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.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (II)

The first part of this serial paper dealt with the medical criteria used in evaluation of the clinical picture caused by physical stress and the evaluation of other candidate causes and was published in issue no. 3/2005 (pp. 711–752) of Trauma and Berufskrankheit. This follow-up paper (II) presents criteria to be used in the evaluation of whether it is necessary to give up the occupations putting the spine at risk and in estimation of the degree of disability.     

Treatment of a recurrent inguinal lymphocele in a penis cancer patient by lymphography and selective ligation of lymphatic vessels

We report a case of recurrent inguinal lymphocele formation after inguinal lymphadenectomy treated by lymphographic mapping and selective ligation of the lymphatic vessels. Lymphographic mapping was performed by puncturing a lymphatic vessel at the dorsum of the foot. After isolating the vessels that drained into the lymphocele, they were clipped and divided through a small skin incision. The described technique showed an instant and complete suspension of the lymph secretion with subsequent complete healing. Lymphatic mapping and selective ligation of afferent lymphatic vessels proved to be an effective treatment of a recurrent inguinal lymphocele.     

Radiofrequency-ablation of unresectable primary and secondary liver tumors: results in 88 patients

Background and aims Radiofrequency-ablation (RFA) is increasingly used for destruction of unresectable primary and secondary liver tumors. We report our experience in the use of RFA for the management of unresectable hepatic malignancies. Patients and methods Between February 2000 and December 2004 we have undertaken 120 RFA procedures to ablate 426 unresectable primary or metastatic liver tumors in 88 patients. RFA was performed via laparotomy (n=68), laparoscopy (n=9) or a percutaneous approach (n=43). Primary liver cancer was treated in seven patients (8%) and metastatic liver tumors were treated in 81 patients (92%). All patients were followed to assess complications, treatment response and recurrence of malignant disease. Results Procedure-related complication rate was low (3.4%). During a mean follow-up of 21.2 months, 15 patients had local tumor progression (17%), 21 patients (23,9%) had new malignant disease and 27 patients (30.7%) died from intervention-unrelated complications of their malignant disease. Additional liver lesions were identified in 27 (35%) of 77 cases by intraoperative ultrasound. Thirty-six patients received simultaneous resection and RFA. Conclusion RFA is a safe, well-tolerated and effective treatment for patients with unresectable primary and secondary liver malignancies.     

Interobserver and interstudy variability of myocardial blood flow and flow-reserve measurements with nitrogen 13 ammonia-labeled positron emission tomography

Background  

Experimental studies have shown that positron emission tomography (PET) with ¹³N-labeled ammonia provides accurate quantification of regional myocardial blood flow (MBF) under rest and stress conditions. To establish the clinical utility of this method, the interobserver variability and the temporal variability of serial measurements of blood flow and coronary flow reserve (CFR) must be known. This study investigated the interobserver and temporal reproducibility of ¹³N-labeled PET for measurement of MBF and CFR.     

An outpatient anticoagulation protocol managed by a vascular nurse-clinician

Lifetime anticoagulation has become a therapeutic option for surgical patients with hypercoagulable states or prosthetic arterial bypass grafts. However, physicians may not achieve optimal anticoagulation or may attempt to limit the length of the therapy period because of the perceived morbidity from hemorrhagic complications of Coumadin therapy. A protocol for anticoagulant therapy monitored and regulated by a vascular nurse-clinician was reviewed. Coumadin was prescribed for 1,891 patient-months to 93 patients to maintain their prothrombin time 1.5 to 2 times control (range: 18 to 24 seconds). The mean (+/- SD) prothrombin time for the study population was 19.8 +/- 1.8 seconds. During follow-up, 472 (14%) of 3,479 prothrombin times measured were below the therapeutic range (n = 232) or prolonged (n = 240), prompting an adjustment in the Coumadin dose in 82 (88%) patients. Four patients developed recurrent vascular graft thrombosis while receiving anticoagulation. There were 6 major and 11 minor hemorrhagic complications. Patients with a chronic risk for arterial or venous thrombosis can have out-patient anticoagulant therapy administered at optimal intensity and regulated safely with a low incidence of hemorrhagic and thrombotic events.