Testicular tumors

Germ cell tumors of the testes represent a unique paradigm of diseases which can be cured even in extremely advanced phase. Unfortunately, this makes them unique among adult solid tumors. Seminoma and non seminoma are relatively rare with approximatively 25,000 patients in Europe per year, but numbers are increasing world wide. Different strategies are needed depending on stage and prognostic scores. Seminoma is extremely sensitive to radiation therapy and chemotherapy, while all germ cell tumors show a very good response to chemotherapy. Clinical stage I seminoma is currently treated with radiation, single course carboplatin or surveillance policy. Clinical stage I non seminoma can also be approached with different strategies such as retroperitoneal lymph node dissection, observation or one-two courses of standard chemotherapy. Stage II seminoma may be treated with either radiation or chemotherapy, while for all advanced stages chemotherapy is mandatory. Since the mid-eighties PEB (Cisplatin, Etoposide and Bleomycin) is the regimen of choice and no other schedule has proved superior in terms of efficacy. Surgery on the residual disease is crucial to the whole strategy and should be performed or attempted in all cases. Consequently, the correct treatment strategy for these tumors does not depend only on the ability of a single physician, but on a skilled team specialized in this particular tumor. Second line therapies (VeIP, PEI, TIP) can cure 25%–40% of patients, but improved strategies for resistant tumors are desperately needed. High-dose chemotherapy has shown very good results in some studies while being less impressive in others. In any case, it should remain an option for relapsing patients and could be used in some cases of upfront chemotherapy in patients with slow marker decline, but this should only be considered in referring centers.     

A novel assay for factor XIII based on cross-linking of synthetic peptides: analysis of different substrates.

A novel assay for factor XIII is described that utilizes exclusively small synthetic peptides as substrates for the cross-linking reaction catalyzed by activated factor XIII (FXIIIa). The acyl donor substrate (selection peptide) is immobilized on a microplate via biotin while the acyl acceptor substrate (detection peptide) is labeled with the fluorochrome Oregon green to allow sensitive detection without the need for secondary enzyme systems for signal amplification. Starting with an amino acid sequence from the fibrin gamma-chain (GQQHHLGGAKQAGDV) as a prototype peptide, the influence of amino acid exchanges were investigated with respect to their impact on the FXIIIa-catalyzed reaction. It was found that FXIIIa readily accepts a broad range of substrate peptides, with a proline neighboring the essential lysine having the most detrimental effect. The assay appears to be valuable for the molecular characterization of factor XIII and may be used for a deeper investigation into the substrate requirements of this final enzyme of wound repair, and eventually also for the characterization of other transglutaminases.     

Baseline characteristics and treatment preferences of oral surgery patients.

PURPOSE: Patient preferences for treatment choices may depend on patient characteristics. Using standard gamble (SG) and willingness to pay (WTP), this study compares preferences for treatment of mandibular fracture among patients in a low-income urban area. PATIENTS AND METHODS: Surveys of African-American and Hispanic adults receiving treatment at King/Drew Medical Center for either mandibular fracture (n = 98) or third molar removal (n = 105) were used to investigate differences in patient characteristics across treatment groups (third molar vs fracture) and treatment preference (wiring vs surgery). RESULTS: The fracture patients were willing to pay more to restore function without scarring or nerve damage than were the third molar patients. Patients who chose surgery were willing to accept a greater risk of possible nerve damage or scarring than those who chose wiring. Among 15 potential predictors of SG and WTP studied in 4 subgroups defined by actual treatment and treatment preference, significant predictors varied, with associations for education and clinical experience for SG and associations with income and psychosocial predictors for WTP. CONCLUSIONS: SG and WTP capture different domains of health values in patients. There is considerable heterogeneity in relationships among patient characteristics and patient preferences across subgroups defined by actual treatment and treatment preferences.     

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.     

Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

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.