ABSTRACT
The single-nucleotide-polymorphism (SNP) 118A>G in the micro-1 opioid receptor gene (OPRM1) is associated with a decrease in the analgesic effects of opioids. The aim of this study is to assess whether 118A >G polymorphism could influence the analgesic response to opioid-based postoperative pain (POP) therapy. The study consisted of two parts: section alpha, observational, included 199 subjects undergoing scheduled surgical procedures with pain management standardized on surgery invasiveness and on expected level of postoperative pain; section beta, randomized, included 41 women undergoing scheduled caesarean delivery with continuous intra-operative epidural anesthesia and post-operative analgesia (CEA). In both sections, POP was measured over 48 h (T6h-T24h-T48h) by the visual analogue scale (VAS). In section beta we also tested the responsiveness of hypothalamic-pituitary-adrenal axis (HPA) expressed by cortisol levels. In section alpha, with cluster analysis, subjects were analyzed according to their genotype: a group (no. 1) of 34 patients reporting VAS score >3 at every time lapse was identified and included only A118G carriers, while wild-type (A118A - absence of 118A>G polymorphism) patients were unevenly distributed between those with cluster no. 2 (VAS score <3 at every study steps) and those with cluster no. 3 (VAS score progressively reducing from T6h). In section beta, A118G carriers receiving epidural sufentanil had the lowest VAS scores at T24h; also in these patients, cortisol levels remained more stable, with a mild decrease at T6h. This study shows that the OPRM1 118A>G polymorphism affects postoperative pain response in heterozygous patients: they have a different postoperative pain response than patients with wild-type genes, which may affect the efficacy of the analgesic therapy.
Subject(s)
Analgesics, Opioid/therapeutic use , Pain, Postoperative/drug therapy , Pain, Postoperative/genetics , Polymorphism, Single Nucleotide , Receptors, Opioid, mu/drug effects , Receptors, Opioid, mu/genetics , Adult , Aged , Analysis of Variance , Cesarean Section/adverse effects , Cluster Analysis , Elective Surgical Procedures , Female , Gene Frequency , Heterozygote , Humans , Hydrocortisone/blood , Hypothalamo-Hypophyseal System/metabolism , Italy , Male , Middle Aged , Pain Measurement , Pain, Postoperative/blood , Pain, Postoperative/diagnosis , Phenotype , Pituitary-Adrenal System/metabolism , Pregnancy , Prospective Studies , Severity of Illness Index , Sufentanil/therapeutic use , Time Factors , Tramadol/therapeutic use , Treatment OutcomeABSTRACT
Immunonephelometric evaluations of 13 serum proteins were made in 71 patients with two types of lymphoproliferative diseases: Hodgkin's disease (32 patients) and non-Hodgkin's lymphomas (39 patients). The subjects were differentiated by discriminant analysis by means of age and three selected proteins: properdin factor B, IgM and ceruloplasmin. The results obtained permitted classification of 90% of the cases reported.
Subject(s)
Blood Proteins/analysis , Hodgkin Disease/diagnosis , Lymphoma/diagnosis , Adolescent , Adult , Age Factors , Ceruloplasmin/analysis , Complement Factor B/analysis , Computers , Diagnosis, Differential , Female , Hodgkin Disease/blood , Humans , Immunoglobulin M/analysis , Lymphoma/blood , Male , Middle Aged , Neoplasm Proteins/blood , Statistics as TopicABSTRACT
The in vitro inhibitory activity of Lonidamine on the aerobic glycolysis of normal as well as leukemic lymphocytes has been investigated. The extent of the impairment of lactate production induced by Lonidamine on normal thymus (T)- and bone marrow (B)-derived lymphocytes was found to be dependent on their source of origin, i.e. residing or circulating pool. Among leukemia tested 'null' and B cell leukemias appeared the most affected metabolically by the compound. Administration in vivo of the drug to the patient with B cell chronic leukemia resulted in a decrease of lactate production by leukemic cells comparable to that induced in vitro. These metabolic changes were paralleled in normal, as well as in leukemic cells by ultrastructural lesions, mainly confined to the mitochondrial compartment.
