Total colonic aganglionosis: multicentre study of surgical treatment and patient-reported outcomes up to adulthood.

BACKGROUND: Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. METHODS: An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. RESULTS: Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age. CONCLUSION: Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.

ANTECEDENTES: La cirugía de la aganglionosis colónica total (total colonic aganglionosis, TCA) está diseñada para preservar la continencia y lograr una calidad de vida satisfactoria. Este estudio evaluó un gran número de resultados clínicos y sociales. MÉTODOS: Se realizó un estudio internacional multicéntrico en ocho hospitales nórdicos en el que se incluyeron las historias clínicas de todos los pacientes nacidos con TCA entre 1987 y 2006. Se invitó a los pacientes y a sus cuidadores a responder una encuesta sobre la función intestinal, el crecimiento y las necesidades nutricionales, así como la repercusión social de la enfermedad a largo plazo. RESULTADOS: De un total de 116 pacientes, 5 (4,3%) habían fallecido y 102 respondieron la encuesta. Con una mediana de seguimiento de 12 años (rango 0,5-33), se había restablecido la continuidad intestinal en 75/102 (74%) a una mediana de edad de 11 meses (0,5-156). La mucosectomía con un manguito muscular corto y anastomosis ileoanal directa (short muscular cuff and straight ileo-anal anastomosis, SIAA) n = 29 o con reservorio en J (JIAA) n = 26 (55/72, 76%) fueron las reconstrucciones más habituales. Las complicaciones postoperatorias precoces que precisaron una intervención quirúrgica fueron muy poco frecuentes, pero se presentaron en 4/72 (5%) pacientes. Los síntomas a largo plazo relacionados con la función intestinal tras la reconstrucción, valorados en 57 niños mayores de cuatro años, fueron la dificultad para retener la defecación en 14 (25%), la encopresis en 21 (37%), las pérdidas fecales > 1/semana en 9 (16%) y el aumento de la frecuencia de defecación en 51 (89%). A largo plazo, se desarrolló una enterocolitis en 35/72 (47%) pacientes. Se precisó de nutrición enteral y/o parenteral suplementaria en algún momento del período de seguimiento en 51/93 (55%) pacientes. En los pacientes que respondieron a la encuesta entre 2 y 20 años (n = 56) de edad, se detectó un índice de masa corporal menor en 20 (35%) y una altura baja en 13 (23%) para su edad. En 35/57 (61%) pacientes mayores de 4 años con restauración del tránsito intestinal había restricciones sociales debido a los síntomas intestinales, de los que en 10 (17%) casos fueron moderadas o graves. CONCLUSIÓN: La reconstrucción de una TCA se asocia con síntomas intestinales persistentes y la enterocolitis sigue siendo frecuente. Un seguimiento multidisciplinario, incluso en la edad adulta, podría mejorar los resultados en la cirugía de la TCA.

Omalizumab rapidly improves angioedema-related quality of life in adult patients with chronic spontaneous urticaria: X-ACT study data.

BACKGROUND: The X-ACT study aimed to examine the effect of omalizumab treatment on quality of life (QoL) in chronic spontaneous urticaria (CSU) patients with angioedema refractory to high doses of H1 -antihistamines. METHODS: In X-ACT, a phase III, double-blind, placebo-controlled study, CSU patients (18-75 years) with ≥4 angioedema episodes during the 6 months before inclusion were randomized (1:1) to receive omalizumab 300 mg or placebo every 4 weeks for 28 weeks. Angioedema-related QoL, skin-related QoL impairment, and psychological well-being were assessed. RESULTS: Ninety-one patients were randomized and 68 (omalizumab, n = 35; placebo, n = 33) completed the 28-week treatment period. At baseline, the mean (SD) total Angioedema QoL (AE-QoL; 56.2 [18.7] and 59.9 [19.2]) and Dermatology Life Quality Index (DLQI; 14.6 [5.7] and 16.6 [7.3]) score were high in the omalizumab and placebo group, respectively. At Week 4 (after the first treatment), the least squares mean difference in the AE-QoL and DLQI score between groups was -17.6 (P < .001) and -7.2 (P < .001), respectively. Significant QoL improvements in the omalizumab vs placebo groups continued until Week 28, but returned to placebo levels at the follow-up visit. The mean (SD) baseline 5-item World Health Organization Well-being Index was 10.0 (5.5, omalizumab) and 7.7 (5.3, placebo), which increased above the depression threshold (<13) from Week 4 and throughout with omalizumab but not placebo treatment. Compared to placebo, omalizumab was also associated with decreased fear of suffocation due to angioedema. CONCLUSIONS: Our findings support omalizumab treatment in patients with severe H1-antihistamine-refractory CSU with angioedema.

Effect of omalizumab on angioedema in H1 -antihistamine-resistant chronic spontaneous urticaria patients: results from X-ACT, a randomized controlled trial.

BACKGROUND: Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. OBJECTIVE: The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. METHODS: X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072). RESULTS: Of the 91 patients randomized to omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P < 0.001). There was a threefold improvement in angioedema-burdened days/week with omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57-63 days with omalizumab and <5 days with placebo. Omalizumab significantly improved angioedema-specific QoL (P < 0.001). The adverse events reported are in line with the established safety profile of omalizumab. CONCLUSION: Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment.

Management of chronic spontaneous urticaria in real life--in accordance with the guidelines? A cross-sectional physician-based survey study.

BACKGROUND: Recently, the updated EAACI/GA(2) LEN/EDF/WAO guidelines for urticaria have been published. OBJECTIVE: To examine how chronic spontaneous urticaria (csU) patients in Germany are diagnosed and treated, and to compare the outcome to the guideline recommendations. METHODS: During this cross-sectional survey study, most dermatologists, paediatricians and 5149 general practitioners in private practice in Germany were asked to participate. All physicians who agreed were requested to complete a standardized questionnaire about their diagnostic and therapeutic management of csU. RESULTS: A total of 776 questionnaires were available for analysis. Most physicians (82%) were attempting to identify underlying causes in their csU patients, but with only limited success. More than 70% reported to check for total serum IgE and to do skin prick testing (not suggested in first line by guideline). In contrast, only 10% applied the autologous serum skin test. The most common first-line treatments were non-sedating antihistamines in standard or higher doses (as recommended). However, many physicians reported still using first generation sedating antihistamines (23%) (not recommended) or systemic steroids (18%). Experience with alternative options was low. Less than one-third of the participants reported to be familiar with the guidelines. Those who did, were found to be more likely to check for underlying causes, to be more experienced with antihistamine updosing and to be more reluctant to use sedating antihistamines or systemic steroids. CONCLUSION: The diagnostic and therapeutic management of csU by private practice physicians does not sufficiently comply with the guidelines. Awareness of the guidelines can lead to improved care.

Validation of Dermaphot(®) for the assessment of steroid-induced skin atrophy.

Currently, there are no accurate and simple methods available to measure this risk of atrophy in patients treated with topical glucocorticosteroids. In the present clinical trial, we validated a new score (Dermaphot(®) score) to assess the atrophogenic potential of glucocorticosteroids. 36 healthy adult volunteers were included in an investigator-initiated, blinded, randomized, intra-individual comparison, vehicle controlled multi-centre study. Subjects were treated in a randomized manner for 3 weeks with pimecrolimus cream 1 %, mometasone furoate (1 mg/g), clobetasol propionate 0.05 % and vehicle. In addition, ultrasound examination for skin thickness was performed. Data demonstrated a direct correlation of the achieved Dermaphot(®) score and the ultrasound thickness measurements. Our study shows that the Dermaphot(®) score can be used as a simple method to evaluate the atrophogenic potential of glucocorticosteroids. Respectively, we showed that the new score is an easy, valid and sensitive new tool for early detecting and quantifying even subclinical glucocorticosteroid-induced skin damage. We demonstrated that the score is able to differentiate the extent of skin atrophy (damage) after 3 weeks of topical glucocorticosteroid application with different levels of skin transparency and levels of telangiectasia.

Selected urticaria patients benefit from a referral to tertiary care centres--results of an expert survey.

BACKGROUND: Urticaria is a frequent reason for consultations. Recently, it has been demonstrated that the management of chronic spontaneous urticaria (csU) in the practice setting does not fully comply with published guidelines. In addition, it was shown that one of four csU patients is referred to specialized centres. OBJECTIVE: To analyse the management of urticaria patients in tertiary referral centres. METHODS: During a standardized expert-to-expert interview, 41 specialists from German tertiary care centres were asked for different aspects of urticaria patient care with a special focus on csU. RESULTS: On average, the participating centres saw 25 csU patients per month. All ran programmes for the identification of underlying causes with an average success rate of 45 ± 3% which is considerably higher as has been found in the practice setting. In those patients where an identification succeeds, infections, drugs, intolerance and autoreactivity were reported to be causes in 41%, 20%, 17% and 16%. In their symptomatic treatment the majority of centres (71%) followed the guidelines by using regular dosed non-sedating H(1)-antihistamines as first line and higher doses (61%) as second line option. In contrast to the practice setting, meaningful experience also existed for alternative therapies in antihistamine-resistant patients, such as dapsone, cyclosporin and omalizumab. The expenditure of time, laboratory costs and frequency of follow-up visits was reported to be above average in case of csU. CONCLUSION: This study indicates that some urticaria patients, especially those with unknown causes or with an H(1)-antihistamine-resistant disease, may benefit from a referral to tertiary care centres.

Intracoronary local paclitaxel delivery by X-ray contrast media for in-stent restenosis: a clinical pilot study to assess safety and tolerability.

AIM: Non-stent-based immediate release formulations of paclitaxel have been shown to reduce in-stent restenosis in animal experiments and clinical trials. In the porcine overstretch model paclitaxel dissolved in the contrast medium iopromide inhibited neointimal proliferation in a dose-dependent manner after intracoronary injection and was well tolerated. METHODS: As a first step entering clinical development, a phase I trial was performed using four ascending paclitaxel dose/concentration levels: samples of up to 100 mL of the contrast medium (iopromide) containing 10, 50, 100 or 200 µM paclitaxel or iopromide (controls) were randomly administered to patients assigned to bare metal stent implantation for single de novo coronary artery lesions. Safety variables, tolerability and angiographic parameters were assessed. RESULTS: Adverse events, ECG, systolic and diastolic blood pressure, left ventricular ejection fraction, leukocyte count, other hematological or clinical chemistry data did not reveal any trend which could be related to the study medication. Short-lasting serum paclitaxel concentrations remained significantly below those known from cancer therapy. Angiographic late lumen loss was 0.72±0.50 mm (N.=7) in controls versus 0.45±0.65 mm (N.=17) in all paclitaxel-treated patients; binary restenosis rate was 5/7(63%) versus 6/17 (35%) and target lesion revascularization rate was 4/8 (50%) versus 4/24 (17%). CONCLUSION: Intracoronary infusion of paclitaxel dissolved in an X-ray contrast medium was well tolerated. The results show restenosis inhibition, but the number of patients examined was too small to demonstrate a statistically significant inhibition.

A randomized placebo-controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy.

BACKGROUND: Specific subcutaneous immunotherapy (SCIT) for seasonal rhinoconjunctivitis with unmodified allergen extracts is effective, but limited by risk of side-effects and involves treatment over 3 years. We examined a depigmented polymerized grass pollen extract for immunogenicity and for clinical efficacy in a rush preseasonal regimen. METHODS: Depigmented polymerized grass pollen extract was tested for proliferation and cytokine production by peripheral blood mononuclear cells. A prospective, double-blind, placebo-controlled trial of 195 grass pollen allergic patients treated with preseasonal rush immunotherapy using depigmented polymerized allergenic extract of mixed grass pollen was performed over 2 years. Primary outcome was combined symptom and medication score (SMS) during the peak of the second grass pollen season. Secondary outcomes included combined score over the whole season, during the first grass pollen season, individual symptom and medication scores, quality of life, well days/hell days and responder analysis. Adverse events were classified using the EAACI scale. Grass pollen-specific IgE and IgG4 were measured before and during treatment. RESULTS: Depigmented polymerized extract stimulated dose-dependent T-cell proliferation and cytokine production. Patients treated with preseasonal SCIT showed improved combined scores during peak season at year 2 (median 3.93, interquartile range 0.77-6.27 vs median 5.86 for placebo, 3.11-8.36, P < 0.01). Most secondary outcomes were significantly better for active treatment. Side-effects were minimal, with no grade 3 or 4 reactions. CONCLUSIONS: Depigmented polymerized grass pollen extract is immunogenic and clinically effective in rush preseasonal SCIT. This form of immunotherapy may be an attractive option for some patients.

Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis.

BACKGROUND: Topical corticosteroids and calcineurin inhibitors are well-known treatments of atopic dermatitis (AD) but differ in their efficacy and side effects. We recently showed that betamethasone valerate (BM) although clinically more efficient impaired skin barrier repair in contrast to pimecrolimus in AD. OBJECTIVE: This study elucidates the mode of action of topical BM and pimecrolimus cream in AD. METHODS: Lesional AD skin samples after topical treatment with either BM or pimecrolimus were subjected to gene expression profile analysis. RESULTS: Betamethasone valerate resulted in a significant reduction in mRNA levels of genes encoding markers of immune cells and inflammation, dendritic cells, T cells, cytokines, chemokines, and serine proteases, whereas pimecrolimus exerted minor effects only. This corroborates the clinical finding that BM reduces inflammation more effectively than pimecrolimus. Genes encoding molecules important for skin barrier function were differently affected. Both BM and pimecrolimus normalized the expression of filaggrin and loricrin. BM, but not pimecrolimus, significantly reduced the expression of rate-limiting enzymes for lipid synthesis and the expression of involucrin and small proline-rich proteins, which covalently bind ceramides. This may explain the lack of restoration of functional stratum corneum layers observed after BM treatment. CONCLUSION: The gene expression profiles are consistent with our previous findings that corticosteroids may exert a more potent anti-inflammatory effect but may impair the restoration of the skin barrier. Corticosteroids are still the main treatment for severe and acutely exacerbated AD; pimecrolimus may be preferable for long-term treatment and stabilization.

Pimecrolimus cream 1% in erosive oral lichen planus--a prospective randomized double-blind vehicle-controlled study.

BACKGROUND: Erosive oral lichen planus (EOLP) is a T-cell mediated inflammatory disease leading to severe pain and impairment. As current therapies are of limited efficacy, application of calcineurin inhibitors is considered to be a potential option. OBJECTIVES: To investigate the efficacy of pimecrolimus cream 1% (Elidel) compared with vehicle cream in the treatment of EOLP. METHODS: Twenty patients were enrolled in a prospective, double-blind, randomized, vehicle-controlled trial and assigned to either pimecrolimus or vehicle group. Study medication was applied for 30 days followed by 30 days of observation without therapy. In case of unresponsiveness, treatment was continued for 30 days with open-label pimecrolimus. EOLP was monitored on days 0, 30 and 60. Safety was assessed by patient documentation, measurement of pimecrolimus levels and blood counts. RESULTS: Within 30 days erosions cleared completely in seven of 10 patients treated with pimecrolimus and in two of 10 patients treated with vehicle. The clinical EOLP 'composite score' including mucosal erosions and pain sensation was significantly reduced in the pimecrolimus-treated group compared with vehicle (P = 0.025). In the three of 10 patients not responding to pimecrolimus, EOLP cleared after an additional 30 days of treatment with pimecrolimus. Following termination of the therapy, sustained remission of EOLP was detected in 83% of patients demonstrating long-lasting effects of pimecrolimus treatment. No severe adverse events were observed. In five patients pimecrolimus blood levels were detected, all of which stayed below 4 ng mL(-1). CONCLUSIONS: Pimecrolimus cream 1% effectively treats EOLP with long-lasting therapeutic effects and is therefore a promising therapeutic option for EOLP.

Long-term management of facial atopic eczema with pimecrolimus cream 1% in paediatric patients with mild to moderate disease.

BACKGROUND: The aim of this post hoc analysis was to evaluate whether treatment of patients with atopic dermatitis (AD) with pimecrolimus cream 1% can decrease the development of flares necessitating the use of a topical corticosteroid on the face and thus reduce the need for use of topical corticosteroids in this sensitive skin area. PATIENTS AND METHODS: In a controlled, double-blind, multicentre study, 140 patients, aged 2 to 17 years, with facial involvement and mild to moderate disease after treatment of the initial flare with prednicarbate 0.25% cream were randomized to an intermittent treatment with pimecrolimus cream 1% twice daily or vehicle for 24 weeks. If a flare occurred, defined as an exacerbation (unacceptable severity of itching/scratching or onset of oozing) not controlled by study medication, patients were treated with prednicarbate 0.25% cream instead. RESULTS: Patients in the vehicle group needed prednicarbate treatment on the face on 20.7% of the days vs. 11.7% of the study days in the pimecrolimus group (P = 0.0024). Fifty per cent of patients in the pimecrolimus group had no flare on the face during the treatment period compared with 37.5% of patients in the vehicle group (P = 0.012). The median time to first flare in pimecrolimus-treated patients was twice as long as in patients receiving vehicle (138 vs. 68 days, P = 0.01). Three adverse events (one case of skin burning) suspected to be related to use of the study medication were reported for three patients (3.9%) in the pimecrolimus group. CONCLUSION: Long-term intermittent treatment of facial AD in children and adolescents with pimecrolimus cream 1% does significantly reduce the need for topical corticosteroids.

Control of atopic eczema with pimecrolimus cream 1% under daily practice conditions: results of a > 2000 patient study.

BACKGROUND: Pimecrolimus cream 1% has been shown to effectively control atopic eczema (AE) when applied twice daily from the first signs or symptoms of AE until clearance. Moreover, pimecrolimus cream 1% has a favourable safety profile, lacking topical corticosteroid-related side-effects such as skin atrophy, making it particularly useful to treat delicate body regions (e.g. the face). OBJECTIVE: The objective of this naturalistic study was to monitor the safety, tolerability and efficacy of pimecrolimus when used in the long-term management of AE in a real-life setting. METHODS: A multicentre, open-label study was conducted in 2034 patients aged >or= 3 months with mild to moderate AE for up to 12 months' duration. Patients applied pimecrolimus cream twice daily, initiating treatment at first signs or symptoms of AE, continuing until clearance. RESULTS: Patients (n= 1847; 91%) completed 3 months of the study. Treatment success (clear or almost clear AE) after 3 months of treatment was observed on the whole body in 59% of patients and on the face in 81% of patients. Disease improvement of whole body and face was seen in 77% and 63% of patients, respectively. Pruritus was absent or mild in 79% of patients. Pimecrolimus cream was well tolerated throughout the study. CONCLUSION: In a daily practice setting, pimecrolimus cream 1% effectively and safely controls AE.

Pimecrolimus cream (1%) efficacy in perioral dermatitis - results of a randomized, double-blind, vehicle-controlled study in 40 patients.

BACKGROUND: Perioral dermatitis (POD) is a common skin disease and difficult to treat. Pimecrolimus cream (1%) successfully controls atopic eczema. OBJECTIVE: Our aim was to investigate its efficacy in POD. STUDY DESIGN: Single-centre, randomized, double-blind, vehicle-controlled study including 40 POD patients with a 4-week treatment and a 4-week follow-up. Efficacy was assessed by a novel Perioral Dermatitis Severity Index (PODSI) and Finlay's Dermatology Life Quality Index (DLQI). SETTING: Outpatient clinics of a large dermatological hospital in Munich, Germany. RESULTS: During treatment, the PODSI was significantly lower in the pimecrolimus group compared with vehicle (P = 0.005-0.02) whereas at follow-up, no significant differences were observed. At week 2, the responder rates (> or = 50% PODSI improvement) were 50% with pimecrolimus cream (1%) and 25% with vehicle (P = 0.095). DLQI was improved in pimecrolimus group compared with vehicle. CONCLUSION: Results suggest that pimecrolimus cream (1%) effectively treats acute-stage POD.

Pimecrolimus cream 1% is effective in asteatotic eczema: results of a randomized, double-blind, vehicle-controlled study in 40 patients.

BACKGROUND AND OBJECTIVE: Pimecrolimus cream 1% is an effective treatment for atopic eczema. The aim was to investigate its efficacy in asteatotic eczema, a skin disease similar to atopic eczema and its associated dry skin and itching. METHODS: Single-centre, randomized, double-blind, vehicle controlled study in 40 patients with asteatotic eczema. Efficacy was assessed by eczema area and severity index (EASI), investigators global assessment (IGA), patient's self-assessment, and pruritus severity. RESULTS: After 4 weeks of treatment, EASI, the primary efficacy variable, was reduced by 62+/-7% from baseline in patients on pimecrolimus, compared to 21+/-14% in patients on vehicle (P=0.013). With pimecrolimus there was also a better control of pruritus (P=0.042) at week 4 whereas a better control of disease according to self-assessment could only be observed at weeks 2 (P=0.01) and week 3 (P=0.08). CONCLUSION: Pimecrolimus cream 1% is effective in patients with asteatotic eczema.

[Miflonide/Foradil via Aerolizer compared with other anti-inflammatory and anti-obstructive therapeutic regimens]. / Miflonide/Foradil via Aerolizer im Vergleich zu anderen antiinflammatorischen und antiobstruktiven Therapieregimes.

Standard therapy of asthma consists of combined, antiinflammatory (steroids) and anti-obstructive (long acting/short acting beta-agonist) treatment via inhalation using two separate or a single inhalation device. Here, we report the results of using Miflonide (Budesonide 400 - 800 microg per day) and Foradil (Formoterol 24 - 48 microg per day) in cases of moderate and severe asthma previously treated insufficiently with another combination therapy. 80 patients with asthma previously treated insufficiently with any other combination therapy of steroid and long acting beta-agonist were included. Instead of their previous therapy all were switched to therapy with Miflonide and Foradil for eight weeks (two office visits at 4 and 8 weeks). Lung function (peak flow [l/min], FEV1 [I], FVC [I], R(tot) [kPa*s/l]) was performed at every visit. Doctors' and patients' estimation of disease severity, physical examination, drug related side-effects and the use of short acting beta-agonist aerosols were registered. Lung function parameters improved significantly compared to the run in phase prior to the change in medication (peak flow: + 18.4 %, FEV 1 : + 10.7 %, FVC: + 6.8 %, R(tot) : -18.0 %). Use of additional short acting inhalative beta-agonists was reduced. Subjectively, patients judged their general condition as improved, effectiveness as greater compared to previous medication and side effects as tolerable. The use of a combination of Miflonide/Foradil lead to an improvement in subjective and objective parameters in asthma patients that had previously been treated with a variety of other antiinflammatory and anti-obstructive therapy regimens. Reasons for this observation are beside change in medication, patients training in asthma therapy, change of application system, and increase of patients compliance.

Body-weight-independent dosing of cyclosporine micro-emulsion and three times weekly maintenance regimen in severe psoriasis. A randomised study.

BACKGROUND: Body-weight-dependent (BWD) treatment of psoriasis with cyclosporine A (CsA is well established. It has recently been reported that this is not necessary for the treatment of atopic dermatitis. OBJECTIVES: (1) To investigate the efficacy and safety of a CsA micro-emulsion administered in a new body-weight-independent (BWI) protocol and to compare it to a BWD dosage regimen in the treatment of severe psoriasis. (2) To investigate the duration of disease remission after intermittent treatment of psoriasis with CsA. PATIENTS AND METHODS: 122 adult patients with severe plaque-type psoriasis (PASI > or = 12) were included in this study which consisted of two treatment periods: period I was a randomised parallel-group comparison of daily CsA doses of 100-300 mg (BWI) or 1.25-5.0 mg/kg (BWD) for 12 weeks; period II was a randomised double-blind placebo-controlled extension treatment of patients, who had responded (>75% PASI recovery) to the treatment in period I and continued the treatment on their last effective dose or placebo 3 times weekly for a further 12 weeks. RESULTS: In period I, the increase in creatinine in the BWI group (2.7 micromol/l) was proven to be non-inferior to that of the BWD group (3.5 micromol/l) at a non-inferiority limit of 5 micromol/l (p < 0.05). The PASI decreased with BWI dosing from 22.0 to 3.0 and with the BWD scheme from 19.5 to 2.5 (p = 0.98). In period II, the relapse rates were 40.5% (17/42) with intermittent CsA and 56.9% (29/51) with placebo (p = 0.15). CONCLUSIONS: BWI dosing is as effective and safe as conventional BWD dosing for the short-term treatment of severe psoriasis. There was a tendency toward a prolongation of remission with intermittent CsA treatment.

[Onset of action of formoterol in patients with moderate to severe, partially reversible airflow obstruction assessed by bodyplethysmography]. / Bodyplethysmographischer Wirkeintritt von Formoterol bei Patienten mit mittel- bis schwergradiger partiell reversibler Atemwegsobstruktion.

BACKGROUND: Formoterol is a long acting beta2-agonist used for the treatment of obstructive airway diseases. Compared with Salmeterol, Formoterol has a rapid onset of bronchodilation. There are only scant data regarding the comparative onset of action using bodyplethysmography in moderate to severely obstructive patients. METHODS: In a mono-center, single-blinded parallel group study 60 patients (age: 61.9 +/- 12.8 years, 65 % male) with moderate to severe (mean FEV(1) 40.6 +/- 15.3 % of predicted), partially reversible (FEV(1) post bronchodilator > 15 % from baseline) airway obstruction were treated with either formoterol 12 microg bid or salmeterol 50 microg bid over a period of two weeks. Onset of action was measured by airway resistance (sRaw) before and after two weeks of treatment. RESULTS: Compared with Salmeterol, Formoterol had a significantly faster onset of action (10 % decrease of Raw) at baseline (F: 1.4 +/- 0.9 vs. S: 15.1 +/- 34.5 min., p < 0.0001) and after two weeks of treatment (F: 6.2 +/- 21.6 vs. S: 51 +/- 135 min., p < 0.0001). Morning FEV(1) improved similarily during treatment in both study groups, when compared with baseline lung function (F: 1.38 +/- 0.64 vs. 1 +/- 0.41 l; S: 1.43 +/- 0.67 vs. 1 +/- 0.4 l, p < 0.05, both comparisons). Both treatments were well tolerated. CONCLUSION: Formoterol produces a rapid improvement of airway resistance in patients with moderate to severe, partially reversible airway obstruction. The onset of bronchodilation was significantly faster for Formoterol compared with Salmeterol. Both drugs improved lung function similarily after two weeks of treatment. It is important to distinguish beta2-agonists not only into short- and long-acting but also into fast- and slow-acting.

Effect of low-dose cyclosporin a microemulsion on disease severity, interleukin-6, interleukin-8 and tumor necrosis factor alpha production in severe pediatric atopic dermatitis.

BACKGROUND: The release of cytokines [interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-alpha)] by skin cells is involved in the pathogenesis of atopic dermatitis (AD). OBJECTIVE: To evaluate the effect of low-dose cyclosporin A (CyA) on clinical symptoms and cytokine secretion in severe pediatric AD. METHODS: Ten children with severe AD (SCORAD index >50) were treated for 8 weeks with CyA. The initial dose of 2.5 mg/kg/day was titrated to a maximum of 5 mg/kg/day until a SCORAD reduction of >or =35% was achieved ("treatment response"). After stopping CyA all patients entered a 4-week follow-up period. Cytokine secretion (IL-6, IL-8 and TNF-alpha) from patients' PBMC was assessed by ELISA before and after CyA treatment and was compared with 18 healthy nonatopic controls. Only the data of patients, who responded to CyA and did not experience a relapse during the follow-up period, were evaluated for this paper. RESULTS: Seven patients responded to CyA without relapse during the follow-up period. The median SCORAD index in these patients improved from 71 at baseline to 22 after CyA treatment (p < 0.001). AD patients' PBMC produced more IL-6, IL-8 and TNF-alpha than PBMC of controls. Suppression of IL-6 (p < 0.05) and IL-8 (p < 0.05) production was observed after CyA treatment. TNF-alpha levels were unchanged by CyA in all patients. CONCLUSIONS: The reduction in severity of pediatric AD with CyA is associated with decreased production of IL-6 and IL-8, but not TNF-alpha by PBMC.

One week terbinafine 1% cream (Lamisil) once daily is effective in the treatment of interdigital tinea pedis: a vehicle controlled study. LAS-INT-06 Study Group.

Duration of therapy is an important factor determining patients' compliance in dermatomycosis clinical practice. We undertook a prospective, randomised, double-blind, parallel group study to investigate the efficacy and tolerability of once daily treatment with terbinafine 1% cream for 1 week, compared to its vehicle, in adult patients with interdigital tinea pedis. Efficacy was assessed in terms of mycological cure, total clinical signs and symptoms scores, and clinical response, 1 day and 1, 5 and 7 weeks after end of treatment. Terbinafine 1% cream was significantly more effective than its vehicle in achieving and maintaining mycological cure for 7 weeks: 91.4% vs. 37.1%, P < 0.001. Terbinafine was also significantly more effective than its vehicle in reducing total clinical signs and symptoms scores, and in achieving clinical response. We conclude that terbinafine 1% cream, applied once daily for 7 days, is an effective and well-tolerated treatment for interdigital tinea pedis in nonimmunocompromised patients. The short duration of treatment needed to achieve mycological cure has important implications for patient compliance and for control of infection within the community.

Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis: clinical and immunological effects.

Cyclosporin A (CsA) is an effective and well-tolerated treatment for severe childhood atopic dermatitis (AD). By starting at a low dose, the therapeutic safety should be further increased. The aim of this study was to evaluate low-dose CsA in childhood AD with respect to clinical outcome and modulation of T-cell dysregulation. In an open prospective study, 10 children (age: 22-106 months) with severe AD (mean objective SCORAD score > 40 on two baseline measurements at a minimum interval of 2 weeks) were treated with CsA solution for 8 weeks. All patients received a starting dose of 2.5 mg/kg/day, which was increased stepwise in non-responders to a maximum of dose of 5 mg/kg/day. Disease activity was monitored using the SCORAD index. The frequency of cytokine-producing peripheral blood T lymphocytes was analyzed by intracellular cytokine staining, and T-cell numbers were measured by fluorescence-activated cell sorter (FACS) analysis. Twenty healthy age-matched children were included as controls for the immunological data. Nine of the 10 patients had a SCORAD reduction of at least 35%. In seven patients this was achieved with low-dose CsA at 2.5 mg/kg/day (n = 4) and 3.5 mg kg/day (n = 3). Seven of the nine responders experienced no relapse within the 4-week follow-up period. At baseline the percentage of interleukin-4 (IL-4), IL-13, and human leucocyte antigen (HLA)-DR-positive CD3(+) cells was higher in the patient group than in the controls. After CsA treatment there was a significant reduction in interferon-gamma (IFN-gamma), IL-2, IL-4, IL-13, and HLA-DR-positive CD3(+) cells. Hence, in severe pediatric AD, CsA microemulsion, when started at a low dose (2.5 mg/kg/day), improves clinical measures of disease, reduces T-lymphocyte cytokine production, and regulates T-cell activation.