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A Histologic Study of Gold Leaf Treated Experimental Wounds*
Vol. 52, No. 6
THa JOURNAL 00' INVESTIGATIVR Daass.roaooy
Printed in U.S.A.
Copyright 0 1969 by The Williams & Wilkins Co.
A HISTOLOGIC STUDY OF GOLD LEAF TREATED EXPERIMENTAL WOUNDS* DAVID R. HARRIS, M.D. AND RICHARD L. KEEFE, M.D. ABSTRACT
Experimental ulcers were created in domestic pigs and treated with gold leaf and polyethylene occlusion while plain gauze dressings served as controls. Entire wounds were excised at 3, 6, 9, and 12 days and observed histologically. 1. The polyethylene treated wounds reepithelialized completely by 9 days.
2. Both the control and gold leaf treated wounds failed to heal completely at the
twelfth day.
3. Gold leaf fragments were seen embedded within the ulcer cavity, within the granulation tissue at the ulcer base and within the migrating epidermis. These findings suggest that gold leaf provides a significant mechanical barrier to wound repair.
In recent years there has been a revival of pared by shaving the back with an Oster heavy interest in the use of gold leaf for the treatment of cutaneous ulcers. Kanof (1) and Wolf et al. (2) have reported favorable results using commercially available gold leaf on ulcers of diverse etiology. In spite of these and other reports on the efficacy of gold dating from the 16th century (3, 5), there has been a paucity of studies compared to abundant speculation on the mode of action of gold leaf. For instance, Wolf has sug-
duty electric animal clipper. Loose hair was removed with toweling. Pentobarbital was injected intraperitoneally, at doses sufficient to produce
electrochemical influence on reepithelialization (2). Epstein has taken issue with this speculation of a complicated mechanism of action (4). He
scribed by Kanof (1) and Wolf (2). Seventy per cent isopropyl alcohol was swabbed over the base and edges of the ulcers. A single sheet of 23 K
light anesthesia. Twelve ulcers, in rows of four, were created on
the backs of the pigs using a 6 mm cutaneous punch. The ulcers measured 8 mm in depth, the distance from the tip to the hilt of the cutting cylinder. Bleeding was allowed to stop spontaneously.
A row of ulcers to one side of the center row gested that gold may have an electrostatic or was dressed with gold leaf in the manner de-
commercial gold leaf was then folded from corner to corner three times, placed over each ulcer, and with a cotton ball to close adherence with cites the work of unman and Maibach (7) pressed the wound. The gold leaf was then covered with a demonstrating the effectiveness of polyethylene 2 x 2 inch coarse mesh gauze pad and the pad was
occlusion in wound therapy and suggests that sutured at its edges to the skin. The sutured gold leaf is but another form of inert occlusive gauze was necessary to protect the wound site. The
gold leaf was replaced every 48 hours. membrane. The center row of four ulcers served as a control In order to more precisely define tile mode of with each ulcer covered only by a gauze pad as action of gold leaf and to test the efficacy of this described. The remaining row of ulcers was occluded with material compared to polyethylene film, the polyethylene film, using Saran wrap® as the following study was carried out.
dressing. An adherent surface was prepared by applying a thin layer of epoxy glue around each ulcer. Over this a gauze pad was placed with a Five domestic pigs, eight to twelve weeks of 2 square inch sheet of Saran® between the folds age, each weighing ten to thirteen kg, were pre- of the pad. The edges of the pad were then sutured to the skin. This maneuver was necessary This study was supported, in part, by IJSPHS to maintain complete occlusion for the entire exTrainee Grant TI-AM-5318-07. METHODS AND MATEItIALS
periment.
Received February 23, 1968; accepted for pub-
On the third day, the first ulcer in each of the The authors wish to acknowledge the kind as- three rows was excised with an 8 mm cutaneous sistance of Dr. Alvin Cox who offered many in- punch. On the sixth, ninth, and twelfth days the valuable comments and suggestions during the remaining ulcers were removed in sequence. The course of this work. We wish to acknowledge also biopsy specimens were fixed in buffered 10% the technical asisstanee of Mrs. Nancy Sutter who formalin. After paraffin embedding, 8 micron secprepared the specimens for histologic study. * From the Department of Dermatology, Stan- tions perpendicular to the skin surface were ford University School of Medicine and Veterans stained with Heinatoxylin and Eosin and with the Verhoeff Elastic-Van Gieson technique. RepreAdministration Hospital, Palo Alto, Calif. 94304. lication November 18, 1968.
487
a
h
C
Fic. 1. (Day 3) a. Control wound. Arrows indicate original wound edge. X 35. b. Gold leaf treated wound. Arrow indicates original wound edge (estimated by measuring 1 mm inward from edge of biopsy specimen). Note black gold leaf fragments in ulcer (g). X 35. c. Polyethylene treated wound. Arrow indicates original wound edge. >< 35. 488
GOLD LEAF TREATED WOUNDS
489
FIG. 2. (Day 6) a. Control wound filled with dense coagulum. Arrow denotes original wound edge. x 35. b. Polyethylene treated wound showing migrating epidermis parallel to
original surface. Arrow denotes original wound edge. >( 35.
sentative sections from the center to the periphery of the ulcers were studied. RESULTS
Day Three. Representative histologic sections showed early epithelial migration at the wound
Day Nine. Polyethylene occluded wounds all were completely reepithelialized, while the control group continued to show only small amounts of epidermal migration (Fig. 4). There were now greater individual differences in the amount of
epidermal migration in the gold leaf treated edges of all three specimens, but significant wounds, although none showed complete redifferences were not apparent (Fig. 1). Dense, epithelialization. Instead, the epidermis was black laminated fragments of gold were seen again seen to advance up to, and to abut, gold within the gold leaf treated ulcers (Fig. 1-b). fragments. The gold leaf fragments also were Day Six. Differences were now apparent in the character of the healing wounds. In comparison to both the control and gold leaf treated wounds, the polyethylene occluded wounds showed extensive epithelial migration (Figs. 2 and 3). The control wound was seen to contain a dense coagulum adherent to the ulcer base and filling the wound cavity. Densely packed laminated gold
fragments were seen within gold leaf treated ulcers. In some zones, epidermal islands were layered between the laminated fragments (Fig. 3).
deeply embedded in the granulation tissue at the ulcer base (Fig. 5).
Day Twelve. The control wounds were reepitbelializing in a plane parallel to the ulcer base beneath the dense coagulum. In comparison, the epithelialized polyethylene occluded wounds
had healed at a superficial level parallel to the original wound surface (Fig. 6). Gold leaf treated wounds continued to show individual differences
in the rate of reepithelialization but had not yet completely reepithelialized. Varying amounts of embedded gold fragments again were seen at the
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
490
—'—p
-
—-
FIG. 3. (Day 6) a. Gold leaf treated wound with black gold fragments filling wound cavity. Arrow indicates original wound edge. Inset denotes edge of advancing epidermis. >< 35. b. Close-up of inset sbowing islands of epidermal cells between laminated gold leaf fragments. )< 100.
edges of the migrating epidermis, as well ns deep
reepithelialize faster when left intact than when to the epithelium in the granulation tissue (Fig. unroofed. Similarly, Winter (8, 12, 13, 20) has shown in pigs, and unman et a!. (7) in humans, 7). that when deep wounds, corresponding to those DISCUSSION in our study, are occluded with polyethylene, Gimbel et a!. (9) and Forage (10) have dem- they reepithelialize twice as fast as wounds exonstrated that experimentally produced blisters posed to air.
"1
fig4 FIG. 4.
(Day 9) a. Control wound with dark eoagulum in the ulcer. Arrow indicates
original wound edge. X 35. b. Polyethylene treated wonnd reepithelielized. Arrow indicates original wound edge. >< 35. —I
Fcc.
,,
5. (Day 9) a. Gold leaf treated wound. Letter e indicates original wound edge.
Inset denotes advancing edge of the epidermis. X 35. b. Close-up of inset showing black gold fragments between epidermal islands and at edge of advancing cells. X 100. 491
492
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
b
FIG. 6. (Day 12) a. Control wound with dense coagulum in ulcer. Arrow indicates
original wound edge. X 35. b. Polyethylene treated wound reepithelialized. Arrow indicates original wound edge. X 35.
These observations can be explained by com- barrier to the migrating epidermis and impedes
paring the healing process in dry and moist repair. wounds. When denuded surfaces arc left exposed
In contrast, an occlusive membrane, such as or underlie a non-occlusive dressing, the tissue polyethylene, maintains hydration. The wound fluid coagulum within the wound dries and forms exudate thus remains serous. Into this serous a crust. Both Forage (10) and Winter (12, 13) wound, granulation tissue quickly forms a solid showed that the denuded dermis at the edges base across which the epidermis migrates unimand base of the wound subsequently becomes peded (Figs. 1-c, 2 and 4-b). dehydrated and is incorporated in the crust. The It has been proposed (4) that the mechanism regenerating epidermis, in order to support me- of action of gold leaf is that of an inert occlusive tabolism, must follow dermal contours, seeking membrane, such as polyethylene. That gold leaf the scrous exudate beneath the drying crust. is not such a dressing has been demonstrated by Therefore, this crust of dried fibrin, inflamma- our study, supporting earlier findings of Gal-
tory cells, serum and dermal remnants at the lagher (3) and Robinson (16). One sheet of wound edges and base becomes a mechanical commercial gold leaf, 98% gold, 2% copper or
493
GOLD LEAF TREATED WOUNDS
a
I,
L' \
Fm. 7. (Day 12) a. Gold leaf treated wound. Arrow illustrates original wound margin. Inset denotes edge of advancing epidermis. )< 35. b. Close-up of inset showing gold fragments inbetween and abutting advancing epidermal edges. X 100.
silver, one to two microns in thickness, is made up of many fragmented layers, the number of which varies from sheet to sheet. Figures 3, 5 and 7 demonstrate the sequelae when several layers of this material are placed over an ulcer. Fragments of gold are seen embedded within the eoagulum, the granulation tissue and the migrating epidermis. These observations suggest that the embedded gold fragments provide a signifi-
cant mechanical barrier to the migrating epidermis whether or not an obstructive crust is present. What is needed for ideal healing of the human skin is a dressing which provides an unimpeded,
moist surface for epidermal migration, while allowing for sufficient drainage or absorption of tissue fluid to keep bacteria at harmless levels (17). Accordingly, neither polyethylene film,
which allows no drainage, nor gold leaf, the fragments of which mechanically impede epidermal migration, appear to fulfill these basic requirements. Based upon the above principles, however, it should be possible to develop a fully satisfactory dressing for the healing wound.
REFERENCES 1. Kanof, N. M.: Gold leaf in the treatment of cutaneous ulcers. J. Invest. Derm., 43: 441, 1964.
494
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
2. Wolf, M., Wheeler, P. and Walcott, L.: Gold
leaf treatment of ischemic skin ulcers. J.A.M.A., 196: 693, 1966.
3. Gallagher, J. P. and Geschechter, C. P.: The use of charged gold leaf in surgery. J.A.M.A., 189: 928, 1964.
4. Epstein, E.: Communications to the Editor. J.A.M.A., 197: 299, 1966.
5. Hoeger, K.: Preoperative treatment of skin ulcers with silver spray and aluminum foil. Acta Chir. Seand., 125: 32, 1963.
6. Smith, K. W., Oden, P. W. and Blayloek, W. K.: A comparison of gold leaf and other oc-
16. Robinson, F. and Johnson, M.: Histopathological studies of tissue reactions to various
metals implanted in cat brain. U.S.A.F. Aerosyst. Div., 61, 1961.
17. Scales, J. T.: Wound healing and the dressing. Brit. J. Indust. Med., 20: 82, 1963. 18. Winter, G. D.: A note on wound healing under dressings with special reference to perforated
film dressings. J. Invest. Derm., 44: 299. 1965. 19. Cillman, T.: The possible importance of
dermal-epidermal interactions in the pathogenesis of human and experimental wound
healing and skin cancers, Pro gress in the Biologicol Sciences in Relotson to Dermoair exposure and occlusion on experimental tology II. Ed., Rook, A., Cambridge Univ. human skin wounds. Nature, 200: 377, 1963. Press, London, 1964. 8. Winter, G. D.: Formation of the scale and 20. Winter, C. D.: Regeneration of the epidermis. rate of epithelialization of superficial wounds Progress in the Bsologicol Sciences in Relein the skin of young domestic pigs. Nature, tion to Dermotology II. Ed., Rook, A., Cam193: 293, 1962. bridge Univ. Press, London, 1964. 9. Gimbel, N., Kapetansky, D., Weissman, F. and 21. Aberchrombie, M.: The behavior of cells toPinkus, H.: A study of epitheliahzation on ward one another, Advonces in the Biology clusive therapy. Arch. Derm., 96: 703, 1967.
7. unman, C. and Maibach, H.: The effects of
blistered burns. Arch. Surg., 74: 800, 1956.
10. Forage, A. V.: The effects of removing the epidermis from burned skin. Lancet, 2: 690, 1962.
of the Skin, Vol. 5. Ed., Montsgna, W., Pergamon Press, N.Y., 1964. 22. Zahir, M.: Contraction of wounds. Brit. J. Surg., 51: 456, 1964.
11. Zahir, M.: Hydroxyproline in scales. 5. Path. 23. Dunphy, J. E.: An ubiquitous ally for the Bact., 84: 79, 1962. surgeon. New Eng. J. Med., 268: 1367, 12. Winter, G. D.: Communication. Nature, 200: 1963. 378, 1963. N., Stoeckinger, J. and Coldblatt, 13. Winter, G. D.: The movement of epidermal 24. Waterman, D.: The effects of various dressings on the cells over the wound surface, Advonces in skin and subcutaneous temperatures. Arch. the Biology of the Skin, Vol. 5. Ed., MonSurg., 95: 464, 1967. tagna, W., Pergamon Press, N.Y., 1964. 14. Gillman, T. and Penn, J.: Studies on repair of 25. Larsen, W. G.: The direction of epidermal growth. Arch. Derm.. 95: 323, 1965. cut wounds. II: The healing of wounds involving loss of superficial portions of the 26. Klenim, W. R.: Enhanced healing of the skin skin. Med. Proc., 2: 150, 1956.
wounds in dogs with systemically and focally
thehum. Brit. J. Derm., 78: 403, 1966.
tia, 23: 55, 1967.
15. Ryan, T. J.: The direction of growth of epi-
administered drugs. Separatum Experimen-
THa JOURNAL 00' INVESTIGATIVR Daass.roaooy
Printed in U.S.A.
Copyright 0 1969 by The Williams & Wilkins Co.
A HISTOLOGIC STUDY OF GOLD LEAF TREATED EXPERIMENTAL WOUNDS* DAVID R. HARRIS, M.D. AND RICHARD L. KEEFE, M.D. ABSTRACT
Experimental ulcers were created in domestic pigs and treated with gold leaf and polyethylene occlusion while plain gauze dressings served as controls. Entire wounds were excised at 3, 6, 9, and 12 days and observed histologically. 1. The polyethylene treated wounds reepithelialized completely by 9 days.
2. Both the control and gold leaf treated wounds failed to heal completely at the
twelfth day.
3. Gold leaf fragments were seen embedded within the ulcer cavity, within the granulation tissue at the ulcer base and within the migrating epidermis. These findings suggest that gold leaf provides a significant mechanical barrier to wound repair.
In recent years there has been a revival of pared by shaving the back with an Oster heavy interest in the use of gold leaf for the treatment of cutaneous ulcers. Kanof (1) and Wolf et al. (2) have reported favorable results using commercially available gold leaf on ulcers of diverse etiology. In spite of these and other reports on the efficacy of gold dating from the 16th century (3, 5), there has been a paucity of studies compared to abundant speculation on the mode of action of gold leaf. For instance, Wolf has sug-
duty electric animal clipper. Loose hair was removed with toweling. Pentobarbital was injected intraperitoneally, at doses sufficient to produce
electrochemical influence on reepithelialization (2). Epstein has taken issue with this speculation of a complicated mechanism of action (4). He
scribed by Kanof (1) and Wolf (2). Seventy per cent isopropyl alcohol was swabbed over the base and edges of the ulcers. A single sheet of 23 K
light anesthesia. Twelve ulcers, in rows of four, were created on
the backs of the pigs using a 6 mm cutaneous punch. The ulcers measured 8 mm in depth, the distance from the tip to the hilt of the cutting cylinder. Bleeding was allowed to stop spontaneously.
A row of ulcers to one side of the center row gested that gold may have an electrostatic or was dressed with gold leaf in the manner de-
commercial gold leaf was then folded from corner to corner three times, placed over each ulcer, and with a cotton ball to close adherence with cites the work of unman and Maibach (7) pressed the wound. The gold leaf was then covered with a demonstrating the effectiveness of polyethylene 2 x 2 inch coarse mesh gauze pad and the pad was
occlusion in wound therapy and suggests that sutured at its edges to the skin. The sutured gold leaf is but another form of inert occlusive gauze was necessary to protect the wound site. The
gold leaf was replaced every 48 hours. membrane. The center row of four ulcers served as a control In order to more precisely define tile mode of with each ulcer covered only by a gauze pad as action of gold leaf and to test the efficacy of this described. The remaining row of ulcers was occluded with material compared to polyethylene film, the polyethylene film, using Saran wrap® as the following study was carried out.
dressing. An adherent surface was prepared by applying a thin layer of epoxy glue around each ulcer. Over this a gauze pad was placed with a Five domestic pigs, eight to twelve weeks of 2 square inch sheet of Saran® between the folds age, each weighing ten to thirteen kg, were pre- of the pad. The edges of the pad were then sutured to the skin. This maneuver was necessary This study was supported, in part, by IJSPHS to maintain complete occlusion for the entire exTrainee Grant TI-AM-5318-07. METHODS AND MATEItIALS
periment.
Received February 23, 1968; accepted for pub-
On the third day, the first ulcer in each of the The authors wish to acknowledge the kind as- three rows was excised with an 8 mm cutaneous sistance of Dr. Alvin Cox who offered many in- punch. On the sixth, ninth, and twelfth days the valuable comments and suggestions during the remaining ulcers were removed in sequence. The course of this work. We wish to acknowledge also biopsy specimens were fixed in buffered 10% the technical asisstanee of Mrs. Nancy Sutter who formalin. After paraffin embedding, 8 micron secprepared the specimens for histologic study. * From the Department of Dermatology, Stan- tions perpendicular to the skin surface were ford University School of Medicine and Veterans stained with Heinatoxylin and Eosin and with the Verhoeff Elastic-Van Gieson technique. RepreAdministration Hospital, Palo Alto, Calif. 94304. lication November 18, 1968.
487
a
h
C
Fic. 1. (Day 3) a. Control wound. Arrows indicate original wound edge. X 35. b. Gold leaf treated wound. Arrow indicates original wound edge (estimated by measuring 1 mm inward from edge of biopsy specimen). Note black gold leaf fragments in ulcer (g). X 35. c. Polyethylene treated wound. Arrow indicates original wound edge. >< 35. 488
GOLD LEAF TREATED WOUNDS
489
FIG. 2. (Day 6) a. Control wound filled with dense coagulum. Arrow denotes original wound edge. x 35. b. Polyethylene treated wound showing migrating epidermis parallel to
original surface. Arrow denotes original wound edge. >( 35.
sentative sections from the center to the periphery of the ulcers were studied. RESULTS
Day Three. Representative histologic sections showed early epithelial migration at the wound
Day Nine. Polyethylene occluded wounds all were completely reepithelialized, while the control group continued to show only small amounts of epidermal migration (Fig. 4). There were now greater individual differences in the amount of
epidermal migration in the gold leaf treated edges of all three specimens, but significant wounds, although none showed complete redifferences were not apparent (Fig. 1). Dense, epithelialization. Instead, the epidermis was black laminated fragments of gold were seen again seen to advance up to, and to abut, gold within the gold leaf treated ulcers (Fig. 1-b). fragments. The gold leaf fragments also were Day Six. Differences were now apparent in the character of the healing wounds. In comparison to both the control and gold leaf treated wounds, the polyethylene occluded wounds showed extensive epithelial migration (Figs. 2 and 3). The control wound was seen to contain a dense coagulum adherent to the ulcer base and filling the wound cavity. Densely packed laminated gold
fragments were seen within gold leaf treated ulcers. In some zones, epidermal islands were layered between the laminated fragments (Fig. 3).
deeply embedded in the granulation tissue at the ulcer base (Fig. 5).
Day Twelve. The control wounds were reepitbelializing in a plane parallel to the ulcer base beneath the dense coagulum. In comparison, the epithelialized polyethylene occluded wounds
had healed at a superficial level parallel to the original wound surface (Fig. 6). Gold leaf treated wounds continued to show individual differences
in the rate of reepithelialization but had not yet completely reepithelialized. Varying amounts of embedded gold fragments again were seen at the
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
490
—'—p
-
—-
FIG. 3. (Day 6) a. Gold leaf treated wound with black gold fragments filling wound cavity. Arrow indicates original wound edge. Inset denotes edge of advancing epidermis. >< 35. b. Close-up of inset sbowing islands of epidermal cells between laminated gold leaf fragments. )< 100.
edges of the migrating epidermis, as well ns deep
reepithelialize faster when left intact than when to the epithelium in the granulation tissue (Fig. unroofed. Similarly, Winter (8, 12, 13, 20) has shown in pigs, and unman et a!. (7) in humans, 7). that when deep wounds, corresponding to those DISCUSSION in our study, are occluded with polyethylene, Gimbel et a!. (9) and Forage (10) have dem- they reepithelialize twice as fast as wounds exonstrated that experimentally produced blisters posed to air.
"1
fig4 FIG. 4.
(Day 9) a. Control wound with dark eoagulum in the ulcer. Arrow indicates
original wound edge. X 35. b. Polyethylene treated wonnd reepithelielized. Arrow indicates original wound edge. >< 35. —I
Fcc.
,,
5. (Day 9) a. Gold leaf treated wound. Letter e indicates original wound edge.
Inset denotes advancing edge of the epidermis. X 35. b. Close-up of inset showing black gold fragments between epidermal islands and at edge of advancing cells. X 100. 491
492
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
b
FIG. 6. (Day 12) a. Control wound with dense coagulum in ulcer. Arrow indicates
original wound edge. X 35. b. Polyethylene treated wound reepithelialized. Arrow indicates original wound edge. X 35.
These observations can be explained by com- barrier to the migrating epidermis and impedes
paring the healing process in dry and moist repair. wounds. When denuded surfaces arc left exposed
In contrast, an occlusive membrane, such as or underlie a non-occlusive dressing, the tissue polyethylene, maintains hydration. The wound fluid coagulum within the wound dries and forms exudate thus remains serous. Into this serous a crust. Both Forage (10) and Winter (12, 13) wound, granulation tissue quickly forms a solid showed that the denuded dermis at the edges base across which the epidermis migrates unimand base of the wound subsequently becomes peded (Figs. 1-c, 2 and 4-b). dehydrated and is incorporated in the crust. The It has been proposed (4) that the mechanism regenerating epidermis, in order to support me- of action of gold leaf is that of an inert occlusive tabolism, must follow dermal contours, seeking membrane, such as polyethylene. That gold leaf the scrous exudate beneath the drying crust. is not such a dressing has been demonstrated by Therefore, this crust of dried fibrin, inflamma- our study, supporting earlier findings of Gal-
tory cells, serum and dermal remnants at the lagher (3) and Robinson (16). One sheet of wound edges and base becomes a mechanical commercial gold leaf, 98% gold, 2% copper or
493
GOLD LEAF TREATED WOUNDS
a
I,
L' \
Fm. 7. (Day 12) a. Gold leaf treated wound. Arrow illustrates original wound margin. Inset denotes edge of advancing epidermis. )< 35. b. Close-up of inset showing gold fragments inbetween and abutting advancing epidermal edges. X 100.
silver, one to two microns in thickness, is made up of many fragmented layers, the number of which varies from sheet to sheet. Figures 3, 5 and 7 demonstrate the sequelae when several layers of this material are placed over an ulcer. Fragments of gold are seen embedded within the eoagulum, the granulation tissue and the migrating epidermis. These observations suggest that the embedded gold fragments provide a signifi-
cant mechanical barrier to the migrating epidermis whether or not an obstructive crust is present. What is needed for ideal healing of the human skin is a dressing which provides an unimpeded,
moist surface for epidermal migration, while allowing for sufficient drainage or absorption of tissue fluid to keep bacteria at harmless levels (17). Accordingly, neither polyethylene film,
which allows no drainage, nor gold leaf, the fragments of which mechanically impede epidermal migration, appear to fulfill these basic requirements. Based upon the above principles, however, it should be possible to develop a fully satisfactory dressing for the healing wound.
REFERENCES 1. Kanof, N. M.: Gold leaf in the treatment of cutaneous ulcers. J. Invest. Derm., 43: 441, 1964.
494
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
2. Wolf, M., Wheeler, P. and Walcott, L.: Gold
leaf treatment of ischemic skin ulcers. J.A.M.A., 196: 693, 1966.
3. Gallagher, J. P. and Geschechter, C. P.: The use of charged gold leaf in surgery. J.A.M.A., 189: 928, 1964.
4. Epstein, E.: Communications to the Editor. J.A.M.A., 197: 299, 1966.
5. Hoeger, K.: Preoperative treatment of skin ulcers with silver spray and aluminum foil. Acta Chir. Seand., 125: 32, 1963.
6. Smith, K. W., Oden, P. W. and Blayloek, W. K.: A comparison of gold leaf and other oc-
16. Robinson, F. and Johnson, M.: Histopathological studies of tissue reactions to various
metals implanted in cat brain. U.S.A.F. Aerosyst. Div., 61, 1961.
17. Scales, J. T.: Wound healing and the dressing. Brit. J. Indust. Med., 20: 82, 1963. 18. Winter, G. D.: A note on wound healing under dressings with special reference to perforated
film dressings. J. Invest. Derm., 44: 299. 1965. 19. Cillman, T.: The possible importance of
dermal-epidermal interactions in the pathogenesis of human and experimental wound
healing and skin cancers, Pro gress in the Biologicol Sciences in Relotson to Dermoair exposure and occlusion on experimental tology II. Ed., Rook, A., Cambridge Univ. human skin wounds. Nature, 200: 377, 1963. Press, London, 1964. 8. Winter, G. D.: Formation of the scale and 20. Winter, C. D.: Regeneration of the epidermis. rate of epithelialization of superficial wounds Progress in the Bsologicol Sciences in Relein the skin of young domestic pigs. Nature, tion to Dermotology II. Ed., Rook, A., Cam193: 293, 1962. bridge Univ. Press, London, 1964. 9. Gimbel, N., Kapetansky, D., Weissman, F. and 21. Aberchrombie, M.: The behavior of cells toPinkus, H.: A study of epitheliahzation on ward one another, Advonces in the Biology clusive therapy. Arch. Derm., 96: 703, 1967.
7. unman, C. and Maibach, H.: The effects of
blistered burns. Arch. Surg., 74: 800, 1956.
10. Forage, A. V.: The effects of removing the epidermis from burned skin. Lancet, 2: 690, 1962.
of the Skin, Vol. 5. Ed., Montsgna, W., Pergamon Press, N.Y., 1964. 22. Zahir, M.: Contraction of wounds. Brit. J. Surg., 51: 456, 1964.
11. Zahir, M.: Hydroxyproline in scales. 5. Path. 23. Dunphy, J. E.: An ubiquitous ally for the Bact., 84: 79, 1962. surgeon. New Eng. J. Med., 268: 1367, 12. Winter, G. D.: Communication. Nature, 200: 1963. 378, 1963. N., Stoeckinger, J. and Coldblatt, 13. Winter, G. D.: The movement of epidermal 24. Waterman, D.: The effects of various dressings on the cells over the wound surface, Advonces in skin and subcutaneous temperatures. Arch. the Biology of the Skin, Vol. 5. Ed., MonSurg., 95: 464, 1967. tagna, W., Pergamon Press, N.Y., 1964. 14. Gillman, T. and Penn, J.: Studies on repair of 25. Larsen, W. G.: The direction of epidermal growth. Arch. Derm.. 95: 323, 1965. cut wounds. II: The healing of wounds involving loss of superficial portions of the 26. Klenim, W. R.: Enhanced healing of the skin skin. Med. Proc., 2: 150, 1956.
wounds in dogs with systemically and focally
thehum. Brit. J. Derm., 78: 403, 1966.
tia, 23: 55, 1967.
15. Ryan, T. J.: The direction of growth of epi-
administered drugs. Separatum Experimen-