Analgésie contrôlée par le patient : étude de la demande en fentanyl chez le brûlé à la phase aiguë

This study assessed over the first post-burn week the patients' demands for opiates delivered with a PCA device, changes in opioid delivery along the day, especially during painful events and the incidence of side effects. Twenty-two patients (8 women, 14 men), mean age 33 years (± 12 SD), mean BSA 21 % (± 13 SD), mean deep dermal burn 12 % (± 11 SD) were included. Fentanyl was delivered by i.v. route using a PCA device during the first 6 days post burn. Bolus dose was fixed at 1 μg · kg⁻¹, lock-out time at 30 min and the 4 h limit dose at 7 μg · kg⁻¹. The following data were collected every day : satisfied and non-satisfied demands, total daily dose, demands during and after dressing change period (4 h), during afternoon (10 h) and overnight periods (10 h). Heart rate (HR), respiratory rate (RR), blood pressure (BP), Paco₂ and Spo₂ were also monitored. The mean total daily demands were similar from D1 to D6 (28 ± 7). Around 7 demands/day were not satisfied. The mean total daily satisfied demands were also the same : 21 ± 5. Individual demands were over a wide range (minimum : 15, maximum : 41 demands/day for total demands and 13 and 34 respectively for the satisfied ones). Mean fentanyl delivery was 1,7 ± 0,1 μg · kg⁻¹ · h⁻¹ during dressing period, 0,9 ± 0,3 μg · kg⁻¹ · h⁻¹ during afternoon period (10 h) and 0,5 ± 0,2 during overnight period (10 h). No-satisfied demands were around 4 boluses during dressing change period, 2 boluses during afternoon period, and one bolus during overnight period. Neither HR nor BP were modified for more than 20 % of control values ; RR never decreased under 12 c · min⁻¹ and Paco₂ remained unchanged. This study showed that the provision of analgesia in burn injury requires large doses of opioids. Individual demands are scattered over a wide range. The need for analgesics remains unchanged for several days. A PCA device is an efficient and safe tool for administration of opioids. Analgesia is appropriate, except during the dressing period.     

Calcium antagonists and intimal cell proliferation in atherogenesis

Smooth muscle cell (SMC) migration and intimal proliferation are major events in the formation of the atherosclerotic lesions. Among other processes, calcium may participate in atherogenesis by affecting SMC proliferation. Calcium antagonists, which possess antiatherosclerotic properties in animal models, are effective in inhibiting SMC proliferation. This effect has been demonstrated both in vitro in cell culture and in vivo in balloon-catheterised rats and rabbits. Such an effect, indicates a possible mechanism involved in the antiatherosclerotic activity elicited by this category of drugs.     

The d-enantiomer form of indobufen totally accounts for the anti-cyclooxygenase and antiplatelet activity ex vivo and for the increase in bleeding time by indobufen in man.

Indobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d-indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d-indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean +/- S.D., 58.7 +/- 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double-blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 +/- 3% for both treatments). At 12 h inhibition was 87 +/- 6% for d-indobufen and 88 +/- 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.     

The Lustgarten Foundation for Pancreatic Cancer Research 3rd Annual Scientific Conference: "Pancreatic Cancer: From Genes to Treatment"

MEETING NOTES: The Lustgarten Foundation for Pancreatic Cancer Research 3rd Annual Scientific Conference: "Pancreatic Cancer: From Genes to Treatment"     

Unique association of non-functioning pheochromocytoma, ganglioneuroma, adrenal cortical adenoma, hepatic and vertebral hemangiomas in a patient with a new intronic variant in the VHL gene

We analyzed the clinical, hormonal, immunohistochemical and genetic features in a 69-yr-old Caucasian woman with a very rare "composite and mixed pheochromocytoma". This was characterized by right adrenal pheochromocytoma associated with homolateral ganglioneuroma and controlateral adrenal cortical adenoma. The three tumors, incidentally discovered, proved to be non-functioning (normal secretion of catecholamines and of other neuroendocrine peptides, glucocorticoids, mineralcorticoids and androgens). Accordingly, the patient showed no sign or symptom of endocrine disease. Computed tomography (CT) and magnetic resonance (MR) demonstrated a typical adenomatous lesion on the left adrenal gland with precocious uptake of the radiotracer on radioidine (131I)-norcholesterol adrenal scintigraphy, while the controlateral gland showed hyperdensity on CT, hyperintensity on MR and no uptake at adrenal scintigraphy. In addition, CT and MR revealed a vertebral and two hepatic hemangiomas. The right adrenal gland was surgically removed and, microscopically, pheochromocytoma and ganglioneuroma areas appeared intermixed without a predominant component. The former showed strong immunoreactivity for chromogranin, synaptophysin, vascular endothelial growth factor (VEGF) and CD34, while the latter appeared positive for neuron-specific enolase (NSE) and S-100. Peripheral blood genomic DNA analysis revealed a new intronic variant (5557A > G) in the von Hippel-Lindau gene (VHL) not observed in our control population.     

Denaturing gradient gel electrophoresis and direct sequencing of PCR amplified genomic DNA: a rapid and reliable diagnostic approach to beta thalassaemia

The analysis of polymerase chain reaction (PCR)-amplified beta-globin DNA with allele-specific oligonucleotide (ASO) probes reveals a very heterogeneous spectrum of beta-thalassaemia in the Netherlands. However about 20% of the beta-thalassemia mutations cannot be identified with this approach. The combination of specific amplification of certain regions of the beta-globin gene with denaturing gradient gel electrophoresis (DGGE) allowed us to rapidly localize several of these mutations to specific regions of the gene, which were again amplified and directly sequenced. We believe that the combination of DGGE and the direct sequence determination of PCR amplified genomic DNA represents a valid alternative to the 'ASO probes' approach, especially in countries where a very heterogeneous spectrum of beta-thalassaemia mutations occurs.