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PubMed1994

In vitro radiation sensitivity of the LNCaP prostatic tumor cell line.

Because there is extremely limited information on the intrinsic radiosensitivity of human prostatic cancer cells, we have investigated the in vitro radiation response of exponentially growing LNCaP cells. Due to the very poor colony-forming potential of the LNCaP cells, radiation survival was investigated using the dose-dependent (0-6 Gy) changes seen after X-irradiation in the shapes of regrowth curves. Survival was described using both the single-hit, multitarget (SHMT) equation and the linear-quadratic (LQ) equation. The values and 95% confidence limits of the extrapolation number (n), quasi-threshold dose (Dq), and mean lethal dose (D(o)) in SHMT terminology were respectively: 0.9 (0.7-1.0), 0.0 Gy, and 1.39 (0.11) Gy. The LQ alpha and beta parameters were respectively 6.80 (1.13) and -0.53 (2.89). The X-ray dose response of the LNCaP line is, therefore, purely exponential. The mean survival at the clinically relevant dose of 2 Gy (S2) was 51.2% for the LNCaP line. Comparison of the S2 value for the LNCaP line with previous investigations with other human prostatic cancer cell lines (DU145 and PC-3) indicates a mean S2 value of 47.6%, which suggests that human prostate cancer cells might lie toward the resistant side of the spectrum for various classes of human neoplasms.

Cell Survival↗
PubMed2005

Detection of lactate threshold by including haemodynamic and oxygen extraction data.

To date, few attempts have been made to correlate cardiovascular variables to lactate threshold (L(T)). This study was designed to determine the relationship between the accumulation of blood lactate and several haemodynamic variables during exercise. Eight male volunteer cyclists performed an incremental test on an electromagnetically braked cycle-ergometer consisting of a 50 W linear increase in workload every 3 min up to exhaustion. Blood lactate was measured with a portable analyser during each exercise step. Oxygen consumption (VO(2)) and pulmonary ventilation were measured by means of a mass spectrometer while heart rate, stroke volume and cardiac output (CO) were assessed by impedance cardiography. The arterio-venous oxygen difference (A-V O(2) Diff) was obtained by dividing VO(2) by CO. By applying the D(max) mathematical method, L(T) and thresholds of ventilatory and haemodynamic parameters were calculated. The Bland and Altman statistics used to assess agreement between two methods of measurement were applied in order to evaluate the agreement between L(T) and thresholds derived from ventilatory and haemodynamic data. The main result was that most of the haemodynamic variables did not provide thresholds which could be used interchangeably with L(T). Only the threshold of A-V O(2) Diff showed mean values that were no different compared to L(T) together with limits of agreement that were not very wide between thresholds (below +/-25%). Hence of the haemodynamic parameters, A-V O(2) Diff appears to be the one most closely coupled with lactate accumulation and consequently it is also the most suitable for non-invasive calculation of the L(T).

Adult↗
PubMedDate not supplied

Long-term audiometric follow-up of click-evoked auditory brainstem response in hearing-impaired infants.

Conventional pure-tone thresholds were collected as determined at ages between 4 and 8 years from a group of 163 infants, tested by auditory brainstem response (ABR) in the age range between 1 and 3 years old for objective hearing assessment. The subjects suffered from a variety of degrees and types of sensorineural hearing impairment. The prognostic value of the ABR peak V thresholds in response to 0.1 ms clicks with respect to the behavioural thresholds at octave frequencies from 125 to 8,000 Hz obtained later is evaluated. Correlation between ABR and behavioural thresholds is largest in the 1,000- to 8,000-Hz frequency range. Predicted pure-tone audiograms (mean and SD) were determined for each 10-dB class of ABR thresholds. SDs are in the order of 15 to 18 dB in the 500- to 4,000-Hz range and slightly higher at adjacent frequencies (i.e., somewhat larger than in comparable adult studies). Mean pure-tone thresholds in the 1,000- to 8,000-Hz frequency range are up to 20 dB worse than ABR thresholds, which is opposite to findings in normally-hearing subjects. Thus, with an increasing degree of sensorineural hearing impairment, pure-tone thresholds increase at a significantly higher rate than ABR thresholds. The observation is explained in terms of reduced temporal integration in cochlear hearing loss. ABR thresholds worse than 80 dB nHL are demonstrated to have very limited predictive value with respect to the amount of residual hearing, not only in the low- but also in the high-frequency range. The presence of otitis media during ABR testing is shown to make estimation errors increase to more than 25 dB (SD).

Acoustic Stimulation↗
PubMed1992

The cell division cycle: a physiologically plausible dynamic model can exhibit chaotic solutions.

A mitotic oscillator with one slowly increasing variable (tau L of the order of hours) and one rapidly increasing variable (tau R of the order of minutes) modulated by a timer (ultradian clock) gives an auto-oscillating solution: cells divide when this relaxation oscillator reaches a critical threshold to initiate a rapid phase of the limit cycle. Increasing values of the velocity constant in the slow equation give quasi-periodic, chaotic and periodic solutions. Thus dispersed and quantized cell cycle times are consequences of a chaotic trajectory and have a purely deterministic basis. This model of the dispersion of cell cycle times contrasts with many previous ones in which cell cycle variability is a consequence of stochastic properties inherent in a sequence of many thousands of reactions or the random nature of a key transition step.

Activity Cycles↗
PubMed2005

Stir bar sorptive extraction for the determination of volatile compounds in oak-aged wines.

Stir bar sorptive extraction (SBSE) followed by a thermal desorption-gas chromatography-mass spectrometry analysis has been optimized for the determination of 13 of the most important oak volatiles in wine samples, all in a single run. The stir bar sorptive extraction method was optimized in terms of temperature, time, pH and NaCl addition, and the best results were obtained after stirring the wine sample with the polydimethylsiloxane stir bar during 90min at room temperature. The addition of sodium chloride did not enhance the volatile extraction. The method proposed showed good linearity over the concentration range tested, with correlation coefficients ranging from 0.92 to 0.99 for all the analytes. The reproducibility and repeatability of the method was estimated between 0.11 and 5.45%. The detection and quantification limits of all analytes were lower than their respective olfactory threshold values, and, most importantly, no artifacts have been observed during the analysis as described in most extractions using other current methodologies.

Flavoring Agents↗
PubMed2006

Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women.

OBJECTIVE: To assess the incidence and consequences of adverse reactions among African HIV-positive pregnant women treated with fixed-dose combinations of a nevirapine-containing antiretroviral (ARV) triple therapy. METHODS: A retrospective analysis of the clinical files of 703 HIV-1-positive pregnant women treated with a nevirapine-containing regimen between May 2002 and July 2004 was conducted. Selection criteria for inclusion in the analysis were: (a) taking ARV for more than 14 days; (b) baseline values of transaminases below the threshold of 2.5 times the upper limit of normal (ULN). The women were on a nevirapine-containing regimen for a median of 127 days [interquartile range (IQR) 86-190 days], starting on average at the 27th week of gestation (standard deviation+/-9.5) and continuing up to a maximum of 6 months after delivery. All women were offered formula milk to feed the babies. Highly active antiretroviral therapy (HAART) was continued beyond 6 months only if the patient qualified on the first visit. The main outcome measures were incidence of hepatotoxicity, skin rashes and Stevens-Johnson syndrome. Multivariate analysis to assess the impact of several factors on the adverse reaction rate was performed. RESULTS: As of 1 August 2004, 554 pregnancies reached term, 96 women were still pregnant, and 53 women dropped out of the programme before giving birth. After 2 months of therapy the percentage of patients with a viral load less than 1000 HIV-1 RNA copies/mL increased to 78.6%; average CD4 cell counts increased from 490 cells/microL before therapy to 630 after therapy. The incidence of grade 3-4 adverse reactions (hepatotoxicity, skin rashes and Stevens-Johnson syndrome) was 6.5, 2.4 and 1.1%, respectively. Five women died during pregnancy (0.88%). Only one of the deaths could be associated with ARV treatment. CONCLUSION: Nevirapine-containing regimens in pregnant woman, at all CD4 cell count levels, appear to be safe in African settings.

Adult↗
PubMed1995

Skin irritation testing in man for hazard assessment--evaluation of four patch systems.

1. The limitations of the Draize rabbit skin irritation test for hazard evaluation for man are widely documented. Nevertheless it remains the prescribed method for determining acute skin irritations hazard. 2. While the use of human testing for risk assessment of irritants is well established, the use of predictive testing in man for hazard identification has not been explored widely, and this is the object of the research programme. 3. The experiment described in this report evaluates the sensitivity of four patch testing systems (Finn chamber, Hill Top patch, Van der Bend chamber, and Webril patch) using a total of six irritant substances. 4. Following preliminary range-finding experiments, test materials were applied to the upper outer arm for up to 4 h. Assessments were performed immediately after patch removal and at 1, 24, 48, and 72 h. 5. Webril and Hill Top patches generated the greatest levels of response, although responses with Finn and Van der Bend were observed. Hill Top patches are recommended for future development work. 6. The use of very small preliminary panels to predict the effects in larger panels using different volunteers was only of limited value as each volunteer was found to have different irritant thresholds.

Acetates↗
PubMed1989

Rotational strength of the femoral neck. Computed tomography in cadavers.

The mean bone density of the femur at different levels was determined by means of quantitative computed tomography (QCT) in 50 pairs of normal cadaveric femora and related to the rotational strength of the femoral neck. All the femora fractured vertically and spirally in the neck. The bone-mass-related measures at different levels were calculated from QCT densities and volumes. Cancellous bone was defined with threshold limits ranging from 50-500 Hounsfield units (HU), and attenuation values exceeding 500 HU were assessed as cortical bone. The recorded QCT mass-related measures of cortical and cancellous bone separately and as total bone masses gave significant right/left correlations. Correlations were found between the ultimate torsional strength of the femoral neck and QCT recordings of bone mass at all the femoral levels. The best correlations were demonstrated between the rotational strength of the femoral neck and the total bone-mass-related measures in the femoral shaft and condylar area. Bone mass of the femur measured by computed tomography may become useful as an index of the mechanical strength of the femoral neck.

Aged↗
PubMedDate not supplied

[Comparison of European standards of swimming pool safety].

European countries follow different procedures to monitor the quality of the water of swimming pools open to the public: some use generally accepted technical standards, some officially recommended guidelines, some rules or regulations by local authorities and some have national laws or regulations. These agree insofar as in every country the water of swimming pools must be disinfected. The microbiological limits are to a certain extent identical with drinking water threshold values, e.g., no faecal coliforms must be present in 100 ml. Other microorganisms as for instance legionellae, staphylococci or Pseudomonas aeruginosa ar not uniformly considered. In all countries the water must be disinfected by chlorination. Big differences exist, however, in respect of the maximum admissible concentrations of free or total chlorine, haloforms and organic carbons. With regard to the common goals, harmonization of the regulations appears possible.

Colony Count, Microbial↗
PubMedDate not supplied

Hemp-seed and olive oils: their stability against oxidation and use in O/W emulsions.

Hemp-seed oil has several positive effects on the skin: thanks to its unsaturated fatty acid (PUFA) content it alleviates skin problems such as dryness and those related to the aging process. We present a comparative study of hemp-seed and olive oils, determining some physicochemical indices and evaluating their stability against oxidation. The peroxide value of hemp-seed oil was below 20, the threshold limit for edible oils. Hemp-seed oil was less stable against peroxidation than olive oil, but MDA and MONO assays showed its stability to be above expectations. The chlorophyll contained in extra virgin olive oil had a higher photostability than that contained in hemp-seed oil, possibly due to the larger amount of antioxidant in the olive oil. A certain amount of Vitamin E was found in hemp-seed oil. Since quality analyses indicated that hemp-seed oil is relatively stable, emulsions were prepared with the two oils, and their stability and rheological characteristics were tested. Some of the resulting gel-emulsions were suitable for spraying on the skin.

Cannabis↗
PubMed1990

[Are legal sanctions for improving traffic safety adequate?].

Referring to the field of traffic legislation the author examines the different possibilities to improve the safety on the road, within the corresponding range of summary offence and criminal law; (1) As far as the rules of conduct are concerned he demands a uniform threshold value of at least 0.8% for blood alcohol within the limits of the German penal code Sections 315 c I, 316. He rejects the plan to introduce a criminal offence of considerable speeding if imminent danger is provoked. (2) On the level of sanctions the traditional measures of traffic legislation are to be supplied sensibly by supplementary training courses concerning alcohol abuse. The legal instruments of (temporary) suspension of a person's driving license on the part of criminal jurisdiction or public authorities ought to be utilized on a larger scale. The (Flensburg) repeated perpetration point system is to be improved with regard to special preventive measures. (3) To increase the risk of being caught the control of the traffic by the police is to be intensified--especially through a larger application of technical means. (4) The extension of the instruments of traffic legislation to immediate measures by the police--preliminary or "mini" suspension of a person's driving license by resort to preventive rights by the police?--meets with constitutional or legal scruples.

Accident Prevention↗
PubMed1989

Predictive value of serum aluminium levels for bone accumulation in haemodialyzed patients.

Uremic patients undergoing long-term dialysis risk accumulating tissue aluminium burdens and developing aluminium-related syndromes, such as dialysis encephalopathy and osteomalacia. A statistical retrospective study on 253 uremic subjects was carried out to verify the predictive value of serum aluminium levels on bone aluminium accumulation. Serum and bone samples collected at the same time were analyzed for aluminium content. Analyses were performed by graphite furnace atomic absorption technique. The results verified bone aluminium concentrations of less than or equal to 60 mg/kg d.w. (dry weight) in 144 patients and greater concentrations in 109 patients. The statistical discriminant analysis showed that serum levels can be predictive in aluminium bone accumulation (lower or greater than 60 mg/kg) with about a 7% margin of error. This value may be further reduced to about 2% if two threshold limits are used (53-81 micrograms/l). The specificity and sensitivity of the test were 89.6% and 83.5%, respectively.

Aluminum↗
PubMed1997

Empirical genomewide significance levels established by whole genome simulations.

The advent of high-resolution genetic maps and semiautomated genotyping technology has opened the way for genome screening in genetically complex traits. Many such screens are now under way, or completed, most using multipoint nonparametric linkage analysis of affected sibling pairs. This type of linkage analysis uses all the available genotype information to calculate the maximum lod score (MLS) value at each point in the genome, and thereby generates MLS profiles along each chromosome. Any positive MLS values indicate potential linkage, but the peaks in these profiles, which may be referred to as "hits," identify the most likely locations of disease susceptibility genes. However, such analysis presents serious problems of multiple testing, and the assessment of the statistical significance of hits has become a contentious issue [Lander and Kruglyak (1995) Nat Genet 11:241-247; Curtis (1996) Nat Genet 12:356-357; Witte et al. (1996) Nat Genet 12:355-356]. Having recently completed a genome screen in multiple sclerosis, we decided to investigate the statistical properties of our study by simulation. We report here in detail the results of this simulation study. Our main conclusion is that, for the particular set of families and markers used in our screen, an MLS of 3.2 carries a genome-wide significance of 5% (that is, there is a 5% probability of observing at least one false hit, above this threshold in a complete genome screen). This value is closer to the familiar limit of 3.0, originally suggested by Morton [1955; Am J Hum Genet 7:277-318] than to the more stringent limit of 4.0 recently proposed by Lander and Kruglyak [1995; Nat Genet 11:241-247]. This is somewhat reassuring, in view of the very large sample sizes that would be necessary to achieve adequate power to detect linkage at the more stringent threshold.

Female↗
PubMed2000

Relationship between early post-mortem muscle pH and shortening-induced toughness in the Pectoralis major muscle of processed broilers air-chilled at 0 degrees C and -12 degrees C.

1. An experiment was conducted to investigate the development of shortening-induced toughness in the Pectoralis major (PM) muscles of commercially processed broilers, air-chilled at 0 degrees C and -12 degrees C, as a function of muscle pH early post-mortem. Electrical stimulation was used immediately after stunning and neck cutting to provide carcases with pH values 15 min post-mortem (pH15 min) ranging between 6.79 and 5.85. 2. The deep PM muscle temperatures of carcases chilled at -12 degrees C were lower (cooler) after primary chilling and at 215 min post-mortem than those chilled at 0 degrees C, although chilling regimen had no major effect on pH values over the 24 h post-mortem period. However, carcases chilled at -12 degrees C had longer sarcomeres, lower cooking losses and lower shear force values than those chilled at 0 degrees C. 3. Correlation analysis of the results for both chilling regimens clearly demonstrated that over the pH15min range 6.79 to 5.85, carcases with the lowest pH15min values had the shortest sarcomeres, the highest cooking losses and the toughest meat. In addition, there was no evidence to support the occurrence of cold shortening within this population. This suggests that an early onset of rigor at higher temperatures in broiler carcases, as well as inducing rigor shortening and toughness, might also induce greater protein denaturation and subsequent loss of water holding capacity as manifested in increased cooking losses. 4. Quadratic regression curves showed that over the pH15min range 6.80 to 6.30, only the fast chilling regimen at -12 degrees C could inhibit rigor shortening and minimise changes in cooking loss and shear force values. However, neither chilling regimen was effective in preventing severe rigor shortening, increased cooking losses and adverse toughness in carcases with pH15min values below 6.30. 5. The benefits of fast chilling carcases with pH15min values above 6.3 can also be quantified in terms of carcases exceeding a 4.00 kg/cm2 toughness threshold. Only 1.9% of these carcases chilled at -12 degrees C exceeded this limit (maximum shear force value of 4.72 kg/cm2) compared to 34.9% of the carcases chilled at 0 degrees C (maximum shear force value of 8.46 kg/cm2), further emphasising the considerable reduction in textural variability and improvement in tenderness gained by fast air-chilling at -12 degrees C.

Animals↗
PubMed1998

Tuning bandwidths for near-threshold stimuli in area MT.

It is not known whether psychophysical performance depends primarily on small numbers of neurons optimally tuned to specific visual stimuli, or on larger populations of neurons that vary widely in their properties. Tuning bandwidths of single cells can provide important insight into this issue, yet most bandwidth measurements have been made using suprathreshold visual stimuli, whereas psychophysical measurements are frequently obtained near threshold. We therefore examined the directional tuning of cells in the middle temporal area (MT, or V5) using perithreshold, stochastic motion stimuli that we have employed extensively in combined psychophysical and physiological studies. The strength of the motion signal (coherence) in these displays can be varied independently of its direction. For each MT neuron, we characterized the directional bandwidth by fitting Gaussian functions to directional tuning data obtained at each of several motion coherences. Directional bandwidth increased modestly as the coherence of the stimulus was reduced. We then assessed the ability of MT neurons to discriminate opposed directions of motion along six equally spaced axes of motion spanning 180 degrees. A signal detection analysis yielded neurometric functions for each axis of motion, from which neural thresholds could be extracted. Neural thresholds remained surprisingly low as the axis of motion diverged from the neuron's preferred-null axis, forming a plateau of high to medium sensitivity that extended approximately 45 degrees on either side of the preferred-null axis. We conclude that directional tuning remains broad in MT when motion signals are reduced to near-threshold values. Thus directional information is widely distributed in MT, even near the limits of psychophysical performance. These observations support models in which relatively large numbers of signals are pooled to inform psychophysical decisions.

Animals↗
PubMed1999

Global spatial normalization of human brain using convex hulls.

UNLABELLED: Global spatial normalization transforms a brain image so that its principal global spatial features (position, orientation and dimensions) match those of a standard or atlas brain, supporting consistent analysis and referencing of brain locations. The convex hull (CH), derived from the brain's surface, was selected as the basis for automating and standardizing global spatial normalization. The accuracy and precision of CH global spatial normalization of PET and MR brain images were evaluated in normal human subjects. METHODS: Software was developed to extract CHs of brain surfaces from tomographic brain images. Pelizzari's hat-to-head least-square-error surface-fitting method was modified to fit individual CHs (hats) to a template CH (head) and calculate a nine-parameter coordinate transformation to perform spatial normalization. A template CH was refined using MR images from 12 subjects to optimize global spatial feature conformance to the 1988 Talairach Atlas brain. The template was tested in 12 additional subjects. Three major performance characteristics were evaluated: (a) quality of spatial normalization with anatomical MR images, (b) optimal threshold for PET and (c) quality of spatial normalization for functional PET images. RESULTS: As a surface model of the human brain, the CH was shown to be highly consistent across subjects and imaging modalities. In MR images (n = 24), mean errors for anterior and posterior commissures generally were <1 mm, with SDs < 1.5 mm. Mean brain-dimension errors generally were <1.3 mm, and bounding limits were within 1-2 mm of the Talairach Atlas values. The optimal threshold for defining brain boundaries in both 18F-fluorodeoxyglucose (n = 8) and 15O-water (n = 12) PET images was 40% of the brain maximum value. The accuracy of global spatial normalization of PET images was shown to be similar to that of MR images. CONCLUSION: The global features of CH-spatially normalized brain images (position, orientation and size) were consistently transformed to match the Talairach Atlas in both MR and PET images. The CH method supports intermodality and intersubject global spatial normalization of tomographic brain images.

Adult↗
PubMed1994

Threshold and limits of magnetic field action at the presynaptic membrane.

The relationship of field intensity and exposure duration to the inhibitory effect of static magnetic fields on presynaptic membrane function was examined in order to further define the mechanism of action of these fields. Miniature endplate potentials (MEPPs) were recorded from the isolated murine neuromuscular junction, maintained at a temperature of 35.5 degrees C, during exposure to static magnetic fields of varying duration and intensity. Inhibition of MEPP generation correlated well with the product of the square of the flux density and exposure time. At lower product values the relationship was linear with an absolute flux density threshold of 37.9 mT. Higher product values were associated with deviation from linearity indicative of a limit on the extent of inhibition. These findings are consistent with the hypothesis that static magnetic fields induce a reorientation of diamagnetic molecular domains within the membrane but with a restriction on the degree of reorientation imposed by the membrane's cytoskeleton.

Acetylcholine↗
PubMed1995

Application of cross-correlation function in the evaluation of objective MLR thresholds in the low and middle frequencies.

In this study, the cross-correlation function was applied in the evaluation of MLR thresholds in the low and middle frequencies. The parameters of the cross-correlation function consist of the correlation coefficient at a lag-time of zero (RO), the maximum correlation coefficient (RM), and the latency delay on the lag-time axis at the point of the maximum correlation coefficient (DL). The normal limits of the parameters of cross-correlation at the MLR threshold level, which was identified by visual detection across frequencies, were obtained in normal-hearing and hearing-impaired subjects. The cross-correlation functions for two traces were also performed below threshold level. All cross-correlation parameters (RO, RM and DL) below threshold level were outside normal limits in 91% of all the subjects. The incidence of the only RM or DL parameter value within normal limits was 6% or 3% of all cases at the subthreshold level. Correlation data allow precise measurements of the MLR threshold and enhance the sensitivity of the definition of the MLR threshold. In addition, our study provides quantifiable information for estimating MLR threshold.

Adult↗