Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.     

The analgesic efficacy of tenoxicam versus placebo in day case laparoscopy: a randomised parallel double-blind trial

The analgesic efficacy and duration of action of tenoxicam, an injectable non-steroidal analgesic with a long elimination half-life, were studied in day case laparoscopy in a double-blind randomised prospective parallel placebo-controlled trial. Tenoxicam 20 mg or saline was given intravenously at induction of anaesthesia in 67 women undergoing day case investigative laparoscopy for infertility or abdominal pain. Outcome measures were time to first analgesia, pain levels at 2, 4 and 24 h plus postoperative analgesic consumption in hospital and at home. The study showed no statistically significant difference in any of these measures between the two groups. Tenoxicam 20 mg intravenously immediately pre-operatively cannot be recommended for day case surgery on the basis of this study.     

Salmeterol compared with slow-release terbutaline in nocturnal asthma. A multicenter, randomized, double-blind, double-dummy, sequential clinical trial. French Multicenter Study Group

The aim of the multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial with a 2-week treatment period was to compare the efficacy and safety of salmeterol (50 micrograms twice daily) with slow-release (SR) terbutaline (5 mg orally, twice daily) in nocturnal asthma. A total of 159 asthmatic adults (FEV, 50-90% of predicted value; sex ratio: 0.87) with at least two nocturnal awakenings during a 7-d run-in period was included in the study. Patients were centrally randomized with a national computer network (Minitel). The main variable (number of awakening-free nights during the last week of treatment) was analyzed according to a sequential method with the one-sided triangular test. The number of awakening-free nights (+/- SD) was significantly higher in the salmeterol group: 5.3 +/- 2.4 vs 4.6 +/- 2.3 (P = 0.006). Salmeterol was significantly more effective than SR-terbutaline in the following factors: number of patients without any awakening during the last week of treatment (50% vs 27%, P = 0.003), mean morning PEF (351 +/- 109 l/min-1 vs 332 +/- 105 l/min-1, P = 0.04), PEF diurnal variation 6 +/- 10% vs 11 +/- 12%, P = 0.01), overall assessment of efficacy by the patient and the investigator (P = 0.001 and 0.005, respectively), and daily rescue salbutamol intakes (P = 0.004). In the salmeterol group, significantly fewer patients reported adverse events (16% vs 29%, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomized, double-blind study comparing twenty-four-week treatment with recombinant interferon-gamma versus placebo in the treatment of rheumatoid arthritis

Carcinosarcoma is a rare neoplasm that displays morphological features of both an adenocarcinoma and a sarcoma. The question is whether two tumors co-exist or whether the two morphological aspects represent sequential steps in tumor progression. We report a case of carcinosarcoma of the caecum in a young female. To characterize the two tumor cell populations and to gain insight into the pathogenesis of the lesion, we conducted immunohistochemical and ultrastructural analyses of the tumor. The biphasic aspect of the tumor showed an admixture of carcinoma and spindle-cell sarcomatoid areas. Both adenocarcinoma and sarcomatous cells were positive for cytokeratins. Vimentin was undetectable in the epithelial portion, but many of the sarcomatous cells stained for vimentin. Electron microscopic analyses of the sarcomatous portion revealed budding of "retroviral particles" from the rough endoplasmic reticulum cisternae. Our data support the contention that "carcinosarcoma" is a part of a single clinicopathological continuum with "spindle-cell carcinoma", the former being the biphasic expression of the neoplasia, the latter the monophasic expression; the presence of productive retroviral infection in the sarcomatous cells could constitute one of the additional support in tumor progression from the carcinomatous to the sarcomatous phase.     

Posatirelin in the treatment of vascular dementia: a double-blind multicentre study vs placebo

INTRODUCTION: The usefulness of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having modulatory activity on the monoaminergic and cholinergic systems and neurotrophic effects, was evaluated in vascular dementia. PATIENTS AND METHODS: A multicentre, parallel groups, double-blind clinical study vs placebo was carried out with patients suffering from probable vascular dementia according to the NINDS-AIREN criteria. The study consisted of a two-week run-in of a once daily, orally administered, placebo phase, followed by 12 weeks of intramuscular treatment with posatirelin 10 mg/ml or placebo given once a day and a follow-up after one month's withdrawal. Efficacy was assessed using the Gottfries-Br?ne-Steen (GBS) Rating Scale for dementia, the Randt Memory Test and the Toulouse-Piéron Attention Test. Data were evaluated using analysis of variance and covariance. RESULTS: As regards GBS scores, patients treated with posatirelin showed a significant improvement in intellectual performance, in orientation, motivation and memory as compared to controls. The improvement of memory performance was also confirmed by the acquisition score and memory index of the Randt Memory Test. At the end of the follow-up period the differences between treatments were still maintained. Tolerability was good. CONCLUSIONS: The significant improvement observed in cognitive functions, attention and motivation of demented patients treated with posatirelin suggests the potential usefulness of this drug in vascular dementia. Furthermore, the presence of a long-lasting effect after drug withdrawal suggests the possibility of administering the drug cyclically.     

Multinational randomised controlled trial of lubeluzole in acute ischaemic stroke. European and Australian Lubeluzole Ischaemic Stroke Study Group

The purpose of this investigation was to examine whether inhaled nitric oxide (NO) may alter oxidative stress parameters and induce lung inflammation in moderate hyaline membrane disease (HMD). Eighteen moderately premature lambs (130 days gestation, term = 147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n = 8) from the onset of ventilation or used as control (n = 10). Except inhaled NO, treatments were intentionally similar to those applied in clinical situations. The main studied parameters were oxidative stress index measurements on lung parenchyma and in circulating blood, lung parenchyma microscopic examination and bronchoalveolar lavage cell count. We found that 20 ppm of inhaled NO for 5 h did not change significantly either malondialdehyde and total antioxidant status levels in circulating blood, or malondialdehyde, reduced glutathione, glutathione peroxidase and glutathione reductase in lung parenchyma. Amino-imino-propene bond generation, which are lipoperoxidation markers, was similar in both groups. Furthermore, no significant changes in the number of inflammatory cells in lung lavage products and in lung parenchyma microscopic examination could be found. Therefore, these data do not support the hypothesis that short-term NO inhalation increases oxidative stress and lung inflammation in an experimental model of moderate HMD.     

Efficacy and safety of 0.3% carbomer gel compared to placebo in patients with moderate-to-severe dry eye syndrome

PURPOSE: Carbomer gel is a water-soluble polymeric resin that has been reported to maintain the tear film in contact with the eye for an extended period. The efficacy and safety of this new artificial tear were assessed. METHODS: A multicenter, single-masked, randomized, placebo-controlled study was carried out on 123 patients with moderate-to-severe dry eyes. The placebo was a mannitol solution with benzalkonium chloride 0.008% as preservative. Patients were observed over an 8-week period, and subjective and objective changes analyzed, compared to a baseline of no therapy, after 1 to 7 days washout period from previous medication. RESULTS: All primary subjective symptoms decreased significantly in the carbomer gel-treated group compared to the placebo group (i.e., dryness, discomfort, and foreign body sensation). The carbomer gel also significantly improved the rose bengal staining score relative to placebo. When data for the primary subjective efficacy variables were stratified for disease severity, there was a statistically significant improvement from baseline by day 10 for severely affected patients and from day 42 for patients with moderate disease. Secondary subjective symptoms that improved significantly in the tear gel group compared to placebo were photophobia, erythema, tear breakup time, blurry-filmy, dry-sandy sensation, and physician impression. However, no significant improvements in the secondary subjective symptoms of tearing, itching, scaling, conjuctival discharge, palpebral conjunctival redness, bulbar conjuctival redness, conjunctival luster, relief of discomfort, ease of use, and overall acceptability were found in either group over the baseline score. In addition, neither carbomer gel nor placebo improved the baseline fluorescein staining score or the Schirmer test score. Two patients suffered local allergic reactions to the carbomer gel or its preservative, which settled on withdrawal of the medication. CONCLUSIONS: Carbomer gel was more efficacious than was placebo in improving a number of subjective and objective symptoms of moderate-to-severe dry eye syndrome. The results of this study indicate that carbomer gel was a safe as was the placebo.     

Salsalate, a nonacetylated salicylate, is as efficacious as diclofenac in patients with rheumatoid arthritis. Salsalate-Diclofenac Study Group

OBJECTIVE: To investigate the efficacy of salsalate, a nonacetylated salicylate, in the treatment of patients with rheumatoid arthritis (RA). METHODS: Three hundred and one patients meeting the ACR criteria for RA were drawn from 16 centers. After withdrawal of nonsteroidal antiinflammatory drugs (NSAID) and subsequent flare, patients were randomized to receive either salsalate or diclofenac for 8 weeks, according to a double blind, double dummy protocol. Initial doses of salsalate 3.0 g/day and diclofenac 75 mg/day were titrated for the first 5 weeks. The primary outcome measure was a multivariate analysis at 8 weeks of tender joint count, pain, visual analog scale score, and physician's global assessment. RESULTS: One hundred and ninety patients completed the study. The mean stabilized dose of salsalate was 3.55 g/day, and that of diclofenac 112 mg/day. Discontinuations were due to lack of efficacy (17 salsalate vs 15 diclofenac); adverse events [19 salsalate (mainly tinnitus and hearing loss; p = 0.0001 and p = 0.04, respectively) vs 9 diclofenac]; laboratory abnormalities (3 salsalate vs 1 diclofenac); and other reasons, including protocol violations, intercurrent illness, and personal factors (24 salsalate vs 23 diclofenac). Both treatments produced significant improvement from flare (p < 0.0001). Post hoc power analysis showed that the study had sufficient power (0.60 to 0.90) to detect clinically important differences between the 2 drugs in the primary outcome measures; however, no statistically significant (p = 0.29) or clinically important treatment differences were recorded. Other than a difference in erythrocyte sedimentation rate that favored salsalate, there were no significant differences in secondary outcome measures between the 2 groups. All outcomes showed a tendency for more improvement with salsalate. CONCLUSION: Salsalate is as efficacious as diclofenac. Salsalate may be considered an alternative to other NSAID in the first line treatment of patients with RA.     

A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: the effect on postnatal depression and serum hormones

OBJECTIVES: To determine the effect of postnatal administration of the long-acting progestogen contraceptive, norethisterone enanthate, on postnatal depression and on serum hormone concentrations, and their association with depression. DESIGN: Double-blind randomised placebo-controlled trial. SETTING: A tertiary care hospital in Johannesburg, South Africa. POPULATION Postnatal women using a non-hormonal method of contraception (n = 180). METHODS: Random allocation within 48 hours of delivery to norethisterone enanthate by injection, or placebo. MAIN OUTCOME MEASURES: Depression scores in the three months postpartum as rated by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Edinburgh Postnatal Depression Scale (EPDS); 2. serum 17beta-oestradiol, progesterone, testosterone and the 17beta-oestradiol:progesterone ratio at six weeks postpartum. RESULTS: There was a chance excess of caesarean section deliveries in the progestogen group. Mean depression scores were significantly higher in the progestogen group than in the placebo group at six weeks postpartum (mean MADRS score 8.3 vs 4.9; P = 0.0111; mean EPDS score 10.6 vs 7.5; P = 0.0022). Mean serum 17beta-oestradiol and progesterone concentrations were significantly lower in the progestogen group compared with the placebo group at six weeks postpartum. There were no correlations between any of the hormone parameters and depression at six weeks except in the formula feeding subgroup of the placebo group, where formula feeding and 17beta-oestradiol concentrations were positively associated with depression. CONCLUSIONS: Long-acting norethisterone enanthate given within 48 hours of delivery is associated with an increased risk of developing postnatal depression and causes suppression of endogenous ovarian hormone secretion.     

Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial. PLESS Study Group. Proscar Long-term Efficacy and Safety Study

The authors report 10 cases of hypercortisolism studied at University's Surgical Clinic of Trieste (Italy). Comparing their results to the recent Literature, they observe the highly reliability of the instrumental and laboratory investigations to achieve an accurate preoperative diagnosis. The effectiveness of surgical therapy evinces not only from absence of surgical mortality and morbility, but also from optimal results of follow-up: all patients, in fact, heal completely in few weeks or months.     

Life events and disability in rheumatoid arthritis: a European cohort

The objective was to study the relationship between life events (LE) and the clinical status of patients suffering from recently diagnosed rheumatoid arthritis (RA) in a 2 yr follow-up. As part of a multicentre European cohort study, 370 French and Dutch patients were questioned three times at 1 yr intervals about LE which had occurred in the previous year. Three criteria were used to quantify the degree of disease activity (Ritchie's index), the level of functional disability [Health Assessment Questionnaire (HAQ)] and perceived health [Overall Evaluation of Health (OEH)]. Total LE and desirable LE showed a weak negative correlation with the HAQ scores. On the other hand, death-related LE did not seem to modify patient status. The higher the number of health-associated LE, the greater the deterioration in HAQ and OEH scores. The results indicate that LE do not affect the course of early RA in a spectacular manner.     

Risperidone compared with both lithium and haloperidol in mania: a double-blind randomized controlled trial

OBJECTIVE: There are many reports about the effects of prostatic intraepithelial neoplasia (PIN) on serum prostate-specific antigen (PSA) level. The aim of this study was to determine the relationship between PIN and serum free PSA/total PSA (fPSA/tPSA) ratios. METHODS: We evaluated 46 patients with PIN, 15 patients with benign prostatic hyperplasia (BPH), and 16 patients with localized prostatic carcinoma (CaP) for the amount of fPSA and tPSA with the chemiluminescent enzyme assay. RESULTS: fPSA values from BPH to high-grade PIN (PIN2 and PIN3) was increased, and then a decrease was observed from high-grade PIN to CaP. fPSA was significantly different between BPH and low-grade PIN and high-grade PIN. There was no significant difference observed between BPH and CaP. tPSA values increased from BPH to CaP. tPSA was significantly different between BPH and high-grade PIN and CaP. fPSA/tPSA ratios decreased from BPH to CaP. This ratio was significantly different between CaP and BPH and low-grade PIN. There was no significant difference between CaP and high-grade PIN. CONCLUSIONS: Our results confirm that fPSA/tPSA ratio is better at discriminating between patients with CaP and those with BPH, but not between patients with CaP and those with high-grade PIN. Due to similarities between CaP and high-grade PIN, we think that decreased fPSA/tPSA ratio obtained at the time of intial diagnosis of PIN without concurrent carcinoma could be used as predictive factors to distinguish patients in whom carcinoma will be found on subsequent biopsies from those with PIN not associated with cancer on repeat biopsy.     

Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial. The Italian IBD Study Group

OBJECTIVE: To examine the outcome of trial second labor after a first cesarean performed because of cephalopelvic disproportion, defined according to strict diagnostic criteria. METHODS: Obstetric details of nulliparous women delivering at 37 or more weeks' gestation by cesarean for cephalopelvic disproportion, between 1975 and 1990, were recorded prospectively. The diagnostic criteria for cephalopelvic disproportion were cervical dilation arrested after 5 cm, unresponsive to oxytocin augmentation, after active dilatation of 2 cm or more in 2 hours. Fetal malpresentations and malpositions were excluded. The outcome of next delivery in our hospital by each woman enrolled was then examined. RESULTS: Eighty-four of 42,793 women met the criteria for disproportion, and 40 with cephalic presentations delivered their next baby in our hospital. All 40 underwent a trial of labor and 27 (68%) delivered vaginally, comprising seven (47%) women with larger second and 20 (80%) with smaller second babies. Of 15 women previously delivered by cesarean at full dilatation, 11 (73%) delivered vaginally with no serious maternal or neonatal morbidity. CONCLUSION: The strictly defined diagnosis of nulliparous cephalopelvic disproportion should not constitute an automatic "recurrent" indication for elective cesarean delivery, because 68% of patients in our series had successful vaginal deliveries in their next pregnancies. This rate is similar to those reported after all nulliparous cesareans for dystocia.     

Treatment with a gonadotrophin releasing hormone agonist before hysterectomy for leiomyomas: results of a multicentre, randomised controlled trial

OBJECTIVES: To ascertain whether uterine shrinkage induced by a gonadotrophin releasing hormone agonist before hysterectomy for fibroids increases the possibility of a vaginal procedure. DESIGN: A multicentre, prospective, randomised, controlled study. PARTICIPANTS: One hundred and twenty-seven premenopausal women with a uterine volume of 12 to 16 gestational weeks. INTERVENTIONS: Twelve weeks of triptorelin depot treatment before hysterectomy or immediate surgery. MAIN OUTCOME MEASURES: Number of vaginal and abdominal hysterectomies, operating time, blood loss, degree of difficulty of the procedure, perioperative serum haemoglobin and haematocrit levels, hospital stay, and patients' overall satisfaction with treatment. RESULTS: After randomisation, four women withdrew from the study, leaving 60 women in the triptorelin arm and 63 in the immediate surgery arm. At baseline evaluation a vaginal hysterectomy was indicated in seven women allocated to pre-operative medical therapy (12%), and in 10 of those allocated to immediate surgery (16%). Clinical assessment after the 12-week GnRH agonist course showed that abdominal hysterectomy was no longer indicated in 25/53 women (47%) as a vaginal procedure appeared appropriate. Thus the overall rate of indication for a vaginal procedure in the pre-operative medical treatment arm was 32/60 cases (53%), with a between-group difference of 37% (95% CI, 26% to 51%; chi2(1) = 19.18, P < 0.0001; OR 6.06; 95% CI, 2.60 to 14.10). Pre- and post-operative serum haemoglobin and haematocrit levels were significantly higher in the GnRH agonist than in the immediate surgery arm. No appreciable difference was observed between the groups in the other intra- and post-operative variables, including patients' satisfaction. CONCLUSIONS: Pre-operative GnRH agonist therapy increased the rate of vaginal hysterectomy in selected women with fibroids and uterine volume of 12 to 16 gestational weeks.     

Pain control after dental surgery: a double-blind, randomised trial of lornoxicam versus morphine

Lornoxicam is a new non-steroidal anti-inflammatory drug of the oxicam class. This randomised, double-blind, placebo controlled trial compared the analgesic efficacy and tolerability of intramuscular (IM) injections of lornoxicam (4, 8, 16 and 20 mg) with morphine (10 and 20 mg) and placebo in 252 patients with mainly moderate to severe pain following surgical removal of an impacted mandibular third molar. Patients treated with lornoxicam or morphine experienced a significantly greater cumulative pain relief over the 4-h post-injection period (TOTPAR0-4) than placebo recipients. This effect appeared to be dose-dependent, with patients in the lornoxicam 4 mg or morphine 10 mg groups recording significantly lower TOTPAR0-4 scores than patients in the higher dosage groups of these drugs. No significant difference was detected between the morphine 20 mg group and the lornoxicam 8, 16 and 20 mg groups. Lornoxicam was well tolerated at all doses and was associated with a significantly lower incidence of adverse events than morphine 10 or 20 mg. Thus, the analgesic efficacy of IM lornoxicam at doses > or = 4 mg is superior to placebo, and doses > or = 8 mg are at least as effective as IM morphine 20 mg. Furthermore, lornoxicam possesses a more favourable tolerability profile than morphine and thus represents an attractive alternative for the treatment of moderate to severe acute pain.     

Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation

In a multicentre trial involving 20 transplant centres from 10 countries haematopoietic stem cells were obtained either from the bone marrow of 33 sibling donors or from the peripheral blood of 33 such donors after administration of filgrastim (10 microg/kg/day). The haematopoietic stem cells were infused into their HLA-identical recipients suffering from acute leukaemias in remission or chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT. Pain and haematoma at the harvest site and mild anaemia were the most frequent complaints of BM donors. Severe or life-threatening complications were not seen with any type of harvest procedure. Time to platelet recovery greater than 20 x 10(9)/l was 15 days (95% confidence interval (CI) 13-16 days) in the PBPCT group and 19 days (CI 16-25) in the BMT group. Time to neutrophil recovery greater than 0.5 x 10(9)/l was 14 days (CI 12-15 days) in the PBPCT group as compared to 15 days (CI 15-16 days) in the BMT group. The numbers of platelet transfusions administered to PBPCT and BMT patients were 12 (range: 1-28) and 10 (range: 3-39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18 patients (54%) transplanted with PBPC developed acute GVHD of grades II-IV; acute GVHD of grades III or IV developed in six (18%) and seven (21%) patients, respectively. Kaplan-Meier plots for transplant-related mortality until day 100 and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no significant differences. Administration of filgrastim and leukapheresis in normal donors were feasible and well tolerated. The number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC. Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted in earlier platelet engraftment. The incidence of moderate to severe acute GVHD, transplant-related mortality, and leukaemia-free survival did not show striking differences. Further investigation of allogeneic PBPCT as a substitute for allogeneic BMT is warranted.     

Tacalcitol ointment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety

Tacalcitol is a vitamin D analogue which ahs been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2 micrograms/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 micrograms/g tacalcitol ointment in Caucasian psoriatics. The data on 122 male and female patients were analysed. The score sum of erythema, infiltration and desquamation was influenced significantly more by tacalcitol ointment than by placebo (P < 0.0001) at every control point, starting from week 2. With regard to the individual symptoms of desquamation, infiltration and erythema, the treatment with tacalcitol was also superior to placebo treatment beginning at week 2. Qualitatively, the same results were obtained with the preference assessment of both treated body sides and also the global assessments of efficacy and benefit. Symptoms of local skin irritation which may be related to the active compound or the ointment base were reported by 12.3% of patients. In only one patient, irritation required discontinuation of tacalcitol treatment. Laboratory criteria, including serum calcium, serum phosphate and serum levels of calcitonin, parathormone, 1 alpha, 24-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, did not reveal any changes of clinical relevance during or after treatment. Furthermore, the global assessment of tolerance was good or very good in more than 90% of cases. The results of this study demonstrate that the once daily application of a 4 micrograms/g tacalcitol ointment is an efficacious therapy for psoriasis vulgaris in Caucasian patients, and that its tolerance is good, wherever the lesion is located, including on the face.