Sedentary Behaviour Intervention as a Personalised Secondary Prevention Strategy (SIT LESS) for patients with coronary artery disease participating in cardiac rehabilitation: rationale and design of the SIT LESS randomised clinical trial.

Patients with coronary artery disease (CAD) are more sedentary compared with the general population, but contemporary cardiac rehabilitation (CR) programmes do not specifically target sedentary behaviour (SB). We developed a 12-week, hybrid (centre-based+home-based) Sedentary behaviour IntervenTion as a personaLisEd Secondary prevention Strategy (SIT LESS). The SIT LESS programme is tailored to the needs of patients with CAD, using evidence-based behavioural change methods and an activity tracker connected to an online dashboard to enable self-monitoring and remote coaching. Following the intervention mapping principles, we first identified determinants of SB from literature to adapt theory-based methods and practical applications to target SB and then evaluated the intervention in advisory board meetings with patients and nurse specialists. This resulted in four core components of SIT LESS: (1) patient education, (2) goal setting, (3) motivational interviewing with coping planning, and (4) (tele)monitoring using a pocket-worn activity tracker connected to a smartphone application and providing vibrotactile feedback after prolonged sedentary bouts. We hypothesise that adding SIT LESS to contemporary CR will reduce SB in patients with CAD to a greater extent compared with usual care. Therefore, 212 patients with CAD will be recruited from two Dutch hospitals and randomised to CR (control) or CR+SIT LESS (intervention). Patients will be assessed prior to, immediately after and 3 months after CR. The primary comparison relates to the pre-CR versus post-CR difference in SB (objectively assessed in min/day) between the control and intervention groups. Secondary outcomes include between-group differences in SB characteristics (eg, number of sedentary bouts); change in SB 3 months after CR; changes in light-intensity and moderate-to-vigorous-intensity physical activity; quality of life; and patients' competencies for self-management. Outcomes of the SIT LESS randomised clinical trial will provide novel insight into the effectiveness of a structured, hybrid and personalised behaviour change intervention to attenuate SB in patients with CAD participating in CR. Trial registration number NL9263.

Sound localization with bilateral bone conduction devices.

PURPOSE: To investigate sound localization in patients bilaterally fitted with bone conduction devices (BCDs). Additionally, clinically applicable methods to improve localization accuracy were explored. METHODS: Fifteen adults with bilaterally fitted percutaneous BCDs were included. At baseline, sound localization, (un)aided pure-tone thresholds, device use, speech, spatial and qualities of hearing scale (SSQ) and York hearing-related quality of life (YHRQL) questionnaire were measured. Settings to optimize sound localizing were added to the BCDs. At 1 month, sound localization was assessed again and localization was practiced with a series of sounds with visual feedback. At 3 months¸ localization performance, device use and questionnaire scores were determined again. RESULTS: At baseline, one patient with congenital hearing loss demonstrated near excellent localization performance and four other patients (three with congenital hearing loss) localized sounds (quite) accurately. Seven patients with acquired hearing loss were able to lateralize sounds, i.e. identify whether sounds were coming from the left or right side, but could not localize sounds accurately. Three patients (one with congenital hearing loss) could not even lateralize sounds correctly. SSQ scores were significantly higher at 3 months. Localization performance, device use and YHRQL scores were not significantly different between visits. CONCLUSION: In this study, the majority of experienced bilateral BCD users could lateralize sounds and one third was able to localize sounds (quite) accurately. The localization performance was robust and stable over time. Although SSQ scores were increased at the last visit, optimizing device settings and a short practice session did not improve sound localization.

The DizzyQuest: relation between self-reported hearing loss, tinnitus and objective hearing thresholds in patients with Meniere's disease.

BACKGROUND: Combining a mobile application-based vestibular diary called the DizzyQuest and an iPad-based hearing test enables evaluation of the relationship between experienced neuro-otological symptoms and hearing thresholds in daily life setting. The aim was to investigate the relationship between self-reported hearing symptoms and hearing thresholds in patients with Meniere's disease (MD), using the DizzyQuest and the iPad-based hearing test simultaneously. METHODS: The DizzyQuest was administered for 3 weeks in 21 patients. Using the experience-sampling-method (ESM), it assessed hearing loss and tinnitus severity for both ears separately. Each day after the DizzyQuest, an iPad-based hearing test was used to measure hearing thresholds. A mixed model regression analysis was performed to investigate relationships between hearing thresholds and self-reported hearing loss and tinnitus severity. RESULTS: Fifteen patients were included. Overall, pure-tone averages (PTAs) were not correlated with self-reported hearing loss severity and tinnitus. Individual differences in PTA results between both ears did not significantly influence the difference in self-reported hearing loss severity between both ears. Self-reported hearing loss and tinnitus scores were significantly higher in ears that corresponded with audiometric criteria of MD (p < 0.001). Self-reported tinnitus severity significantly increased with self-reported hearing loss severity in affected (p = 0.011) and unaffected ears (p < 0.001). CONCLUSION: Combining the DizzyQuest and iPad-based hearing test, facilitated assessment of self-reported hearing loss and tinnitus severity and their relationship with hearing thresholds, in a daily life setting. This study illustrated the importance of investigating neuro-otological symptoms at an individual level, using multiple measurements. ESM strategies like the DizzyQuest should therefore be considered in neuro-otological research.

A mobile sound localization setup.

In this paper, a mobile sound localization setup is described that can be used to measure a persons' localization performance in a sophisticated way. With this mobile setup, researchers can travel to subjects, and studies are not limited by the willingness of participants to visit the clinic. In the setup, sounds are presented within a partial sphere in both the horizontal (-70° to 70° azimuth) and vertical (-35° to 40° elevation) plane. Participants are asked to indicate the perceived sound origin by pointing with a head-mounted LED. Head movements are recorded and instantly visualized (i.e. online target response plots). Depending on the research question, the setup can be adjusted for more advanced or simplified measurements, making the setup suitable for a wide range of research questions. The rationale for building this mobile setup was to test horizontal sound localization abilities (binaural hearing) and vertical sound localization abilities (monaural hearing) of children and patients who were otherwise not accessible for testing. In this setup loudspeakers are not visible and subjects are asked to indicate the perceived sound direction by a natural head-pointing response towards the perceived location. An advantage of the implemented pointing-method is the playful manner in which children are tested. They are 'shooting' at the perceived sound target location with a head-mounted LED and have fun while performing the test. •We present a mobile sound localization setup suitable for measuring horizontal and vertical sound localization in children and adult patients in the convenience of their own environment.

Bilateral vestibulopathy and age: experimental considerations for testing dynamic visual acuity on a treadmill.

INTRODUCTION: Bilateral vestibulopathy (BVP) can affect visual acuity in dynamic conditions, like walking. This can be assessed by testing Dynamic Visual Acuity (DVA) on a treadmill at different walking speeds. Apart from BVP, age itself might influence DVA and the ability to complete the test. The objective of this study was to investigate whether DVA tested while walking, and the drop-out rate (the inability to complete all walking speeds of the test) are significantly influenced by age in BVP-patients and healthy subjects. METHODS: Forty-four BVP-patients (20 male, mean age 59 years) and 63 healthy subjects (27 male, mean age 46 years) performed the DVA test on a treadmill at 0 (static condition), 2, 4 and 6 km/h (dynamic conditions). The dynamic visual acuity loss was calculated as the difference between visual acuity in the static condition and visual acuity in each walking condition. The dependency of the drop-out rate and dynamic visual acuity loss on BVP and age was investigated at all walking speeds, as well as the dependency of dynamic visual acuity loss on speed. RESULTS: Age and BVP significantly increased the drop-out rate (p ≤ 0.038). A significantly higher dynamic visual acuity loss was found at all speeds in BVP-patients compared to healthy subjects (p < 0.001). Age showed no effect on dynamic visual acuity loss in both groups. In BVP-patients, increasing walking speeds resulted in higher dynamic visual acuity loss (p ≤ 0.036). CONCLUSION: DVA tested while walking on a treadmill, is one of the few "close to reality" functional outcome measures of vestibular function in the vertical plane. It is able to demonstrate significant loss of DVA in bilateral vestibulopathy patients. However, since bilateral vestibulopathy and age significantly increase the drop-out rate at faster walking speeds, it is recommended to use age-matched controls. Furthermore, it could be considered to use an individual "preferred" walking speed and to limit maximum walking speed in older subjects when testing DVA on a treadmill.

Introducing the DizzyQuest: an app-based diary for vestibular disorders.

BACKGROUND: Most questionnaires currently used for assessing symptomatology of vestibular disorders are retrospective, inducing recall bias and lowering ecological validity. An app-based diary, administered multiple times in daily life, could increase the accuracy and ecological validity of symptom measurement. The objective of this study was to introduce a new experience sampling method (ESM) based vestibular diary app (DizzyQuest), evaluate response rates, and to provide examples of DizzyQuest outcome measures which can be used in future research. METHODS: Sixty-three patients diagnosed with a vestibular disorder were included. The DizzyQuest consisted of four questionnaires. The morning- and evening-questionnaires were administered once each day, the within-day-questionnaire 10 times a day using a semi-random time schedule, and the attack questionnaire could be completed after the occurrence of a vertigo or dizziness attack. Data were collected for 4 weeks. Response rates and loss-to-follow-up were determined. Reported symptoms in the within-day-questionnaire were compared within and between patients and subgroups of patients with different vestibular disorders. RESULTS: Fifty-one patients completed the study period. Average response rates were significantly higher than the desired response rate of > 50% (p < 0.001). The attack-questionnaire was used 159 times. A variety of neuro-otological symptoms and different disease profiles were demonstrated between patients and subgroups of patients with different vestibular disorders. CONCLUSION: The DizzyQuest is able to capture vestibular symptoms within their psychosocial context in daily life, with little recall bias and high ecological validity. The DizzyQuest reached the desired response rates and showed different disease profiles between subgroups of patients with different vestibular disorders. This is the first time ESM was used to assess daily symptoms and quality of life in vestibular disorders, showing that it might be a useful tool in this population.

Comparison of three video head impulse test systems for the diagnosis of bilateral vestibulopathy.

INTRODUCTION: A horizontal vestibulo-ocular reflex gain (VOR gain) of < 0.6, measured by the video head impulse test (VHIT), is one of the diagnostic criteria for bilateral vestibulopathy (BV) according to the Báràny Society. Several VHIT systems are commercially available, each with different techniques of tracking head and eye movements and different methods of gain calculation. This study compared three different VHIT systems in patients diagnosed with BV. METHODS: This study comprised 46 BV patients (diagnosed according to the Báràny criteria), tested with three commercial VHIT systems (Interacoustics, Otometrics and Synapsys) in random order. Main outcome parameter was VOR gain as calculated by the system, and the agreement on BV diagnosis (VOR gain < 0.6) between the VHIT systems. Peak head velocities, the order effect and covert saccades were analysed separately, to determine whether these parameters could have influenced differences in outcome between VHIT systems. RESULTS: VOR gain in the Synapsys system differed significantly from VOR gain in the other two systems [F(1.256, 33.916) = 35.681, p < 0.000]. The VHIT systems agreed in 83% of the patients on the BV diagnosis. Peak head velocities, the order effect and covert saccades were not likely to have influenced the above mentioned results. CONCLUSION: To conclude, using different VHIT systems in the same BV patient can lead to clinically significant differences in VOR gain, when using a cut-off value of 0.6. This might hinder proper diagnosis of BV patients. It would, therefore, be preferred that VHIT systems are standardised regarding eye and head tracking methods, and VOR gain calculation algorithms. Until then, it is advised to not only take the VOR gain in consideration when assessing a VHIT trial, but also look at the raw traces and the compensatory saccades.

The Functional Head Impulse Test to Assess Oscillopsia in Bilateral Vestibulopathy.

Introduction: Bilateral vestibulopathy (BV) is a chronic condition in which vestibular function is severely impaired or absent on both ears. Oscillopsia is one of the main symptoms of BV. Oscillopsia can be quantified objectively by functional vestibular tests, and subjectively by questionnaires. Recently, a new technique for testing functionally effective gaze stabilization was developed: the functional Head Impulse Test (fHIT). This study compared the fHIT with the Dynamic Visual Acuity assessed on a treadmill (DVAtreadmill) and Oscillopsia Severity Questionnaire (OSQ) in the context of objectifying the experience of oscillopsia in patients with BV. Methods: Inclusion criteria comprised: (1) summated slow phase velocity of nystagmus of <20°/s during bithermal caloric tests, (2) torsion swing tests gain of <30% and/or phase <168°, and (3) complaints of oscillopsia and/or imbalance. During the fHIT (Beon Solutions srl, Italy) patients were seated in front of a computer screen. During a passive horizontal head impulse a Landolt C optotype was shortly displayed. Patients reported the seen optotype by pressing the corresponding button on a keyboard. The percentage correct answers was registered for leftwards and rightwards head impulses separately. During DVAtreadmill patients were positioned on a treadmill in front of a computer screen that showed Sloan optotypes. Patients were tested in static condition and in dynamic conditions (while walking on the treadmill at 2, 4, and 6 km/h). The decline in LogMAR between static and dynamic conditions was registered for each speed. Every patient completed the Oscillopsia Severity Questionnaire (OSQ). Results: In total 23 patients were included. This study showed a moderate correlation between OSQ outcomes and the fHIT [rightwards head rotations (r s = -0.559; p = 0.006) leftwards head rotations (r s = -0.396; p = 0.061)]. No correlation was found between OSQ outcomes and DVAtreadmill, or between DVAtreadmill and fHIT. All patients completed the fHIT, 52% of the patients completed the DVAtreadmill on all speeds. Conclusion: The fHIT seems to be a feasible test to quantify oscillopsia in BV since, unlike DVAtreadmill, it correlates with the experienced oscillopsia measured by the OSQ, and more BV patients are able to complete the fHIT than DVAtreadmill.

Microbiome on the Bone-Anchored Hearing System: A Prospective Study.

The bone-anchored hearing system (BAHS) has evolved to a common treatment option for various types of hearing revalidation. The BAHS consists of an implant in the skull that breeches the skin. Soft tissue reactions are a common complication associated with BAHS and are generally poorly understood. This study aims to investigate the influence of BAHS and associated skin reactions around the implant. A total of 45 patients were prospectively followed from implantation up to at least 1 year. Swabs were obtained at baseline, 12 weeks follow-up and during cases of inflammation (Holgers score ≥2). The microbiota was assessed using IS-proTM, a bacterial profiling method based on the interspace region between the 16S-23S rRNA genes. Detection of operational taxonomic units, the Shannon Diversity Index, sample similarity analyses and Partial Least Squares Discriminant Analysis (PLS-DA) were employed. Staphylococcus epidermidis, Streptococcus pneumoniae/mitis, Propionibacterium acnes, Staphylococcus capitis, Staphylococcus hominis, Bifidobacterium longum, Haemophilus parainfluenzae, Lactobacillus rhamnosus, Bordetella spp., Streptococcus sanguinis, Peptostreptococcus anaerobius, Staphylococcus aureus, Lactococcus lactis, Enterobacter cloacae, and Citrobacter koseri were the most commonly found bacterial species. S. pneumoniae/mitis was significantly more often observed after implantation, whereas P. acnes was significantly less observed after implantation compared with baseline. The relative abundance of S. epidermidis (17%) and S. aureus (19.4%) was the highest for the group of patients with inflammation. The Shannon Diversity Index was significantly increased after implantation compared with pre-surgical swabs for Firmicutes, Actinobacteria, Fusobacteria, Verrucomicrobia (FAFV), but not for other phyla. When combining all phyla, there was no significant increase in the Shannon Diversity Index. The diversity index was similar post-surgically for patients experiencing inflammation and for patients without inflammation. With a supervised classifier (PLS-DA), patients prone to inflammation could be identified at baseline with an accuracy of 91.7%. In addition, PLS-DA could classify post-surgical abutments as non-inflamed or inflamed with an accuracy of 97.7%. This study shows the potential of using IS-proTM to describe and quantify the microbiota associated with the percutaneous BAHS. Furthermore, the results indicate the possibility of an early identification of patients susceptible to adverse skin reaction following implantation. Both S. aureus and S. epidermidis should be considered as relevant bacteria for BAHS-associated inflammation.

The Video Head Impulse Test and the Influence of Daily Use of Spectacles to Correct a Refractive Error.

OBJECTIVE: To determine the influence of daily use of spectacles to correct a refractive error, on the vestibulo-ocular reflex (VOR) gain measured with the video head impulse test (vHIT). STUDY DESIGN: This prospective study enrolled subjects between 18 and 80 years old with and without a refractive error. Subjects were classified into three groups: (1) contact lenses, (2) spectacles, and (3) control group without visual impairment. Exclusion criteria comprised ophthalmic pathology, history of vestibular disorders, and alternated use of spectacles and contact lenses in daily life. Corrective spectacles were removed seconds before testing. One examiner performed all vHIT's under standardized circumstances using the EyeSeeCam system. This system calculated the horizontal VOR gain for rightward and leftward head rotations separately. RESULTS: No statistically significant difference was found in VOR gain between the control group (n = 16), spectacles group (n = 48), and contact lenses group (n = 15) (p = 0.111). Both the spectacles group and contact lenses group showed no statistically significant correlation between VOR gain and amount of refractive error, for rightwards (p = 0.071) and leftwards (p = 0.716) head rotations. There was no statistical significant difference in VOR gain between testing monocularly or binocularly (p = 0.132) and between testing with or without wearing contact lenses (p = 0.800). CONCLUSION: In this study, VOR gain was not influenced by wearing corrective spectacles or contact lenses on a daily basis. Based on this study, no corrective measures are necessary when performing the vHIT on subjects with a refractive error, regardless of the way of correction.

An Exploratory Study to Detect Ménière's Disease in Conventional MRI Scans Using Radiomics.

OBJECTIVE: The purpose of this exploratory study was to investigate whether a quantitative image analysis of the labyrinth in conventional magnetic resonance imaging (MRI) scans using a radiomics approach showed differences between patients with Ménière's disease (MD) and the control group. MATERIALS AND METHODS: In this retrospective study, MRI scans of the affected labyrinths of 24 patients with MD were compared to the MRI scans of labyrinths of 29 patients with an idiopathic asymmetrical sensorineural hearing loss. The 1.5- and 3-T MRI scans had been previously made in a clinical setting between 2008 and 2015. 3D Slicer 4.4 was used to extract several substructures of the labyrinth. A quantitative analysis of the normalized radiomic image features was performed in Mathematica 10. The image features of the two groups were statistically compared. RESULTS: For numerous image features, there was a statistically significant difference (p-value <0.05) between the MD group and the control group. The statistically significant differences in image features were localized in all the substructures of the labyrinth: 43 in the anterior semicircular canal, 10 in the vestibule, 22 in the cochlea, 12 in the posterior semicircular canal, 24 in the horizontal semicircular canal, 11 in the common crus, and 44 in the volume containing the reuniting duct. Furthermore, some figures contain vertical or horizontal bands (three or more statistically significant image features in the same image feature). Several bands were seen: 9 bands in the anterior semicircular canal, 1 band in the vestibule, 3 bands in the cochlea, 0 bands in the posterior semicircular canal, 5 bands in the horizontal semicircular canal, 3 bands in the common crus, and 10 bands in the volume containing the reuniting duct. CONCLUSION: In this exploratory study, several differences were found in image features between the MD group and the control group by using a quantitative radiomics approach on high resolution T2-weighted MRI scans of the labyrinth. Further research should be aimed at validating these results and translating them in a potential clinical diagnostic method to detect MD in MRI scans.

Left atrial thrombus under dabigatran in a patient with nonvalvular atrial fibrillation.

Dabigatran is a new direct competitive inhibitor of thrombin and is equally effective and safe as warfarin in the prevention of thromboembolism in patients with nonvalvular atrial fibrillation. We present a case of a 60-year-old man with persistent nonvalvular atrial fibrillation who switched from acenocoumarol to dabigatran 110 mg twice daily. After five months the patient developed a large atrial thrombus, occlusion of the tibial arteries of the right foot, cerebellar infarction and multiple infarctions in kidneys and spleen. Blood test showed a dabigatran concentration of 35 ng/ml six hours after intake, correlating with a low trough concentration of 24-27 ng/mL and significantly increased thromboembolic risk. Other risk factors for thromboembolism were excluded. The present case indicates that in selected patients, there might be an indication for dose adjustments based on serum levels of dabigatran to ensure patient efficacy (thromboembolic events) and safety (bleeding).

The occurrence of tinnitus after CI surgery in patients with severe hearing loss: A retrospective study.

OBJECTIVE: An often reported side-effect of a cochlear implant (CI) is suppression of tinnitus. However, induction of tinnitus is also a known complication of CI surgery. To date, it remains unclear why some CI recipients experience larger tinnitus complaints due to CI surgery while most others do not. The goal of this study was to investigate the effect of deterioration of residual hearing due to CI surgery on tinnitus. DESIGN: In this retrospective database study, pre- and postoperative audiometric hearing thresholds were retrieved from patients' clinical files. Furthermore, tinnitus questionnaires were sent to all patients who fitted inclusion criteria. STUDY SAMPLE: Of the 512 CI patients who were implanted within the last ten years, 197 patients fitted the inclusion criteria and returned the questionnaires. RESULTS: We identified 39 cases (19.8%) who suffered from a newly developed (25) or deteriorated (14) tinnitus following CI surgery. No statistically significant association between perioperative deterioration of hearing thresholds measured by pure-tone audiometry and the development or deterioration of tinnitus was found. CONCLUSIONS: There is a small risk for deteriorated residual hearing after cochlear implantation. However, for patients with preoperative residual hearing, there appears to be no increased risk of developing chronic tinnitus after hearing deterioration due to cochlear implantation.

The influence of sulcus width on simulated electric fields induced by transcranial magnetic stimulation.

Volume conduction models can help in acquiring knowledge about the distribution of the electric field induced by transcranial magnetic stimulation. One aspect of a detailed model is an accurate description of the cortical surface geometry. Since its estimation is difficult, it is important to know how accurate the geometry has to be represented. Previous studies only looked at the differences caused by neglecting the complete boundary between cerebrospinal fluid (CSF) and grey matter (Thielscher et al 2011 NeuroImage 54 234-43, Bijsterbosch et al 2012 Med. Biol. Eng. Comput. 50 671-81), or by resizing the whole brain (Wagner et al 2008 Exp. Brain Res. 186 539-50). However, due to the high conductive properties of the CSF, it can be expected that alterations in sulcus width can already have a significant effect on the distribution of the electric field. To answer this question, the sulcus width of a highly realistic head model, based on T1-, T2- and diffusion-weighted magnetic resonance images, was altered systematically. This study shows that alterations in the sulcus width do not cause large differences in the majority of the electric field values. However, considerable overestimation of sulcus width produces an overestimation of the calculated field strength, also at locations distant from the target location.

Tribological properties of neutral polysaccharide solutions under simulated oral conditions.

Predictability of the perception of foods thickened by polysaccharides is only poor. Therefore, the effect of saliva on the lubrication properties of 2 types of neutral polysaccharides, cross-linked starch and locust bean gum, was studied. Despite the similar bulk rheological behavior of the 2 polysaccharides, the starch solution exhibited a significantly lower friction coefficient. Although starch viscosity was strongly decreased upon 10 s incubation with human saliva, a low friction coefficient was retained. The presence of remaining granules is held partly responsible for this. Addition of starch granules to locust bean gum also resulted in a decrease in the friction coefficient, but the effect was smaller compared to starch solutions digested by saliva. Smaller contact angles were measured for (digested) starch compared to locust bean gum solutions. This points to other parameters that assist in lubrication, such as the interaction of starch solution constituents with the rubbing surfaces. In addition, the importance of bulk viscosity for spreadability on surfaces was demonstrated. This study illustrates that the type of starch will determine not only the viscosity change but also the presence of intact granules upon digestion by saliva in the oral cavity; the combination of these 2 properties is regarded to be responsible for the poor predictability of sensory responses of starch containing foods.

Exploring imperfect squeezing flow measurements in a Teflon geometry for semisolid foods.

The method of imperfect lubricated squeezing flow in a Teflontrade mark geometry has been explored for the characterization of elongational behavior of custard and mayonnaise. Two Newtonian products, one of low (0.07 Pas) and one of high (18 Pas) shear viscosity, were used as references. Measurements of custards and mayonnaises did not behave according to either the theory of lubricated or nonlubricated squeezing flow, as there were effects of the initial sample height and compression speed. Also, calculated values for the flow index were not as we had expected. The same was true for the Newtonian samples. An important factor explaining the effect of compression speed was the presence of a certain amount of friction, rendering both lubricated theory and nonlubricated theory nonapplicable. Correcting for (pseudo-) thixotropic behavior of custard and mayonnaise appears to be an effective way of obtaining realistic values for the flow index. The presence of buoyancy also affected the results, especially in the case of low viscous products and the effect of initial sample height. Other factors that played a role in the results were yield stress for custard and mayonnaise and instrumental artifacts associated with the imperfect setup of the measurement, especially for the highly viscous products. Quantitatively correcting the results for all of these factors is not possible at this point. Although the imperfect squeezing flow technique in a Teflon geometry is a very practical way to measure semisolids such as custard and mayonnaise under (partly) elongational deformation, the results should be regarded as more qualitative than quantitative.

[Vagus nerve stimulation in patients with drug-resistant epilepsy]. / N.-vagusstimulatie bij patiënten met medicatieresistente epilepsie.

OBJECTIVE: To describe the mechanism and first results of vagus nerve stimulation at the Medisch Spectrum Twenty, the Netherlands, for the treatment of patients with drug-resistant epilepsy. DESIGN: Descriptive retrospective. METHOD: Fifteen patients, 8 male and 7 female, aged 18-45 years with drug-resistant epilepsy, who were not eligible for surgical resection of an epileptic focus, received a vagus nerve stimulator implant in the period April 1999-December 2000. Whilst the vagus nerve stimulator was being adjusted, the medication remained unchanged. RESULTS: Due to vagus nerve stimulation the mean seizure frequency decreased by 32% (range: +20% to -100%). In 6 patients there was a strong reduction in seizure frequency, in 3 there was a mild reduction, and in 6 patients there was no apparent effect. The most common adverse events during stimulation were a mild prickly cough and a change of voice during stimulation. In one patient a temporary left vocal cord paralysis was observed, which may possibly have been a result of the procedure. CONCLUSION: Vagus nerve stimulation is an effective means of treatment for drug-resistant epilepsy and is therefore a treatment option that deserves more attention in the Netherlands.

Metallothionein in human gastrointestinal cancer.

Metallothionein (MT) is a small thiol-rich metalloprotein with antioxidant properties, involved in tumour pathophysiology and therapy resistance. In order to assess the contribution of MT in gastrointestinal carcinogenesis, this study examined both the MT content by radioimmunoassay and the MT localization by immunohistochemistry in pairs of neoplastic and normal-appearing human gastrointestinal tissues. In addition, the relationship between MT expression and major clinicopathological parameters was assessed. The MT concentration of gastric carcinomas and of colorectal adenomas, carcinomas, and liver metastases was found to be significantly lower than that of corresponding normal-appearing tissue. A relatively high MT content, however, was found to be associated with the villous character of colorectal adenomas and with the Dukes' stage of colorectal carcinomas, indicating a relationship between MT level and malignant potential. Immunohistochemical evaluation showed a fairly good correlation with these quantitative data. MT was found to be expressed at a low level and in a patchy pattern in the gastrointestinal neoplastic and metastatic tissues, whereas in normal-appearing gastrointestinal mucosa MT was uniformly distributed in the cytoplasm and/or nucleus of apical cells. Although in the gastric cancer patients no association was found between the MT concentration and the clinicopathological parameters, the strong MT expression in areas with intestinal metaplasia, known to have neoplastic potential, further points to a relationship between this antioxidant metalloprotein and the malignant character of cells. Gastrointestinal neoplasms are apparently accompanied by a low level and decreased expression of MT, but those with a relatively high level seem to have an increased malignant potential. Further studies will be required to determine the clinical relevance of these observations.

Superoxide dismutases in gastric and esophageal cancer and the prognostic impact in gastric cancer.

The oxidant-antioxidant balance is thought to be important in the initiation, promotion, and therapy resistance of cancer. In the present study, we assessed the expression of the antioxidants manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase in gastric and esophageal carcinomas and their relation with clinical outcome. Adenocarcinomas of the stomach (n = 81) as well as squamous cell carcinomas of the esophagus (n = 10) showed an enhanced immunohistochemical expression of Mn-SOD, which was accompanied by a significantly higher tissue level (P < or = 0.007) compared with their corresponding normal mucosa. In contrast, copper/zinc superoxide dismutase was found to be marginally lower in these malignant tissues in comparison with the normal tissues. The superoxide dismutase levels were not found to be associated with major clinicopathological features of the gastric cancer patients. Univariate analysis revealed, however, that a high Mn-SOD level in gastric carcinomas, a low level in the normal gastric mucosa, and a high ratio of these two levels in gastric cancer patients are indicative of a poor overall survival. Multivariate analysis, including all clinicopathological parameters, revealed that the Mn-SOD ratio in particular is an independent prognostic parameter in gastric cancer patients.

Superoxide dismutases in the human colorectal cancer sequence.

PURPOSE: The oxidant-antioxidant balance within tissues is thought to contribute to the development and progression of cancer. Previous investigations have indicated changes in this balance during the colorectal oncogenic process that merit further investigation. The aim of the present study was to evaluate whether the human colorectal cancer sequence is accompanied by changes in the protein and activity levels of the antioxidant enzymes manganese- and copper/zinc-superoxide dismutase (Mn-SOD and Cu/Zn-SOD). PATIENTS AND METHODS: SOD levels were assessed in colorectal adenomas, carcinomas, and liver metastases and were compared with those in the corresponding normal tissues (n = 35 in each group). Mn- and Cu/Zn-SOD expression was first evaluated semiquantitatively by electrophoretic activity analysis, immunoblotting, and immunohistochemistry and was subsequently quantified by enzyme-linked immunosorbent assays (ELISAs) and spectrophotometric activity assays. RESULTS: The semiquantitative analyses showed enhanced Mn-SOD levels, primarily localized in (neoplastic) epithelial cells, in carcinomas, and in liver metastases as compared with adenomas and normal mucosa, whereas no consistent pattern was observed for Cu/Zn-SOD. Normal liver tissue expressed the highest levels of both SODs. The quantitative SOD analyses confirmed these observations and revealed that carcinomas and liver metastases expressed 2-4 times more Mn-SOD protein and enzymatic activity (0.0005 < P < 0.01) than did the normal mucosa. Adenomas expressed intermediate Mn-SOD levels, which increased significantly with the diameter and tended to increase with the grade of dysplasia and presence of a villous component. In contrast, adenomas, carcinomas, and the corresponding normal mucosa were found to have a similar Cu/Zn-SOD content, whereas liver metastases contained significantly (P < 0.02) more Cu/Zn-SOD as compared with these tissues. In addition, the Cu/Zn-SOD content was not related to any histopathological characteristic of the carcinomas or adenomas. CONCLUSIONS: Our study indicates that the development of neoplasia in the human colorectum is accompanied by major changes in the level and activity of Mn-SOD. This observation illustrates that Mn-SOD might have a functional role in human colorectal carcinogenesis.