Odontogenic myxoma: review of the literature and report of 30 cases from South Africa.

OBJECTIVE: The purpose of the study was to analyze the clinical and radiographic features of central odontogenic myxomas (OM) of the jaws diagnosed over 23 years in a black South African patient sample. STUDY DESIGN: Records of 30 cases of OMs with radiographs of diagnostic quality were retrieved from 52 cases of histopathologically verified OMs from the archives of the Oral Health Center at the University of Limpopo, South Africa. The age, sex, size, location, and radiographic features were compared with the literature. RESULTS: The study consisted of 21 females and 9 males. The correlation between age and size of the tumor was found to be statistically significant (P = .004). Septa were shown to be either reorientated cortical bone or sheets of dense fibrous connective tissue. Indistinct borders mimicked malignancy. The most common radiographic feature was the tennis-racket appearance. CONCLUSIONS: Variations in radiographic presentation make a radiological differential interpretation of OM challenging because the radiographic features overlap with those of other benign and malignant neoplasms.     

Membrane-seeded autologous chondrocytes: cell viability and characterization at surgery

The implantation of chondrocytes, seeded on matrices such as hyaluronic acid or collagen membranes, is a method that is being widely used for the treatment of chondral defects. The aim of the present study was to evaluate the distribution, viability and phenotype expression of the cells seeded on a collagen membrane just at the time of the implantation. Twelve patients who were suffering from articular cartilage lesions were treated by the MACI^® procedure. The residual part of each membrane was tested by colorimetric assay (MTT) and histochemical and ultrastructural analyses were carried out. In all of the samples a large number of viable cells, quite homogenously distributed, was detected. The cells expressed the markers of the differentiated hyaline chondrocytes. These data reassure in that the MACI procedure provides a suitable engineered tissue for cartilage repair, in line with the clinical evidences emerging in the literature.     

Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.

The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. METHODS: A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). RESULTS: After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81 vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 +/- 9.5 mg/kg. CONCLUSION: Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB.     

Laryngeal damage due to an unexpectedly large and inappropriately designed cuffed pediatric tracheal tube in a 13-month-old child

PURPOSE: To present a case of laryngeal damage in an infant caused by a too large and inappropriately designed cuffed tracheal tube. CLINICAL FEATURES: A 13-month-old child undergoing cardiac surgery was intubated with an uncuffed endotracheal tube with an internal diameter (ID) of 4.0 mm. Because of an important air leak around the tracheal tube during mechanical ventilation, a cuffed endotracheal tube ID 4.0 mm was inserted. The air leak with the tube cuff not inflated was acceptable at 25 cm H2O airway pressure. After extubation on the third postoperative day, the patient showed increasing stridor and respiratory deterioration. Fibreoptic laryngoscopy of the spontaneously breathing patient showed a large intra-laryngeal web. After surgical removal of the web, the child rapidly recovered and was discharged from the hospital on the 12th postoperative day. Inspection of the 4.0 mm (ID) cuffed tracheal tube revealed a cuff positioned inappropriately high and an increase of 0.7 mm in outer tube diameter compared to the 4.0 mm (ID) uncuffed tracheal tube from the same manufacturer. The tube cuff is likely to be situated within the larynx when placed in accordance to insertion depth formulas or radiological criteria, as used for uncuffed tracheal tubes in children. CONCLUSION: The larger than expected tracheal tube with its intra-laryngeal cuff position in a 13-month-old child likely caused mucosal damage and an inflammatory reaction within the larynx resulting in granulation tissue formation and fibrous healing around the tracheal tube.     

Effect of selected fluorinated drugs in a "ringing" gel on rheological behaviour and skin permeation.

The purpose of the present study was to investigate the influence of different drugs exhibiting different solubility on the viscoelastic properties and on the skin diffusion profile of a ringing gel. In a preliminary rheology study with the placebo gel predominating elastic properties were confirmed and a temperature influence was indicated. Fluconazole, fludrocortisone-acetate, flumethasone-pivalate, flutamide and flufenamic-acid each 1% (w/w) were incorporated into the preparation and oscillatory measurements were performed at temperatures of 25, 28, 32 and 37 degrees C. In all drug containing formulations a high elastic G' value predominated the viscous G' value. The highest G' value could be obtained with the incorporated flumethasone-pivalate. Additionally in almost all cases the G' values decreased with increasing temperature compared to the placebo gel. Additionally in vitro standard diffusion experiments using Franz-type cells and porcine skin were performed. Following rank order of the cumulative drug release after 48 h was obtained: fluconazole>flufenamic-acid>flumethasone-pivalate>flutamide>fludrocortisone-acetate. Furthermore an excellent chemical stability of all incorporated drugs was confirmed over 10 weeks.     

The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment.

Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.     

The Influence of a New Timing Strategy of Band Adjustment on the Vomiting Frequency and the Food Consumption of Obese Women Operated with Laparoscopic Adjustable Silicone Gastric Banding (LAP-BAND)

Objective: To evaluate the effects of a new timing strategy of band adjustment on the short-term outcome of obese women operated with adjustable silicone gastric banding. Subjects: The outcome of 30 women without binge-eating disorder operated with laparoscopic adjustable silicone gastric banding with a wider intraoperatory band calibration (LAP-BAND) was compared to that of 30 body mass index-matched women without binge-eating disorder previously operated with adjustable silicone gastric banding (ASGB) applied by laparotomy with the usual intraoperatory band calibration. The patients were evaluated 3, 6 and 12 months after surgery. Measurements: (1) weight loss; (2) total daily energy intake; (3) percent as liquid, soft or solid food; (4) vomiting frequency; (5) rate of postoperative percutaneous band adjustments; (6) rate of band-related complications. Results: Both the weight loss and the daily energy intake did not differ between patients with LAP-BAND and patients with ASGB. After surgery, the patients with LAP-BAND ate more solid food and less liquid food than the patients with ASGB. Vomiting frequency was higher in patients with ASGB than in patients with LAP-BAND. The total number of percutaneous band adjustments was higher in women with LAP-BAND than in women with ASGB. Band inflation because of weight stabilization was performed in six (20.0%) women with ASGB and in 19 (63.3%) women with LAP-BAND. Neostoma stenosis occurred in one women with ASGB, but in none of the women with LAP-BAND. One patient with LAP-BAND presented band slippage. Conclusions: The wider intraoperatory band calibration performed in patients with LAP-BAND did not reduce the short-term efficacy of adjustable silicone gastric banding. This new timing strategy of band adjustment required more postoperative percutaneous band inflations, but it improved the eating pattern of the patients (low vomiting frequency and high intake of solid food).     

Interaction between thiol-modifying agents and P1075, a KATP channel opener, in rat isolated aorta

In vascular smooth muscle, openers of ATP-dependent potassium channels (K _ATP channels), such as P1075 (N-cyano-N’-(1,1-dimethylpropyl)-N’’-3-pyridylguanidine), produce relaxation. In this study we have investigated the effects of thiol-modifying agents on the binding of P1075 and on the ⁸⁶Rb⁺ efflux stimulating and vasorelaxant effects of the opener in rat aortic rings. The increase in ⁸⁶Rb⁺ efflux induced by P1075 was taken as a qualitative measure of K⁺ channel opening. The hydrophilic SH-group-oxidizing substance, thimerosal (1 to 100μM), abolished specific binding of [³H]-P1075 with an IC₅₀ value of 7.6±1.2μM; at 30μM, the half time for inhibition was 38min. Two other thiol-oxidizing agents, PMB (4-hydroxy-mercuribenzoic acid) and DTBNP (2,2’-dithio-bis(5-nitropyridine)), inhibited binding up to 86% and 44%, respectively. The disulphide bond reducing substance, DTT (1,4-dithiothreitol, 0.1 to 1mM), reduced [³H]-P1075 binding by up to 20% and partially reversed the inhibitory effect of thimerosal. In ⁸⁶Rb⁺ efflux experiments, thimerosal (3 to 100μM) concentration-dependently increased basal efflux but inhibited P1075-stimulated tracer efflux with an IC₅₀ value of 7±1μM. The inhibitory effect occurred with a half-time of approximately 8min and was essentially reversed by DTT. In rings precontracted with noradrenaline, thimerosal inhibited the vasorelaxant effect in a noncompetitive manner, shifting the concentration-relaxation curves to the right and reducing maximum relaxation.The data show that oxidation of thiol groups interferes with the binding of the K _ATP channel opener, P1075; concomitantly, the ⁸⁶Rb⁺ efflux stimulating and the vasorelaxant effects are inhibited. Reduction of disulphide bonds by DTT has only minor effects on the action of P1075. Collectively, the results suggest that intact thiol groups are essential for the functioning of the K_ATP channel in rat aorta. The different kinetics governing the inhibition of opener binding and of opener-stimulated ⁸⁶Rb⁺ efflux suggest that the SH-groups involved in the two processes differ in their accessibility to thimerosal and/or in their reactivity. Received: 7 April / Accepted: 9 July 1997     

Genotype/phenotype correlation of the G85E mutation in a large cohort of cystic fibrosis patients.

In this European study, the phenotype in 68 patients, homozygous or compound heterozygous for the G85E mutation, was investigated. Each index case was compared with two cystic fibrosis (CF) patients from the same clinic, matched for age and sex: one with pancreatic sufficiency (PS) and one with pancreatic insufficiency (PI). When comparing 31 G85E/F508del and F508del/F508del patients, there were no differences in median age at diagnosis, mean sweat chloride value, most recent weight for height, most recent forced expiratory volume in one second % predicted, prevalence of chronic Pseudomonas aeruginosa colonisation and typical CF complications. However, PI was less frequent in the G85E/F508del group. Comparison of 55 G85E patients (with second mutation known and not classified as mild) with PS controls (n=44) showed that the G85E patients had a significantly higher sweat chloride, more often failure to thrive at diagnosis, higher prevalence of PI, worse current weight for height, higher prevalence of chronic P. aeruginosa colonisation and liver cirrhosis. Pulse-chase experiments revealed that G85E cystic fibrosis transmembrane conductance regulator failed to mature on a M470 as well as on a V470 background. Therefore, G85E is a class II mutation. Although there is variability in its clinical presentation, G85E mutation results in a severe phenotype.