We have previously shown that it is possible to measure Po2 transcutaneously by means of an electrode according to CLARK [1], This Po2 correlates with the arterial values both in newborns and in adults [2, 5, 8, 10, 11]. In order to obtain reproducible and representative tcPo2 measurements, attention must be paid to several factors, such as the shape of the electrode, the size of the platinum cathodes, the thickness of the electrode membranes and the local "arterialization" of the skin at the site of measurement.

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Transcutaneous measurement of blood Po2 (tcPo2) -- Method and application in perinatal medicine.

Malaria is initiated when the mosquito introduces sporozoites into the skin of a mammalian host. To successfully continue the infection, sporozoites must invade blood vessels in the dermis and be transported to the liver. A significant number of sporozoites, however, may enter lymphatic vessels in the skin or remain in the skin long after the mosquito bite. We have used fluorescence microscopy of Plasmodium berghei sporozoites expressing a fluorescent protein to evaluate the kinetics of sporozoite disappearance from the skin. Sporozoites injected into immunized mice were rapidly immobilized, did not appear to invade dermal blood vessels and became morphologically degraded within several hours. Strikingly, mosquitoes introduced significantly fewer sporozoites into immunized than into non-immunized mice, presumably by formation of an immune complex between soluble sporozoite antigens in the mosquito saliva and homologous host antibodies at the proboscis tip. These results indicate that protective antibodies directed against sporozoites may function both by reducing the numbers of sporozoites injected into immunized hosts and by inhibiting the movement of injected sporozoites into dermal blood vessels.

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Kinetics of mosquito-injected Plasmodium sporozoites in mice: fewer sporozoites are injected into sporozoite-immunized mice.

Microcirculation in psoriasis: blood vessels, lymphatics and tissue fluid.

The number of malaria sporozoites delivered to a host by mosquitoes is thought to have a significant influence on the subsequent course of the infection in the mammalian host. We did studies with Anopheles stephensi mosquitoes with salivary gland infections of Plasmodium berghei sporozoites expressing a red fluorescent protein. After individual mosquitoes fed on an ear pinna or the ventral abdomen of a mouse, fluorescence microscopy was used to count numbers of sporozoites. Mosquitoes allowed to feed on the ear for periods of 3 versus 15 min deposited means of 281 versus 452 sporozoites, respectively, into the skin; this may have epidemiological implications because mosquitoes can feed for longer periods of time on sleeping hosts. Mosquitoes feeding on the ventral abdomen injected sporozoites not only into the skin but also into the underlying peritoneal musculature. Although mosquitoes injected fewer sporozoites into the abdominal tissues, more of these were reingested into the mosquito midgut, probably a consequence of easier access to blood intake from the abdominal area. The most consistent parameter of sporozoite transmission dynamics under all conditions of mosquito probing and feeding was the relatively slow release rate of sporozoites (∼1 to 2.5 per second) from the mosquito proboscis. The numbers of sporozoites introduced into the host by mosquitoes and the transmission efficiencies of sporozoite delivery are multifactorial phenomena that vary with length of probing time, skin site being fed upon, and numbers of sporozoites within the salivary glands.

Direct microscopic quantification of dynamics of Plasmodium berghei sporozoite transmission from mosquitoes to mice.

To the Editor: In 1981 a burn care team in Australia made the serendipitous discovery that topical silicone gel sheeting effectively reduces the severity of burn hypertrophic scars. Since the publication of their work in 1982, scores of additional studies have documented the value of this therapy. Hypertrophic scars of all types become less raised, less red, less puritic, and more flexible. These conclusions are from both published case studies ( for an example), and from well-done controlled studies where quantitative measurements were recorded. The treatment is as effective as steroid injections, and very much preferred by patients to that option. When applied in the right protocol, silicone sheets are effective at preventing the formation of new hypertrophic scars after surgery. Silicone sheeting has also given positive results in the treatment of existing keloid scars. Authors have tried to show keloid prophylaxis using silicone sheets, but this does not seem to be reliable. The effective regimen for preventing hypertrophic scars with silicone sheets begins about two weeks after the wounding, however, existing scars that are years old can be effectively treated. The scar is covered with silicone sheet for at least 12 hours per day, for at least eight weeks. The only complication reported is an occasional skin rash. The rash clears when the treatment is discontinued for a few days. Some other materials have shown this same ability. However, a sheet hydrogel wound dressing product is the only well-characterized nonsilicone material with efficacy proven in a prospective, controlled trial. The positive results with other materials establish that silicone is not needed for efficacy. However, 20 years after the discovery, there is still no satisfactory explanation of the mechanism for effectiveness of silicone sheets in scar treatment and prevention. The purpose of this communication is to propose a mechanism not considered before and to include some preliminary laboratory results that are supportive of this proposal. This new mechanism also has implications for the pathogenesis of hypertrophic scars. The proposal made here is based on a key, and perhaps underappreciated, observation published in 1985. Quinn et al. covered an effective silicone sheet with a 60 lmthick urethane film and reported that this structure was then not effective in scar therapy. Dr. Quinn interpreted her result to mean that silicone oil leaching from the sheet was important for efficacy. I have found through my laboratory studies, however, that a 60 lm-thick polyurethane film can dramatically reduce the oxygen permeability of a silicone sheet, by about a factor of 10. I have also confirmed in my laboratory, using transepidermal water loss measurements on human volunteers, that silicone sheets have a water vapor permeability that is low enough to cause a buildup of moisture on the skin surface under the silicone sheet (as reported in several existing references). Based in part on these observations, I propose the following as the mechanism for the effectiveness of silicone sheet in the prevention and treatment of hypertrophic scarring: that there are two key features of silicone sheets that account for their efficacy in scar therapy. First, the sheet limits the escape of moisture from the skin surface and causes a hydration of the stratum corneum. Second, the sheet does not limit the access of oxygen to the surface of the skin due to it’s exceptionally high oxygen permeability. The hydrated stratum corneum is significantly more permeable to oxygen, and because oxygen has free access to the skin surface, the oxygen tension in the epidermis and perhaps in the upper dermis rises. This increased oxygen tension in the tissue near the skin surface may shut down signaling from this tissue that had been stimulating growth and maintenance of the scar. For example, all cells have a system that will send an angiogenic signal in response to hypoxia. Knighton et al. have shown that hypoxia is a stimulus to angiogenesis and tissue growth in wound healing and that removing the hypoxia stops the new tissue growth. Several other items of literature support this line of thinking. It has been shown that stratum corneum is a significant barrier to the diffusion of oxygen, and that hydration increases stratum corneum permeability. Some

Silicone sheet for treatment and prevention of hypertrophic scar: a new proposal for the mechanism of efficacy

SUMMARY

Oxygen tension differences across the mouse ear have been measured polarographically under conditions of no blood flow. For some experiments the ear was split into two by cleavage along the central cartilage plate, and the diffusion of oxygen measured in both directions across these asymmetrical preparations. Measurements were also made on ears from which the stratum corneum had been removed by stripping with Sellotape. It was possible to relate these results to a simple multi-layer diffusion model. The main barrier to diffusion of oxygen resides in the stratum corneum, whose permeability is estimated to be 1.2 × 10−8 ml O2 atm−1 cm−1 s−1. The permeability of the rest of the ear is 4.7 × 10−7 ml O2 atm −1 cm−1 s−1.



The inhibition of tissue respiration by the local injection of solutions of sodium amytal, potassium eyanide and other substances reduced the oxygen gradients by factors of between 3 and 7. Cooling the ear from room temperature to o C reduced the gradients by a factor of about 4.

Diffusion of oxygen through the mouse ear.

SUMMARY.— Barbiturate solutions were applied to skin after removal of the stratum corneum with Sellotape, and skin surface oxygen tension was measured polarographically. These produced a rise in surface oxygen tension of 30–50 mm. Hg. The rate at which surface oxygen tension fell following arterial occlusion gave a measure of the rate of skin oxygen utilization. This was reduced by a factor which could be as large as 8 after application of barbiturate solutions. It is shown that both epidermal and dermal oxygen utilization rates are reduced, and their return to normal depends on skin blood flow.

The action of locally applied barbiturates on skin oxygen tension and rate of oxygen utilization.

SUMMARY.— Oxygen tension at the surface of inflamed skin and alveolar oxygen tension were measured polarographically. Changes in blood flow were indicated by a water perfused thermocouple disc resting on the skin. Breath holding, voluntary hyperventilation, Valsalva's manoeuvre, coughing, Muller's manoeuvre and arterial occlusion all produced transient changes in skin oxygen tension. These could largely be explained in terms of the observed changes in alveolar oxygen tension and skin blood flow.

The effect of respiratory manoeuvres upon skin oxygen tension and blood flow.

SUMMARY. Heat flux across the surface of human skin may be measured with copper-tellurite-copper thermocouple discs perfused on one side by water at a constant temperature. If the water is at about 45° C., inflammation develops in the skin under the disc within 15 min., and the changes in e.m.f. corresponding to acute changes in skin blood flow can be recorded. With a water temperature of 33° C., these blood flow changes are not easily followed.

N. T. S. Evans

Papers

Diffusion of oxygen through the mouse ear.

The action of locally applied barbiturates on skin oxygen tension and rate of oxygen utilization.

The effect of respiratory manoeuvres upon skin oxygen tension and blood flow.

Copper-tellurite-copper thermocouples for measuring acute changes in skin blood flow.

Oxygen transport through skin