A pilot study of 220 mg/m2 melphalan followed by autologous stem cell transplantation in patients with advanced haematological malignancies: pharmacokinetics and toxicity

We studied the pharmacokinetics and toxicity of 220 mg/m² melphalan (HDM 220) followed by autologous stem cell transplantation in 16 patients with advanced haematological malignancies. Pharmacokinetic parameters (mean values of steady-state volume of distribution 14.6 l/m², total body clearance 313 ml/min/m², elimination half-life 46 min) were the same as those of 140 or 200 mg/m² melphalan in previous reports. HDM 220 was feasible. Extramedullary toxicity was mainly W.H.O. grade 4 mucositis (13/16 patients). The median duration of 41 d (10, not reached) of thrombocytopenia <25 × 10⁹/l was long. In multiple myeloma the response rate was 89% in heavily pretreated patients, suggesting that HDM 220 could be considered earlier in the course of the disease as an alternative consolidation therapy.     

The hemodynamic effects of pediatric caudal anesthesia assessed by esophageal Doppler

Pediatric caudal anesthesia is an effective method with an infrequent complication rate. However, little is known about its cardiovascular consequences. Transesophageal Doppler, a noninvasive method, provides the opportunity for a reappraisal of the hemodynamic effects of this technique. After parental informed consent, we studied 10 children aged 2 mo to 5 yr who were scheduled for lower abdominal surgery. General anesthesia was induced using sevoflurane and was followed by the insertion of a transesophageal Doppler probe. Caudal anesthesia was performed using 1 mL/kg of 0.25% bupivacaine with 1/200,000 epinephrine. Hemodynamic variables were collected before and after caudal anesthesia. No complications arose during insertion of the probe. The mean time between the two sets of measurements was 15 min. Heart rate, systolic, diastolic, and mean arterial blood pressures were not modified by caudal anesthesia. Descending aortic blood flow increased significantly from 1.14 to 1.92 L/min. (P = 0.0002). Aortic ejection volume increased from 8.5 to 14.5 mL (P = 0.0002). Aortic vascular resistances decreased from 6279 to 3901 dynes. s(-1) x m(-5) (P = 0.005). Caudal anesthesia did not affect heart rate and mean arterial blood pressure but induced a significant increase in descending aortic blood flow. IMPLICATIONS: Although pediatric caudal anesthesia does not alter heart rate nor arterial blood pressure, significant changes occur in regional blood flow distribution. Descending aortic blood flow increases significantly after caudal anesthesia, whereas lower body vascular resistances decrease.     

Clinical data on COX-1 and COX-2 inhibitors: what possible alerts in pharmacovigilance?

Adverse effects of NSAIDs are serious, mainly related to gastrointestinal bleeding, and throughout the world cause about 260,000 hospitalizations and 26,000 deaths a year, but each day at least thirty million patients take NSAIDs. Selective COX-2 inhibitors (i.e. celecoxib, rofecoxib) have demonstrated in clinical trials better gastrointestinal tolerability but their safety in patients with active ulcer, cardiovascular or renal disease has still to be further investigated. When their long-term safety has been established by pharmacovigilance studies they could be prescribed in the at-risk population or for other indications, including pre-term labour, colorectal cancer and Alzheimer's disease, provided they have shown efficacy and safety in controlled trials.     

Use of the CD-ROM "Tox-Didact" for teaching of toxicology and pharmacology

Tox-Didact is a multimedia teaching software package for initial training, continuing training and self-learning of toxicology and pharmacology. This software covers a large part of toxicology in its acute and chronic pathology using several approaches: drugs (salicylics, paracetamol, lithium ...); toxins (lead, methanol, carbon monoxide ...); drug addiction and doping (cocaine, heroin, LSD, amphetamines ...); systemic targets (kidneys, skin, liver ...). Tox-Didact is currently composed of 39 modules in validation, each tackling the diagnosis, biological surveillance, treatment, prevention and documentation of a real clinical case. Each module is organized around four types of questions, requiring a choice either (drug, symptom, formula ...) or an open response. Each validated answer is analysed by software which then comments on or corrects it. The essential points which characterize this software are: its multidisciplinarity (toxicology, pharmacology, semiology ...), its reliability (validated by experts), its simplicity of use. It is modular and offers an interactive teaching approach. The objective is to create a portable multimedia tool operational with all computer systems (IBM PC, Macintosh). This program is sustained by the Région des Pays de la Loire and by the Multimedia Resource Office of the French Ministry of National Education.     

Warning! One buflomedil may hide another one!

A 75-year-old woman experienced fever and convulsions. She was treated for diabetes mellitus, angina pectoris and also for arteritis with Buflomedil Merck (3 tab/d). Further investigations failed to find any aetiology. Buflomedil dosage was elevated to 6.3 mg/l (N = 4-4.5 mg/l). The drug was discontinued and there was no recurrence of symptoms. There was no evidence of error in dosage or interaction. A failure of the generic product was suspected. Only a pharmacist solved the problem. Fonzylane (buflomedil) had recently been switched to Buflomedil Merck. The patient misunderstood the change and took both drugs! Our purpose is not to report a known effect but to emphasize the importance of extending the information given to the patient and the risk of misuse of the generic product.     

Small-dose bupivacaine-sufentanil prevents cardiac output modifications after spinal anesthesia

Spinal injection of small-dose (SD) bupivacaine decreases the likelihood of hypotension compared with large-dose (LD) bupivacaine. We assumed that a SD of bupivacaine could also prevent the decrease in cardiac output (CO). Patients undergoing elective urologic, lower abdominal, or lower limb surgery under spinal anesthesia were included in this prospective randomized study. Spinal injection consisted of 5 mug of sufentanil and either SD (7.5 mg of hyperbaric bupivacaine with glucosemonohydrate 80 mg/mL; n = 19 patients) or LD (12.5 mg of hyperbaric bupivacaine with glucosemonohydrate 80 mg/mL; n = 19 patients). CO (impedance cardiography), arterial blood pressure, and heart rate) were measured at 1 min before performance of spinal block and 2, 10, and 30 min after the intrathecal injection. Sensory level was also assessed at 30 min. CO was higher in the SD group as compared with the LD group from 2 min to 30 min after spinal anesthesia. Moreover, CO increased at 2 min in the SD group and decreased at 10 and 30 min in the LD group compared with baseline value. In conclusion, SD bupivacaine provides successful anesthesia and gives better CO stability than LD.