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The influence of epidermal spray cooling on laser effects within the cutis – 2nd message: Influence of the delay (latency)
ARTICLE IN PRESS
Medical Laser Application 23 (2008) 21–24 www.elsevier.de/mla
The influence of epidermal spray cooling on laser effects within the cutis – 2nd message: Influence of the delay (latency) Hartmut Strempel, Fritz Strempel Laser Zentrum Marburg, Wettergasse 1, 35037 Marburg, Germany Received 8 August 2007; accepted 12 November 2007
Abstract Background: The length of epidermal spray cooling time influences the cutaneous laser effect within the cutis. The aim of this study is to examine whether – and to which extent – the time delay between the application of cooling spray and the emission of the laser pulse (latency) varies this effect. Method: Caucasian individuals were exposed to dye laser pulses with and without epidermal spray cooling (V-beam, Candela Corp., Boston: 4, 4.5 and 5 J/cm2, l ¼ 595 nm). The cooling duration and latency (DCD, Candela Corp., Boston) were varied systematically and the purpuric reaction was measured quantitatively by means of reflectometry. Results: The cooling-induced attenuation of laser effects in the cutis is significantly intensified through an increase in latency in the range of 10–100 ms. Conclusions: In addition to cooling duration, cooling latency also influences the effects of laser pulses in the cutis. This underlines the importance of using cooling systems which facilitate proper adjustment and documentation of cooling time and latency for scientific purposes, particularly to allow for meaningful comparison between different studies. The cooling duration should be as short as necessary and the latency as short as possible. r 2008 Elsevier GmbH. All rights reserved. Keywords: Spray cooling; DCD; Dye laser; Purpuric reaction; Delay; Latency
Introduction Epidermal spray cooling not only provides protection to the epidermis, but it also attenuates the desired effects of the laser pulses within the cutis [1]. Since a certain amount of time is necessary to allow the cooling effect to propagate from the epidermal surface to deeper levels of the skin, we try to examine whether and how the time delay (latency) between the end of coolant application Corresponding author. Tel.: +49 6421 24004; fax: +49 6421 25911.
E-mail address: [email protected] (H. Strempel). URL: http://www.laser-zentrum-marburg.de (H. Strempel). 1615-1615/$ - see front matter r 2008 Elsevier GmbH. All rights reserved. doi:10.1016/j.mla.2007.11.006
and the beginning of the laser pulse influences its cutaneous effects.
Method As basis for our experiments, we once again used the purpuric reaction as an indicator for the effects of a short dye laser pulses on the skin [1,2]. In the first part of the present study (40 ms latency) 16 Caucasian (Fitzpatrick II–III) informed subjects (age: 18–61) were exposed to dye laser pulses on the inner side of their upper arm. The used laser parameters (V-Beam,
ARTICLE IN PRESS 22
H. Strempel, F. Strempel / Medical Laser Application 23 (2008) 21–24
Candela Corp., Boston) were l ¼ 595 nm, pulse width ¼ 450 ms, beam diameter ¼ 7 mm. The second part (100 ms latency) comprised 15 such volunteers. In both trials we chose laser fluence settings of 4, 4.5 and 5 J/cm2. The duration of cooling spurt (DCD, Candela Corp., Boston) was varied as follows: 30, 50, 80 and 100 ms. The latency was chosen at 40 and 100 ms. The purpuric reaction at the exposed areas (see Figs. 1 and 2) was quantified in each case 24 h after exposure by means of reflectometry (Chromameter CR300, Minolta Corp.) with an aperture diameter of 10 mm (for further details of the method, see Ref. [1]). We measured the average red value (ao) of the nonexposed skin and the experimental red value (ae) of the irradiated area [3,4]. The laser-induced red value (aD) is derived from the difference (aeao ¼ aD). Finally, the arithmetic mean (x) of red values (aD) was calculated for all combinations of fluence, cooling duration and
latency, as well as the standard error of means (SEM).
Results The averaged red value of the non-exposed skin ao was 15.18 in the first part and 17.76 in the second part of our study. Exposure to a pulse at 4 J/cm2 fluence without cooling increased the red value by aD ¼ 12.17 (Table 1, 40 ms latency) and aD ¼ 11.10 (Table 4, 100 ms latency), respectively. When applying the same fluence, but a cooling duration of 30 and 40 ms latency, the red value increased by only aD ¼ 4.77. But the same fluence and cooling duration produced significantly lower red values (aD ¼ 1.11) if the latency was increased to 100 ms (Table 4). The other results are shown in Tables 1–6. Tables 7–9 show the relative loss of laser efficacy in percent of the respective dye laser purpura without cooling.
Discussion The results of this study fully support the observation that laser effects in the cutis, as measured by the Table 1. Red values aD at 4 J/cm2 without and with cooling; 40 ms latency; n ¼ 16 Cooling
Fig. 1. Example of experimental site 24 h after pulsed dye laser exposure (40 ms latency).
x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
12.17 1.25
4.77 1.29
1.17 0.61
1.51 0.50
1.45 0.49
Table 2. Red values aD at 4.5 J/cm2 without and with cooling; 40 ms latency; n ¼ 16 Cooling
x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
16.71 1.40
11.77 2.16
5.48 1.85
1.97 0.67
2.07 0.42
Table 3. Red values aD at 5 J/cm2 without and with cooling; 40 ms latency; n ¼ 16 Cooling
Fig. 2. Example of experimental site 24 h after pulsed dye laser exposure (100 ms latency).
x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
21.45 1.00
18.29 1.79
15.94 2.00
4.72 0.99
4.03 0.90
ARTICLE IN PRESS H. Strempel, F. Strempel / Medical Laser Application 23 (2008) 21–24
Table 4. Red values aD at 4 J/cm2 without and with cooling; 100 ms latency; n ¼ 15
Table 9. Loss of laser efficacy in percent of the dye laser purpura, latency 100 ms; n ¼ 15 Cooling
Cooling
x SEM
23
0 ms
30 ms
50 ms
80 ms
100 ms
11.10 1.54
1.11 0.67
1.83 1.80
2.00 0.64
1.89 0.68
Table 5. Red values aD at 4.5 J/cm2 without and with cooling; 100 ms latency; n ¼ 15
4 J/cm2 4.5 J/cm2 5 J/cm2
0 ms
30 ms
50 ms
80 ms
100 ms
100 100 100
90 77 57
84 90 61
82 94 86
83 92 88
Table 10. Loss of laser efficacy in percent of the 5 J/cm2 purpura (L ¼ latency; D ¼ cooling duration)
Cooling L x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
19.59 1.07
5.40 1.32
2.51 1.01
1.28 0.47
1.97 0.58
10 ms 40 ms 100 ms
D 0 ms
30 ms
50 ms
80 ms
100 ms
100 100 100
22 24 57
25 34 61
54 81 86
70 84 88
Table 6. Red values aD at 5 J/cm2 without and with cooling; 100 ms latency; n ¼ 15 Cooling
x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
23.05 0.80
10.76 2.31
9.81 1.89
3.64 1.02
3.00 1.03
Table 7. Loss of laser efficacy in percent of the dye laser purpura; latency 10 ms; n ¼ 17 [1] Cooling
4 J/cm2 4.5 J/cm2 5 J/cm2
0 ms
30 ms
50 ms
80 ms
100 ms
100 100 100
69 38 22
89 66 25
96 84 54
100 98 70
Table 8. Loss of laser efficacy in percent of the dye laser purpura, latency 40 ms; n ¼ 16 Cooling
4 J/cm2 4.5 J/cm2 5 J/cm2
0 ms
30 ms
50 ms
80 ms
100 ms
100 100 100
70 43 24
91 74 34
88 91 81
89 90 84
purpuric reaction, are attenuated by epidermal cooling. The extent of the attenuation depends on the cooling duration. Using 10 ms latency and a fluence of 4.5 J/cm2, the attenuation of the purpuric reaction was significant
at 80 ms cooling duration [1]. Using 40 ms latency, the attenuation of a 4.5 J/cm2 laser pulse is already significant with 50 ms cooling time (see Table 2). Furthermore with the 100 ms latency the attenuation of a 4.5 J/cm2 laser pulse is significant even with 30 ms cooling time (see Table 5). Table 10 (as synopsis out of Tables 7–9) and Fig. 3 summarize the percentile efficacy loss of a 5 J/cm2 dye laser impact depending on the different cooling variables. In addition to the attenuation of cutaneous effects due to increasing cooling duration, the laser effects are further attenuated if latency is increased in the range of 10–100 ms. The purpuric reaction at 30 ms cooling duration and 10 ms latency is reduced to 78% compared to the purpuric reaction with no cooling. By increasing latency to 100 ms, laser effects are further reduced to 43%. A very unusual combination of 100 ms cooling duration and 100 ms latency reduces the purpuric reaction to only 12% of the reaction with no cooling. If even very small variations of the temporal variables of epidermal spray cooling (fractions of tenths of seconds) can cause reasonable variations in laser efficacy, our results lead to two main conclusions: 1. (Scientific approach): In laser trials with epidermal cooling all cooling variables should be carefully recorded and documented. Cooling systems or studies which do not meet this requirement can only offer qualitative results with poor reliability. 2. (Practical approach): In view of our findings we recommend to chose the cooling time as short as necessary in order to avoid undesired side effects and
ARTICLE IN PRESS 24
H. Strempel, F. Strempel / Medical Laser Application 23 (2008) 21–24
100ms 40ms
90 80 70 60 10ms
50 40
40ms
30 20 10
latency
Red value a Δ in% of the no-cooling purpura
10ms
100
100ms
0 0ms
30ms
50ms 80ms cooling duration
100ms
Fig. 3. Loss of laser efficacy (5 J/cm2 pulse) resulting from different spray cooling durations and different latencies, in percent of the no-cooling-purpura.
to chose the latency as short as possible in order to preserve the desired main effects.
Zusammenfassung U¨ber den Einfluss der epidermalen Spray-Ku¨hlung auf die Laserwirkung in der Cutis - 2. Mitteilung: Einfluss der Pausendauer (Latenz) Hintergrund: Die Dauer der epidermalen Spray-Ku¨hlung bei der Lasertherapie beeinflusst die Laserwirkung in der Cutis. Es soll hier gepru¨ft werden, ob und in welchem Ausmaß die zeitliche Gestaltung des Ku¨hlvorganges diesen Effekt variiert. Methodik: An hellha¨utigen Probanden wurde die Purpurareaktion nach Farbstofflaserpulsen ohne und mit epidermaler Ku¨hlung (Spray-Ku¨hlung) quantitativ reflektometrisch gemessen. Dabei wurde die La¨nge der Ku¨hldauer und der Pausen mehrfach variiert. Ergebnisse: Die Abschwa¨chung der cutanen Laserwirkung durch eine vorangehende epidermale Ku¨hlung wird durch eine Verla¨ngerung der dazwischen liegenden Pause in einem Bereich 10 ms bis 100 ms noch deutlich versta¨rkt. Schlussfolgerungen: Wenn neben der epidermalen Ku¨hldauer auch die Pausendauer zwischen dem Ende des
Ku¨hlvorgangs und dem Beginn des Laserimpulses die cutane Laserwirkung messbar beeinflusst, unterstreicht dies die Notwendigkeit, mo¨glichst epidermale Ku¨hlsysteme zu benutzen, deren Parameter exakt zu definieren und zu dokumentieren sind, um eine Vergleichbarkeit wissenschaftlicher Ergebnisse zu ermo¨glichen. Die Ku¨hldauer sollte so kurz wie no¨tig, die Pause dagegen so kurz wie mo¨glich sein. Schlu¨sselwo¨rter: Spray-Ku¨hlung; Farbstofflaser; Purpurareaktion; Ku¨hldauer; Pausendauer
References [1] Strempel H, Strempel F. The influence of epidermal spray cooling on laser effects within the cutis – 1st message: influence of the cooling duration. Med Laser Appl 2007;22(2):135–8. [2] Strempel H, Klein G. U¨ber den Einfluss der zeitlichen und der ra¨umlichen Gestalt eines Farbstofflaserpulses auf seine Wirkung an der Haut. Z Hautkr 1996;71:765–8. [3] Agache P, Giradot J, Bermengo JC. Optical properties of the skin. In: Leveque JL, editor. Cutaneous investigation in health and disease. New York, Basel: Marcel Dekker Inc.; 1990. p. 241–78. [4] Blazek V, Wienert V. Objektive Hautfarbmessung mit Hilfe der Spektral photometrie. Arch Derm Res 1979;265: 235–44.
Medical Laser Application 23 (2008) 21–24 www.elsevier.de/mla
The influence of epidermal spray cooling on laser effects within the cutis – 2nd message: Influence of the delay (latency) Hartmut Strempel, Fritz Strempel Laser Zentrum Marburg, Wettergasse 1, 35037 Marburg, Germany Received 8 August 2007; accepted 12 November 2007
Abstract Background: The length of epidermal spray cooling time influences the cutaneous laser effect within the cutis. The aim of this study is to examine whether – and to which extent – the time delay between the application of cooling spray and the emission of the laser pulse (latency) varies this effect. Method: Caucasian individuals were exposed to dye laser pulses with and without epidermal spray cooling (V-beam, Candela Corp., Boston: 4, 4.5 and 5 J/cm2, l ¼ 595 nm). The cooling duration and latency (DCD, Candela Corp., Boston) were varied systematically and the purpuric reaction was measured quantitatively by means of reflectometry. Results: The cooling-induced attenuation of laser effects in the cutis is significantly intensified through an increase in latency in the range of 10–100 ms. Conclusions: In addition to cooling duration, cooling latency also influences the effects of laser pulses in the cutis. This underlines the importance of using cooling systems which facilitate proper adjustment and documentation of cooling time and latency for scientific purposes, particularly to allow for meaningful comparison between different studies. The cooling duration should be as short as necessary and the latency as short as possible. r 2008 Elsevier GmbH. All rights reserved. Keywords: Spray cooling; DCD; Dye laser; Purpuric reaction; Delay; Latency
Introduction Epidermal spray cooling not only provides protection to the epidermis, but it also attenuates the desired effects of the laser pulses within the cutis [1]. Since a certain amount of time is necessary to allow the cooling effect to propagate from the epidermal surface to deeper levels of the skin, we try to examine whether and how the time delay (latency) between the end of coolant application Corresponding author. Tel.: +49 6421 24004; fax: +49 6421 25911.
E-mail address: [email protected] (H. Strempel). URL: http://www.laser-zentrum-marburg.de (H. Strempel). 1615-1615/$ - see front matter r 2008 Elsevier GmbH. All rights reserved. doi:10.1016/j.mla.2007.11.006
and the beginning of the laser pulse influences its cutaneous effects.
Method As basis for our experiments, we once again used the purpuric reaction as an indicator for the effects of a short dye laser pulses on the skin [1,2]. In the first part of the present study (40 ms latency) 16 Caucasian (Fitzpatrick II–III) informed subjects (age: 18–61) were exposed to dye laser pulses on the inner side of their upper arm. The used laser parameters (V-Beam,
ARTICLE IN PRESS 22
H. Strempel, F. Strempel / Medical Laser Application 23 (2008) 21–24
Candela Corp., Boston) were l ¼ 595 nm, pulse width ¼ 450 ms, beam diameter ¼ 7 mm. The second part (100 ms latency) comprised 15 such volunteers. In both trials we chose laser fluence settings of 4, 4.5 and 5 J/cm2. The duration of cooling spurt (DCD, Candela Corp., Boston) was varied as follows: 30, 50, 80 and 100 ms. The latency was chosen at 40 and 100 ms. The purpuric reaction at the exposed areas (see Figs. 1 and 2) was quantified in each case 24 h after exposure by means of reflectometry (Chromameter CR300, Minolta Corp.) with an aperture diameter of 10 mm (for further details of the method, see Ref. [1]). We measured the average red value (ao) of the nonexposed skin and the experimental red value (ae) of the irradiated area [3,4]. The laser-induced red value (aD) is derived from the difference (aeao ¼ aD). Finally, the arithmetic mean (x) of red values (aD) was calculated for all combinations of fluence, cooling duration and
latency, as well as the standard error of means (SEM).
Results The averaged red value of the non-exposed skin ao was 15.18 in the first part and 17.76 in the second part of our study. Exposure to a pulse at 4 J/cm2 fluence without cooling increased the red value by aD ¼ 12.17 (Table 1, 40 ms latency) and aD ¼ 11.10 (Table 4, 100 ms latency), respectively. When applying the same fluence, but a cooling duration of 30 and 40 ms latency, the red value increased by only aD ¼ 4.77. But the same fluence and cooling duration produced significantly lower red values (aD ¼ 1.11) if the latency was increased to 100 ms (Table 4). The other results are shown in Tables 1–6. Tables 7–9 show the relative loss of laser efficacy in percent of the respective dye laser purpura without cooling.
Discussion The results of this study fully support the observation that laser effects in the cutis, as measured by the Table 1. Red values aD at 4 J/cm2 without and with cooling; 40 ms latency; n ¼ 16 Cooling
Fig. 1. Example of experimental site 24 h after pulsed dye laser exposure (40 ms latency).
x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
12.17 1.25
4.77 1.29
1.17 0.61
1.51 0.50
1.45 0.49
Table 2. Red values aD at 4.5 J/cm2 without and with cooling; 40 ms latency; n ¼ 16 Cooling
x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
16.71 1.40
11.77 2.16
5.48 1.85
1.97 0.67
2.07 0.42
Table 3. Red values aD at 5 J/cm2 without and with cooling; 40 ms latency; n ¼ 16 Cooling
Fig. 2. Example of experimental site 24 h after pulsed dye laser exposure (100 ms latency).
x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
21.45 1.00
18.29 1.79
15.94 2.00
4.72 0.99
4.03 0.90
ARTICLE IN PRESS H. Strempel, F. Strempel / Medical Laser Application 23 (2008) 21–24
Table 4. Red values aD at 4 J/cm2 without and with cooling; 100 ms latency; n ¼ 15
Table 9. Loss of laser efficacy in percent of the dye laser purpura, latency 100 ms; n ¼ 15 Cooling
Cooling
x SEM
23
0 ms
30 ms
50 ms
80 ms
100 ms
11.10 1.54
1.11 0.67
1.83 1.80
2.00 0.64
1.89 0.68
Table 5. Red values aD at 4.5 J/cm2 without and with cooling; 100 ms latency; n ¼ 15
4 J/cm2 4.5 J/cm2 5 J/cm2
0 ms
30 ms
50 ms
80 ms
100 ms
100 100 100
90 77 57
84 90 61
82 94 86
83 92 88
Table 10. Loss of laser efficacy in percent of the 5 J/cm2 purpura (L ¼ latency; D ¼ cooling duration)
Cooling L x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
19.59 1.07
5.40 1.32
2.51 1.01
1.28 0.47
1.97 0.58
10 ms 40 ms 100 ms
D 0 ms
30 ms
50 ms
80 ms
100 ms
100 100 100
22 24 57
25 34 61
54 81 86
70 84 88
Table 6. Red values aD at 5 J/cm2 without and with cooling; 100 ms latency; n ¼ 15 Cooling
x SEM
0 ms
30 ms
50 ms
80 ms
100 ms
23.05 0.80
10.76 2.31
9.81 1.89
3.64 1.02
3.00 1.03
Table 7. Loss of laser efficacy in percent of the dye laser purpura; latency 10 ms; n ¼ 17 [1] Cooling
4 J/cm2 4.5 J/cm2 5 J/cm2
0 ms
30 ms
50 ms
80 ms
100 ms
100 100 100
69 38 22
89 66 25
96 84 54
100 98 70
Table 8. Loss of laser efficacy in percent of the dye laser purpura, latency 40 ms; n ¼ 16 Cooling
4 J/cm2 4.5 J/cm2 5 J/cm2
0 ms
30 ms
50 ms
80 ms
100 ms
100 100 100
70 43 24
91 74 34
88 91 81
89 90 84
purpuric reaction, are attenuated by epidermal cooling. The extent of the attenuation depends on the cooling duration. Using 10 ms latency and a fluence of 4.5 J/cm2, the attenuation of the purpuric reaction was significant
at 80 ms cooling duration [1]. Using 40 ms latency, the attenuation of a 4.5 J/cm2 laser pulse is already significant with 50 ms cooling time (see Table 2). Furthermore with the 100 ms latency the attenuation of a 4.5 J/cm2 laser pulse is significant even with 30 ms cooling time (see Table 5). Table 10 (as synopsis out of Tables 7–9) and Fig. 3 summarize the percentile efficacy loss of a 5 J/cm2 dye laser impact depending on the different cooling variables. In addition to the attenuation of cutaneous effects due to increasing cooling duration, the laser effects are further attenuated if latency is increased in the range of 10–100 ms. The purpuric reaction at 30 ms cooling duration and 10 ms latency is reduced to 78% compared to the purpuric reaction with no cooling. By increasing latency to 100 ms, laser effects are further reduced to 43%. A very unusual combination of 100 ms cooling duration and 100 ms latency reduces the purpuric reaction to only 12% of the reaction with no cooling. If even very small variations of the temporal variables of epidermal spray cooling (fractions of tenths of seconds) can cause reasonable variations in laser efficacy, our results lead to two main conclusions: 1. (Scientific approach): In laser trials with epidermal cooling all cooling variables should be carefully recorded and documented. Cooling systems or studies which do not meet this requirement can only offer qualitative results with poor reliability. 2. (Practical approach): In view of our findings we recommend to chose the cooling time as short as necessary in order to avoid undesired side effects and
ARTICLE IN PRESS 24
H. Strempel, F. Strempel / Medical Laser Application 23 (2008) 21–24
100ms 40ms
90 80 70 60 10ms
50 40
40ms
30 20 10
latency
Red value a Δ in% of the no-cooling purpura
10ms
100
100ms
0 0ms
30ms
50ms 80ms cooling duration
100ms
Fig. 3. Loss of laser efficacy (5 J/cm2 pulse) resulting from different spray cooling durations and different latencies, in percent of the no-cooling-purpura.
to chose the latency as short as possible in order to preserve the desired main effects.
Zusammenfassung U¨ber den Einfluss der epidermalen Spray-Ku¨hlung auf die Laserwirkung in der Cutis - 2. Mitteilung: Einfluss der Pausendauer (Latenz) Hintergrund: Die Dauer der epidermalen Spray-Ku¨hlung bei der Lasertherapie beeinflusst die Laserwirkung in der Cutis. Es soll hier gepru¨ft werden, ob und in welchem Ausmaß die zeitliche Gestaltung des Ku¨hlvorganges diesen Effekt variiert. Methodik: An hellha¨utigen Probanden wurde die Purpurareaktion nach Farbstofflaserpulsen ohne und mit epidermaler Ku¨hlung (Spray-Ku¨hlung) quantitativ reflektometrisch gemessen. Dabei wurde die La¨nge der Ku¨hldauer und der Pausen mehrfach variiert. Ergebnisse: Die Abschwa¨chung der cutanen Laserwirkung durch eine vorangehende epidermale Ku¨hlung wird durch eine Verla¨ngerung der dazwischen liegenden Pause in einem Bereich 10 ms bis 100 ms noch deutlich versta¨rkt. Schlussfolgerungen: Wenn neben der epidermalen Ku¨hldauer auch die Pausendauer zwischen dem Ende des
Ku¨hlvorgangs und dem Beginn des Laserimpulses die cutane Laserwirkung messbar beeinflusst, unterstreicht dies die Notwendigkeit, mo¨glichst epidermale Ku¨hlsysteme zu benutzen, deren Parameter exakt zu definieren und zu dokumentieren sind, um eine Vergleichbarkeit wissenschaftlicher Ergebnisse zu ermo¨glichen. Die Ku¨hldauer sollte so kurz wie no¨tig, die Pause dagegen so kurz wie mo¨glich sein. Schlu¨sselwo¨rter: Spray-Ku¨hlung; Farbstofflaser; Purpurareaktion; Ku¨hldauer; Pausendauer
References [1] Strempel H, Strempel F. The influence of epidermal spray cooling on laser effects within the cutis – 1st message: influence of the cooling duration. Med Laser Appl 2007;22(2):135–8. [2] Strempel H, Klein G. U¨ber den Einfluss der zeitlichen und der ra¨umlichen Gestalt eines Farbstofflaserpulses auf seine Wirkung an der Haut. Z Hautkr 1996;71:765–8. [3] Agache P, Giradot J, Bermengo JC. Optical properties of the skin. In: Leveque JL, editor. Cutaneous investigation in health and disease. New York, Basel: Marcel Dekker Inc.; 1990. p. 241–78. [4] Blazek V, Wienert V. Objektive Hautfarbmessung mit Hilfe der Spektral photometrie. Arch Derm Res 1979;265: 235–44.