Toll-like receptor 5 and 7 expression in adenoid cystic carcinoma of major salivary glands.

Adenoid cystic carcinoma (ACC) of the salivary glands has a poor long-term prognosis and high metastatic rate. Toll-like receptors (TLRs) have been related to tumour progression but have also tumour growth-inhibiting responses. To the best of our knowledge, they have not been studied previously in ACC. We studied the immunoexpression of TLR 5 and 7 in ACC of the major salivary glands. From a cohort of 54 patients with ACC of the major salivary glands treated at the Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland in 1974-2009, there were 34 primary tumours and six metastases available for immunohistochemical analysis. Immunohistochemical expression of TLR 5 and 7 were correlated to clinicopathological findings and patient survival. Both TLR 5 and 7 were expressed in ACCs and their metastases, mostly on the cell membranes. The expression was heterogeneous in individual tumours. TLR 5 was expressed less in male samples, and TLR 7 had lower expression in ACCs with solid growth pattern. No correlation with survival was found. In the normal salivary gland, the TLR 5 and 7 expression was mainly negative. Both TLR 5 and 7 are expressed in salivary adenoid cystic carcinoma on the cell membranes as well as in cytoplasm.

Beneficial effects of antiepileptic medication on absence seizures and cognitive functioning in children.

In this prospective clinical study, the effects on cognitive functioning of absence seizures, epileptiform EEG discharges, and their abolishment by antiepileptic medication were evaluated in patients newly diagnosed with childhood absence epilepsy or juvenile absence epilepsy. Eleven children in the study group and ten age- and gender-matched controls with mild asthma underwent combined video/EEG and neurocognitive assessment (IQ, fine-motor fluency, attention, visual and spatial memory). The neuropsychological assessment was repeated after the introduction of antiepileptic medication. Ten children with absence epilepsy became clinically seizure free. The study group improved in attention, fine-motor fluency, and visual memory. The controls improved only in fine-motor and attention skills. Duration of generalized 3-Hz spike-wave discharges and clinical absence seizures was negatively correlated with performance on the visual memory task. Cessation of seizures induced by antiepileptic medication may support neurocognitive functioning in children.

Effects of after-midnight intake of zolpidem and temazepam on driving ability in women with non-organic insomnia.

BACKGROUND: Occasionally, insomniac patients may take a sleeping pill after midnight. This may have consequences on their ability to drive a car and result in an increased risk of car accidents. METHODS: This double-blind, randomized, placebo-controlled, three-treatment three-period cross-over study investigated the effects of two frequently prescribed hypnotics of different classes in a real life condition on driving performance and psychomotor skills in insomniac women. Single doses of zolpidem 10 mg (Z), temazepam 20 mg (T) or placebo (P) were administered at 2:00 a.m. to 19 women aged 35-60 years in three treatment periods separated by wash-out periods of 3-14 days. After polysomnography at baseline and each treatment night, patients underwent, 5.5 h after drug intake at 7:30 a.m. on the next morning, a STISIM driving simulator test, and a subsequent neuropsychological test (FePsy). RESULTS: Eighteen insomniac women were included in the analysis (mean age 50 years, mean weight 69 kg, mean BMI 25.6 kg/m2). There were no differences between treatments for the primary outcome measure (mean time to collision; baseline: 0.120 s, P: 0.124, T: 0.118, Z: 0.124; P> or =0.12 for all pairwise comparisons). No differences were recorded for speed deviation and reaction time to tasks for the verum treatments, however, lane position deviation was greater after administration of zolpidem in comparison to both placebo and temazepam (P=0.025 and 0.05, respectively). There were no differences between treatments in the FePsy test. Both medications were well tolerated. CONCLUSIONS: 5.5 h after drug administration there were no major differences in psychomotor performances between both zolpidem and temazepam compared to placebo, which indicates the absence of significant residual effects at that time. However, certain patients were more susceptible than others to the drug effects (two patients with high number of collisions). This underlines the necessity to strongly advocate against the late intake of hypnotics if patients intend to drive a car early the next morning.

A dose-response study of total sleep time and the ability to maintain wakefulness.

The apparent connection between sleep debt, performance decrements and workplace accidents has generated a need for feasible vigilance tests that focus on the quantification of daytime sleepiness in occupational settings. The objective of this study was to evaluate the sensitivity of the Maintenance of Wakefulness Test (MWT) to acute sleep deprivation of various doses. Eight healthy female volunteers, mean age 28.9 years (range 23-36), participated in this laboratory study. After an adaptation night, the subjects were assigned to four counterbalanced, randomly ordered night sleep conditions. These four conditions allowed for a time in bed (TIB) of 0, 2, 4 or 8 h, producing a total sleep time of 0, 113, 218 and 427 min, respectively. The ability to sustain wakefulness was measured after the TIB period at 11.00 and 17.00 hours by the MWT. Analysis of variance with repeated measures was used to study the dependence of MWT sleep latencies on the immediately prior TIB period. Both the latency of stage 1 sleep onset and the appearance of slow eye movements reduced significantly with increased sleep loss. The quantitative relationship between the previous total sleep time and the subsequent MWT sleep latencies followed an exponentially decaying function showing a high sensitivity to acute, severe night sleep loss but low sensitivity to less severe sleep restrictions. It is concluded that the MWT seems to be a sensitive method for the estimation of acute sleep deprivation. The test results appear, however, non-linearly related to the earlier sleep debt.

The detection of drowsiness and sleep onset periods from ambulatory recorded polygraphic data.

A 30 min sample recording at the sleep onset of 7 healthy male subjects was used to further develop a computer-scoring algorithm applied earlier for the analysis of MSLT recordings. The performance of this algorithm was tested on 7 patients with obstructive sleep apnea by using 6 h daytime recordings including drowsiness and sleep episodes. The total epoch-by-epoch agreement between visual and computer scoring was over 90% and the accurate detection rate of non-REM sleep was 64%. The hypnograms produced by the computer scoring corresponded sufficiently to those obtained by visual scoring. Our automatic scoring system can give a good estimation of the daytime vigilance profile but for clinical diagnosis the results have to be verified visually. However, by using modern digital recording, analyzing and scoring techniques the speed of analysis and thus the costs can markedly been reduced as compared to traditional visual analysis.

Distributed clinical neurophysiology.

We have developed a consultation forum for clinical neurophysiology in Finland. The system connects local digital electroencephalography (EEG) recording and analysing networks using a high-speed asynchronous transfer mode (ATM) network. Clinicians can obtain a second opinion using interactive data and video consultations or using data-only consultations. In addition, the system can be used for off-line review of pre-recorded data. During a one-month evaluation, 66 EEG recordings were made altogether in Satakunta Central Hospital and consultations were required on 12 occasions. Nine of them were data-only consultations and three were data and video consultations. A data consultation lasted 15-20 min and a data and video consultation 35-45 min. Clinically, there were numerous benefits for the hospitals. The system established a link to a centre of excellence for second opinions or continuing education. It also helped with on-duty arrangements and enabled the construction of national data banks.

Nonlinear eye movement detection method for drowsiness studies.

Automatic long-term vigilance analysis systems require information about the occurrence and type of eye movements, in addition to information about other physiological signals. This paper presents a method to detect different types of eye movements in ambulatory recordings. The method is based on the application of a weighted FIR-median-hybrid filter in the preprocessing of the signal and on the novel use of linear correlation between two EOG signals which are obtained using a new, improved electrode montage. The evaluation of the method showed that it performed well in detecting isolated unambiguous eye movements, but differences were observed in comparison to visual scoring in borderline cases. The method was found to be suitable for use as part of a signal analysis system for drowsiness studies.

Multi-centre comparison of five eye movement detection algorithms.

Although various investigators have suggested algorithms for the automatic detection of eye movements during sleep, objective comparisons of the proposed methods have previously been difficult due to different recording arrangements of different investigators. In this study the results of five eye movement detection algorithms applied to the same data were compared to visually scored data. The percentages of true and false detections are given for various threshold levels in rapid and slow eye movement detections. The methods gave best results when they were used with the same electrode montage they were designed for but the performance decreased when other montages were used. Subtracting the cross-talk of EEG delta activity improved the correctness of eye movement detections.

Metabolic polymorphism affecting DNA binding and excretion of carcinogens in humans.

A case-control study on lung cancer patients demonstrated the pronounced effect of tobacco smoke on pulmonary carcinogen metabolism and suggested the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer. Lung cancer patients who were recent smokers showed in their lungs (i) significantly induced CYP1A1-related enzyme activity vs smoking non-lung cancer patients; (ii) increased benzo(a)pyrene (BP) tetrol formation from BP 7,8-diol by lung microsomes; and (iii) high levels of cytochrome P4501a1 by immunohistochemical staining. Levels of bulky aromatic DNA adducts (by 32P-postlabelling) and of BP-diol-epoxide (BPDE) adducts (by HPC/fluorometry) were quantified in lung parenchyma. Aryl hydrocarbon hydroxylase activity and the level of BPDE-DNA adducts (r = 0.91; p < 0.001) and to a lesser degree bulky DNA adducts were correlated. Thus pulmonary CYP1A1 expression (inducibility) controls in part polycyclic aromatic hydrocarbon-DNA adduct formation in tobacco smokers and, therefore, appears to be associated with lung cancer risk. High risk subjects for lung cancer among smokers may be identifiable through genotyping for polymorphic drug metabolizing enzymes in combination with molecular dosimetry of carcinogen-DNA adducts and mutation analysis in target (surrogate) cells. Such studies in a Finnish cohort of lung cancer patients and controls are in progress. Interim results of the effect of metabolic polymorphism on the level of PAH-DNA adducts and on the excretion of mutagens in urine are summarized.

Adaptation of the troponin T ELISA test to a microplate immunoassay reader.

Troponin T concentration in serum is usually measured by the automated method developed by Boehringer Mannheim for the ES-series of analysers. These instruments need at least 140 microliters of serum and 700 microliters of reagents for a single analysis, which takes 90 min. We describe an alternative procedure, using streptavidin-coated microtitre plates, troponin T reagents of Boehringer Mannheim and an ELISA-reader to measure the concentration of troponin T. The present assay needs only 30 microliters of sample and 200 microliters of reagents, and it takes 75 min; the detection limit is 0.10 microgram/l. We also assessed the microtitre plate method for sensitivity and precision and compared the results with those measured by an ES-300 automatic analyser. Both methods have the same measurement range for troponin T of 0.1 to 15 micrograms/l. For daily routine use of the microtitre plate method we recommend duplicate determinations.

Validation of computer analysed polygraphic patterns during drowsiness and sleep onset.

A computer system for the automatic analysis of polygraphic records was validated. Records from 9 subjects made during routine MSLT tests were analysed both by two preliminary and one consensus scorer and by a computer system. Special attention was paid to the analysis of drowsiness periods. Therefore a classification system including 7 stages, three for wakefulness and movement, one for drowsiness and three for the sleep stages S1, S2 and SREM was used. Adaptive segmentation was used to divide the records into short segments of variable length (mean 1.6 sec, range 0.5-13.7 sec). The agreements between the computer and visual scores were relatively good for 5 subjects having a prominent occipital alpha activity during wakefulness (range 70-79%) but less promising (range 64-70%) for the other 4 subjects with "poor" occipital alpha activity. The values obtained corresponded to the inter-scorer agreements. Most of the discrepancies were between adjacent stages. At times in the presence of strongly fluctuating EEG amplitudes and especially with the "low-alpha" subjects it was very difficult to determine exactly even by visual scoring when, for instance, drowsiness became sleep. It is concluded that the reliability of the system is sufficient for practical purposes especially if critical parts of the records are visually reexamined. It was found to be difficult to define unambiguous scoring criteria for subjects with poorly defined EEG rhythms giving insufficient landmarks for stage determination.

The effect of small differences in electrode position on EOG signals: application to vigilance studies.

The primary aim of the study was to determine the best electrode positions for EOG signals in vigilance studies. Two-channel recordings were conducted in analogy to the Rechtschaffen and Kales (1968) system. Twenty electrodes (10 electrode pairs) were compared. Both EOG amplitudes and amplitude asymmetries within an electrode pair were studied. The amplitude of the EOG signal is sensitive to relatively small differences in electrode position. This concerns especially distance from the eye, the direction of eye movement and the effect of the upper eye lid movement. Larger and more symmetrical EOG amplitudes were obtained for different eye movements by placing the electrodes more medially than in the conventionally used system. EOG asymmetry in different electrode positions was dependent on the eye movement direction and even on the starting and end points of a movement with equal angular degrees. Most of the data could be explained by a simple monopolar model when combined with the effects of the upper eye lid movements. The most unexpected finding was that the EOG amplitudes of the horizontal and oblique eye movements were significantly larger when the eyes were moving towards an electrode than when they were moving to the opposite direction.

A computerized analysis system for vigilance studies.

A digital signal analysis system for vigilance studies is presented. The analysis is based on adaptive segmentation, band pass filtering, nonlinear eye movement detection and rule-based decision making. A preliminary evaluation of seven subjects falling asleep showed that the system is able to detect small vigilance fluctuations reliably.