Frequency and type of adverse drug reactions in two Seine-Saint-Denis departments of pneumology

The aim of this study was to explore the frequency and type of adverse drug reactions between January and June 2001 in hospitalised patients. A prospective study was conducted in two pneumology departments of public hospitals in the Seine-Saint-Denis area. Adverse drug reactions were collected by hospital pharmacists after spontaneous notification by nurses and physicians, except for deliberate drug overdose. The drugs implicated, causality and the severity of each adverse drug reaction were analysed. The mean age of patients was 69 +/- 15 years (63% male and 37% female). The total sample comprised 1598 patients. During the period of the study, 190 patients experienced at least one adverse drug reaction. This amounts to a prevalence of 12% (95% confidence interval [95% CI: 7.4-16.6%). The percentage of severe adverse effects was 28.4% (95% CI: 25.1-31.6%) and adverse reactions were rated avoidable in 35.8% of cases (95% CI: 32.3-39.3%). Antibiotics (23%), corticosteroids (15%), analgesics (13%) and anticoagulants (9%) were the drugs most frequently implicated in adverse effects. Preventable adverse drug events were more serious than non-preventable adverse events (p = 0.001). With regard to the level of severity, antibiotics, corticosteroids and bronchodilators were associated with a low severity level, whereas anticoagulants and antineoplastics were associated with a high severity level.     

Defect in epinephrine production in children with craniopharyngioma: functional or organic origin?

Despite pituitary hormone replacement, patients with craniopharyngioma often complain of fatigue. They may have deficient control of catecholamine secretion caused by hypothalamic lesion. Another hypothesis is a functional defect in catecholamine production through either glucocorticoid deficiency because high intraadrenal glucocorticoid concentration is necessary for epinephrine synthesis or unrecognized hypoglycemia, which can intrinsically alter epinephrine secretion. We measured catecholamine response to insulin-induced hypoglycemia and orthostasis, and 24-h urinary catecholamine excretion, in 16 children with craniopharyngioma (patients) and 27 sex- and age-matched short children. We also studied the influence of a 4-fold increase in the usual daily dose of hydrocortisone on catecholamine excretion (50 vs. 12 mg/m(2) of body surface area) in the glucocorticoid-deficient patients. Last, we compared 24-h continuous sc glucose in patients and 10 sex- and age-matched healthy children. The results are expressed as medians (25th, 75th). For a similar blood glucose nadir after insulin administration, peak plasma epinephrine in response to hypoglycemia was lower in patients vs. controls [420 (120, 715) vs. 730 (460, 1200) ng/liter, P < 0.01], whereas peak plasma norepinephrine was higher [390 (280, 550) vs. 270 (180, 280) ng/liter, P < 0.05]. Catecholamine response to orthostasis did not differ between groups. Urinary epinephrine was significantly lower in patients (P < 0.001), whereas urinary norepinephrine was similar. The extent of epinephrine deficiency correlated with neither tumor size nor hypothalamic involvement. A 4-fold higher hydrocortisone dose did not correct the defective epinephrine excretion in the glucocorticoid-deficient patients. Last, the 24-h sc glucose values were similar between patients and controls. In conclusion, children with craniopharyngioma have a defect in epinephrine but not norepinephrine production. There is no proof of a univocal origin, either organic or functional. Whether abnormal catecholamine secretion alters glucose level during fasting or acute illness, or hampers adaptation to exercise, requires further studies.     

Gamma irradiation induces acetylcholine-evoked, endothelium-independent relaxation and activates K-channels of isolated pulmonary artery of rats

PURPOSE: To test the effects of irradiation (R*) on the pulmonary artery (PA). METHODS AND MATERIALS: Isolated PA rings were submitted to gamma irradiation (cesium, 8 Gy/min(-1)) at doses of 20 Gy-140 Gy. Rings were placed in an organ chamber, contracted with serotonin (10(-4) M 5-hydroxytryptamine [5-HT]), then exposed to acetylcholine (ACh) in incremental concentrations. Smooth muscle cell (SMC) membrane potential was measured with microelectrodes. RESULTS: A high dose of irradiation (60 Gy) increased 5HT contraction by 20%, whereas lower (20 Gy) doses slightly decreased it compared with control. In the absence of the endothelium, 5-HT precontracted rings exposed to 20 Gy irradiation developed a dose-dependent relaxation induced by acetylcholine (EI-ACh) with maximal relaxation of 60 +/- 17% (n = 13). This was totally blocked by L-NAME (10(-4) M), partly by 7-nitro indazole; it was abolished by hypoxia and iberiotoxin, decreased by tetra-ethyl-ammonium, and not affected by free radical scavengers. In irradiated rings, hypoxia induced a slight contraction which was never observed in control rings. No differences in SMC membrane potential were observed between irradiated and nonirradiated PA rings. CONCLUSION: Irradiation mediates endothelium independent relaxation by a mechanism involving the nitric oxide pathway and K-channels.     

Quantitative motor assessment in myotonic dystrophy

OBJECTIVE: To establish baseline data, using a quantitative motor evaluation protocol, prior to a prospective longitudinal study of the natural history of muscular involvement in myotonic dystrophy (DM). DESIGN/METHODS: We conducted a cross-sectional study using a protocol consisting of manual muscle testing (MMT), quantitative muscle testing (QMT), and timed functional testing (TFT) on 50 definite DM patients (27 men, 23 women), aged 16 to 67 years. The relationships between MMT, QMT and TFT scores and disease duration were examined using linear regression analysis. RESULTS: The muscle weakness was symmetric and the neck flexors and the distal muscles of upper and lower extremities were weaker than proximal muscles. Using MMT scores, the average strength decline was 0.95% per year and was similar for men and women. The strength decline was significantly more rapid for distal muscles than for proximal muscles. Quantitative muscle testing scores documented a strength decline per year of disease duration of 1.2-1.6% for the hip flexors and of 2.0-3.0% for the hand grip flexors. CONCLUSIONS: We observed significant linear relationships between the scores generated by this protocol and disease duration. These data illustrate the distal to proximal progression of muscular involvement in DM, a pattern of progression well-recognized by the clinicians. The follow-up assessment of a large DM cohort in a longitudinal study will establish whether this quantitative protocol provides sensitive measures of the disease progression.     

Post-lesion transcommissural growth of olivary climbing fibres creates functional synaptic microzones

In the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, postlesion plasticity may generate alternate paths, providing models to investigate reinnervating axon-target interactions. After unilateral transection of the neonatal rat olivocerebellar path, axons from the ipsilateral inferior olive grow into the denervated hemicerebellum and develop climbing fibre (CF)-like arbors on Purkinje cells (PCs). However, the synaptic function and extent of PC reinnervation remain unknown. In adult rats pedunculotomized on postnatal day 3 the morphological and electrophysiological properties of reinnervating olivocerebellar axons were studied, using axonal reconstruction and patch-clamp PC recording of CF-induced synaptic currents. Reinnervated PCs displayed normal CF currents, and the frequency of PC reinnervation decreased with increasing laterality. Reinnervating CF arbors were predominantly normal but 6% branched within the molecular layer forming smaller secondary arbors. CFs arose from transcommissural olivary axons, which branched extensively near their target PCs to produce on average 36 CFs, which is six times more than normal. Axons terminating in the hemisphere developed more CFs than those terminating in the vermis. However, the precise parasagittal microzone organization was preserved. Transcommissural axons also branched, although to a lesser extent, to the deep cerebellar nuclei and terminated in a distribution indicative of the olivo-cortico-nuclear circuit. These results show that reinnervating olivocerebellar axons are highly plastic in the cerebellum, compensating anatomically and functionally for early postnatal denervation, and that this reparation obeys precise topographic constraints although axonal plasticity is modified by target (PC or deep nuclear neurons) interactions.     

Comparison of predictive values of inhibins A and B, and plasma estradiol in IVF patients treated with GnRH agonists and recombinant FSH

The objectives of this study were to determine the mean plasma inhibin A and B kinetics in normoovulatory patients treated by GnRH agonist and rec-FSH and to compare their predictive value with that of plasma estradiol on retrieved oocytes number and pregnancy rate. The study was carried out retrospectively in 36 normoovulatory IVF patients stimulated by GnRH agonist from D21 and rec-FSH from D2 of the following cycle. Two groups of 18 patients (having obtained or not a pregnancy) were paired for age and cause of infertility. Estradiol was measured by direct immunoassay. Inhibin A and B were measured by ELISA (Serotec Limited, Oxford, UK). Inhibin A was correlated with estradiol until P-2 (P0: day of follicles aspiration). Inhibin B rose earlier, its concentration reached its maximum at P-5. Plasma estradiol and inhibin A kinetics were not different among pregnant and nonpregnant women. There was a trend for a broader plasma Inhibin B surface under the curve in pregnant than in nonpregnant women. Estradiol and Inhibin A were correlated to the oocytes number at the end of stimulation (P-2 and D10). Inhibin B was correlated earlier than estradiol and inhibin A, at P-8 and D7. Plasma inhibin A did not demonstrate a better predictive value than estradiol neither of the oocytes number nor the chance of pregnancy. Inhibin B could be useful for early decision of cycle cancellation or stimulation adjustment.     

Sentinel node biopsy in breast cancer. Will this lead to the end of lymphadenectomy for small tumors without suspected axillary adenopathy?

Sentinel node (SN) biopsy in breast cancer is still in a crucial stage of evaluation. Many teams have obtained excellent results using this method, with a detection rate always higher than 90% and a false negative rate between 0 and 8%, in prospective series. The main question is to know if lymphadenectomy can now be avoided when the SN is negative. The answer will come from the results of the two ongoing trials comparing sentinel node biopsy to axillary lymphadenectomy. But their results will be available only in two or three years. However, many teams, as at Institute Gustave Roussy, are now applying the technique routinely, because of the excellent results obtained during their learning curve. But there are some methodological differences between teams, which can influence the detection and false negative rates. Thus, several methodological standards remain to be defined. This review enable us to clarify a certain number of questions. Today, SN biopsy can only be performed by trained teams, with prospective evaluation of their results or participation in phase III trials.