Comparable spirometric efficacy of tiotropium compared with salmeterol plus fluticasone in patients with COPD: a pilot study.

BACKGROUND: International guidelines recommend the long-acting anticholinergic, tiotropium, or long-acting beta 2-agonists as maintenance therapy in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). The efficacy of long-acting beta(2)-agonists combined with inhaled corticosteroids (ICS) in the treatment of COPD has also been confirmed for severe and very severe COPD, but data comparing tiotropium with the combination of a long-acting beta 2-agonist and an ICS are lacking. METHODS: This 6-week multicentre, randomised, double-blind, triple-dummy pilot study compared the bronchodilator effects of tiotropium 18 microg once daily (n=56) vs. the combination of salmeterol 50 microg plus fluticasone 250 microg twice daily (n=51) in patients with moderate-to-very severe COPD. Serial spirometry was performed over 12h after 6 weeks of treatment. The primary endpoint was forced expiratory volume in 1s (FEV1) area under the curve from 0 to 12h (AUC0-12h) on Day 43. RESULTS: Randomization failed to provide treatment groups with comparable baseline characteristics for smoking history, current smokers, duration of COPD, FEV1, forced vital capacity (FVC) and reversibility. Mean+/-SD FEV1 was 1.31+/-0.47 l in the tiotropium group vs. 1.46+/-0.53 l in the salmeterol plus fluticasone group. Fewer patients in the tiotropium showed a 12% and 200 ml acute increase to short-acting bronchodilators at baseline. However, treatment with tiotropium alone resulted in comparable bronchodilation compared with salmeterol plus fluticasone, as measured by all the spirometric parameters at the end of the 6-week study period. FEV1 AUC0-12h was 1.55+/-0.03 l in the tiotropium group vs. 1.57+/-0.04 l in the salmeterol plus fluticasone groups (p=0.63). Trough (predose) FEV1 was 1.54+/-0.03 l in the tiotropium group vs. 1.46+/-0.03 l in the combination group (p=0.07), and peak FEV(1) was 1.68+/-0.04 l vs. 1.66+/-0.04 l, respectively, (p=0.77). FVC AUC0-12h, trough and peak were also comparable between groups at study end (p>0.05, for all). Further, rescue salbutamol use was similar in the tiotropium and combination groups and both treatment regimens were well tolerated. CONCLUSIONS: Six weeks of treatment with tiotropium resulted in comparable bronchodilation compared with salmeterol plus fluticasone in patients with moderate-to-very severe COPD, despite tiotropium patients having lower lung function and fewer patients considered reversible at baseline. The results of this pilot study will aid planning for further large-scale comparative studies.

Peripheral large nerve fibre function in patients with chronic plaque psoriasis.

Accumulating evidence suggests the involvement of neurogenic inflammation in the pathogenesis of psoriasis. Moreover, the concomitant occurrence of peripheral neuropathy has been reported in several psoriatic patients. Thus, the aim of the present study was to answer the question whether an impairment of peripheral large nerve fibre function may exist in psoriasis. Thirty-two patients with severe and generalized chronic plaque psoriasis and 32 sex- and age-matched healthy controls were evaluated by detailed clinical neurological and standard neurophysiological examination. The latter included motor nerve conduction study of one nerve in the upper and one in the lower extremities and sensory nerve conduction study of one nerve in the upper and two in the lower extremities. Neurological examination failed to demonstrate any clinical evidence of large fibre neuropathy. Furthermore, all values of the examined neurophysiological parameters were within normal limits; comparisons of the corresponding mean values in the patient and the control group showed no statistically significant differences. These findings demonstrate no measurable abnormalities of the peripheral large nerve fibres in psoriatic patients and therefore an association of psoriasis with peripheral large fibre neuropathy cannot be suggested.

Hospitalizations for childhood asthma in Athens, Greece, from 1978 to 2000.

Trends in rates of asthma admissions among children have shown a variety of patterns in different countries in the last decades. We undertook the present study to determine the time trends in asthma admissions and readmissions of children in Athens, Greece. Data were obtained retrospectively from hospital registries of the three main children's hospitals in Athens from 1978 to 2000. Children admitted with the diagnoses of asthma, asthmatic bronchitis or wheezy bronchitis were included. Hospital admission rate for asthma among children 0-14 yr from 1978 to 2000 rose by 271% (p <0.001). The rise in rates among those aged 0-4 and 5-15 yr were 250% and 276%, respectively. The mean annual increase in admission rate was 12.2% for 1978-1987, 4.7% for 1988-1993 and 0.6% for 1994-2000. The readmission rate among children 0-14 yr was increased from 15.3% to 23.3%. A positive correlation between admission and readmission rates in all age groups was observed. In conclusion, our findings show an increase in the childhood asthma admission rate in Athens in late 1970's and during the 1980's, which has decelerated in the 1990's, particularly in the second-half of the decade. The readmission rate paralleled that of admissions over the entire study period.

Qualitative and quantitative alterations of cell surface carbohydrate residues during epidermal morphogenesis.

The purpose of this study was to investigate the carbohydrate residue composition of cell surface in the developing epidermis and to define the chronological sequence of its alterations in human fetuses from the 10th to the 20th weeks of gestation and at the 23rd week of gestation, using a panel of six biotinylated lectins: Concanavalin A, Ulex europaeus agglutinin-I, Ricinus communis agglutinin-I, Peanut agglutinin, Wheat germ agglutinin, and Dolichos biflorus agglutinin. Distinct qualitative and quantitative alterations in the expression of cell surface carbohydrate residues were found during epidermal morphogenesis prior to keratinization (10th to 20th weeks). At the 23rd week of gestation, the already keratinized fetal human epidermis revealed a pattern of cell surface glycosylation very similar to that of the adult human epidermis. Further studies are now warranted to answer the question regarding whether the glycosylation pattern in the developing human epidermis is disturbed in fetuses with genodermatoses and whether these disturbances might be important for prenatally diagnosing the latter.

Calcipotriol plus short-contact dithranol: a novel topical combination therapy for chronic plaque psoriasis.

The purpose of this double-blind randomised parallel-group study was to compare the efficacy and safety of short-contact treatment with dithranol ointment (2%) with its combination with calcipotriol ointment (50 microg/g) in 2 groups of in-patients with chronic plaque psoriasis. The patients of the first group (n = 23) topically applied dithranol once daily for 30 min and the vehicle of calcipotriol twice daily. The patients of the second group (n = 23) used a single topical application of dithranol for 30 min daily and additionally applied calcipotriol twice daily. The extent and the severity of psoriasis were assessed by means of psoriasis area and severity index score (PASI score) before the onset of the 6-week therapy and weekly thereafter. The difference between the two groups with regard to the mean PASI score became statistically significant already after the first week of treatment and remained so until the end of the trial. No significant differences were observed between the two groups with respect to the cutaneous adverse events. These findings indicate that the addition of calcipotriol ointment to short-contact dithranol markedly augments the therapeutic efficacy of the latter in chronic plaque psoriasis and impressively accelerates the response of psoriatic plaques to this well-tolerated regimen.

Treatment of condylomata acuminata with oral isotretinoin.

PURPOSE: The aim of our study was to evaluate the efficacy and safety of oral isotretinoin in the treatment of condylomata acuminata. MATERIALS AND METHODS: A total of 56 male patients with a history of condylomata acuminata refractory to at least 1 standard therapeutic regimen was treated orally with isotretinoin (1 mg./kg. daily) during a 3-month period. RESULTS: At the end of treatment 21 of the 53 evaluated patients (39.6%) had complete response, 7 (13.2%) had partial response and 25 (47.1%) had no response. A statistically significant inverse relationship was found between age and area of treated lesions and response to medication. Two complete responders (9.5%) revealed recurrence during the 1-year followup. CONCLUSIONS: Oral isotretinoin may be regarded as an effective, fairly well tolerated and noninvasive alternative form of therapy for immature and small condylomata acuminata.

Promoters of progression of diabetic nephropathy: the relative roles of blood glucose and blood pressure control.

BACKGROUND AND AIMS: Hyperglycaemia is a strong risk factor for the development of renal disease in insulin dependent diabetes mellitus but it is uncertain whether it contributes to the progression of incipient or established nephropathy. The rigorous treatment of blood pressure in recent years may help uncover the contribution of hyperglycaemia, if any, to the progression of renal failure. Our aim therefore, was to assess in a current cohort of insulin dependent diabetic patients with diabetic nephropathy the relative importance of glycaemic control and blood pressure on disease progression. METHODS: All insulin dependent diabetic patients with persistent albuminuria (> 300 mg/24 h) attending the diabetic clinic at Guy's Hospital between 1977 and 1993 were recruited. Serial measurements of blood pressure, HbA1 and GFR were performed every 6 months until end-stage renal disease or death. Only patients with at least 1 year of follow up were analysed. The mean follow up period was 8 years (range 1.5-15.5 years). Baseline and time dependent variables were related to the rate of change of GFR using weighted linear regression and stepwise multiple regression analysis. The impact of each variable on the change of GFR with time was adjusted for the effect of other potentially confounding variables by analysis of co-variance. RESULTS: Patients had well-controlled blood pressure throughout the observation period (mean arterial pressure 97 +/- 8 mmHg) and the average rate of decline of GFR was 4.32 +/- 4.08 ml/min/year. In univariate analysis baseline and mean HbA1 were linearly related to the rate of decline of GFR (baseline r5-0.565, P < 0.001; mean r-0.5107, P < 0.001) with those with a higher HbA1 having a faster rate of progression. In stepwise multivariate analysis both mean HbA1 mean diastolic blood pressure (P < 0.0001 and P = 0.019, respectively) was significantly and independently related with a faster rate of decline of GFR. CONCLUSIONS: Worse glycaemic control is associated with a faster rate of progression of diabetic nephropathy once blood pressure is controlled. Thus improvement of glycaemic control in patients where good blood pressure control has been achieved may potentially further delay the progression of nephropathy.