & 3)
“The findings of this preliminary clinical study suggest that untreated, elevated [homocysteine] should be considered an important risk factor for impaired wound healing with dermal substitute therapy and may be a common finding among chronic wound patients,” the authors write.
Key to the connection between homocysteine and wound repair may be the suppression of nitric oxide, the researchers suggest. Homocysteine may also disrupt provisional wound matrix formation, they add. The findings appear in the April 2006 issue of Wounds.
5. New Antimicrobials Rising to Challenge Resistant Staphylococcus
The Golden Age of Antibiotics seems long past. Staphylococcus aureus in particular has proven to be a stubborn and creative enemy of human health. Given time, the microbe has managed to acquire resistance to the most potent antibiotics, from penicillin to methicillin to, most recently, vancomycin.
Pharmaceutical companies have tried to keep pace with S. aureus, and with some success. Several recent additions to the antibiotic armamentarium show strong activity against even the most virulent forms of the microbe, according to a review by South African researchers reported in the May 2006 issue of Wounds.
Quinupristin-dalfopristin (Synercid), linezolid (Zyvox) and daptomycin (Cubicin) are three relatively new agents that have proved useful against serious infections of the skin and other organs caused by MRSA.
Tigecycline (Tygacil), the first tetracycline analogue to be approved in more than three decades, is another newer antimicrobial for treating infections from MRSA and several other organisms.
In addition to these drugs, the antibiotic pipeline has several promising candidates for treating MRSA. These include novel b-lactamase-stable cephalosporins, the antibiotics nisin and gallidermin and a variety of other experimental agents.
“It is evident that the emergency of resistant forms of S. aureus seems to coincide with the introduction of new classes of antibiotics,” the researchers write.
“Therefore, the importance of the search for and development of new antimicrobials cannot be overemphasized.”
However, the researchers caution, “rational antimicrobial usage along with effective infection control measures is required to avert the rapid emergence of resistant strains of S. aureus to these new agents.”
6. Gel Speeds Ulcer Repair
A gel containing human epidermal growth factor can significantly hasten healing of diabetic foot ulcers, according to a Phase III study.
Regen-D 150 (Bharat Biotech International Ltd.), which contains 150 µg/gram of recombinant human growth factor, has been tested in animals for safety, although those data remain unpublished, according to the researchers.
Led by Vijay Viswanathan, M.D., Ph.D., of M.V. Hospital for Diabetes & Diabetes Research Centre in Chennai, the study compared twice-daily application of Regen-D 150 to placebo in 60 men and women between ages 18 and 65. The double-blind trial was completed by 57 people.
Dr. Viswanathan’s group found that after 15 weeks, the ulcers of 25 of 29 patients who received the gel, and 14 of 28 who received sham therapy, had healed, as defined by ruler-based assessments, transparency tracings, and optical evaluation. “Healing occurred in about 13 weeks for placebo-treated ulcers and 9 weeks for the [Regen-D 150]-treated ulcers,” the researchers write.
Data from a post-marketing surveillance study further support efficacy of the gel in diabetic ulcers, with an average healing time of 5.5 weeks and average wound closure of 83%. (See Figure 4.) “Growth factor therapy would lead to prevention of leg amputations and would serve as a major treatment therapy to facilitate faster healing of chronic wounds and, thereby, wound closure.”
A report on the findings appeared in the July 2006 issue of Wounds.
7. Leg Ulcer Infections Often Missed
Infected leg ulcers are widely underdiagnosed, according to a group of wound researchers that found that more than one-quarter of patients who underwent screening biopsies had infected lesions unannounced by clinical evidence.
Led by Thomas Serena, M.D., of Penn North Centers for Advanced Wound Care in Warren, PA, the study looked at 352 of 614 patients who had screening biopsies as part of a trial comparing two doses of the growth factor repifermin (KGF-2). Of the larger group, 122 (20%) had colony counts of at least 1 million bacteria, suggesting infection. In the subset, 92 (26%) were positive for infection.
“This may have been a more accurate reflection of the rate of infection given that at least 10% of the screen failures may not have had ulcers of venous origin as evidenced by a lack of ultrasonic evidence of venous insufficiency,” the researchers write.
The predominate germs in the study were strains of Staphylococcus aureus, followed by Pseudomonas aeruginosa and other enterobacteriaceae, in particular, according to the investigators. (See Figure 5 below.) “The presence of wound infection prior to enrollment in the trial resulted in a trend toward poorer healing even after the wound bed infection had been treated,” the researchers write.
Patients who had three biopsies fared worse than those who had two or one. “The best explanation for this finding,” the researchers explain, “may be that active infection led to changes in the wound microenvironment that persisted after antimicrobial treatment or infection that had to be overcome before the salubrious effect(s) of any treatment occurred.”
A report on the study appeared in the July 2006 issue of Wounds.
8. Progress in Keloid Care?
Keloids are a problem for patients and clinicians alike. They represent scarring gone wild, unsightly at the least and, if in the wrong spot — joints or orifices — they can significantly impair quality of life.
Little is known about why keloids develop after some wounds, but Chinese researchers have found early evidence of a potential way to treat the condition. The study found that recombinant human decorin causes dose-dependent cellular and molecular changes in fibroblasts and collagen with implications for keloid formation. These include cell cycle arrest — although not apoptosis — of fibroblasts, preventing them from proliferation. Cells treated with decorin also secreted less type I (but not type III) collagen.
The researchers, led by Zhi Zhang, M.D., of Guangzhou Red Cross Hospital, note that decorin inactivates transforming growth factor beta 1 (TGF-b1). “Alteration of the concentrations of TGF-b1 in keloid, by the addition of decorin, could possibly modify the wound environment and convert it from one of excessive scarring to one in which the normal processes of extracellular matrix accumulation during repair terminate appropriately.”
A report on the study appeared in the August 2006 issue of Wounds.
9. Vasodilator Offers Relief for Most Intractable Wounds
Intensive treatment with L-arginine can safely restore blood flow to venous ulcers in patients with vascular disease, reducing or even healing wounds and relieving pain, a recent study suggests.
The study, by Dennis Weiland, M.D., of Scottsdale Health Care in Arizona, included six elderly men and women with ulcers of their lower extremities whose occlusions were refractory to vascular therapies such as angioplasty, stenting, and bypass. Patients received 2-week courses of twice-daily L-arginine, a potent vasodilator that is a precursor to nitric oxide. By the end of treatment, every patient showed at least some improvement in wound size, Dr. Weiland reports, and four had full healing. Patients also reported less pain. (See Figure 6 below.)
“The early and prolonged response to the short-term administration of L-arginine was surprising and gratifying,” the author writes. “These patients had little hope of achieving relief from conventional therapy yet received comfort from a product that is natural and relatively inexpensive.”
The author notes that L-arginine has a “dark side” in treating vascular disease. One study of it in people who had suffered myocardial infarctions was halted after six (nearly 9%) died. “The use of L-arginine in this acute care setting is not advised,” Dr. Weiland writes. “However, in other clinical settings, it appears to be beneficial and has minimal or no adverse effects.”
The findings appeared in the August 2006 issue of Wounds.
10. Laser Study Highlights Harm
Wounds irradiated with a low-level gallium arsenide laser heal more slowly and show more signs of skin damage than unirradiated lesions, according to a recent study that adds fodder to the ongoing controversy surrounding this therapy.
The study involved a small number of rats with experimental wounds, so it is unlikely to convince everyone. However, the findings suggest that laser therapy promotes undesirable changes in skin cells while retarding wound healing.
Led by Necat Yilmaz, Ph.D., M.D., of Mersin University in Turkey, the investigators studied 24 Wistar rats with bilateral wounds. Half of the lesions were treated for a week with daily doses of irradiation from a gallium arsenide laser (GaAs laser, 904 nm) — at 0.31, 2.48, and 19 J/cm2 — and the rest were left alone. After 21 days, wound tissue was examined using light microscopy.
Tissue from the untreated animals healed appropriately, the researchers found. But that from rats exposed to the laser was abnormal. Collagen bundle formation appeared to be slow; skin appendages, particularly hair follicles, were degenerated; and, in rodents exposed to the dose of 19 J/cm2, new epidermis formation did not occur and fibroblast count was significantly reduced.
“The current study findings suggest that high-dose GaAs laser irradiation negatively affects the normal wound healing process,” the authors conclude. A report on the findings appears in the November 2006 issue of Wounds.
Skin & Aging’s sister journal Wounds is the nation’s leading wound care research journal, and it’s the major source of current research, treatment methodology, and current protocol in the field of wound care. In addition, this journal is the standard reference tool of those healthcare professionals who are leaders in establishing wound care programs and treatment centers both nationally and internationally.
This month, we bring you the top 10 selections from the whole body of research published in Wounds in 2006.
Dermatologist and wound care expert, Dr. Robert Kirsner, who is a Section Editor for Wounds and an Editorial Advisory Board member for Skin & Aging, selected the following research findings as the most relevant to dermatology. Read on for synopses of these wound care findings and for Dr. Kirsner’s commentary regarding the relevance of each selection.
1. Sexual Healing
Wounds in the elderly tend to heal more slowly than those in younger people. It’s not entirely clear why, but researchers have been exploring a possible explanation: the effects of sex hormones on tissue repair.
A review of the animal and human data by Boston University investigators suggests that while estrogen and testosterone do play important roles in wound healing, they work at cross-purposes.
Estrogen, especially topically, seems to be generally beneficial for wound healing in both women and men, according to the report, by Desiree May Oh, M.D., and Tania J. Phillips, M.D. Studies in animals and humans suggest that the hormone can reduce collagen loss, promote skin elasticity, mollify inflammation and stimulate other physiologic changes valuable for healing.
Systemic estrogen may also help. A U.K. study found that post-menopausal women who underwent estrogen replacement therapy developed fewer pressure and venous ulcers than their peers who did not use the drugs.
Testosterone, on the other hand, may be less salubrious for wounds. One study found that the wounds of men with higher testosterone levels healed more slowly than those of men with lower concentrations of the hormone. Like other androgens, testosterone is known to enhance inflammation. These substances may interact adversely with Smad3, which mediates TGF-ß function and has been shown to slow healing.
“Since most of the data has been gathered from animal studies,” the authors write, “it will be of great importance to conduct more studies on human subjects.” Ultimately, they add, the research could have “special utility for the geriatric population and post-menopausal women, a high percentage of whom are at risk for chronic wounds.”
The study appeared in the January 2006 issue of Wounds and was funded by ConvaTec Wound Therapies.
2. Gold Standard for Silver Dressings?
The various brands of silver dressings appear to affect fibroblast function differently, producing changes in cell viability that may have clinically significant implications for wound healing, U.K. researchers have found.
Christine A. Cochrane, Ph.D., of the University of Liverpool, and her colleagues analyzed the in vitro effects of seven silver dressings — Aquacel Ag, Acticoat Absorbent, Silvercel, Contreet Foam, PolyMem Silver, SilvaSorb and Urgotul S.Ag — on fibroblast behavior. They exposed cells in a dish to the dressings for four days, measuring fibroblast contraction every 24 hours and performing trypan blue exclusion assays to determine cell viability.
The dressings produced minimal changes on collagen cell contraction. However, three — Acticoat, Contreet and SilvaSorb — led to sharp drops in cell viability, with a death rate greater than 80%, according to the investigators. Aquacel, Silvercel, PolyMem and Urgotul S.Ag were “least detrimental to cells” in the study, they write.
The researchers suggest that the variability observed with different silver dressings reflects both the active ingredient and the “physiochemical properties of the different dressings.” The results, they add, “have provided further evidence that dressing selection should not be based on one particular attribute but … on the overall characteristics of a dressing, such as its antimicrobial, fluid handling, physical, and chemical properties.”
A report on the findings appeared in the February 2006 issue of Wounds.
3. Scar Tissue Model May Aid Keloid Studies
Treatment of excessive scarring such as keloids and hypertrophic lesions is a significant problem for clinicians. But lack of a solid understanding of how heavy scars form has effectively relegated therapy to the realm of the empirical. Now, California researchers have developed a rabbit model of elevated scarring that could improve the prospects for better treatments for the condition.
The model relies on three proteins: platelet-derived growth factor-BB (PDGF-BB), transforming growth factor-b1 (TFG-b1), and basic fibroblast growth factor (FGF-2). Dan-Ling Gu, M.D., and colleagues at Canji Inc. in San Diego, injected the growth factors into the margins of ear lesions they’d made in New Zealand white rabbits.
Compared to control wounds injected with saline, bovine serum albumin or nothing at all, scars on the animals that received growth factors grew significantly larger and did so in a dose-dependent manner, according to the researchers. “Wounds treated with the highest dose of PDGF-BB displayed the thickest elevated scar formation,” they write. (See Figure 1 below.) (Interestingly, they add, wounds treated with albumin also produced elevated scars at day 14 compared to saline-treated wounds.)
“The mechanism of actions of these growth factors in the rabbit ear excessive scar model is unknown, and additional factors may also contribute to human excessive scar formation,” the researchers continue. “This improved model might still provide a useful tool for evaluation of newly produced anti-scarring agents.”
The findings appeared in the March 2006 issue of Wounds.
4. Does Homocysteine Hinder Wound Healing?
Homocysteine gets the most attention for its role in cardiovascular disease, but a new study suggests that the substance may be a “stealth” agent in suppressing wound repair.
The study, by Joseph V. Boykin Jr., M.D., Ph.D., of HCA Retreat Hospital Wound Healing Center in Richmond, VA, and Chris Baylis, Ph.D., of the University of Florida in Gainesville, included 12 patients with non-healing lower-extremity wounds. The researchers found a statistically significant correlation (P<0.05) between higher blood levels of homocysteine and delayed wound healing. Elevated homocysteine was also linked to lower nitric oxide bioactivity.
Tests of other patients found elevated homocysteine levels in half of those with chronic non-healing wounds, 63% of those with diabetic, neuropathic ulcers and nearly 47% of non-diabetics with chronic venous stasis ulcers.
Furthermore, researchers showed in one patient that lowering homocysteine levels — with a regimen of L-methylfolate, pyridoxal 5’-phosphate, and methylcobalamin — restored healthy wound repair. (See Figures 2 & 3)
“The findings of this preliminary clinical study suggest that untreated, elevated [homocysteine] should be considered an important risk factor for impaired wound healing with dermal substitute therapy and may be a common finding among chronic wound patients,” the authors write.
Key to the connection between homocysteine and wound repair may be the suppression of nitric oxide, the researchers suggest. Homocysteine may also disrupt provisional wound matrix formation, they add. The findings appear in the April 2006 issue of Wounds.
5. New Antimicrobials Rising to Challenge Resistant Staphylococcus
The Golden Age of Antibiotics seems long past. Staphylococcus aureus in particular has proven to be a stubborn and creative enemy of human health. Given time, the microbe has managed to acquire resistance to the most potent antibiotics, from penicillin to methicillin to, most recently, vancomycin.
Pharmaceutical companies have tried to keep pace with S. aureus, and with some success. Several recent additions to the antibiotic armamentarium show strong activity against even the most virulent forms of the microbe, according to a review by South African researchers reported in the May 2006 issue of Wounds.
Quinupristin-dalfopristin (Synercid), linezolid (Zyvox) and daptomycin (Cubicin) are three relatively new agents that have proved useful against serious infections of the skin and other organs caused by MRSA.
Tigecycline (Tygacil), the first tetracycline analogue to be approved in more than three decades, is another newer antimicrobial for treating infections from MRSA and several other organisms.
In addition to these drugs, the antibiotic pipeline has several promising candidates for treating MRSA. These include novel b-lactamase-stable cephalosporins, the antibiotics nisin and gallidermin and a variety of other experimental agents.
“It is evident that the emergency of resistant forms of S. aureus seems to coincide with the introduction of new classes of antibiotics,” the researchers write.
“Therefore, the importance of the search for and development of new antimicrobials cannot be overemphasized.”
However, the researchers caution, “rational antimicrobial usage along with effective infection control measures is required to avert the rapid emergence of resistant strains of S. aureus to these new agents.”
6. Gel Speeds Ulcer Repair
A gel containing human epidermal growth factor can significantly hasten healing of diabetic foot ulcers, according to a Phase III study.
Regen-D 150 (Bharat Biotech International Ltd.), which contains 150 µg/gram of recombinant human growth factor, has been tested in animals for safety, although those data remain unpublished, according to the researchers.
Led by Vijay Viswanathan, M.D., Ph.D., of M.V. Hospital for Diabetes & Diabetes Research Centre in Chennai, the study compared twice-daily application of Regen-D 150 to placebo in 60 men and women between ages 18 and 65. The double-blind trial was completed by 57 people.
Dr. Viswanathan’s group found that after 15 weeks, the ulcers of 25 of 29 patients who received the gel, and 14 of 28 who received sham therapy, had healed, as defined by ruler-based assessments, transparency tracings, and optical evaluation. “Healing occurred in about 13 weeks for placebo-treated ulcers and 9 weeks for the [Regen-D 150]-treated ulcers,” the researchers write.
Data from a post-marketing surveillance study further support efficacy of the gel in diabetic ulcers, with an average healing time of 5.5 weeks and average wound closure of 83%. (See Figure 4.) “Growth factor therapy would lead to prevention of leg amputations and would serve as a major treatment therapy to facilitate faster healing of chronic wounds and, thereby, wound closure.”
A report on the findings appeared in the July 2006 issue of Wounds.
7. Leg Ulcer Infections Often Missed
Infected leg ulcers are widely underdiagnosed, according to a group of wound researchers that found that more than one-quarter of patients who underwent screening biopsies had infected lesions unannounced by clinical evidence.
Led by Thomas Serena, M.D., of Penn North Centers for Advanced Wound Care in Warren, PA, the study looked at 352 of 614 patients who had screening biopsies as part of a trial comparing two doses of the growth factor repifermin (KGF-2). Of the larger group, 122 (20%) had colony counts of at least 1 million bacteria, suggesting infection. In the subset, 92 (26%) were positive for infection.
“This may have been a more accurate reflection of the rate of infection given that at least 10% of the screen failures may not have had ulcers of venous origin as evidenced by a lack of ultrasonic evidence of venous insufficiency,” the researchers write.
The predominate germs in the study were strains of Staphylococcus aureus, followed by Pseudomonas aeruginosa and other enterobacteriaceae, in particular, according to the investigators. (See Figure 5 below.) “The presence of wound infection prior to enrollment in the trial resulted in a trend toward poorer healing even after the wound bed infection had been treated,” the researchers write.
Patients who had three biopsies fared worse than those who had two or one. “The best explanation for this finding,” the researchers explain, “may be that active infection led to changes in the wound microenvironment that persisted after antimicrobial treatment or infection that had to be overcome before the salubrious effect(s) of any treatment occurred.”
A report on the study appeared in the July 2006 issue of Wounds.
8. Progress in Keloid Care?
Keloids are a problem for patients and clinicians alike. They represent scarring gone wild, unsightly at the least and, if in the wrong spot — joints or orifices — they can significantly impair quality of life.
Little is known about why keloids develop after some wounds, but Chinese researchers have found early evidence of a potential way to treat the condition. The study found that recombinant human decorin causes dose-dependent cellular and molecular changes in fibroblasts and collagen with implications for keloid formation. These include cell cycle arrest — although not apoptosis — of fibroblasts, preventing them from proliferation. Cells treated with decorin also secreted less type I (but not type III) collagen.
The researchers, led by Zhi Zhang, M.D., of Guangzhou Red Cross Hospital, note that decorin inactivates transforming growth factor beta 1 (TGF-b1). “Alteration of the concentrations of TGF-b1 in keloid, by the addition of decorin, could possibly modify the wound environment and convert it from one of excessive scarring to one in which the normal processes of extracellular matrix accumulation during repair terminate appropriately.”
A report on the study appeared in the August 2006 issue of Wounds.
9. Vasodilator Offers Relief for Most Intractable Wounds
Intensive treatment with L-arginine can safely restore blood flow to venous ulcers in patients with vascular disease, reducing or even healing wounds and relieving pain, a recent study suggests.
The study, by Dennis Weiland, M.D., of Scottsdale Health Care in Arizona, included six elderly men and women with ulcers of their lower extremities whose occlusions were refractory to vascular therapies such as angioplasty, stenting, and bypass. Patients received 2-week courses of twice-daily L-arginine, a potent vasodilator that is a precursor to nitric oxide. By the end of treatment, every patient showed at least some improvement in wound size, Dr. Weiland reports, and four had full healing. Patients also reported less pain. (See Figure 6 below.)
“The early and prolonged response to the short-term administration of L-arginine was surprising and gratifying,” the author writes. “These patients had little hope of achieving relief from conventional therapy yet received comfort from a product that is natural and relatively inexpensive.”
The author notes that L-arginine has a “dark side” in treating vascular disease. One study of it in people who had suffered myocardial infarctions was halted after six (nearly 9%) died. “The use of L-arginine in this acute care setting is not advised,” Dr. Weiland writes. “However, in other clinical settings, it appears to be beneficial and has minimal or no adverse effects.”
The findings appeared in the August 2006 issue of Wounds.
10. Laser Study Highlights Harm
Wounds irradiated with a low-level gallium arsenide laser heal more slowly and show more signs of skin damage than unirradiated lesions, according to a recent study that adds fodder to the ongoing controversy surrounding this therapy.
The study involved a small number of rats with experimental wounds, so it is unlikely to convince everyone. However, the findings suggest that laser therapy promotes undesirable changes in skin cells while retarding wound healing.
Led by Necat Yilmaz, Ph.D., M.D., of Mersin University in Turkey, the investigators studied 24 Wistar rats with bilateral wounds. Half of the lesions were treated for a week with daily doses of irradiation from a gallium arsenide laser (GaAs laser, 904 nm) — at 0.31, 2.48, and 19 J/cm2 — and the rest were left alone. After 21 days, wound tissue was examined using light microscopy.
Tissue from the untreated animals healed appropriately, the researchers found. But that from rats exposed to the laser was abnormal. Collagen bundle formation appeared to be slow; skin appendages, particularly hair follicles, were degenerated; and, in rodents exposed to the dose of 19 J/cm2, new epidermis formation did not occur and fibroblast count was significantly reduced.
“The current study findings suggest that high-dose GaAs laser irradiation negatively affects the normal wound healing process,” the authors conclude. A report on the findings appears in the November 2006 issue of Wounds.
Skin & Aging’s sister journal Wounds is the nation’s leading wound care research journal, and it’s the major source of current research, treatment methodology, and current protocol in the field of wound care. In addition, this journal is the standard reference tool of those healthcare professionals who are leaders in establishing wound care programs and treatment centers both nationally and internationally.
This month, we bring you the top 10 selections from the whole body of research published in Wounds in 2006.
Dermatologist and wound care expert, Dr. Robert Kirsner, who is a Section Editor for Wounds and an Editorial Advisory Board member for Skin & Aging, selected the following research findings as the most relevant to dermatology. Read on for synopses of these wound care findings and for Dr. Kirsner’s commentary regarding the relevance of each selection.
1. Sexual Healing
Wounds in the elderly tend to heal more slowly than those in younger people. It’s not entirely clear why, but researchers have been exploring a possible explanation: the effects of sex hormones on tissue repair.
A review of the animal and human data by Boston University investigators suggests that while estrogen and testosterone do play important roles in wound healing, they work at cross-purposes.
Estrogen, especially topically, seems to be generally beneficial for wound healing in both women and men, according to the report, by Desiree May Oh, M.D., and Tania J. Phillips, M.D. Studies in animals and humans suggest that the hormone can reduce collagen loss, promote skin elasticity, mollify inflammation and stimulate other physiologic changes valuable for healing.
Systemic estrogen may also help. A U.K. study found that post-menopausal women who underwent estrogen replacement therapy developed fewer pressure and venous ulcers than their peers who did not use the drugs.
Testosterone, on the other hand, may be less salubrious for wounds. One study found that the wounds of men with higher testosterone levels healed more slowly than those of men with lower concentrations of the hormone. Like other androgens, testosterone is known to enhance inflammation. These substances may interact adversely with Smad3, which mediates TGF-ß function and has been shown to slow healing.
“Since most of the data has been gathered from animal studies,” the authors write, “it will be of great importance to conduct more studies on human subjects.” Ultimately, they add, the research could have “special utility for the geriatric population and post-menopausal women, a high percentage of whom are at risk for chronic wounds.”
The study appeared in the January 2006 issue of Wounds and was funded by ConvaTec Wound Therapies.
2. Gold Standard for Silver Dressings?
The various brands of silver dressings appear to affect fibroblast function differently, producing changes in cell viability that may have clinically significant implications for wound healing, U.K. researchers have found.
Christine A. Cochrane, Ph.D., of the University of Liverpool, and her colleagues analyzed the in vitro effects of seven silver dressings — Aquacel Ag, Acticoat Absorbent, Silvercel, Contreet Foam, PolyMem Silver, SilvaSorb and Urgotul S.Ag — on fibroblast behavior. They exposed cells in a dish to the dressings for four days, measuring fibroblast contraction every 24 hours and performing trypan blue exclusion assays to determine cell viability.
The dressings produced minimal changes on collagen cell contraction. However, three — Acticoat, Contreet and SilvaSorb — led to sharp drops in cell viability, with a death rate greater than 80%, according to the investigators. Aquacel, Silvercel, PolyMem and Urgotul S.Ag were “least detrimental to cells” in the study, they write.
The researchers suggest that the variability observed with different silver dressings reflects both the active ingredient and the “physiochemical properties of the different dressings.” The results, they add, “have provided further evidence that dressing selection should not be based on one particular attribute but … on the overall characteristics of a dressing, such as its antimicrobial, fluid handling, physical, and chemical properties.”
A report on the findings appeared in the February 2006 issue of Wounds.
3. Scar Tissue Model May Aid Keloid Studies
Treatment of excessive scarring such as keloids and hypertrophic lesions is a significant problem for clinicians. But lack of a solid understanding of how heavy scars form has effectively relegated therapy to the realm of the empirical. Now, California researchers have developed a rabbit model of elevated scarring that could improve the prospects for better treatments for the condition.
The model relies on three proteins: platelet-derived growth factor-BB (PDGF-BB), transforming growth factor-b1 (TFG-b1), and basic fibroblast growth factor (FGF-2). Dan-Ling Gu, M.D., and colleagues at Canji Inc. in San Diego, injected the growth factors into the margins of ear lesions they’d made in New Zealand white rabbits.
Compared to control wounds injected with saline, bovine serum albumin or nothing at all, scars on the animals that received growth factors grew significantly larger and did so in a dose-dependent manner, according to the researchers. “Wounds treated with the highest dose of PDGF-BB displayed the thickest elevated scar formation,” they write. (See Figure 1 below.) (Interestingly, they add, wounds treated with albumin also produced elevated scars at day 14 compared to saline-treated wounds.)
“The mechanism of actions of these growth factors in the rabbit ear excessive scar model is unknown, and additional factors may also contribute to human excessive scar formation,” the researchers continue. “This improved model might still provide a useful tool for evaluation of newly produced anti-scarring agents.”
The findings appeared in the March 2006 issue of Wounds.
4. Does Homocysteine Hinder Wound Healing?
Homocysteine gets the most attention for its role in cardiovascular disease, but a new study suggests that the substance may be a “stealth” agent in suppressing wound repair.
The study, by Joseph V. Boykin Jr., M.D., Ph.D., of HCA Retreat Hospital Wound Healing Center in Richmond, VA, and Chris Baylis, Ph.D., of the University of Florida in Gainesville, included 12 patients with non-healing lower-extremity wounds. The researchers found a statistically significant correlation (P<0.05) between higher blood levels of homocysteine and delayed wound healing. Elevated homocysteine was also linked to lower nitric oxide bioactivity.
Tests of other patients found elevated homocysteine levels in half of those with chronic non-healing wounds, 63% of those with diabetic, neuropathic ulcers and nearly 47% of non-diabetics with chronic venous stasis ulcers.
Furthermore, researchers showed in one patient that lowering homocysteine levels — with a regimen of L-methylfolate, pyridoxal 5’-phosphate, and methylcobalamin — restored healthy wound repair. (See Figures 2 & 3)
“The findings of this preliminary clinical study suggest that untreated, elevated [homocysteine] should be considered an important risk factor for impaired wound healing with dermal substitute therapy and may be a common finding among chronic wound patients,” the authors write.
Key to the connection between homocysteine and wound repair may be the suppression of nitric oxide, the researchers suggest. Homocysteine may also disrupt provisional wound matrix formation, they add. The findings appear in the April 2006 issue of Wounds.
5. New Antimicrobials Rising to Challenge Resistant Staphylococcus
The Golden Age of Antibiotics seems long past. Staphylococcus aureus in particular has proven to be a stubborn and creative enemy of human health. Given time, the microbe has managed to acquire resistance to the most potent antibiotics, from penicillin to methicillin to, most recently, vancomycin.
Pharmaceutical companies have tried to keep pace with S. aureus, and with some success. Several recent additions to the antibiotic armamentarium show strong activity against even the most virulent forms of the microbe, according to a review by South African researchers reported in the May 2006 issue of Wounds.
Quinupristin-dalfopristin (Synercid), linezolid (Zyvox) and daptomycin (Cubicin) are three relatively new agents that have proved useful against serious infections of the skin and other organs caused by MRSA.
Tigecycline (Tygacil), the first tetracycline analogue to be approved in more than three decades, is another newer antimicrobial for treating infections from MRSA and several other organisms.
In addition to these drugs, the antibiotic pipeline has several promising candidates for treating MRSA. These include novel b-lactamase-stable cephalosporins, the antibiotics nisin and gallidermin and a variety of other experimental agents.
“It is evident that the emergency of resistant forms of S. aureus seems to coincide with the introduction of new classes of antibiotics,” the researchers write.
“Therefore, the importance of the search for and development of new antimicrobials cannot be overemphasized.”
However, the researchers caution, “rational antimicrobial usage along with effective infection control measures is required to avert the rapid emergence of resistant strains of S. aureus to these new agents.”
6. Gel Speeds Ulcer Repair
A gel containing human epidermal growth factor can significantly hasten healing of diabetic foot ulcers, according to a Phase III study.
Regen-D 150 (Bharat Biotech International Ltd.), which contains 150 µg/gram of recombinant human growth factor, has been tested in animals for safety, although those data remain unpublished, according to the researchers.
Led by Vijay Viswanathan, M.D., Ph.D., of M.V. Hospital for Diabetes & Diabetes Research Centre in Chennai, the study compared twice-daily application of Regen-D 150 to placebo in 60 men and women between ages 18 and 65. The double-blind trial was completed by 57 people.
Dr. Viswanathan’s group found that after 15 weeks, the ulcers of 25 of 29 patients who received the gel, and 14 of 28 who received sham therapy, had healed, as defined by ruler-based assessments, transparency tracings, and optical evaluation. “Healing occurred in about 13 weeks for placebo-treated ulcers and 9 weeks for the [Regen-D 150]-treated ulcers,” the researchers write.
Data from a post-marketing surveillance study further support efficacy of the gel in diabetic ulcers, with an average healing time of 5.5 weeks and average wound closure of 83%. (See Figure 4.) “Growth factor therapy would lead to prevention of leg amputations and would serve as a major treatment therapy to facilitate faster healing of chronic wounds and, thereby, wound closure.”
A report on the findings appeared in the July 2006 issue of Wounds.
7. Leg Ulcer Infections Often Missed
Infected leg ulcers are widely underdiagnosed, according to a group of wound researchers that found that more than one-quarter of patients who underwent screening biopsies had infected lesions unannounced by clinical evidence.
Led by Thomas Serena, M.D., of Penn North Centers for Advanced Wound Care in Warren, PA, the study looked at 352 of 614 patients who had screening biopsies as part of a trial comparing two doses of the growth factor repifermin (KGF-2). Of the larger group, 122 (20%) had colony counts of at least 1 million bacteria, suggesting infection. In the subset, 92 (26%) were positive for infection.
“This may have been a more accurate reflection of the rate of infection given that at least 10% of the screen failures may not have had ulcers of venous origin as evidenced by a lack of ultrasonic evidence of venous insufficiency,” the researchers write.
The predominate germs in the study were strains of Staphylococcus aureus, followed by Pseudomonas aeruginosa and other enterobacteriaceae, in particular, according to the investigators. (See Figure 5 below.) “The presence of wound infection prior to enrollment in the trial resulted in a trend toward poorer healing even after the wound bed infection had been treated,” the researchers write.
Patients who had three biopsies fared worse than those who had two or one. “The best explanation for this finding,” the researchers explain, “may be that active infection led to changes in the wound microenvironment that persisted after antimicrobial treatment or infection that had to be overcome before the salubrious effect(s) of any treatment occurred.”
A report on the study appeared in the July 2006 issue of Wounds.
8. Progress in Keloid Care?
Keloids are a problem for patients and clinicians alike. They represent scarring gone wild, unsightly at the least and, if in the wrong spot — joints or orifices — they can significantly impair quality of life.
Little is known about why keloids develop after some wounds, but Chinese researchers have found early evidence of a potential way to treat the condition. The study found that recombinant human decorin causes dose-dependent cellular and molecular changes in fibroblasts and collagen with implications for keloid formation. These include cell cycle arrest — although not apoptosis — of fibroblasts, preventing them from proliferation. Cells treated with decorin also secreted less type I (but not type III) collagen.
The researchers, led by Zhi Zhang, M.D., of Guangzhou Red Cross Hospital, note that decorin inactivates transforming growth factor beta 1 (TGF-b1). “Alteration of the concentrations of TGF-b1 in keloid, by the addition of decorin, could possibly modify the wound environment and convert it from one of excessive scarring to one in which the normal processes of extracellular matrix accumulation during repair terminate appropriately.”
A report on the study appeared in the August 2006 issue of Wounds.
9. Vasodilator Offers Relief for Most Intractable Wounds
Intensive treatment with L-arginine can safely restore blood flow to venous ulcers in patients with vascular disease, reducing or even healing wounds and relieving pain, a recent study suggests.
The study, by Dennis Weiland, M.D., of Scottsdale Health Care in Arizona, included six elderly men and women with ulcers of their lower extremities whose occlusions were refractory to vascular therapies such as angioplasty, stenting, and bypass. Patients received 2-week courses of twice-daily L-arginine, a potent vasodilator that is a precursor to nitric oxide. By the end of treatment, every patient showed at least some improvement in wound size, Dr. Weiland reports, and four had full healing. Patients also reported less pain. (See Figure 6 below.)
“The early and prolonged response to the short-term administration of L-arginine was surprising and gratifying,” the author writes. “These patients had little hope of achieving relief from conventional therapy yet received comfort from a product that is natural and relatively inexpensive.”
The author notes that L-arginine has a “dark side” in treating vascular disease. One study of it in people who had suffered myocardial infarctions was halted after six (nearly 9%) died. “The use of L-arginine in this acute care setting is not advised,” Dr. Weiland writes. “However, in other clinical settings, it appears to be beneficial and has minimal or no adverse effects.”
The findings appeared in the August 2006 issue of Wounds.
10. Laser Study Highlights Harm
Wounds irradiated with a low-level gallium arsenide laser heal more slowly and show more signs of skin damage than unirradiated lesions, according to a recent study that adds fodder to the ongoing controversy surrounding this therapy.
The study involved a small number of rats with experimental wounds, so it is unlikely to convince everyone. However, the findings suggest that laser therapy promotes undesirable changes in skin cells while retarding wound healing.
Led by Necat Yilmaz, Ph.D., M.D., of Mersin University in Turkey, the investigators studied 24 Wistar rats with bilateral wounds. Half of the lesions were treated for a week with daily doses of irradiation from a gallium arsenide laser (GaAs laser, 904 nm) — at 0.31, 2.48, and 19 J/cm2 — and the rest were left alone. After 21 days, wound tissue was examined using light microscopy.
Tissue from the untreated animals healed appropriately, the researchers found. But that from rats exposed to the laser was abnormal. Collagen bundle formation appeared to be slow; skin appendages, particularly hair follicles, were degenerated; and, in rodents exposed to the dose of 19 J/cm2, new epidermis formation did not occur and fibroblast count was significantly reduced.
“The current study findings suggest that high-dose GaAs laser irradiation negatively affects the normal wound healing process,” the authors conclude. A report on the findings appears in the November 2006 issue of Wounds.
