Drug safety in the treatment of Crohn's disease.

The management of Crohn's disease usually consists of a succession of short-term acute phase treatments followed by long-term maintenance therapy. The disease affects young patients and for this reason the long-term safety of the drugs needs to be especially taken into consideration. The safety, dose, duration for optimal efficacy and the most frequent adverse events will be described in this article.

Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study.

OBJECTIVE: A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression. The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. METHODS: Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale. Women were also asked to evaluate their study participation. RESULTS: Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. CONCLUSION: In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again.

Thrombose veineuse cérébrale après ponction lombaire et stéroïdes intraveineux chez deux patients souffrant d'une sclérose en plaques [Cerebral venous thrombosis after lumbar puncture and intravenous steroids in two patients with multiple sclerosis]

Two patients affected with a multiple sclerosis developed cerebral venous thrombosis after lumbar puncture and treatment with intravenous methylprednisolone. In one case, the course was favorable. The second patient died in spite of intracerebral thrombolysis. The autopsy confirmed the diagnosis of cerebral venous thrombosis and multiple sclerosis. We discuss the relationship between lumbar puncture, steroid treatment and cerebral venous thrombosis.

Alvéolite aux isocyanates chez une couturière [Isocyanate-induced alveolitis in a furniture manufacture worker]

A 41-year-old woman who worked in a furniture plant was admitted to hospital for acute dyspnea that had developed a few hours she marked pieces of "Alcantara" material with a heated metallic blade. The chest x-ray showed a restrictive syndrome. The lymphocyte count was high in the bronchioalveolar lavage fluid with a CD4/CD8 ratio of 0.11, leading to the diagnosis of alveolitis. Investigations at the work place allowed identification and evaluation of the causal agent. Alcantara is a synthetic fabric composed of 70% polyurethane fibers, which when burned produces isocyanate monomers. After eliminating exposure and institution of corticosteroid therapy, the outcome was good with complete recovery. The risk was eliminated by changing the work procedure. This risk has not been reported earlier for furniture manufacture.

Exacerbations aiguës au cours de la fibrose pulmonaire idiopathique [Acute exacerbations of idiopathic pulmonary fibrosis].

Although generally considered as a slowly evolving disease, idiopathic pulmonary fibrosis (IPF) is also characterized by episods of rapid deterioration with worsening of dyspnea and hypoxemia, and new ground glass opacities at imaging. These events called "acute exacerbations" (AE) are responsible for half of all deaths in IPF. Pathophysiologic mechanisms of AE are poorly understood. The effectiveness of corticosteroids and immunosuppressive agents appears limited. The mortality of AE is 60-70%. Preventing or controlling AE could improve the overall prognosis of IPF. AE also exist in other interstitial lung diseases.

Hormonal and metabolic changes following severe head injury or noncranial injury.

In order to evaluate the effect of head injury in severely traumatized patients on the response of plasma cortisol, glucagon, insulin, glucose, and FFA as well as urinary N and catecholamines excretions, 36 patients were prospectively studied over 5 consecutive days following injury. They were divided into three groups: group I, severe isolated head injury (n = 14); group II, multiple injury combined with severe head injury (n = 12); group III multiple injury without head injury (n = 10). The results demonstrate similar hormonal and metabolic changes between these three groups of patients, characterized by elevated urinary adrenaline, noradrenaline excretion, increased cortisol, glucagon, insulin plasma levels throughout the study and elevated N urinary excretion with strongly negative N balances during the first 5 days postinjury. A significant correlation was observed between N intake and 5 day cumulated N balance (r = 0.63, p less than 0.001). In addition, N balance was negatively correlated with urinary excretion of adrenaline (r = -0.47, p less than 0.01) and noradrenaline (r = -0.44, p less than 0.05) as well as plasma levels of glucagon (r = -0.44, p less than 0.05). Isolated severe head injury seems to induce a full response in the secretion of the catabolic counterregulatory hormones comparable to that encountered in patients with multiple injury and associated with a marked increase in protein catabolism; additional noncranial major injury does not seem to enhance these responses.

Prise en charge de l'asthme en médecine de premier recours [Management of asthma in primary care medicine].

The international recommendations issued by GINA (Global Initiative for Asthma) have undergone considerable adaptations over the last years. This article proposes the local adaptation of those guidelines bearing on the practical aspects of the treatment for the general practitioner's use. One of the fundamental changes in these new guidelines on good practice relates to the permanent adaptation of the treatment on the basis of symptom control rather than on the severity of the asthma. Another change from the old recommendations concerns the manner in which the asthma is categorised into different phases.

Hirsutisme: que faire [Hirsutism, what can be done?]

Hirsutism is a relatively frequent condition in an ambulatory setting affecting about 4% of women. A rational clinical and biochemical diagnostic approach assures an optimal treatment directed at etiologic and pathogenetic factors. The diagnosis of hyperandrogenism is evaluated considering the pathophysiologic mechanisms responsible for excessive growth of hair. Ovarian and adrenal tumors are the most serious diseases that have to be excluded by clinical and biochemical tests. The other causes for hirsutism are treatable by a great variety of modalities, available drugs can inhibit pituitary gonadotropins, the hypothalamo-pituitary axis and the conversion of testosterone into biologically active substrate. Finally the binding of androgens to its receptor can be blocked. These possibilities for treatment and their indications for the different etiologies of hirsutism are discussed.

Lésions cutanées et infiltrats pulmonaires d'évolution défavorable sans cause infectieuse [Progressive cutaneous and pulmonary lesions without infectious etiology: two cases reports of sweet syndrome with pulmonary involvement].

Sweet syndrome is a non infectious febrile disease with a neutrophilic infiltrate of dermis. Extracutaneous involvement can occur. We report two cases of Sweet syndrome with cutaneous and pulmonary involvement and give a short review of the literature of pulmonary involvement in Sweet syndrome.

Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes.

Despite the fact that mineralocorticoid receptor (MR) antagonist drugs such as spironolactone and eplerenone reduce the mortality in heart failure patients, there is, thus far, no unambiguous demonstration of a functional role of MR in cardiac cells. The aim of this work was to investigate the activation pathway(s) mediating corticosteroid-induced up-regulation of cardiac calcium current (ICa). In this study, using neonatal cardiomyocytes from MR or glucocorticoid receptor (GR) knockout (KO) mice, we show that MR is essential for corticosteroid-induced up-regulation of ICa. This study provides the first direct and unequivocal evidence for MR function in the heart.