A randomized controlled trial of resorbable versus titanium fixation for orthognathic surgery

OBJECTIVES: To determine any differences in the intra- and postoperative morbidities and complications between resorbable and titanium plating systems for fixation in orthognathic surgery. STUDY DESIGN: This prospective randomized clinical trial was conducted in the Oral and Maxillofacial Surgery unit of the University of Hong Kong. Patients with dentofacial deformities were randomly assigned into the titanium and resorbable fixation groups. Intraoperative data such as the surgical procedures, time for fixing each plate, and number of broken plates and screws were recorded. Subjective and objective parameters related to clinical morbidities were assessed postoperatively. RESULTS: A total of 60 patients with 177 osteotomies were included in this study. Eighty-seven osteotomies fixated with 196 titanium plates and 784 titanium screws were performed in 30 patients, whereas 90 osteotomies fixated with 165 resorbable plates and 658 resorbable screws were done in another 30. The postoperative infection rate was 1.53% (3/196) and 1.82% (3/165) in the titanium and resorbable fixation groups, respectively. These infections were mainly due to loose screws and wound dehiscence. The plate exposure rate was 1.02% (2/196) for the titanium group and 1.21% (2/165) for the resorbable group. The plate removal rate in the titanium and resorbable groups was 1.53% (3/196) and 3.63% (6/165), respectively. Statistically significant difference was shown in the plating time of step (mandibular body) and Hofer (mandibular subapical) osteotomies. There was no significant difference in the subjective clinical parameters such as wound discomfort, clinical stability of the osteotomy segments, palpability of plate, and overall satisfaction of the results between the 2 fixation groups. Similarly, objective parameters including wound dehiscence, rate of infection, plate exposure, occurrence of sinus tract, and palpability assessed by surgeons in both groups also showed no significant difference. CONCLUSION: Bioresorbable fixation devices offer similar function as titanium in fixation for orthognathic surgery and do not impose an increase in the clinical morbidities.     

The phytocannabinoid Delta(9)-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum

BACKGROUND AND PURPOSE: The phytocannabinoid Delta(9)-tetrahydrocannabivarin (Delta(9)-THCV) has been reported to exhibit a diverse pharmacology; here, we investigate functional effects of Delta(9)-THCV, extracted from Cannabis sativa, using electrophysiological techniques to define its mechanism of action in the CNS. EXPERIMENTAL APPROACH: Effects of Delta(9)-THCV and synthetic cannabinoid agents on inhibitory neurotransmission at interneurone-Purkinje cell (IN-PC) synapses were correlated with effects on spontaneous PC output using single-cell and multi-electrode array (MEA) electrophysiological recordings respectively, in mouse cerebellar brain slices in vitro. KEY RESULTS: The cannabinoid receptor agonist WIN 55,212-2 (WIN55) decreased miniature inhibitory postsynaptic current (mIPSC) frequency at IN-PC synapses. WIN55-induced inhibition was reversed by Delta(9)-THCV, and also by the CB(1) receptor antagonist AM251; Delta(9)-THCV or AM251 acted to increase mIPSC frequency beyond basal values. When applied alone, Delta(9)-THCV, AM251 or rimonabant increased mIPSC frequency. Pre-incubation with Delta(9)-THCV blocked WIN55-induced inhibition. In MEA recordings, WIN55 increased PC spike firing rate; Delta(9)-THCV and AM251 acted in the opposite direction to decrease spike firing. The effects of Delta(9)-THCV and WIN55 were attenuated by the GABA(A) receptor antagonist bicuculline methiodide. CONCLUSIONS AND IMPLICATIONS: We show for the first time that Delta(9)-THCV acts as a functional CB(1) receptor antagonist in the CNS to modulate inhibitory neurotransmission at IN-PC synapses and spontaneous PC output. Delta(9)-THCV- and AM251-induced increases in mIPSC frequency beyond basal levels were consistent with basal CB(1) receptor activity. WIN55-induced increases in PC spike firing rate were consistent with synaptic disinhibition; whilst Delta(9)-THCV- and AM251-induced decreases in spike firing suggest a mechanism of PC inhibition.     

Pharmacokinetics of mycophenolic acid in live donor liver transplant patients vs deceased donor liver transplant patients

The exposure of mycophenolic acid in live donor liver transplant patients (those receiving a partial hepatic volume) in comparison to deceased donor liver transplant patients (those receiving the whole hepatic volume) after administration of mycophenolate mofetil has not been reported earlier. The aim of the present study is to compare the pharmacokinetics parameters of mycophenolic acid and mycophenolic acid glucuronide in live donor liver transplant patients versus deceased donor liver transplant patients. Twelve live donor liver transplant and 12 deceased donor liver transplant recipients were studied over a dosing interval after intravenous administration of mycophenolate mofetil. The maximum concentration (Cmax) and the area under the plasma concentration versus time curve (AUC) for mycophenolic acid in live donor liver transplant patients were significantly higher than in deceased donor liver transplant patients (Cmax/AUC: live donor liver transplant patients: 16.1 +/- 6.6 microg/mL/43.9 +/- 12.6 microg/mL.h vs deceased donor liver transplant patients: 10.7 +/- 2.0 microg/mL/28.9 +/- 7.1 microg/mL.h; P = .046/.002). The volume of distribution was higher in the deceased donor liver transplant patients compared with live donor liver transplant patients. However, the mean plasma concentration at 12 hours (Clast), drug disposition rate constant, half-life (t 1/2), and mean residence time were similar in both groups. The mean plasma concentration of mycophenolic acid glucuronide was 1.4 to 2.0 times higher in deceased donor liver transplant patients compared with live donor liver transplant patients. These observations point to the need to use a lower dosage (approximately 30%) of mycophenolate mofetil in live donor liver transplant patients compared with deceased donor liver transplant patients.     

Altered expression of the RON receptor tyrosine kinase in various epithelial cancers and its contribution to tumourigenic phenotypes in thyroid cancer cells

Aberrant expression of the RON receptor tyrosine kinase has been implicated in the pathogenesis of epithelial tumours. The aim of this study was to determine RON expression in various normal epithelial cells and their corresponding tumours by immunohistochemistry. The role of RON in regulating tumourigenic phenotypes was also studied using thyroid cancer cells as a model. RON was almost exclusively expressed at variable levels in normal epithelial cells from the digestive track, lung, kidney, pancreas, liver, breast, bladder, skin, and others. Among 15 types of cancer studied, RON was overexpressed in significant numbers in cancers derived from breast (56%), colon (51%), lung (48), thyroid (42%), skin (37%), bladder (36%), and pancreas (33%). In contrast, limited RON overexpression was observed in cancers from stomach, kidney, brain, liver, ovary, and prostate. Detailed analysis of thyroid tissues showed that RON was hardly detected in normal thyroid cells, moderately expressed in adenoma samples, but overexpressed in about half of papillary and follicular cancer specimens. Overexpression correlated with advanced clinical stage and was associated with lymph node metastasis. In cultured thyroid cancer cells, RON was highly expressed, with constitutive phosphorylation. Activation of RON increased cell growth and migration via the MAP kinase and AKT pathways. Silencing RON expression significantly prevented cell growth and increased cell apoptotic death. These findings show that RON overexpression occurs in a particular group of epithelial cancers. The requirement for RON in sustaining tumourigenic phenotypes suggests that it is a potential target for therapeutic intervention.     

Etiology and pathogenesis of epithelial ovarian cancer

Ovarian cancer is complex disease composed of different histological grades and types. However, the underlying molecular mechanisms involved in the development of different phenotypes remain largely unknown. Epidemiological studies identified multiple exogenous and endogenous risk factors for ovarian cancer development. Among them, an inflammatory stromal microenvironment seems to play a critical role in the initiation of the disease. The interaction between such a microenvironment, genetic polymorphisms, and different epithelial components such as endosalpingiosis, endometriosis, and ovarian inclusion cyst in the ovarian cortex may induce different genetic changes identified in the epithelial component of different histological types of ovarian tumors. Genetic studies on different histological grades and types provide insight into the pathogenetic pathways for the development of different disease phenotypes. However, the link between all these genetic changes and the etiological factors remains to be established.     

An internal clock reaction used in a one-step enzyme immunochromatographic assay of theophylline in whole blood

We describe the development and performance of a second-generation enzyme immunochromatography method for visually quantifying theophylline in whole blood without the use of instrumentation. We have developed the novel concept of an internal chemical clock reaction to combine the capillary-migration and color-generation protocol of the two-step immunochromatographic assay into a single-step, simultaneous protocol. The two assay components are (a) chromatographic paper to which glucose oxidase (EC 1.1.3.4) and monoclonal antibody to theophylline have been immobilized, and (b) an enzyme reagent consisting of glucose, dicarboxidine, ascorbate, and theophylline-labeled horseradish peroxidase (EC 1.11.1.7). The ascorbate acts as an internal clock by inhibiting premature color formation until the ascorbate has been completely consumed in the peroxidase-mediated reaction. Color is then generated rapidly, producing a clearly visible front on the paper. Performance evaluations of the 20-min one-step assay show very good precision, analytical recovery, specificity, and accuracy. This simplified protocol is reliable and convenient for therapeutic drug monitoring in the physician's office.