Characteristics of EPI-hNE4 aerosol: a new elastase inhibitor for treatment of cystic fibrosis.

The purpose of this study was to define nebulization conditions providing delivery of aerosols of EPI-hNE4, an inhibitor of human neutrophil elastase (HNE). EPI-hNE4 was nebulized with Pari LC Star and tested at three concentrations (2.5, 5, and 10 mg/mL). The inhaled mass was measured over 15 min. Particle size distribution was measured by cascade impaction. The effect was also tested of mixing EPI-hNE4 with a (99m)Tc human serum albumin (HSA) tracer on the aerodynamic properties of the aerosol. The inhibitory activity of EPI-hNE4 after nebulization was assessed on purified HNE. The inhaled mass was 32.3 +/- 3.5% (mean +/- SD) after 10 min and 44.2 +/- 3.8% (mean +/- SD) after 15 min. Mass median aerodynamic diameter ranged between 1.2 and 1.8 microm. The (99m)Tc HSA EPI-hNE4 aerosol was similar in terms of particle size distribution (y = 1.0338x - 0.003, r = 0.83). (99m)Tc activity was predictive of EPI-hNE4 mass distribution (y = 1.0278x - 1.6991, r = 0.89). The inhibitory capacity of aerosolized samples remained unchanged after up to 10 min of nebulization. EPI-hNE4 can be nebulized efficiently without decrease in its activity. Mixing this inhibitor with (99m)Tc HSA should allow quantification of its deposition in CF patients.

[Lethal hydrops fetalis secondary to an umbilical cord hemangioma]. / Anasarque foeto-placentaire létale secondaire à un hémangiome du cordon ombilical.

We report an umbilical cord hemangioma associated with an hydrops fetalis and detected by ultrasonography at 21 week's gestation. Because of the fetal distress, a caesarean section was performed at 28 weeks'. The infant died soon after birth despite resuscitation. The post-mortem examination showed an extensive accumulation of serous fluid in the fetal tissues and the body cavities, and major pulmonary hypoplasia. The umbilical cord contained a grossly fusiform tumor which fulfilled the pathological criteria of an umbilical cord hemangioma. Umbilical cord hemangiomas are very unusual tumors and are rarely associated with a fetal hydrops. This tumor is a cause of increased maternal serum and amniotic fluid alpha-foetoprotein levels. Although it is usually isolated, it is imperative to search for associated malformations or angiomas that may clinically manifest later.

Efficiency and side effects of intracavernous injections of moxisylyte in impotent patients: a dose-finding study versus placebo.

We assessed the efficiency and tolerance of the alpha-blocking agent moxisylyte in 2 double-blind studies versus placebo performed in 12 neurogenic patients with spinal cord lesions and in 61 patients presenting with either psychogenic impotence (30) or erectile dysfunction that was predominantly neither psychogenic, hormonal nor neurogenic (31). In each etiological group patients were randomized (according to latin square method) to receive 3 single doses (10, 20 and 30 mg.) of moxisylyte and a placebo. The erectile response was determined 5, 10, 15, 20 and 30 minutes after each injection. Whatever etiology of impotence and dosage tested, the erectile response induced by moxisylyte was significantly higher than the placebo-induced response. No difference occurred among the 3 doses. In 93% of the patients moxisylyte induced an erectile response, including tumescence in 6, partial rigidity in 16 and complete rigidity in 46. Thus, in 62 of 73 patients (85%) the drug allowed initiation of erection adequate for intercourse. Placebo induced such erection in only 25% of the cases and in 55% there was no response. Tolerance was good and no priapism occurred. Only 4 patients (5%) reported mild pain during injection but erections were never painful, 1 presented with moderate and transient hypotension at the 20 mg. dose and a painless prolonged erection was observed in 1 case after the lowest dose. Drugs such as moxisylyte should be given before less well tolerated drugs.

Is the volume injected a parameter likely to influence the erectile response observed after intracavernous administration of an alpha-blocking agent?

In 12 impotent patients with spinal cord injury, we assessed the erectile response induced by intracavernous administration of 20 mg moxisylyte dissolved in 4 different volumes of solvent. We tested successively in each patient 0.4, 0.8, 1.2 ml and the volume usually injected of 2 ml, with a 7-day interval between 2 injections. The reduction in the volume from 2 to 0.4 ml did not thwart the quality of erection obtained by the intracorporeal administration of 20 mg moxisylyte. Indeed, for each erectile parameter (rigidity, abdominopenile angle, length and circumference of the penis), no statistically significant difference arose between the 4 tests. All patients achieved full rigidity. Neither priapism nor prolonged erection occurred. These results suggest that discreet and easily handled small-sized injection pens, containing little solution, could be conceived for autoinjection therapy.

A comparative study of controlled-release morphine (CRM) suspension and CRM tablets in chronic cancer pain.

This study compared the efficacy and the adverse effects of controlled-release morphine (CRM) suspension (SAR 213) and CRM tablets (Moscontin) in the treatment of cancer pain. This multicenter, randomized, double-blind, double-dummy, crossover study was carried out on 52 patients. Each patient received both study treatments given at an equivalent dosage of morphine during each of two 7-day periods. The primary outcome variable was the severity of pain assessed three times daily by means of a visual analogue scale. Secondary criteria of efficacy were the severity of pain assessed by verbal rating scale, the need for "rescue" doses of immediate-release morphine, treatment preference, and indices of quality of life (activity, mood, sleep). There were no statistically significant differences in the parameters assessed when comparing the two groups. This study shows that, when prescribed at the same doses, CRM suspension and CRM tablets have similar efficacy and adverse effects, as well as the same duration of action. The results of this first clinical study carried out on CRM suspension are especially relevant for patients with cancer pain who have difficulty swallowing.

Azelastine reduces allergen-induced nasal response: a clinical and rhinomanometric assessment.

The effect of azelastine 2 mg b.d. p.o. for 10 days on grass pollen-induced nasal responses in 16 patients with grass pollen allergic rhinitis has been assessed. The study was a double blind, randomized, placebo controlled, crossover trial, with a 10-14 day wash-out period. Patients were challenged with grass pollen before and after placebo and azelastine. The response was assessed by measurement of nasal resistance using active posterior rhinomanometry, by weighing nasal secretions, and by counting sneezes. The sensation of nasal obstruction was assessed with a visual analogue scale. After measurement of baseline total nasal resistance, doubling doses of allergen were sprayed into both nostrils at 15 min intervals until the nasal resistance was doubled. Cumulative doses of allergen that doubled prechallenge nasal resistance, numbers of sneezes and the amounts of nasal secretions were similar before azelastine as well as before and after placebo (cumulative dose, mean, (microgram): 2.3, 4.2 and 2.1 respectively, N.S.). After azelastine, the cumulative dose of allergen was increased (7.3 micrograms), and nasal secretions and the number of sneezes were decreased. The visual analogue scores were similar before and after azelastine as well as before and after the placebo. It is concluded that azelastine reduced the allergen-induced nasal responses.

[Iodized polyvidone (betadine) and prevention of postoperative infection. A multicenter study]. / Polyvidone iodée (bétadine) et prévention de l'infection postopératoire. Etude multicentrique.

A multicentre study of a new preparation of povidone iodine (5% betadine) was carried out on 150 patients undergoing cataract surgery. Pre-operatively the eye was prepared by daubing the peri-ocular skin and a two-minute instillation into the conjunctival fornices. No other antiseptic was applied. Tolerance to the product was evaluated in all the patients: clinical evaluation postoperatively and during a 60-day follow-up period confirmed that the preparation was harmless to the eye. Microbiological investigations (comprising conjunctival swabbing, bacterial culture and count of the bacterial species isolated, before and after application of the product) performed on 60 patients showed a significant fall in the number of colonies after treatment.