Tumour staged surgery of endolymphatic sac tumors (ELST)

BACKGROUND: Endolymphatic sac tumours (ELST) have only been known as own tumour entities since 1984. ELST might occur solitarily and sporadically as well as hereditary connected to von Hippel-Lindau disease (VHL). This connection has been observed in 1992 for the first time and confirmed by molecular genetic analyses of the VHL gen. There is no agreement yet concerning diagnostics and therapy. METHODS: Our attempt of classifying this type of tumour is the first one. According to our own experience and to literature, we suggest the following classification: ELST type A is locally confined without erosions of the temporal bone nor infiltration of the subarachnoidal area; ELST type B with bony infiltration of the labyrinth block and clinical hearing loss, and ELST type C with additional infiltration of the sigmoid sinus and the vein of jugular bulb. Preoperative diagnostics are performed according to defined radiological criteria in CT and MRI scans including MR-angiography. RESULTS: In 6 patients, including two with a VHL syndrome, ELST was completely sanitized by stage-compatible surgery, using translabyrintine to infratemporal approaches, according to the tumour classification that we developed. The VII (th) nerve could be saved in all tumour stages, and in stage ELST type A the VIII (th) nerve as well. All patients remained without local recurrence in MRI check during the observation period of 4 to 38 months. CONCLUSION: Our stage-compatible surgery of ELST allows total tumor removal with minor morbidity. In contrast to the antero-, retrosigmoidal and suboccipital approaches, the tumour matrix can be safely removed via transmastoidal approach to exclude local recurrences.     

Electrophysiologic examinations in low frequency hearing impairment: clinical and prognostic aspects

INTRODUCTION: Low-frequency hearing impairment (LFHI) is mainly associated to endolymphatic hydrops and shows a high variety of possible outcomes. Electrophysiologic examinations are widely recommended in diagnostics of LFHI, wheras up to now no data exist about the prognostic value of these examinations in a conservative therapeutic regimen. METHODS: In a quality assessment, we retrospectively evaluated the records of 90 patients, and performed an audiometric follow-up for analysis of long-time hearing data. All patients had undergone diagnostic electrocochleographic examination (ECochG) and then had been treated with rheologic infusions, followed by dehydrating infusions in patients lacking complete remission. The results of both therapeutic strategies and of long-time results were correlated to electrophysiologic findings. RESULTS: The prognosis of LFHI is significantly reflected by pretherapeutic electrocochleographic data. All significant parameters were associated to compound action potential (CAP) whereas parameters associated to cochlear microphonics (CM) did not include any utilizable prognostic value. In patients with a good outcome, the latency of CAP complex was significantly shorter, and the width of CAP complex significantly smaller than in patients with poor hearing outcome after rheologic and after dehydrating therapy and in long time assessment. The relation of summating potential (SP) und CAP was significantly smaller when the outcome was sufficient or good for either therapy and in long time analysis. Steep CAP-input-output-curves were associated to insufficient outcome after rheologic therapy and in long time assessment, but not for dehydrating therapy. CONCLUSIONS: The results indicate that ECochG is of significant prognostic value concerning hearing outcome after conservative therapy in patients suffering from LFHI. It can help the physician to counsel the patient and perform an effective management of the disease. We conclude that ECochG should be performed before the onset of therapy, including collection of SP and CAP data whereas CM parameters may be omitted.     

Assessing comorbidity in patients with Parkinson's disease.

The aim of this study was to assess the accuracy of an interview-based assessment of comorbidity, in patients with Parkinson's disease (PD). The Cumulative Illness Rating Scale-Geriatric (CIRS-G) was completed (1) in an interview with 31 PD patients and their caregivers, and (2) by reviewing the patient's medical charts from their general practitioners. Based on the interview, all patients had some comorbidity, 84% had one or more moderate comorbid diseases. The most frequently affected organ systems were "lower gastrointestinal" and "genitourinary". The mean +/- SD total score of the interview-based (chart-based) CIRS-G was 6.9 +/- 3.8 (7.6 +/- 3.5) with a mean of 4.3 +/- 1.9 (5.0 +/- 1.9) affected organ systems and a mean of 2.1 +/- 1.7 (2.3 +/- 1.6) organ systems with at least moderate comorbidity per patient. The agreement (intraclass correlation coefficients) between the interview-based and chart-based assessments for the six summary scores ranged from 0.69 to 0.81. The agreement for the 14 organ systems ranged from 0.13 to 1.00 (weighted kappa); 12 had a K(w) above 0.40 (moderate agreement). The comorbidity summary scores had a moderate correlation with age and disability. The interview-based assessment of the CIRS-G is easy to apply and is an accurate method to assess comorbidity in patients with PD.     

Preparation of solid drug/cyclodextrin complexes of acidic and basic drugs

One of the main obstacles in pharmaceutical applications of cyclodextrins is their increase of the formulation bulk. Even at maximum incorporation 500 mg of a solid drug/cyclodextrin complex will only contain between 50 and 125 mg of the drug, assuming a low molecular weight drug (MW 200 to 400 Dalton) and an average molecular weight cyclodextrin (MW about 1500 Dalton). In general, the complexation efficiency is low and consequently the complex powder contains a significant amount of empty cyclodextrin molecules. In the present study the complexation efficiency is increased by ionization of the drug molecule through addition of volatile acid (i.e. acetic acid) or base (i.e. ammonia) to the aqueous complexation media of basic or acidic drugs, respectively. The volatile acid or base was then removed during lyophilization and heating in a vacuum oven resulting in formation of solid cyclodextrin complexes of the unionized drug. Thus, the complexation efficiency was temporary increased by the ionization but then again decreased leading to formation of the thermodynamically unstable solid drug/cyclodextrin complexes. When dissolved the energy of the system was lowered by expelling the drug molecules from the cyclodextrin cavities resulting in formation of supersaturated drug solutions and ultimately precipitation of the drug.     

Intra- and interlaboratory calibration of the DR CALUX bioassay for the analysis of dioxins and dioxin-like chemicals in sediments

In the Fourth National Policy Document on Water Management in The Netherlands, it is defined that in 2003, in addition to the assessment of chemical substances, special guidelines for the assessment of dredged material should be recorded. The assessment of dredged material is based on integrated chemical and biological effect measurements. Among others, the DR CALUX (dioxin responsive-chemically activated luciferase expression) bioassay has tentatively been recommended for inclusion in the dredged material assessment. To ensure the reliability of this bioassay, an intra- and interlaboratory validation study, or ring test, was performed, organized by the Dutch National Institute for Coastal and Marine Management (RIKZ) in cooperation with BioDetection Systems BV (BDS). The intralaboratory repeatability and reproducibility and the limit of detection (LOD) and quantification (LOQ) of the DR CALUX bioassay were determined by analyzing sediment extracts and dimethyl sulfoxide (DMSO) blanks. The highest observed repeatability was found to be 24.1%, whereas the highest observed reproducibility was calculated to be 19.9%. Based on the obtained results, the LOD and LOQ to be applied for the bioassay are 0.3 and 1.0 pM, respectively. The interlaboratory calibration study was divided into three phases, starting with analyzing pure chemicals. During the second phase, sediment extracts were analyzed, whereas in the third phase, whole sediments had to be extracted, cleaned, and analyzed. The average interlaboratory repeatability increased from 14.6% for the analysis of pure compound to 26.1% for the analysis of whole matrix. A similar increase in reproducibility with increasing complexity of handlings was observed with the interlaboratory reproducibility of 6.5% for pure compound and 27.9% for whole matrix. The results of this study are intended as a starting point for implementing the integrated chemical-biological assessment strategy and for systematic monitoring of dredged materials and related materials in the coming years.     

HPV testing can reduce the number of follow-up visits in women treated for cervical intraepithelial neoplasia grade 3

OBJECTIVE: We evaluated high-risk human papillomavirus (HPV) testing by Hybrid Capture II (HC II) in addition to cytology to predict recurrent/residual cervical intraepithelial neoplasia (CIN) 2/3 and cervical cancer in women treated for CIN 3. METHODS: Follow-up study of 108 women with histologically confirmed CIN 3. RESULTS: Pretreatment, in 96% (104/108) of the smears high-risk HPV DNA was present. Posttreatment, 71% (77/108) of the women had normal cytology and negative HC II test and none developed recurrent/residual disease during a median follow-up of 28.8 months with a range of 2.4-64.8 months. One of the 12% (13/108) of women with normal cytology and positive HC II test was diagnosed with cervical adenocarcinoma. One of the 7% (8/108) of women with abnormal cytology (borderline dyskaryosis or worse) and negative HC II test was diagnosed with CIN 2. Three of the 9% (10/108) of women with abnormal cytology and a positive HC II test were diagnosed with CIN 2/3. These results show an increased risk for recurrent/residual CIN 2/3 and cervical carcinoma when at least one posttreatment test is positive. The highest relative risk (72.9, 95% CI 25-210) was present in women with both tests positive. CONCLUSIONS: HPV testing with Hybrid Capture II in conjunction with cytology can be used as a tool to select women with an increased risk for recurrent/residual CIN 2/3 and cervical cancer. The standard policy in The Netherlands is cytology at 6, 12, and 24 months posttreatment. However, for women with both normal cytology and negative HC II test at 6 months the chance to develop recurrent/residual CIN 2/3 and cervical carcinoma is so low that retesting at 12 months can be omitted.     

Dynamic contrast enhancement of paragangliomas of the head and neck: evaluation with time-resolved 2D MR projection angiography

Our objective was to evaluate tumor hemodynamics of paragangliomas of the head and neck. A 2D magnetic resonance projection angiography (MRPA) protocol was developed. Six patients with histologically proven paragangliomas were included in the study. The sequence protocol and data post-processing procedure were optimized in view of a high temporal resolution and maximum contrast-to-noise ratio. Image-time series of two freely orientated slabs could be obtained. Correlation analysis was performed to generate selective arterial and venous weighted angiographic images. Glomus tumors showed a rapid and intense homogeneous enhancement following the intravenous administration of contrast material. The smallest tumors investigated measured 10 mm and could be visualized clearly. Time-resolved analysis of the tumor enhancement revealed an early bolus arrival within the vascular bed of the tumor and prolonged incomplete washout indicating blood pooling. The dynamic contrast enhancement of glomus tumors can be evaluated non-invasively with MRPA providing a high temporal resolution and high image quality. The characteristic contrast enhancement of glomus tumors can be helpful in the diagnostic workup of lesions that may mimic glomus tumors.     

Transvestibular closure with an autologous bone graft as surgical repair of a nasoseptal defect due to Le Fort-I osteotomy

Defects of the nasal septum are a common complication after nasal surgery. Affected patients frequently suffer from bleeding, crusting and impaired nasal air flow. The surgical closure of septal defects remains a distinctive challenge. Though many different techniques have been described, the failure rate of this procedure remains high. In the case presented here, a large basal septum defect occurred after a prosthetic Le Fort-I osteotomy. The attempt to cover the distance between the bony nasal floor and the nasal septum with pedicled mucosal flaps failed due to extensive scar formation of the nasal mucosa. Therefore a nasal floor elevation by insertion of an autologous bone graft from the iliac crest was conducted. The bone graft was connected with the hard palate via two titanium screws. Other than with an autologous cartilage graft, no major resorption of the bone graft is to be expected. This indirect method for the closure of a basal nasal septum defect is new.     

Deriving default dermal exposure values for use in a risk assessment toolkit for small and medium-sized enterprises

This paper describes the derivation of default task-based dermal exposure values for use in a risk assessment toolkit for small and medium-sized enterprises (SMEs). A set of separately determined dermal exposure modifiers have been applied to published studies of dermal exposure to obtain 'normalized' dermal exposure data sets. These data sets are grouped according to task and then further subdivided by making a distinction between processes involving solid and liquid products. For each of the resulting 12 groups, two default exposure rates are required: potential exposure rate to the hands and potential exposure rate to the body. Default values for risk assessment are then derived by taking a weighted average of the 75th percentiles of these normalized exposure distributions. In addition, a measure of peak surface concentration is required to take into account the risk of local skin effects. The higher of the (modified) hand and body exposure rates after applying the relevant penetration factors for clothing and gloves is used. Usually this will be the hand exposure rate. These default values serve as robust initial exposure estimates in a risk assessment toolkit for SMEs.