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.

Scleredema adultorum associated with a monoclonal gammopathy and generalized hyperpigmentation.

Scleredema associated with a monoclonal gammopathy and generalized skin pigmentation is described in a 56-year-old man with hyperlipoproteinemia and cardiovascular disease. The patient had IgG-lambda paraproteinemia, without any evidence of multiple myeloma or immunoglobulin deposition in affected skin. Ultrastructural studies of pigmented lesional skin showed increased transfer of melanosomes to basal keratinocytes and dermal melanophages containing complex melanosomes. In addition, cytoplasmic, electron-opaque lipid droplets were seen in approximately every third keratinocyte or melanocyte, while only an occasional dermal cell contained lipid droplets. The hyperpigmentation appeared to be directly related to the scleredema, while the lipid deposition in skin was a likely consequence of the hyperlipoproteinemia. The findings further support the contention that paraproteinemia and hyperpigmentation may, in some patients, be associated features of scleredema adultorum.

The influence of atrioventricular conduction and heart rate on the pulmonary venous flow pattern.

The pulmonary venous flow (PVQ) pattern usually has two antegrade flow waves, corresponding to ventricular systole and diastole, respectively, and is used to assess left atrial pressure. To study the effects of atrioventricular conduction (AVD) and heart rate (HR) on the PVQ pattern, transthoracic pulsed Doppler recordings of pulmonary venous, transmitral, and aortic flow were made in five healthy subjects with dual-chamber pacemakers. Recordings were made at HRs of 80, 100, and 120 beats/min, with AVDs of 75, 150, and 220 msec at each HR. When the AVD was increased, the biphasic PVQ changed to a monophasic pattern in which a single flow wave covered the transition between ventricular diastole and systole. There was a shift of flow from ventricular systole to diastole. When HR was increased, the systolic fraction of the PVQ increased as a result of an increase in the relative duration of systole. In conclusion, AVD and HR influenced the PVQ pattern in subjects without signs of ventricular dysfunction. This may be a limitation to the use of the flow pattern to assess left atrial pressure.

Dietary habits among patients with atopic dermatitis.

OBJECTIVE: To evaluate the dietary habits among adult patients with moderate to severe atopic dermatitis and relate intake to clinical symptoms. DESIGN: Data were obtained from a clinical trial. SETTING: Five departments of dermatology at Norwegian University hospitals. SUBJECTS: Outpatients, 46 men (median age 27 y) and 92 women (median age 28 y). METHOD: A quantitative food frequency questionnaire was filled in before attending the clinical trial. The results were compared to the diet of age- and sex-matched reference groups. RESULTS: Male patients had higher content of refined sugar in their diet than reference men (P=0.014). Among female patients, the intake of saturated fatty acids was higher (P=0.049), whereas the intake of very long-chain n-3 fatty acids was lower (eicosapentaenoic acid, P=0.032, docosahexaenoic acid, P=0.017) than in the reference group. In both genders, more patients than reference subjects had vitamin D intake below recommended level. Furthermore, the female patients had significantly lower intake of fruit compared to the reference group (P=0.002). No correlation was found between nutrient intake of the patients and their clinical scores. CONCLUSIONS: The patients's diet were fairly similar to the diet of reference groups. The intake of vitamin D and very long-chain n-3 fatty acids was low, especially among female patients. Furthermore, we could not detect any association between dietary habits and clinical status. European Journal of Clinical Nutrition (2000) 54, 93-97

Acute and chronic hemodynamic effects of enalapril (MK-421) in congestive heart failure.

Enalapril, a new long-acting angiotensin-converting enzyme inhibitor, was administered orally to 12 patients with stable congestive cardiac failure, NYHA function class III-IV. Acute and chronic hemodynamic effects were evaluated in addition to clinical response. The results of this open pilot study indicated marked reduction of pulmonary capillary wedge pressure from 21.8 +/- 5.9 mm Hg (mean +/- 1 SD) to 13.3 +/- 4.5 mm Hg (P less than 0.01) and peripheral resistance from 1837 +/- 860 dynes X sec-1 X cm-5 to 1063 +/- 584 dynes X sec-1 X cm-5 at 6 hr (P less than 0.01). Well-tolerated hypotension with mean arterial pressure from 88.0 +/- 11.6 mm Hg to 73.1 +/- 11.7 mm Hg at 6 hr (P less than 0.01) was recorded. No significant increase in cardiac output was observed. Angiotensin-converting enzyme activity was powerfully inhibited at the time of peak hemodynamic effect from 25.3 +/- 9.8 U/ml to 4.9 +/- 3.4 U/ml (P less than 0.01) and sustained, but attenuated reduction at 24 hr (8.7 +/- 4.7 U/ml) was observed. All patients reported subjective improvement and this clinical improvement has been sustained during follow-up from 19 to 21 months although baseline hemodynamic parameters at chronic re-catheterization did not demonstrate significant improvement. The pharmacodynamics and toxicity of enalapril as compared to captopril are discussed. The long half-life, low toxicity and gradual onset of action are seen as representing a clinical advantage with regard to patient therapy.

Sustained haemodynamic effects of enalapril in left ventricular failure.

Enalapril, a novel angiotensin converting enzyme inhibitor, was given orally to 12 patients with chronic heart failure (NYHA functional class III and VI) and cardiomegaly. Heart rate, systemic arterial blood pressure, pulmonary arterial pressure, right and left ventricular filling pressures and cardiac index were monitored during dose efficacy titration. The optimal dose averaged 17 mg given once-daily. All patients were recatheterized three months later. After stabilization of cardiac filling pressures, all patients had left ventricular filling pressures in excess of 18 mmHg. Enalapril increased cardiac index acutely by 34% but at 12 weeks follow-up, cardiac index was not different from control levels. Left ventricular filling pressure was reduced acutely by 36% and by 41% at three months. Heart rate, systemic arterial and right atrial pressures and plasma concentrations of aldosterone were reduced during the observation period. Renin was markedly elevated. These changes were accompanied by marked and sustained clinical improvement and subjective well-being.

Difference between beta-1-selective and non-selective beta-blockade during continuous and intermittent exercise.

Limiting factors of maximal exercise performance are not clearly defined. In order to differentiate between various factors, maximal exercise was studied during continuous (n = 12) and intermittent (n = 9) exercise. The non-selective beta-blocker timolol (10 mg b.i.d. for 5 days) was compared double-blind and placebo controlled with the beta-1-selective beta-blocker metoprolol (100 mg b.i.d. for 5 days), with respect to effect on maximal exercise tolerance. Total cumulated work was comparable during continuous and intermittent exercise. Timolol and metoprolol reduced maximal exercise performance. No difference was observed between the two beta-blockers during intermittent exercise. The non-selective beta-blocker caused a greater reduction in exercise performance (10.4%) than the beta-1-selective beta-blocker (4.7%) (P less than 0.05) during continuous exercise. Maximal heart rate was higher with metoprolol than timolol during continuous exercise. The non-selective beta-blocker caused a slightly greater inhibition of lipolysis than the beta-1 selective one. No significant differences in glucose concentrations were observed between the treatment regimens. Exercise caused a marked increase in serum potassium concentrations. Beta-blockade caused further increase in potassium at any given workload. This study indicates that maximal working capacity is comparable during continuous and intermittent exercise. Beta-1-selective and non-selective beta-blockade reduce the maximal working capacity, non-selective more than beta-1-selective. Substrate availability was not responsible for the beta-blocker induced reduction of the working capacity. The rate of rise in serum potassium was significantly higher during beta-blockade and may, therefore, be a limiting factor for the maximal working capacity.

[Beta blockaders and physical performance. Limiting factors]. / Betablokkere og fysisk arbeidstoleranse. Begrensende faktorer.

Beta blockers are known to cause reduced exercise performance in hypertensive and healthy subjects. Additive effects of selective blockade of beta-1 and beta-2 receptor subtypes seems to account for the total reduction in exercise capacity observed with non-selective beta-1,2 blockade. The mechanism is as yet undefined. The magnitude of the reduction is dependent of type of exercise and level of fitness. Hemodynamic parameters, substrate delivery to the working muscles, mental factors, and interference with potassium homeostasis may be involved.

Cardiovascular responses to face immersion and apnea during steady state muscle exercise. A heart catheterization study on humans.

The cardiovascular adjustments to face immersion and apnea (FIA) in human beings during steady-state muscle exercise (163 and 98 watt) have been investigated. Using a triple lumen flow directed catheter inserted into the pulmonary artery we were able to measure cardiac output (CO) by thermodilution technique, pulmonary arterial pressure (PPA) right atrial pressure (PRA) and left ventricular filling pressure (PAD). Phasic arterial blood pressure (BP) was measured via a cannula in the radial artery. A 12 lead ECG was recorded continuously. FIA caused an immediate rise in BP (median 61%), the highest level being 25.33 kPa. CO during the last half of FIA was reduced by 49% (range 46-59, n = 7) systemic vascular resistance increased by median 200% (range 111-280). Myocardial oxygen demand determined by the heart rate pressure double product fell from median 33.6 to 16.8 (163 W) and 28.5 to 19.1 (98 W) given as beats/min X kPa X 10(2). Mean reduction was by 42%. PPA and PRA immediately increased and remained constant until a further pronounced increase was seen towards the end of FIA when pulmonary vascular resistance (PVR) went up. PACO2 and PAO2 at the end of 30 sec FIA (163 W) was 10.0 and 5.6 kPa, respectively, values which expectedly would cause pulmonary vasoconstriction. Our findings demonstrate that humans are able to make principally the same cardiovascular adjustments to diving as aquatic mammals, although the response patterns are slower and less efficient.(ABSTRACT TRUNCATED AT 250 WORDS)

Escape rhythm in complete A-V block. The recovery phase after overdrive suppression from artificial ventricular suppression from artificial ventricular pacing.

In 60 patients with third degree A-V block, recovery of escape rhythm from overdrive suppression after ventricular pacing has been studied. Implanted unipolar VVI pacemakers were inhibited by chest wall stimuli. A total of 165 rhythmograms were studied. In 37, the rate was irregular, in the other 128 the escape rate increased gradually, following an exponential curve until stabilization after 3 minutes. In 29 of these rhythmograms, a possible exit block of the first escape impulse was observed. In 99 rhythmograms without exit block, escape rhythm recovery time was an average 1.45 times basal escape RR intervals. Overdrive suppression was most marked in patients with a slow escape rhythm.

Dietary supplementation with very long-chain n-3 fatty acids in man decreases expression of the interleukin-2 receptor (CD25) on mitogen-stimulated lymphocytes from patients with inflammatory skin diseases.

T-cell activation and cytokine production play an important role in several chronic inflammatory diseases. Because n-3 fatty acids exert beneficial effects on the clinical state of some of these diseases, we examined the effect of dietary supplementation of n-3 fatty acids on T-cell proliferation, expression of CD25 (interleukin-2 receptor alpha-chain), secretion of interleukin-2, interleukin-6 and tumour necrosis factor from T-cells from patients with psoriasis and atopic dermatitis. During 4 months, 21 patients supplied 6 g of highly concentrated ethyl esters of EPA and DHA in gelatin capsules daily to their diet. In the control group 20 patients supplied 6 g per day of corn oil in gelatin capsules to their diet. Eicosapentaenoic acid (20:5, n-3) of serum phospholipids increased from 14 (min 4-max 42) to 81 (min 59-max 144) mg l-1 (P < 0.01) in patients with atopic dermatitis receiving n-3 fatty acids, and from 25 (min 7-max 66) to 74 (min 46-max 142) mg l-1 (P < 0.01) in patients with psoriasis, whereas docosahexaenoic acid (22:6, n-3) increased from 65 (min 46-max 120) to 92 (min 54-max 121) mg l-1 (P < 0.05) and from 81 (min 38-max 122) to 92 (min 63-max 169) mg l-1 (NS) in atopic and psoriatic patients, respectively. The changes in the serum phospholipid fatty acid profile in the groups receiving n-3 fatty acids, correlate to the dietary intake of corresponding fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of n-3 fatty acid supplement to patients with atopic dermatitis.

The effects of dietary supplement with n-3 fatty acids to patients with atopic dermatitis were investigated in a 12-week, prospective, double-blind study. The experimental group received daily 10 g of fish oil, containing 3 g n-3 fatty acids, of which eicosapentaenoic acid represented about 1.8 g. The controls received an isoenergetic placebo supplement containing olive oil. Compliance was monitored by gas chromatographic analysis of fatty acid pattern in serum phospholipids. Results favoured the experimental group with regard to scale (P less than 0.05), itch (P less than 0.05) and overall subjective severity (P less than 0.02) as compared to the controls.

Effect of dietary supplementation with eicosapentaenoic acid in the treatment of atopic dermatitis.

The effects of a dietary supplement of n-3 fatty acids in patients with atopic dermatitis were investigated in a 12-week, double-blind study. The experimental group received 10 g of fish oil daily, of which about 1.8 g was eicosapentaenoic acid. This amount of eicosapentaenoic acid can be obtained from a daily intake of fat fish. The controls received an iso-energetic placebo supplement containing olive oil. Compliance was monitored by gas-chromatographic analysis of the fatty acid pattern in serum phospholipids. Results favoured the experimental group with regard to scale (P less than 0.05), itch (P less than 0.05) and overall subjective severity (P less than 0.02) as compared to the controls.

Oral magnesium supplementation improves metabolic variables and muscle strength in alcoholics.

Magnesium deficiency is common among chronic alcoholics, but the knowledge of oral magnesium supplementation to this group is limited. We, therefore, randomized 49 chronic alcoholics, moderate to heavy drinkers for at least 10 years to receive oral magnesium or placebo treatment for 6 weeks according to a double-blind protocol. Effects on metabolic variables and muscle strength were analyzed. Significant reduction of aspartate-aminotransferase (ASAT), alanine-aminotransferase (ALAT) and gamma-glutamyl-transpeptidase (GGT) were seen after magnesium, whereas no change was observed with placebo. Bilirubin decreased in both groups. Serum Na, Ca, and P increased significantly during magnesium therapy compared with no statistically significant change in the placebo group. Serum K and Mg increased slightly after magnesium supplementation and decreased in the placebo group, resulting in a significant difference between the two groups at the end of the study. Muscle strength increased significantly during magnesium treatment, contrasting to no change with placebo. Blood pressure, heart rate, hematological variables, serum lipids (cholesterol, HDL, TG), glucose tolerance, and creatinine were unchanged in the two groups after treatment. Alcohol consumption was similar before and during the trial and does not explain the differences between the two groups The results shows that short-term oral magnesium therapy may improve liver cell function, electrolyte status, and muscle strength in chronic alcoholics.

Acute and long-term response to enalapril in congestive failure.

Enalapril, a novel long acting angiotensin converting enzyme (ACE) inhibitor, was given orally to 12 patients with chronic heart failure (NYHA functional class III and IV) and cardiomegaly. The optimal dose averaged 17 mg given once-daily. Heart rate, systemic arterial blood pressure, pulmonary arterial pressure, right and left ventricular filling pressures and cardiac index were monitored during dose efficacy titration. Eleven patients were recatheterised 3 months later. After stabilisation of cardiac filling pressures, all patients had left ventricular filling pressures in excess of 20 mmHg. Enalapril increased cardiac index acutely by 34% but at 12 weeks follow-up, cardiac index was not different from control levels. Left ventricular filling pressure was reduced acutely by 36% and by 41% at 3 months. Heart rate, systemic arterial and right atrial pressures and plasma concentrations of aldosterone were reduced during the observation period. ACE activity was inhibited at the time of peak haemodynamic effect from 25.3 +/- 9.8 to 4.9 +/- 3.4 U/ml (P less than 0.01). Renin was markedly elevated. These changes were accompanied by marked and sustained clinical improvement and subjective well-being.

Treatment of hypertensive and hypercholesterolaemic patients in general practice. The effect of captopril, atenolol and pravastatin combined with life style intervention.

OBJECTIVE: To elucidate the effect on blood pressure and blood lipids of an angiotensin converting enzyme inhibitor (captopril), and a beta-receptor blocking agent (atenolol), given alone or in combination with a cholesterol reducing drug, the beta-hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin, in patients who were also encouraged to improve their lifestyle. DESIGN: A longitudinal study consisting of three phases. I: Lifestyle intervention alone. II: Continued lifestyle intervention combined with captopril or atenolol. III: Continued lifestyle intervention combined with the same drugs as in phase II and in addition pravastatin or placebo. SETTING: Fifty-four general practice surgeries in Norway. PARTICIPANTS: Hypertensive patients, 210 females and 160 males, treated or untreated with antihypertensive drugs with a sitting diastolic blood pressure between 95 and 115 mmHg and a serum total cholesterol between 6.5 mmol/l (7.0 for those age 60-67 years) and 9.0 mmol/l. RESULTS: The antihypertensive effect of captopril and atenolol was not influenced by concurrent administration of pravastatin. The effect of pravastatin was not limited by concurrent medication with captopril or atenolol. Improvement in lifestyle seemed to reduce the need for supplementary treatment with diuretics. CONCLUSION: Pravastatin can be used in combination with captopril or atenolol in the treatment of hypertensive and hypercholesterolaemic patients.