An auditory brainstem implant system

Neurofibromastosis type II (NF2) is a condition that may result in bilateral acoustic neuromas. The tumors and their removal may cause profound bilateral deafness. Because the auditory nerve is compromised, people with NF2 are unable to receive a cochlear implant to restore a sensation of hearing. Electrical stimulation of the auditory pathway can provide hearing in such people. This is possible by means of an auditory brainstem implant (ABI). This article focuses on the MED-EL high-rate multichannel ABI system. The system consists of the implanted and external components. Appropriate placement of the ABI is dependent on electrical auditory brainstem response testing performed intra-operatively. Data on a group of European patients implanted with the MED-EL ABI are presented. Results are promising and include some open-set speech ability.     

Helicobacter DNA in bile: correlation with hepato-biliary diseases

BACKGROUND: Helicobacter has been identified in isolated cases of hepato-biliary diseases, but its role in the pathogenesis of these conditions remains unclear. AIM: To determine whether Helicobacter could be detected in bile obtained at endoscopic retrograde cholangiopancreatography, and to evaluate the prevalence of this infection in patients with hepato-biliary diseases. METHODS: Bile was collected from 125 patients with various hepato-biliary diseases undergoing endoscopic retrograde cholangiopancreatography. Among them, 75 were diagnosed with biliary stones, 15 with pancreatico-biliary malignancies and four with primary sclerosing cholangitis. The detection of Helicobacter in DNA extracted from these bile samples was performed using Helicobacter genus-specific primers (capable of detecting 100-1000 organisms/mL). RESULTS: Helicobacter was detected in all positive controls. Only three samples had polymerase chain reaction inhibitors. All remaining bile samples (122 patients with hepato-biliary diseases) were negative for Helicobacter DNA. CONCLUSIONS: Helicobacter can be detected in bile samples using polymerase chain reaction. This infection, however, was not present in any of our patients diagnosed with gallstones or hepato-biliary malignancies, raising doubt as to the possible association between Helicobacter and these entities. Given the low sample size of patients with primary sclerosing cholangitis, more studies are required to determine whether an association exists with this condition.     

Somatostatin receptor scintigraphy in the management of cerebral malignant ectomesenchymoma: a case report

A 10-year-old girl presented with a cerebral malignant ectomesenchymoma (MEM), a very unusual tumour with undifferentiated mesenchymal as well as ectodermal elements. Somatostatin receptor scintigraphy (SRS) was performed during the diagnostic workup. The recurrent residual tumour mass was exactly visualized with SRS, and was negative after successful treatment of the patient. The potential application of SRS in initial staging, follow-up and therapy planning in MEM is discussed. This is the first application of SRS in MEM. Received: 14 May 1999 Accepted: 8 May 2000     

Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension

BACKGROUND: Inhalation of iloprost, a stable prostacyclin analog, is an effective therapy for pulmonary hypertension with few side effects. This approach may, however, be handicapped by limitations of currently available nebulization devices. We assessed whether the physical characterization of a device is sufficient to predict drug deposition and pharmacologic effects. METHODS: We investigated the effects of a standardized iloprost aerosol dose (5 micro g; inhaled within approximately 10 min) in 12 patients with severe pulmonary hypertension in a crossover design employing three well-characterized nebulizers. The nebulizers use different techniques to increase efficiency and alveolar targeting (Ilo-Neb/Aerotrap [Nebu-Tec; Elsenfeld, Germany], Ventstream [MedicAid; Bognor Regis, UK], and HaloLite [Profile Therapeutics; Bognor Regis, UK]). Measurements were performed using a Swan-Ganz catheter and determination of arterial iloprost plasma levels. RESULTS: During inhalation of iloprost, the pulmonary vascular resistance decreased substantially (baseline, approximately 1,250 dyne.s.cm(-5); decrease, - 35.5 to - 38.0%) and pulmonary artery pressure decreased substantially (baseline, approximately 58 mm Hg; decline, - 18.4 to -21.8%), whereas the systemic arterial pressure was largely unaffected. Cardiac output and mixed venous and arterial oxygen saturation displayed a marked increase. The pharmacodynamic profiles with the three devices were superimposable. Moreover, rapid entry of iloprost into the systemic circulation was noted, peaking immediately after termination of the inhalation maneuver, with very similar maximum serum concentrations (158 pg/mL, 155 pg/mL, and 157 pg/mL), and half-lives of serum levels (6.5 min, 9.4 min, and 7.7 min) for the three nebulizers, respectively. Interestingly, the "half-life" of the pharmacodynamic effects in the pulmonary vasculature (eg, decrease in pulmonary vascular resistance, ranging between 21 and 25 min) clearly outlasted this serum level-based pharmacokinetic half-life. CONCLUSIONS: A standardized dose of aerosolized iloprost delivered by different nebulizer types induces comparable pharmacodynamic and pharmacokinetic responses. Pulmonary vasodilation, persisting after disappearance of the drug from the systemic circulation, supports the hypothesis that local drug deposition largely contributes to the preferential pulmonary vasodilation in response to inhaled iloprost.     

Influence of somatostatin receptor scintigraphy and CT/MRI on the clinical management of patients with gastrointestinal neuroendocrine tumors: an analysis in 188 patients

AIM: Many studies describe the sensitivities and specificities of computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) in patients with gastrointestinal neuroendocrine tumors (GNT). We performed a study to evaluate the influence of these techniques on the therapeutic management of patients with advanced stages of GNT. PATIENTS AND METHODS: The results of either CT/MRI scans or SRS were reviewed by two independent observers who decided on the therapy of a patient. They then had to determine whether the results of the complementary imaging modality would change the decision. The study design was a matched cross-over study with two groups matching in respect to tumor type, imaging modality known first to the observer, and number of patients. For further analysis, patients were divided into three subgroups dependent on tumor stage (group 1, without metastases, group 2, liver metastases, group 3, recurrent disease/extrahepatic metastases). RESULTS: 188 patients were included into the study. If SRS was known to the observers first, CT/MRI changed the therapeutic management in 16.2, 13.9 and 11.4% of the patients (subgroups 1-3). SRS changed the therapeutic management in 13.5, 12.5 and 10.3%. Overall, CT/MRI would have changed the management in 13.3% and SRS in 11.7% of the patients. CONCLUSION: Though the patients studied mainly suffered from already advanced stages of the disease, all imaging techniques change the therapeutic management to a comparable extent. Our results support the importance of combined imaging in the management of patients with GNT.     

Intra-operative electromyographic monitoring of the lower cranial motor nerves (LCN IX-XII) in skull base surgery

The functional preservation of lower (motor) cranial nerves (LCN) is endangered during skull base surgery. Intra-operative EMG monitoring of the LCN IX-XII was investigated in 78 patients undergoing 80 operations on various skull base tumors with regard to technical feasibility and clinical efficacy. Ongoing 'spontaneous muscle activity' (SMA) and 'compound muscle action potentials' (CMAP) following supramaximal bipolar stimulation were intra-operatively recorded applying needle electrodes into the soft palate (CN IX: n=76), the vocal cord (CN X: n=72), the trapezius muscle (CN XI: n=18), and the tongue (CN XII: n=71). From 24/22/8 cases with LCN IX/X/XII deficits (despite monitoring) only 5/6/4 remained unchanged (3-6 months postoperative). An irreversible plegia of the LCN IX/X/XII occurred in three (1/1/1) patients. In 7/6/1 patients postoperative (3-6 months) LCN IX/X/XII function was better than preoperatively. In all patients accessory nerve function remained unchanged. 'Pathological' SMA of the LCN IX/X/XII occurred in 12/16/8 cases, but in only 6/5/3 cases corresponded to postoperative LCN deficits. Corresponding 'pathological' SMA patterns were found in 18/17/5 out of 24/22/8 cases with postoperative LCN IX/X/XII dysfunction. Reproducible CMAP of LCN IX/X/XI/XII could be recorded in 59/56/11/32 patients. Approximate 'normal' values were calculated and compared to (very few) data so far given in the literature. Electromyographic monitoring proved to be a safe tool for the intra-operative identification and localization of the LCN contributing to their anatomical and functional preservation. The predictive value of standard neurophysiological parameters for functional outcome, however, is limited.     

(99m)Tc-E-selectin binding peptide for imaging acute osteomyelitis in a novel rat model

INTRODUCTION: In the present study, (99m)Tc-radiolabelled E-selectin binding peptide ((99m)Tc-IMP-178) was investigated for its potential to image acute pyogenic osteomyelitis in a new animal model. Intraindividual comparisons were performed using an irrelevant peptide ((99m)Tc-IMP-100) to demonstrate specificity. METHODS: An acute pyogenic osteomyelitis was induced by injecting 0.05 ml of 5% sodium morrhuate and 5x10(8) CFU of Staphylococcus aureus into the medullary cavity of the right tibia in 16 rats. Sixteen additional rats served as untreated controls. Whole-body imaging of pyogenic (n=4) and untreated (n=4) animals was performed continuously during the first 8 h (12 MBq i.v. of (99m)Tc-IMP-178 and (99m)Tc-IMP-100 for control), and one further single image was acquired after 16 h p.i. Tissue biodistribution studies were performed in 12 rats with an acute pyogenic osteomyelitis and in 12 untreated rats 1, 4 and 24 h after injection. Data of the histological/radiological and haematological investigations were obtained in all animals. RESULTS: Histopathologically, 15 of 16 treated rats (93%) developed an acute pyogenic osteomyelitis showing a major infiltration of the bone marrow by polymorphonuclear leukocytes as well as the formation of sequestra. Haematologically, the number of leukocytes increased by 100%, the lymphocytes by 11% and the granulocytes decreased by 39%. After i.v. injection, (99m)Tc-IMP-178 rapidly cleared from the body resulting in good scintigraphic target-to-background (T/B) ratios. The highest uptake of the tracer in the pyogenic bone was observed at 60 min p.i. (0.43+/-0.02% ID.g-1 for (99m)Tc-IMP-178 and 0.30+/-0.02% ID.g-1 for (99m)Tc-IMP-100), resulting in a higher osteomyelitis-to-healthy collateral ratio with T/B of 2.40+/-0.65 ((99m)Tc-IMP-178) compared with 1.85+/-0.48 ((99m)Tc-IMP-100). No adverse reactions were seen after injection of (99m)Tc-IMP-178. CONCLUSIONS: (99m)Tc-IMP-178 allows imaging of an acute osteomyelitic lesions, presumably by interaction of (99m)Tc-IMP-178 with activated upregulated vascular endothelium.     

Feasibility of computer-assisted recognition of different dental hard tissues

For pattern recognition, fuzzy set theory has been proven to be highly useful. The aim of the present investigation was to combine the fuzzy set with an ultrasonic scaler, to test its suitability for automatic detection of different tooth substances. An experienced operator placed the tip of a piezoceramic ultrasonic scaler on a tooth, thereby inducing oscillations in the contact area around the ultrasonic tip. Each surface showed a characteristic oscillatory behavior in the immediate vicinity of the tip. The oscillations were then re-transmitted to the scaler tip and recorded by the measurement of variations in current and voltage. Because the ultrasonic scaler is driven by piezoceramics, it can be used as both an oscillatory excitation and a sensor system. The data were processed with Fast Fourier transformation and analyzed by means of a fuzzy pattern recognition algorithm. Re-classification of the different measurements was carried out by the experienced operator's assessment. With a combination of six features (frequencies), re-classification was correct for 99% of all surfaces. The diagnostic reliability of the system was tested by the assessment of 50 teeth for which no learning data had previously been recorded. The unknown samples were correctly classified to 100%. The excellent results of these experiments suggest promising possibilities for the implementation of new diagnostic and therapeutic instruments in periodontology practice.     

Improvement of nonviral p53 gene transfer in human carcinoma cells using glucosylated polyethylenimine derivatives

Polyethylenimine (PEI) derivatives are potent polycationic nonviral vectors for gene transfer. The gene transfer efficiency of glucosylated and galactosylated PEI derivatives was optimized using green fluorescent protein gene as reporter gene in FaDu and PANC3 human carcinoma cell lines. Glucosylated or galactosylated PEI derivatives were found to be slightly less cytotoxic than unsubstituted PEI. Gene transfer efficiency was found to be related to DNA/cell number ratio and optimal gene transfer efficiency was achieved at 4 microg DNA/10(5) cells. PEI-DNA complexes were found to enter cells rapidly and were detected into cytoplasmic vesicles 2 hours post-transfection. Green fluorescent protein gene expression was detected 4-6 hours after transfection and reached maximal value 24 hours post-transfection. The results achieved demonstrated that glucosylated PEI yield higher and longer gene transfer efficiency than unsubstituted PEI. Using glucosylated PEI allowed to achieve significant gene transfer in more than 10% of the total cell population for more than 4 days. These data were then applied to p53 gene transfer in PANC3 cells bearing p53 gene deletion and consequently unable to initiate apoptosis. Using glucosylated PEI, p53 gene transfer was successfully achieved with subsequent recovery of p53 mRNA expression and transient P53 protein expression. P53 protein functionality was further demonstrated because transfected cells underwent apoptosis.