Patch test reactions in atopic patients

Patch testing was carried out in 851 atopic patients; 181 atopic dermatitis (AD) patients were additionally tested with 50% dilutions of the test substances. The occurrence of allergic and irritant reactions was frequent, being 57% and 33% for AD patients aged 28-41 years and 19-27 years, respectively. Among age-matched allergic rhinitis (AR)/allergic conjunctivitis (AC) or asthma (A) patients, the number of allergic reactions varied from 25 to 30%, and for irritant reactions was 24%. In all groups, nickel, fragrance-mix, balsam of Peru and neomycin were the commonest allergens. Contact allergy to ingredients of topical medicaments was common among AD patients and patients with severe and long-lasting dermatitis were most frequently sensitized. However, sensitivity to multiple substances was not common among those patients. The number of irritant reactions was considerable, but 50% dilution of the test substances did not solve the problem.     

Effects of alpha 2-drugs and pilocarpine on the high-voltage spindle activity of young and aged control and DSP4-lesioned rats.

The present study investigates the effects of alpha 2-drugs and pilocarpine on the neocortical high-voltage spindle (HVS) activity in young and aged control and DSP4-lesioned rats. DSP4 partially decreased cortical and thalamic noradrenaline levels, but had no effect on HVS activity. The alpha 2-adrenoceptor agonist guanfacine (0.004, 0.02, 0.1 mg/kg) increased HVS activity in young and aged control and DSP4-lesioned rats. Guanfacine produced a significantly smaller increase in HVS activity in aged rats. A combination of pilocarpine (3 mg/kg), a muscarinic agonist, and atipamezole (1 mg/kg), an alpha 2-adrenoceptor antagonist, suppressed HVS activity more effectively than either of the drugs alone in young or aged control and DSP4-lesioned rats. The present results demonstrate that 1) the alpha 2-adrenoceptor antagonist and muscarinic agonist interact in suppressing HVSs in noradrenergically lesioned young and aged rats; 2) alpha 2-adrenoceptor agonists produce a greater increase in HVS activity in young than aged rats; and 3) partial noradrenergic lesions do not affect the HVS-modulating effects of alpha 2-adrenoceptor active drugs in young or aged rats.     

Effects of ospemifene, a novel SERM, on vascular markers and function in healthy, postmenopausal women

OBJECTIVE: Ospemifene, a novel selective estrogen receptor modulator (SERM), shows promise for bone preservation in postmenopausal women. This study examined the effects of ospemifene on different vascular surrogate markers. DESIGN: A double-blinded study was conducted in 160 healthy, postmenopausal women who used, in a randomized order, ospemifene (at daily doses of 30, 60, or 90 mg) or placebo for 3 months. RESULTS: Although ospemifene caused falls from basal levels in total cholesterol, low-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, and a rise in high-density lipoprotein cholesterol, the only statistically significant difference between ospemifene and placebo was an increase of triglyceride levels (11.3%) in the 90-mg group. Ospemifene caused no significant effect on endothelial markers or homocysteine. Of the markers reflecting coagulation and fibrinolysis, plasma fibrinogen was significantly reduced in the 60- and 90-mg groups of ospemifene (8.7% and 8.5%, respectively) when compared with the placebo group. No changes were seen in generation of thrombin or degradation of crosslinked fibrin D-dimer. The uterine or carotid arteries and 24-h ambulatory blood pressure were not affected by ospemifene. Ospemifene caused no changes in basal insulin or in a 2-h glucose tolerance test, suggesting unaltered insulin sensitivity. CONCLUSIONS: Neutral effects of short-term use of ospemifene on vascular surrogate markers imply no effect for ospemifene on the risk for cardiovascular disorders in healthy, postmenopausal women.     

Nickel sensitivity and the course of atopic dermatitis in adulthood

The course of dermatitis was followed in nickel-sensitive and nickel-negative atopic and non-atopic patients. Manifest dermatitis was seen in 70% of the nickel-allergic and in 64% of the nickel-negative female atopic dermatitis (AD) patients. Those atopic subjects who had minor symptoms in their teens suffered more from dermatitis if they had developed nickel allergy (p less than 0.025). Hands and the head region were the most common sites for current dermatitis in both groups.     

Course of hand dermatitis in hospital Workers

The occurrence and course of hand dermatitis in hospital workers was studied on the basis of the patient register of an occupational specialist and by a clinical follow-up study. About 1% of all the hospital workers had had dermatitis, cleaners, kitchen workers and nurses most frequently. 54% of the patients who were clinically studied had suffered from periodic symptoms and 35% had current hand dermatitis. Those who had previous or present atopic dermatitis had most frequently developed dermatitis during the first year of their service. An atopic constitution seemed to predispose to the development of permanent or periodic hand dermatitis. The patients with sensitivity to nickel or fragrances had relapses in the majority of cases.
During the study period, the incidence of new dermatitis cases was constant, but the number of days sick leave showed a decreasing tendency.     

Pharmacokinetics and metabolism of selegiline

Abstract– Selegiline is readily absorbed from the gastrointestinal tract. It is distributed rapidly into the tissues, including the brain. It is the L-form of selegiline that is an active MAO-B inhibitor, the D-(+)-form being 25 times less active. Selegiline is metabolised into L-(−)-desmethylselegiline (DES), L-(−)-amphetamine (A) and L-(−)-methamphetamine (MA), mainly in the liver. We measured the steady state concentrations of the metabolites in the serum and cerebrospinal fluid (CSF) of patients with Parkinson's or Alzheimer's diseases who were on continuous selegiline therapy. The mean concentrations in serum and CSF were similar, and were not affected by the addition of levodopa. The mean concentrations of patients with Alzheimer's or Parkinson's disease were 6.5±2.5 ng/ml for A, 14.7±6.5 ng/ml for MA and 0.9±0.7 ng/ml for DES. The metabolites of selegiline were excreted in urine, and the recovery as metabolites was 87%. Due to the stereospecificity and the low CSF concentrations of the (−)amphetamine metabolites during the therapy with 10 mg selegiline, these metabolites do not seem to contribute significantly to the clinical efficacy of selegiline.     

Pharmacokinetics of Nitrazepam in Saliva and Serum after a Single Oral Dose

Abstract The pharmacokinetics of nitrazepam in saliva and serum was studied in 12 healthy volunteers after a single administration of a 5 mg nitrazepam tablet. The binding of nitrazepam to plasma proteins was determined 4 hours after the administration by ultracentrifugation. The analysis of nitrazepam concentrations was performed by ⁶³Ni-EC-GLC. The pharmacokinetic parameters were evaluated manually or by AUTOAN-program in serum, and manually in saliva. The concentrations of nitrazepam in serum and saliva correlated significantly (r=0.472, P<0.001, n=97). The ratio saliva: serum was, however, time dependent. The protein free fraction in serum was significantly higher (P<0.01) than the salivary concentration at the same time (4 hours after administration). The peak concentrations in serum and saliva were 40.7 and 1.9 ng/ml (P<0.001) and the times to reach the peak maximum 2.4 and 2.5 hours, respectively (difference not significant). The mean half-life of nitrazepam in serum was 30.5 hrs and in saliva 39.9 hrs, the difference being significant at P<0.05. The distribution phase parameters, poorly described before, were calculated. The clinical value of nitrazepam analysis in saliva seems to be negligible.     

Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women

Ospemifene is a novel selective estrogen receptor modulator (SERM) that is initially being developed for the treatment of vaginal atrophy in postmenopausal women. However, it also shows promise in the prevention and treatment of osteoporosis. As a part of a phase II trial, we compared the effects of ospemifene and raloxifene on bone turnover in postmenopausal women. The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n = 29) raloxifene for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal cross-linking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All markers were studied before and at 3 months and 2–4 weeks after cessation of the medication. Urine NTX outputs decreased in all study groups, and the only statistically significant difference in NTX was observed between raloxifene and 30 mg ospemifene, which was reduced more in the raloxifene group. The output of CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant differences between study groups emerged. A significant difference was found between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene. No other differences in bone formation markers emerged between ospemifene and raloxifene. The study confirms the bone-restoring activity of ospemifene, which is comparable to that of raloxifene.     

Maternal and fetal plasma renin activity during ritodrine infusion to the mother.

The effect of ritodrine to the mother on plasma renin activity (PRA) in the mother and fetus was examined in 10 mothers coming to elective cesarean section. 10 comparable mothers without ritodrine infusion served as controls. At the end of 2 h infusion of ritodrine, the mean maternal PRA was significantly (p less than 0.001) higher than in the control group. Also the mean PRA levels in the umbilical vein (p less than 0.001) and umbilical artery (p less than 0.01) were significantly higher after ridodrine infusion to the mother than the respective levels in the control group.