Occupational dermatitis in a highly industrialized Italian region: the experience of four occupational health departments.

There is a need for several research centers to carry out coordinated large-scale evaluation of the spread of occupational irritant and allergic dermatitis. The Occupational Health Departments of Bergamo, Brescia, Lecco and Cremona therefore decided to join their experiences and bring together all the cases of occupational irritant and allergic dermatitis diagnosed by these Departments between 1993 and 1998. In this period, 1169 cases of occupational dermatitis were diagnosed, subdivided into 768 cases of allergic contact dermatitis (ACD), 337 of irritant contact dermatitis (ICD), 54 of urticaria and 10 of airborne contact dermatitis, and there has not been a trend towards increase of occupational dermatitis over the years. Our population included 724 males and 445 females and average latency after the beginning of exposure to occupational allergens was 8.01 years for ACD, 6.4 for ICD, 3.22 for urticaria and 5.57 for airborne contact dermatitis. The frequency of atopy was 33.9%, in females and 19.5% in males. The frequency of atopy was particularly high (89%) in subjects with urticaria. Among subjects with allergic dermatitis, 362 had had only one sensitization while 406 had had two or more sensitizations. The working areas where we found the highest number of ACD were metal working industry, building, health care workers and hairdressers and the frequency of ICD was high in metal workers and health care workers. Most of the cases of urticaria were diagnosed in health care workers (68.5%) and the main causing agent was latex. These are only preliminary data but occupations at risk and the substances expected to be the most frequent etiological agents do not differ significantly from those reported in the literature. It is hoped that as a result of this project there will be in the future: standardization of diagnostic procedures, uniform assessment of allergological risk in working environments not yet fully investigated, standardization of preventative measures and proper evaluation of their effectiveness.

Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain.

A prospective double-blind randomized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone (50 mg q.i.d.) or in combination with a weak opioid (codeine 40 mg q.i.d.), or with an anti-depressant (imipramine, 10 or 25 mg t.i.d.). All demographic and clinical characteristics including cancer type, presence of bone metastases, baseline pain severity, neuropathic and nociceptive pain, and depressive state, were well balanced between the three treatment groups. The main analysis of the study was on the VAS scores at visit 2 (day 4). The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac. Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy, while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events. In conclusion, in a short-term evaluation the addition of a tricyclic anti-depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone.

Efficacy and tolerability of Estraderm MX, a new estradiol matrix patch.

OBJECTIVES: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. METHODS: A multicenter, double-blind, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. RESULTS: Estraderm MX was significantly superior to placebo (P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6-5.8). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo (P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. CONCLUSIONS: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.

Diclofenac dispersible provides superior analgesia with faster onset of action compared to naproxen granular in patients with acute, painful, minor sports injuries.

BACKGROUND: To compare the efficacy and tolerability of single doses of diclofenac dispersible and naproxen granular in patients with acute, painful, minor sports injuries. METHODS: Forty-eight adult outpatients with moderate-to-severe pain on movement, following a traumatic event < or = 36 hours previously, participated in this double-blind, between-patient comparative study. Patients were randomised in equal comparative study. Patients were randomised in equal number to receive diclofenac dispersible 50 mg or naproxen granular 500 mg. Pain on movement, pain on pressure, spontaneous pain and pain relief were assessed at 15, 30, 45, 60 minutes and 4 hours after dosing. RESULTS: Both treatments were effective at reducing pain from the 15 minute time point. At 15 minutes there was no significant difference between the treatments for pain on movement (p = 0.4) but diclofenac was significantly superior to naproxen with respect to pain on pressure (p = 0.004), spontaneous pain (p = 0.0022) and pain relief (p = 0.034). In addition, diclofenac was significantly superior to naproxen with respect to AUC0-4 hours for percentage reduction in intensity of pain on movement (p = 0.04) and spontaneous pain (p = 0.0047), and for pain relief scores (p = 0.015). Both treatments were well tolerated. CONCLUSIONS: The study results suggest that diclofenac dispersible 50 mg provides faster and overall better analgesia compared to naproxen granular 500 mg in the acute relief of pain following minor sports injuries.

Sequential addition of low dose of medrogestone or medroxyprogesterone acetate to transdermal estradiol: a pilot study on their influence on the endometrium.

We evaluated bleeding pattern and endometrium following the administration of two of the most common types of progestogens used in hormone replacement therapy, medroxyprogesterone acetate (MPA) and medrogestone acetate. Twenty eight patients in spontaneous menopause were randomly allocated to two groups. Group 1 (n = 14) received 5 mg/day of of MPA and group 2 (n = 14) received 5 mg/day of medrogestone: both the progestogens were sequentially added for the last 12 days of a 21-day period of transdermal estradiol administration (50 micrograms per day). A 7-day treatment-free period completed the cycle. The study treatments were administered for 6 cycles. The endomtria were checked for their thickness by transvaginal ultrasound before starting treatment and at 6th treatment cycle (days 6-10 of the estrogen-only phase and during the period between days 8 and 12 of the progestogen addition). Endometrial biopsies were performed before starting treatment only in the patients with a positive progesterone challenge test and in all the patients at the end of the study during the addition of the progestogen. The bleeding pattern was closely monitored. MPA is accompanied by a thick endometrium with full secretory transformation in all cases. On the contrary, the same dose of medrogestone induced a consistent decrease of estrogen primed endometrium with only 4 cases of full secretory transformation. Four medrogestone-treated patients dropped out due to unscheduled bleeding. A low dose of medrogestone added to transdermal estradiol induced incomplete transformation of endometrium and oligo-amenorrhea more frequently than MPA, but it increased the chances of irregular bleeding. MPA fully transformed the endometrium: periods were thus heavier but regular. None of the patients in either group had endometrial hyperplasia.

Plasma and synovial fluid interleukin-1, interleukin-6 and substance P concentrations in rheumatoid arthritis patients: effect of the nonsteroidal anti inflammatory drugs indomethacin, diclofenac and naproxen.

We performed an open, between patients, placebo controlled study in order to evaluate the effect of the treatment with the non steroidal anti inflammatory drugs indomethacin, diclofenac and naproxen on the concentrations of the cytokines IL-1 beta and IL-6 and of the neuropeptide substance P in plasma and synovial fluid of 24 rheumatoid arthritis patients. All patients had high synovial fluid cytokine and substance P levels, and high plasma cytokine levels at the beginning of the study. The treatment with the non steroidal anti inflammatory drugs significantly decreased both plasma and synovial fluid IL-6 and synovial fluid substance P in comparison to placebo, but did not affect IL-1 beta concentrations. This effect can participate in the therapeutic effect of non steroidal anti inflammatory drugs in rheumatoid arthritis.

Evaluation of the bronchodilating activity and the tolerability of broxaterol administered as a solution by inhalation.

The aim of this study was to evaluate the bronchodilating activity and the tolerability of broxaterol (B, CAS 76596-57-1) given as drops by inhalation after single administration at different doses and after repeated administrations for 1 month. Two groups of 12 patients each were treated in a double-blind fashion and according to a within-subject design: one group with B at the single doses of 1.25 mg and 2.50 mg and with placebo (P), and the other with B at the dose of 0.75 mg and with P. A further group of 12 patients was treated in open fashion for 1 month with B at the dose of 1.25 mg 3 times a day. On each study day for the single doses and on the 1st and 30th days for the repeated doses, forced vital capacity (FVC), forced expiratory volume (FEV1), maximal middle expiratory flow (MMEF), heart rate (HR) and systolic and diastolic blood pressure (BP) were measured immediately before and 15, 30, 60, 120 and 240 min after the conclusion of the treatment. At the beginning and at the end of the 1-month treatment period, haematology and biochemistry were checked. After B 0.75 mg, 1.25 mg and 2.50 mg the values of spirometric variables proved significantly and dose-dependently higher than the basal values. The changes from baseline in lung function test values with B (all doses) were significantly greater than with P.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the effect of thymoxamine solution 0.5% on mydriasis induced by ibopamine solution 1%.

The effects of thymoxamine 0.5% solution and of a placebo solution (mannitol) on the mydriasis induced by ibopamine 1% solution were evaluated in 8 healthy volunteers and 12 patients with eye diseases. One drop of ibopamine was instilled into each eye and 30 min later 1 drop of thymoxamine was instilled into one eye and 1 drop of placebo into the contralateral eye. Pupillary diameter was measured before and 30 min after the instillation of ibopamine, immediately before the treatment with thymoxamine and placebo and 30, 60 and 90 min after the instillation of thymoxamine or of placebo. Within 30 min of treatment, ibopamine had produced a statistically and clinically significant mydriatic effect. In eyes treated with thymoxamine, prompt reversal of mydriasis was observed, the baseline diameter being observed within 60 min. No difference in the time-course of the mydriatic effect was detected between healthy subjects and patients. The pupillary response to thymoxamine was not influenced by the colour of the iris. The tolerability of ibopamine and of thymoxamine was good. No local or systemic adverse events were seen or reported.

Bronchodilation and beta 2-selectivity of broxaterol in asthmatics: a crossover, single-blind, terbutaline- and placebo-controlled study.

To investigate the beta 2-receptor selectivity of a new beta 2-adrenoceptor agonist, broxaterol, we compared the respiratory and cardiovascular effects of this compound with those of terbutaline and placebo. Twelve asthmatic patients were evaluated in a randomized, single blind, crossover study. A single dose of each study treatment (broxaterol 400 micrograms and terbutaline 500 micrograms was administered with metered dose inhalers. Measurements of lung function (vital capacity, forced expiratory volume in one second, airway resistance and specific airway conductance), heart rate and systolic/diastolic blood pressure were performed before and at 15, 30, 60, 120, 240 and 360 min after each study treatment. No significant difference was observed between broxaterol and terbutaline in VC, FEV1 and Raw changes, although a greater and significant increase in sGaw was found only with broxaterol. Significant increases in heart rate and systolic blood pressure were observed only with terbutaline. The results of this study suggest that broxaterol can promote a greater bronchodilator effect with less cardiovascular side effects than terbutaline, probably through a greater beta 2-receptor selectivity.

Bronchodilating activity of broxaterol transdermal patch and its protective effect on bronchial constriction induced by inhaled distilled water mist.

The bronchodilating activity and the ability of broxaterol transdermal patch to inhibit bronchial constriction in response to distilled water mist (UNH2O) inhalation were assessed. The study was performed in 10 asthmatic patients in clinical remission according to a placebo-controlled, double-blind, randomized crossover design. Test medications were broxaterol patch (size = 1.75 cm2; programmed delivery = 105 mcg/h) and a matched placebo patch. A spirometric examination was performed before patch application (at 8:30-9:00 a.m.) and 24 hours later. Immediately afterwards, the UNH2O inhalation test was made, consisting of 3 bronchial exposures lasting 30, 60 and 120 s respectively with 3-minute intervals between challenges. Immediately after each exposure, a spirometric examination and specific airway resistance measurements were made. The results obtained show that broxaterol patch exerts a statistically significant bronchodilating effect and has a better protective effect than placebo patch on UNH2O-induced bronchial constriction. The local tolerability of patches was very good. Slight tremors were observed in some subjects.