A telephone-based motivational interviewing intervention has positive effects on psoriasis severity and self-management: a randomized controlled trial.

BACKGROUND: Psoriasis is a common skin disease with extensive comorbidity risks, which may affect multiple aspects of life. Self-management is essential for skin treatment and lifestyle choices, but few disease-specific tailored self-management and educational programmes appear to be available. OBJECTIVES: To evaluate the effects of a 3-month individual motivational interviewing intervention in patients with psoriasis (with a total follow-up of 6 months) after climate therapy/heliotherapy (CHT). METHODS: A randomized controlled trial with 169 patients with psoriasis was conducted in the context of CHT at Gran Canaria, Spain. The main outcome measures were Self-Administered Psoriasis Area and Severity Index (SAPASI) and Health Education Impact Questionnaire (heiQ), and the secondary outcomes were illness perception, psoriasis knowledge and lifestyle change assessments. Outcomes were measured at baseline, after 3 weeks of CHT, and 3 months and 6 months later. RESULTS: There were significant overall treatment effects in the study group in terms of the SAPASI score, three self-management domains of heiQ and the self-efficacy scores (P < 0∙05). The lifestyle change parameters were significantly better in the study group. Illness perception differed between the groups at 3 months (P = 0∙014), and psoriasis knowledge was significantly better in the study group at 6 months (P = 0∙017). CONCLUSIONS: A 3-month motivational interviewing intervention following CHT had positive overall effects on disease severity, self-efficacy, psoriasis knowledge and health behaviour change. This approach has the potential to be an important complement to medical management, self-management and education in patients with psoriasis.

Sun exposure rapidly reduces plasmacytoid dendritic cells and inflammatory dermal dendritic cells in psoriatic skin.

BACKGROUND: Interferon (IFN)-α-producing plasmacytoid dendritic cells (pDCs), inflammatory CD11c+CD1c- myeloid dendritic cells (mDCs) and macrophages have been found to contribute to the pathogenesis of psoriasis. Heliotherapy is a well-established treatment modality of this disease, although the details of how the effects are mediated are unknown. OBJECTIVES: To test the hypothesis that exposure to natural sun affects pathogenic DC subsets in lesional skin. METHODS: Skin biopsies were obtained from lesional and nonlesional skin in 10 patients with moderate to severe psoriasis subjected to controlled sun exposure on Gran Canaria. Biopsies were obtained at baseline, day 2 and day 16 and examined by immunohistochemistry. RESULTS: Sixteen days of heliotherapy had excellent clinical effect on patients with psoriasis, with significant reductions in Psoriasis Area and Severity Index (PASI) scores. In lesional skin pDC numbers and expression of MxA, a surrogate marker for IFN-α, were rapidly reduced. Inflammatory CD11c+CD1c- mDCs were significantly reduced whereas resident dermal CD11c+CD1c+ mDCs were unaffected. Expression levels of the maturation marker DC-LAMP (CD208) on mDCs were significantly reduced after sun exposure, as were the numbers of lesional dermal macrophages. A decrease of dermal DC subsets and macrophages was already observed after 1 day of sun exposure. An additional finding was that DC-SIGN (CD209) is primarily expressed on CD163+ macrophages and not DCs. CONCLUSIONS: The clinical improvement in psoriasis following sun exposure is associated with rapid changes in dermal DC populations and macrophages in lesional skin, preceding the clinical effect. These findings support the concept that these DC subsets are involved in the pathogenesis of psoriasis and suggest that sun-induced clinical benefit may partly be explained by its effect on dermal DCs.

Sun exposure induces rapid immunological changes in skin and peripheral blood in patients with psoriasis.

BACKGROUND: Ultraviolet (UV) radiation has immunosuppressive effects and heliotherapy is a well-described treatment modality for psoriasis. OBJECTIVES: To characterize early sun-induced immunological changes both local and systemic in patients with psoriasis. METHODS: Twenty patients with moderate to severe psoriasis were subjected to controlled sun exposure on Gran Canaria, Canary Islands, Spain. Psoriasis Area and Severity Index (PASI) scores were evaluated. Skin biopsies were obtained from lesional and nonlesional skin in 10 patients at baseline and on day 16 and from five additional patients on day 2. Specimens were examined with immunohistochemistry and polymerase chain reaction. Blood samples were obtained from all patients at the same time points and were examined for T-cell subsets and cytokine production. RESULTS: Significant clinical improvement was achieved during the study period. CD4+ and CD8+ T cells in lesional skin were significantly reduced in both the epidermis and dermis. In contrast, dermal FOXP3+ T cells were relatively increased. In the peripheral blood skin homing cutaneous lymphocyte-associated antigen (CLA)+ T cells were significantly decreased after only 1 day in the sun and in vitro stimulated peripheral blood mononuclear cells demonstrated reduced capacity to secrete cytokines after 16 days. CONCLUSIONS: Our data show that clinical improvement of psoriasis following sun exposure is preceded by a rapid reduction in local and systemic inflammatory markers, strongly suggesting that immune modulation mediated the observed clinical effect. We cannot completely rule out that other mechanisms, such as stress reduction, may contribute, but it is extensively documented that UV irradiation is a potent inducer of immunosuppression and we therefore conclude that the observed effect was primarily due to sun exposure.

Effect of climate therapy at Gran Canaria on vitamin D production, blood glucose and lipids in patients with psoriasis.

BACKGROUND: Climate therapy (heliotherapy) of psoriasis is an effective and natural treatment. Ultraviolet radiation (UVB) from the sun improves psoriasis and induces vitamin D(3) synthesis. OBJECTIVE: The aim of the study was to investigate the effect of climate therapy on vitamin D(3) synthesis, blood glucose, lipids and vitamin B12 in psoriasis patients. METHODS: Twenty Caucasian patients (6 women and 14 men; mean age, 47.2 years; range, 24-65) with moderate to severe psoriasis [mean Psoriasis Area and Severity Index (PASI) score 9.8; range, 3.8-18.8] received climate therapy at the Gran Canarias for 3 weeks. Blood samples were drawn before and after 15 days of sun exposure. In addition, the patients' individual skin UV doses based on UV measurements were estimated. RESULTS: Sun exposure for 15 days lead to a 72.8% (+/- 18.0 SD) reduction in the PASI score in psoriasis patients. Although no direct correlation was observed between PASI score improvement and UVB dose, the sun exposure improved the vitamin D, lipid and carbohydrate status of the patients. The serum concentrations of 25-hydroxyvitamin D [25(OH)D] increased from 57.2 +/- 14.9 nmol/L before therapy to 104.5 +/- 15.8 nmol/L (P < 0.0001) after 15 days of sun exposure; the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] increased from 146.5 +/- 42.0 to 182.7 +/- 59.1 pmol/L (P = 0.01); the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol decreased from 2.4 to 1.9 (P < 0.001); and the haemoglobin A(1)c (HbA(1)c) levels decreased from 5.6 +/- 1.7% to 5.1 +/- 0.3% (P < 0.0001). CONCLUSION: Climate therapy with sun exposure had a positive effect on psoriasis, vitamin D production, lipid and carbohydrate status.

Bioavailability of aminolaevulinic acid and methylaminolaevulinate in basal cell carcinomas: a perfusion study using microdialysis in vivo.

BACKGROUND: Photodynamic therapy is becoming a popular treatment for superficial nonmelanoma precancerous and cancerous lesions, showing excellent cosmetic results. Nevertheless, the reported cure rates vary and the transdermal penetration of drugs has been discussed as a limiting factor, particularly for treatment of nodular basal cell carcinoma (BCC). OBJECTIVES: To investigate the transdermal penetration of aminolaevulinic acid (ALA) and methylaminolaevulinate (MAL) in BCC in vivo using a microdialysis technique. The different prodrugs were compared and the effect of curettage was studied. METHODS: Twenty patients with 27 histologically verified BCCs (13 superficial, 14 nodular) were included. All lesions were located at the front of the body (head and face excluded). The first 10 patients included were treated with MAL (13 BCCs), and the following 10 patients with ALA (14 BCCs). A light curettage was performed on every second lesion (curettage, n = 13; noncurettage, n = 14). Microdialysis catheters were inserted into the tumours at tissue depths varying from 0.4 to 1.9 mm. Dialysates were collected at 15-30-min intervals for 4 h and the interstitial concentrations of MAL and ALA were determined using high-performance liquid chromatography. RESULTS: No significant difference in interstitial drug concentration was observed between lesions treated with ALA or MAL during the 4-h measurement period. However, for the lesions with deeper catheter locations, i.e. at or below 1 mm (n = 11), drug concentrations above the detection limit were obtained in only six lesions. All but one BCC with superficial catheter location, i.e. < 1 mm (n = 16), exhibited detectable drug concentration (P = 0.026). The interstitial peak concentrations were reached within 90 min in 23 of the 27 BCCs, but were not found to be correlated with the depth of the catheters. No difference was found when comparing superficial and nodular BCCs, and the effect of curettage was found to be negligible. CONCLUSIONS: The results imply that there is no significant difference in transdermal penetration of ALA and MAL in tumour tissue. Detectable levels of drug were not obtained in almost 50% of the lesions where catheters were situated 1-1.9 mm in the lesion. Curettage was not found to affect the interstitial concentration, indicating that penetration of drug indeed might be a problem when treating BCCs thicker than 1 mm.

Patients with hyperhidrosis have changed grip force, coefficient of friction and safety margin.

OBJECTIVE: To evaluate whether subjects with palmar hyperhidrosis have functional problems with the handgrip caused by the wet slippery surface of palm and fingertips. We used two different dosages of botulinum toxin to explore its impact on sweating and on muscle strength in the hand. METHOD: Using an object equipped with force sensors we measured the muscle strength and calculated the coefficients of friction and safety margin (SM) in the precision grip before and 2, 4, 6, 8 10-12 weeks and 6 months after treatment of 13 patients with two different doses of botulinum toxin. Sweat evaporation was measured simultaneously. RESULTS: A significant decrease in evaporation and a parallel reduction of grip force in the dominant hand of the patients were observed. The SM used by the patients was significantly lower after the treatment, and increased gradually when sweating reappeared. CONCLUSION: These measurements showed, for the first time, that hyperhidrosis of the palms may cause an objective perturbation of the hand function which may be partially corrected by botulinum toxin treatment.

Daily pattern of sweating and response to stress and exercise in patients with palmar hyperhidrosis.

BACKGROUND: Focal hyperhidrosis is an embarrassing condition that can have a significant negative impact on patient quality of life. It is characterized by excessive sweating affecting a variety of areas, including the palms. Little is known about the daily pattern of sweating in patients with palmar hyperhidrosis. OBJECTIVES: To compare the variation of sweating in patients with primary palmar hyperhidrosis with healthy individuals during daily activities. METHODS: Twenty patients with primary palmar hyperhidrosis and 20 healthy age- and sex-matched subjects were studied. Each participant self-assessed rates of sweating for 7 days on an hourly basis using a subjective evaluation scale (SES) ranging from 0 to 10. RESULTS: The 3763 assessments showed clear differences between patients and healthy controls (median SES score 5 and 0, respectively; P < 0.0001). Stress and exercise significantly increased SES by scores of 2-5 in both groups, with stress influencing patients more than controls. SES scores in patients varied significantly, from 0 to 2 during mornings and evenings, and between 5 and 6 at mid-day, while scores in control subjects remained consistently close to 0. The pattern of change depended weakly on sex and weekday/weekend distinction. Dynamic responses to stress and exercise in patients had the tendency to return to baseline more slowly than in controls. CONCLUSIONS: Hourly changes in sweating rates can be assessed successfully through self-assessment. Patients with primary palmar focal hyperhidrosis reported significantly increased palmar sweating and daily patterns of sweating showing considerable variation dependent on factors such as time of day and emotional stimuli.

No compensatory sweating after botulinum toxin treatment of palmar hyperhidrosis.

BACKGROUND: Primary focal hyperhidrosis is caused by excessive secretion by eccrine sweat glands, usually at the palms, soles and axillae. The underlying mechanism is unclear. In recent years botulinum toxin A has emerged as a useful treatment. Compensatory sweating, which is a major problem in many patients who have undergone transthoracic endoscopic sympathectomy for hyperhidrosis, has only rarely been reported after botulinum toxin. However, this potential side-effect of botulinum toxin treatment has not been systematically examined. OBJECTIVES: To investigate if treatment with botulinum toxin A in hyperhidrotic hands may cause compensatory sweating at other skin locations. METHODS: In 17 patients with a history of palmar hyperhidrosis repeated measurements of evaporation were made before and up to 6 months after treatment of the hands with botulinum toxin A. Recordings were made at 16 skin areas and compared with subjective estimates of sweating. RESULTS: Following treatment, palmar evaporation decreased markedly and then returned slowly towards pretreatment values, but was still significantly reduced 6 months after treatment. No significant increase of sweating was found after treatment in any nontreated skin area. CONCLUSIONS: Successful treatment of palmar hyperhidrosis with botulinum toxin does not evoke compensatory hyperhidrosis in nontreated skin territories.

A new calcipotriol/betamethasone formulation with rapid onset of action was superior to monotherapy with betamethasone dipropionate or calcipotriol in psoriasis vulgaris.

In this study, we compared a new combination ointment containing both calcipotriol and betamethasone dipropionate with betamethasone dipropionate ointment (Diprosone) and calcipotriol ointment (Daivonex) in patients with psoriasis vulgaris; 1106 patients were randomized to twice daily double-blind treatment with combination, betamethasone dipropionate or calcipotriol for 4 weeks. Patients then received twice daily calcipotriol, unblinded, for a further 4 weeks. Mean percentage change in PASI at end of the double-blind phase was -74.4 (combination group), -61.3 (betamethasone group) and -55.3 (calcipotriol group). Mean difference (95% Cl) combination-betamethasone was -13.1 (-16.9 to -9.3, p < 0.001) and for combination-calcipotriol -19.0 (-22.8 to -15.2, p <0.001). The differences in PASI were also statistically significant after 1 week. In the double-blind phase, 8.1% of patients (combination) reported lesional/ perilesional adverse reactions compared to 4.7% (betamethasone) and 12.0% (calcipotriol). In the combination group, mean PASI at the end of the double-blind phase was 2.5, and at end of the unblinded phase 3.6, compared with 3.9 and 4.1 (betamethasone) and 4.4 and 3.7 (calcipotriol). Calcipotriol/betamethasone combination is more effective and has a more rapid onset of action than either active constituent used alone, and is well tolerated. It is safe to transfer patients from combination to calcipotriol, with maintenance of clinical effect.

Thin fibre territories of nerves innervating hairs in the human forearm estimated from axon reflex vasodilatations.

1. To study the territories of thin nerve fibres innervating hair follicles, we extracted single hairs from forearm skin. Scanning laser Doppler methodology was used to measure the evoked local increase of skin perfusion, the underlying assumption being that axon reflex vasodilatation would be evoked within the territory of extraction-activated thin nerve fibres. Ninety-two single hairs were extracted in 14 healthy males. 2. In 93 % of the cases perfusion increased transiently near the site of the extracted hair. No responses occurred when arm blood flow was occluded. In support of an underlying axon reflex mechanism the intensity of hair extraction-evoked pain correlated with the peak area of the response. In addition, after pre-extraction local anaesthesia, response components were seen in only 50 % of the cases and when they occurred they were very small. 3. The response had two components which could occur independently of each other. An early short-lasting component consisted of one or several separate areas with a peak total extension of 176 +/- 176 mm(2) (mean +/- S.D.), a peak maximal intensity (in percentage of pre-extraction perfusion) of 484 +/- 272 %, and a duration of 6-8 min. A later long-lasting component consisted of a single area of 51 +/- 107 mm(2), an intensity of 342 +/- 301 % and a duration of up to approximately 60 min. Perfusion could be influenced from a single hair in an asymmetrical skin area with diameters at right angles of 23 +/- 9 and 16 +/- 9 mm, respectively. 4. We suggest that the responses were evoked by two sets of thin nerve fibres, one at a superficial level with fairly large innervation territories, and the other located more deeply close to the hair follicle and with smaller innervation territories.

Microdialysis of histamine in the skin of patients with mastocytosis.

Mastocytosis represents a group of disorders characterized by the proliferation and accumulation of mast cells in tissue. The aim of the present study was to examine whether the interstitial histamine concentration in the skin is increased in mastocytosis patients and whether it correlates with the number of mast cells, the amount of metabolite N-methyl-imidazole acetic acid in the urine and the tryptase in serum. In 7 mastocytosis patients on a standardized diet, the analysis of histamine was performed on microdialysates obtained from catheters positioned intracutaneously in involved and uninvolved skin. N-methyl-imidazole acetic acid in the urine was collected for 24 h. Biopsies for analyses of mast cells were taken from skin adjacent to the microdialysis catheters. The histamine concentrations were 42+/-14, 12+/-3 (P<0.05) and 8+/-2 nmol/l (mean+/-SEM, n=7) in skin eruptions, non-lesional skin and plasma respectively. Mean N-methyl-imidazole acetic acid in the urine (9.7+/-3.5 mmol/mol creatinine) and mean tryptase (124+/-54 microg/l) had increased in all patients. In the present study, no linear correlation was found between these parameters and interstitial histamine in lesional skin. This finding corresponds to the fact that the concentration of histamine metabolites and tryptase derives from the entire mast-cell population, while interstitial histamine in the dermis represents the local tissue concentration before metabolic transformation. The microdialysis of histamine in the skin of mastocytosis patients could be used as a tool to investigate the effects of dermal mast-cell histamine release in different kinds of treatment regimen.

Delta-aminolevulinic acid in superficial basal cell carcinomas and normal skin-a microdialysis and perfusion study.

Delta-aminolevulinic acid (ALA) is used for photodynamic therapy of basal cell carcinoma (BCC) as it is converted to protoporphyrin IX in tumour tissue. During illumination with 635 nm light a photochemical reaction takes place, singlet oxygen is generated and the tumour destroyed. In this study we used the microdialysis technique to quantify the concentration of ALA at a certain depth in tumour and healthy skin. The penetration ability of ALA was investigated as a function of time in BCCs (n = 14) and in normal skin (n = 4) after topical application. The microdialysis catheters were inserted intracutaneously and the depth position recorded by means of ultrasound. Microdialysate sample concentrations of amino acids and ALA were determined by high performance ion-exchange chromatography. A laser Doppler perfusion imager measured perfusion in the BCCs. The data show that the average depth of the microdialysis catheters was 0.5 mm. The interstitial ALA concentration in the BCCs increased from 0 to 3.1 mmol/L 15 min after application of ALA, whereas no measurable amounts of ALA were found in healthy skin. The blood perfusion was 2.5-fold increased in the BCCs. The interstitial levels of amino acids were not significantly changed during the ALA treatment. In summary, we found that ALA rapidly penetrates tumour skin. We conclude that microdialysis seems to be well suited for pharmacodynamic studies of ALA in skin.

Capsaicin treatment induces histamine release and perfusion changes in psoriatic skin.

To determine whether neurogenic factors may be of importance in the regulation of histamine release and blood flow in psoriatic plaque, the effect of capsaicin was studied in 22 psoriatic patients with active, untreated psoriatic lesions. In each of 12 patients, one microdialysis fibre was placed in non-lesional skin and one was placed in lesional skin at depths of 0.7 and 0.9 mm, respectively. Dialysates were collected for the analysis of histamine in the resting state and after 60 min of repetitive epicutaneous application of 1% capsaicin above the microdialysis catheter. In 10 patients, topical capsaicin and placebo were applied for 24 h to lesional/lesion-free skin. Skin blood flow and perfusion (evaluated using the 133xenon clearance technique and scanning laser Doppler, respectively) were measured before the application of capsaicin and after removal. After 60 min of capsaicin treatment, both the perfusion and interstitial concentration of histamine, as well as the net release of histamine, were significantly increased in affected (from 38 +/- 6 to 45 +/- 6 nmol/L, mean +/- SEM) and unaffected (from 15 +/- 2 to 19 +/- 2 nmol/L) skin. Compared with placebo, 24 h of treatment with capsaicin caused a 15% decrease in perfusion in lesional skin. The results are compatible with the hypothesis that capsaicin-sensitive nerves may induce histamine release in non-lesional and lesional skin and that afferent unmyelinated nerve fibres may contribute to the high blood flow in psoriatic plaques.

Nerve-induced histamine release is of little importance in psoriatic skin.

Psoriatic plaques contain an increased number of mast cells. Both the histamine concentration and release are increased in lesional skin but the underlying mechanisms are unclear. One hypothesis is that neuropeptides transmitted from thin sensory cutaneous nerves continuously stimulate mast cell release of histamine. The aim of this study was to test this hypothesis by examining if topical anaesthesia of these nerves inhibits histamine release in psoriatic skin. The concentration of histamine was measured in microdialysates obtained from lesional and non-lesional skin before and during topical anaesthesia. Concomitantly skin blood flow was measured with scanning laser Doppler (perfusion) and/or 133Xe clearance (flow) techniques in the microdialysis area. The histamine concentrations (mean +/- SEM) were 34 +/- 4 (n = 21), 14 +/- 1.5 (n = 18) (P < 0. 001) and 2.8 +/- 1 nmol/L (n = 10) in lesional and non-lesional skin and plasma, respectively. After anaesthesia of the microdialysis areas the histamine concentration in psoriatic skin increased to 44 +/- 4 nmol/L (n = 19, P < 0.05), but remained unaltered in uninvolved skin. In anaesthetized lesional skin the perfusion decreased from 3.7 +/- 0.2 to 2.5 +/- 0.3 V and blood flow decreased from 14 +/- 5 to 9 +/- 1 mL/min per 100 g (P < 0.001, n = 10). The calculated release of dermal histamine in involved skin (198 +/- 30 pmol/min per 100 g, n = 10) remained unchanged after local anaesthesia. The results indicate that neurogenic activation of mast cells is of minor importance for continuous histamine release in psoriatic skin and that the vasodilatation in the psoriatic plaque is not mediated by histamine.

Increased interstitial histamine concentration in the psoriatic plaque.

The psoriatic plaque contains an increased number of mast cells that are thought to have an important role in the initiation and maintenance of psoriatic lesions through the release of mediators such as histamine, proteoglycans, lipid mediators, and cytokines. It is not known, however, whether the interstitial concentration of histamine (and other mediators) is truly increased in the psoriatic plaque. The aim of the present study was to examine histamine concentration and histamine release from involved and uninvolved skin of psoriatic patients. Intracutaneous microdialysis was performed in lesional and nonlesional skin of 23 psoriatic subjects. The relative recovery of histamine was assessed after calibration in situ to approximately 76% in both lesional and nonlesional skin. The interstitial histamine concentration was 32 +/- 3 nmol per liter in lesional skin and 13 +/- 1 nmol per liter in nonlesional skin (mean +/- SEM) (p < 0.001). Dermal histamine release was estimated according to the Fick principle after measurements of the arterialized venous plasma histamine concentration (3 +/- 1 nmol per liter) and blood flow and was found to be 10-fold increased in lesional compared with nonlesional skin. The results are compatible with the hypothesis that mast cells in lesional skin secrete an increased amount of histamine that may contribute to the immunostimulation and inflammation in the psoriatic plaque.

Assessment of erythema and skin perfusion by digital image analysis and scanner laser Doppler.

BACKGROUND/AIMS: In the present study, a model for measuring the intensity of skin erythema by computer-assisted digital image analysis (DIA) was elaborated. The DIA technique was compared with laser Doppler perfusion imaging (PIM) to evaluate the relationship between erythema and skin perfusion. METHODS: To produce erythema, three different types of nicotine patches (Nicotinell®, Nicorette® and Nicorette® placebo) were randomly applied ventrally on the upper arms for the time period recommended by the manufactures. After removal of the patches, colour photographs for subsequent DIA were taken and laser Doppler scanning for PIM was performed. The relationship between PIM and DIA was estimated intra- and inter-individually. RESULTS/CONCLUSIONS: A statistically significant linear correlation between PIM and DIA data was found, but the relationship was relatively weak. This may be explained by the fact that DIA and PIM are influenced by different physiological factors such as skin chromophores and velocity of moving cells. The results strengthen the theory that erythema and perfusion measurements reflect separate physiological phenomena and that the methods should be considered complements to each other in the experimental situation.

Microdialysis measurements in skin: evidence for significant lactate release in healthy humans.

To assess net lactate release from dermal skin, seven lean, healthy men were studied after overnight fasting. Two microdialysis catheters were inserted in the upper dermal tissue, as ensured by ultrasound scanning, in the periumbilical area. Each catheter was calibrated in situ to get an estimate of the lactate concentration in interstitial fluid (1,001 +/- 24 mumol/l), which in turn enabled calculation of the local capillary-venous lactate concentration (963 +/- 25 mumol/l). Concomitantly, arterialized venous plasma lactate (673 +/- 32 mumol/l), blood hematocrit (43 +/- 1%), and skin blood flow (3.8 +/- 0.9 ml.100 g-1.min-1) as measured by 133Xe clearance were determined, and dermal apparent lactate release (570 +/- 89 nmol.100 g-1.min-1) was estimated according to the Fick principle. During an oral glucose tolerance test (OGTT, 75 g), the dermal interstitial-arterial lactate difference decreased significantly to reach a nadir at 60 min. Moreover, no significant increase in skin blood flow was seen during the OGTT. In conclusion, we found a significant net lactate release from abdominal dermal skin after overnight fasting, whereas no significant increase was observed during an OGTT.

Microdialysis methodology for the measurement of dermal interstitial fluid in humans.

In this study we aimed to validate the microdialysis technique for metabolic measurements in the dermal interstitial fluid. The abdominal and forearm skin was used for microdialysis in 15 healthy normal weight volunteers. The depth of the microdialysis catheter was assessed by ultrasound measurement. Structural impairment and blood flow were judged from biopsies and from laser Doppler measurements taken adjacent to the catheters. Dermal interstitial lactate and pyruvate concentrations were measured, under steady state fasting conditions, after equilibrium calibration of each catheter in situ. The dermal interstitial glucose concentration was estimated by means of the retrodialysis calibration method, which has previously not been evaluated for skin microdialysis. The mean catheter depth (+/- standard deviation) was 0.8 +/- 0.3 mm. Small areas of localized bleeding, but no inflammatory reaction, was found surrounding the catheters. The perfusion in the microdialysis region was slightly increased (15-25%). The lactate/pyruvate ratio (12 +/- 0.7) showed non-ischaemic values. The dermal interstitial lactate concentration was significantly higher (1171 +/- 228 mumol/l) than the plasma lactate (781 +/- 180 mumol/l), indicating an ongoing nonoxidative glucose metabolism. Retrodialysis calibration correctly estimated the dermal glucose level to be similar to that in plasma, which may indicate the usefulness of this calibration method for microdialysis studies of endogenous substrates in the dermal interstitial fluid.

Visual scoring and laser Doppler perfusion imaging of skin irritancy induced by different nicotine patches.

BACKGROUND/AIMS: Local skin reactions are the most common reason for discontinuation of transdermal nicotine replacement therapy in smoking cessation programs. The aims of the present study were (1) to quantify the intensity of skin reactions induced by different types of nicotine patches and (2) to compare the clinical evaluation of skin erythema using visual scores with independently performed quantitative estimates of skin perfusion. METHODS: Thirty-three subjects were included in the study, each receiving 2 different types of nicotine patches (Nicotinell and Nicorette) and 1 type of placebo patch (Nicorette), placed ventrally on the upper arms according to a randomized protocol. Patches were removed after 24 h (Nicotinell) and 16 h (Nicorette), respectively, according to recommended application times. Visual scoring and laser Doppler perfusion imaging were performed 45 min after removal of patches, in a randomized order. RESULTS: Nicotinell patches induced the highest cumulative clinical score for skin irritancy. All 3 investigated patches gave rise to a slight but significant skin perfusion increase and individual visual scores and perfusion data correlated. Conclusion The degree of skin irritancy and underlying perfusion increase induced by 1 daily maintenance dose of transdermal nicotine via a patch is low, but differs between patch types.

Arteriovenous anastomoses and the thermoregulatory shift between cutaneous vasoconstrictor and vasodilator reflexes.

The reflex changes in skin blood flow which occur in response to various non-thermal stimuli (e.g., deep inspiratory gasps, arousing or painful stimuli, emotional stress) are profoundly influenced by the thermoregulatory state. The aim of the present study was to evaluate the involvement of arteriovenous anastomoses in the thermoregulatory modulation of skin vasomotor reflexes elicited by painful intraneural electrical stimulation and emotional stress (forced arithmetics), respectively. Vasomotor responses were recorded with laser Doppler flowmeters (LDF) placed on glabrous skin containing arteriovenous anastomoses (3rd finger and thenar eminence) and hairy skin which lack them (dorsal side of the first metacarpal bone). In some experiments, a laser Doppler flowmeter emitting laser light of two different wavelengths (infrared and green light) into the same skin site was used to record skin perfusion at different depths of glabrous skin on the thenar eminence. 40 subjects were investigated, both in the cold state (finger skin temperatures below 25 degrees C) and after subsequent warming (finger skin temperatures above 30 degrees C). Thermoregulatory modulation of electrical stimulation- or stress-induced vasomotor reflexes occurred both in glabrous and hairy skin, but hairy skin differed from glabrous skin by showing no significant vasoconstrictions. Relative perfusion changes were most marked in laser Doppler flowmeter recordings using the deeper penetrating infrared light. The results suggest that arteriovenous anastomoses are major contributors to the vasoconstrictor component of vasomotor reflexes in glabrous skin of warm subjects. The reflex increase in perfusion, on the other hand, which occurs in both glabrous and hairy skin of cold subjects may be mediated by resistance vessels.