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[How badly does the "normal-hearing" young man of 1992 hear in the high frequency range?].

In the course of a clinical study we examined young men believed to have normal hearing. Volunteers with a positive history for noise deafness were excluded from further study. Normal hearing was verified by pure-tone audiometry if the hearing loss did not exceed 15 dB for each test tone between 250 Hz and 8000 Hz. As this limit is far below normative threshold values (DIN ISO 7029) we expected to find a large number of otological normal subjects. Using pure-tone audiometry, ABR and noise exposure, we found that 65% of the young male volunteers (mean age 25 years) did not meet the criteria for audiologic normality. The pure-tone thresholds for these subjects were comparable to the expected levels of their fathers' generation.

Adult↗

Accuracy of breath-by-breath analysis of flow-volume loop in identifying sleep-induced flow-limited breathing cycles in sleep apnoea-hypopnoea syndrome.

1. Inspiratory flow limitation is involved in the pathophysiology of sleep-related breathing disorders. Since the definition of flow-limited cycle is based on a dissociation between flow and respiratory efforts, identification of inspiratory flow limitation requires upper airway or intrathoracic pressure measurements. We examined the accuracy of the analysis of the flow-volume loop of a tidal breath in identifying inspiratory flow limitation during sleep in ten patients with a sleep apnoea-hypopnoea syndrome. 2. Measurements were taken during continuous positive airway pressure trials. After data acquisition, the presence of inspiratory flow limitation was identified by the presence of an inspiratory plateau or decrease in inspiratory flow independently of the increase in inspiratory efforts. The flow-volume loop was reconstructed for each breathing cycle by plotting the instantaneous flow and the tidal volume. The instantaneous inspiratory and expiratory flows were measured at 50% of the respective portion of the tidal volume, and a breath-by-breath analysis of the mid-tidal volume-flow ratio (inspiratory/expiratory ratio) was obtained. The analysis of the flow-volume loop was compared with standard inspiratory flow limitation criteria using different values of the inspiratory/expiratory ratio threshold, below which breathing cycles were classified as flow-limited. With a lower limit of the normal inspiratory/expiratory ratio threshold of 0.97, the sensitivity and specificity of the method were both 76%. In each subject, the proportion of breathing cycles identified as flow-progressively decreased with an increasing positive pressure level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fluoride intake and fractional urinary fluoride excretion of Colombian preschool children.

AIMS: The purpose of this study was to assess the total fluoride intake and the fractional urinary fluoride excretion (FUFE) relative to the customary daily fluoride (F) ingestion in preschool children between 48-59 months of age. DESIGN: Total fluoride ingestion, from dietary and toothpaste samples was determined in 120 young children, dwellers of four Colombian cities. A "duplicate plate" technique was used. In Colombia, table salt is fluoridated to a concentration of between 180-220 mg F/kg. Individual (n=96) FUFE values were calculated as the ratio between the total amount of F excreted in the urine and the total amount of F ingested, over a 24-hour period. RESULTS: The average daily F-intake was 0.098 mg F/kg/day; 95% C.I. = 0.085-0.111 mg F/kg/day. The proportion of fluoride ingestion from toothpaste to the total fluoride intake was higher than 66% in all cities. The average FUFE values of subjects from each of the four Colombian cities under study did not differ significantly (ANOVA; p >0.91). The average 24-hour FUFE value for preschool children was 0.33; 95% C.I. = 0.29-0.37. CONCLUSIONS: The results obtained suggest that preschool children residing in Colombian urban areas are ingesting amounts of fluoride above the upper limit of the proposed safe threshold. FUFE values are similar to those reported in previous studies where daily F-doses were equal or higher than 0.064 mg F/kg.

Beverages↗

Penile thermal sensation.

PURPOSE: To our knowledge no direct measurement of autonomic failure in the penis is currently available. Indirect techniques in clinical use, such as bulbocavernosus reflex, genital somatosensory evoked potentials and biothesiometry, all rely on large nerve fiber function. Since micturition and potency depend on small fibers of the peripheral system, tests of these fibers might be more relevant in the clinical diagnostic evaluation. We provide upper normal limits and demonstrate repeatability of small fiber mediated sensations of warm and cold sensory thresholds on penile skin. MATERIALS AND METHODS: Penile warm and cold sensory thresholds were measured in 35 healthy volunteers (at 2 sessions in 27) via 2 methods. RESULTS: Upper normal values, expressed as 95% confidence limits for warm and cold thresholds, through methods of limits and levels as well as inter-session repeatability are given. CONCLUSIONS: Penile thermal thresholds are repeatable and can be used as a valid diagnostic tool to assess somatic small fiber function in patients with lower urinary tract disorders.

Adult↗

Multiple session experimental pain measurement.

Experimental heat pain transients were administered to 30 normal volunteers over four weekly sessions, measuring both heat pain (HP) threshold and suprathreshold magnitude estimation through VAS. Repeatability and bias for these two factors were evaluated. Heat pain thresholds measured through the method of limits were previously shown to have inter-session bias, presumably due to a practice effect. Existence of such a bias between first and second measurement sessions casts doubt on the usefulness of this parameter for pain assessment of individuals over time. In the present study, measurements of normal HP thresholds over four sessions showed that bias exists between the first and successive sessions, but not among sessions other than the first. It is concluded that (i) HP thresholds obtained from a single session are of limited value, and should be carefully interpreted. (ii) Long-term studies that use the HP threshold should take results from the second (or later) session as their baseline. The Visual Analog Scale (VAS) is considered the 'gold standard' for assessment of clinical and suprathreshold experimental pain, and changes in VAS score are regarded as significant evidence of individual response to treatment, placebo, or experimental manipulation. Although its overall group accuracy and precision have been examined for both clinical and experimental pain, and found adequate (Price 1988), the VAS has not been rigorously assessed for repeatability. Stimuli at three pain levels, 1.5, 3 and 4.5 degrees C above each individual's heat pain threshold as determined at each session, were given. Several models of analysis of the VAS were tested and repeatabilities (r) obtained from these analyses demonstrate poor precision for each of the tested analysis models. For example, inter-session repeatabilities for the three individual pain levels ranged from r = 3.8-4.7, effectively providing a confidence interval of 7.6-9.4 for any VAS reading on a 0- to 10-point scale. An examination of intra-session VAS provided somewhat better results. Thus, use of the VAS in similar experimental settings is called into question. The use of the VAS in clinical settings, where individual assessments are necessary, is also called into question, but remains to be specifically tested.

Adolescent↗

Attenuation correction reveals gender-related differences in the normal values of transient ischemic dilation index in rest-exercise stress sestamibi myocardial perfusion imaging.

BACKGROUND: Transient ischemic dilation (TID) has been established as an important independent marker of severe and extensive coronary artery disease (CAD) in myocardial perfusion imaging (MPI). The accuracy of the TID index is dependent on a well-determined threshold (normal limits) between normal and abnormal values for each study protocol. To date, the effects of neither gender nor attenuation correction (AC) on TID normal limits have been established. Thus, the objectives of this study were to determine if AC processing changes the normal value of the TID index and if there were gender-related differences in the TID index of normal patients who had undergone rest/exercise-stress technetium-99m sestamibi MPI. METHODS AND RESULTS: Seventy-five patients (33 women, 42 men; mean age, 57.7 +/- 11.7 y and 55.9 +/- 10.0 y, respectively) with less than a 5% likelihood of CAD, who had undergone low-dose rest/high-dose exercise-stress Tc-99m sestamibi MPI, were studied. All studies were acquired using simultaneous emission/transmission scans and were corrected for attenuation, scatter, and resolution effects using the ExSPECT II method. Both the AC and non-AC studies were analyzed using the Emory Cardiac Toolbox (ECTb; Syntermed, Inc, Atlanta, Ga) quantitative software. The TID index was calculated automatically as the ratio of stress mean left ventricular volumes to rest mean left ventricular volumes by ECTb. Patients were grouped by gender and the TID indices from AC and non-AC studies were compared. Linear regressions of the TID index and body mass index were analyzed to exclude differences in body size between male and female patients as a confounding factor in gender-related differences in TID. The TID index upper normal limits were calculated as the mean value plus 2 standard deviations (SDs). AC processing did not change the TID index significantly whether the genders were combined or separated (AC TID = 0.97 +/- 0.14 vs non-AC TID = 0.98 +/- 0.12 for all patients). Female patients showed higher mean TID indices than male patients in both AC (1.01 +/- 0.15 vs 0.95 +/- 0.12) and non-AC studies (1.00 +/- 0.15 vs. 0.97 +/- 0.10), but this difference was statistically significant only in AC studies (p = .03). TID indices remained constant across the range of body mass index studied. The TID index upper normal limit was 1.31 for female and 1.18 for male patients. CONCLUSION: TID normal values for rest/exercise-stress Tc-99m sestamibi MPI are gender-dependent and not affected by AC processing. Thus, diagnosticians should take into account these gender-related differences, as compared with the traditional value generated from mostly male populations, to ensure both men and women have the same overall accuracy of using the TID index in the diagnosis and prognosis of CAD.

Adult↗

[Can exposure to low doses have effects?].

This paper aims to discuss the scientific evidence to answer the question in the title. After a brief mention of the fundamental toxicological principles of risk assessment (hazard, exposure, susceptibility, risk), the concepts of dose-response, dose-effect and threshold-dose are presented. The difference between adverse effects with and those without a threshold is highlighted, together with the corresponding methodologies used in risk assessment for the definition of the limit values, i.e. the No Observed Adverse Effect Level (NOAEL) and Safety Factor (SF) method and the Virtually Safe Dose (VSD) method. The two methods correspond to two different types of effect, i.e. deterministic and stochastic, and to two different shapes of the dose-response curve at low doses. The various possible meanings (semantic, toxicological and practical) of the terms "low doses" are discussed: a dose (or concentration) may be low because it does not cause measurable adverse effects (as from Paracelsus' aphorism) or because it is too low to be (analytically) measurable or because it is close to or within the "normal" values of a reference population or because it is well below the exposure limit(s). These various concepts are presented also in relation with the controversial concept of "moderate risk" introduced by a recent Italian legislation (D. Lgs 25/02) on the protection of the workers against chemical risk. It would not be appropriate to set a level of risk simply based on the dose (or the level of exposure) without considering the two other components of risk, i.e. hazard and susceptibility, whose estimation also needs a careful and competent evaluation by the occupational physician. For a thorough discussion of the "moderate risk" concept see a specific paper in these Proceedings. So, clinical, epidemiological and toxicological evidence indicates that in some individuals, groups of the population or circumstances, adverse effects can be observed or expected even at low doses, at which the large majority of the population shows no effect. This is due to a number of factors including toxicological interactions, immunoallergic mechanisms, metabolic hypersusceptibility, both genetic (polymorphism) and acquired (phenotype), preexisting traits or diseases, living habits, diet and others. The Authors conclude therefore that to ensure the protection of all the workers' health and safety, the clinical, toxicological and epidemiological expertise of the occupational physician appears to be fundamental and unreplacable.

Dose-Response Relationship, Drug↗

Frequency doubling technology perimetry in normal children.

PURPOSE: To test visual field thresholds of normal children with frequency doubling technology (FDT) perimetry to quantify testing times and reliability characteristics in a pediatric population and to determine whether current methods of stratifying adult threshold values need revision for children. DESIGN: Prospective cross-sectional study. METHODS: Ninety-four children, ages 5 to 17 years, were recruited from local pediatric clinics and the general community and were tested at one center. Children likely to have abnormal visual fields or abnormal test taking ability because of ophthalmic, neurologic, or behavioral problems were excluded. Children were asked to perform a threshold FDT visual field with each of their eyes. Threshold results were gathered, analyzed, and compared with the standards that have been established for tests in adults. Results were validated by testing a further 72 children, with the same protocol, at a different center. RESULTS: For children older than 14 years, threshold mean deviation values were within normal limits according to the adult normative database that is used currently in FDT perimetry. Below 15 years of age, mean deviations for normal children decreased with decreasing age. The best linear fit was given by a mean deviation of -11.43 +/- 0.82 dB x age (R2 = 0.18; P < 10(-5)). CONCLUSION: This research establishes a normative model for pediatric visual field testing with FDT and, by a comparison of threshold results for normal children to established adult norms, provides evidence that parameters for normal sensitivity must be revised for children younger than 15 years.

Adolescent↗

Effect of analytical variability on measurements of population blood lead levels.

The effect of analytical error on the interpretation of blood lead data obtained from population studies is discussed. Statistical analysis of measured blood lead values reported in four representative population studies shows over 40 percent of the variability in blood lead measurements is due to analytical error. Because of this analytical error, a large percentage of the observed lead measurements which exceed a threshold limit are "false positives" in that the true blood lead values for these individuals do not exceed the threshold. The EPA has suggested that the distribution of blood lead values could be used as a guide for determining the portion of a population at risk. "At risk" is defined as having blood lead values above a certain threshold. If this is done, the effect of analytical error which causes "false positives" should be considered properly to obtain an accurate estimate of the population at risk.

Analysis of Variance↗

Relationship of cyclic AMP binding capacity and estrogen receptor to hormone sensitivity in human breast cancer.

Estrogen receptor (ER) and total binding capacity for cyclic AMP (cAR) were measured in cytosols from human mammary tumors. Patients with advanced, evaluable breast cancer were biopsied before the start of endocrine treatment, and ER and cAR measurements were performed. All patients included in this study were ER positive. Sixteen of 30 patients (53%) had an objective response to endocrine treatment. When ER and cAR were expressed as a ratio and this ratio was related to treatment response, it was found that all objective responders had ratio values above 2.5 X 10(-3). Nine of 14 nonresponders had ER/cAR ratios below this value. In our limited series of patients a threshold limit of 2.5 X 10(-3) would have correctly predicted the response to endocrine treatment in 25 of 30 patients (83%). In patients with ER values below 100 fmol/mg protein and PgR negative or unknown, cAR might strengthen the predictive value of steroid receptor measurements.

Adult↗

Amylase, lipase, pancreatic isoamylase, and phospholipase A in diagnosis of acute pancreatitis.

To determine the utility of serum amylase (AMY), lipase (Lp), pancreatic isoamylase (isoA), phospholipase A (PLA), and urine AMY in the diagnosis of acute pancreatitis, samples of serum and urine were obtained on admission and every day thereafter for 5 days from 384 patients with acute abdominal pain. Diagnostic accuracy, determined as the area under the receiver operating characteristic curve, was > 0.975 for serum AMY, Lp, isoA, and urine AMY. For each of these enzymes, a threshold value (twice to sixfold the upper limit of the reference values) offering diagnostic efficiency > 95% could be determined. In contrast, accuracy and efficiency of serum PLA were low. The profiles of these enzymes in acute pancreatitis decreased in a parallel fashion over 5 days except for PLA. We conclude that diagnostic utilities are similar for serum AMY, Lp, isoA, and urine AMY for acute pancreatitis, provided that an appropriate threshold is established.

Acute Disease↗

Quantitative estimation of aesthesiometric thresholds for assessing impaired tactile sensation in workers exposed to vibration.

To evaluate the usefulness of aesthesiometric threshold testing in the quantitative assessment of peripheral sensorineural disorders occurring in the hand-arm vibration syndrome, two point discrimination (TPD) and depth sense perception (DSP) thresholds were measured by means of two aesthesiometers in the fingertips of 65 forestry workers exposed to chain saw vibration and 91 healthy males unexposed to local vibration or neurotoxic chemicals. Among the healthy subjects, divided into three age groups, there was no difference in the mean values of TPD and DSP thresholds. Assuming 1.28 or 2 standard deviations above the mean to be the upper limits of normality, in the present study the threshold values for TPD were 2.5 and 3.13 mm, respectively. Using the same assumptions, the normal threshold values for DSP were 0.36 and 0.49 mm. Among the 65 chain saw operators the prevalence of peripheral sensory disturbances was 70.8%. On the basis of the aesthesiometric results obtained for the group of 46 chain sawyers affected with sensorineural symptoms and a control group of 46 manual workers, the specificity of the aesthesiometric testing method was found to range between 93.4 and 100%, while the sensitivity varied from 52.2 to 71.7%. In its predictive value aesthesiometry had a positive accuracy of 84.6-96.0% and a negative accuracy of 42.8-50.0%. Aesthesiometric testing was able to differentiate between normals and vibration workers with sensory disturbances on a group basis (P less than 0.001), but due to the high rate of false negatives among vibration exposed patients, it was unsuitable to confirm objectively sensorineural symptoms on an individual basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Individual exposure to particulate air pollution and its relevance to thresholds for health effects: a study of traffic wardens.

OBJECTIVE: To investigate the differences between measurements of personal exposure to particulate air pollution and static area measurements in a group of people working close to traffic and to determine whether such differences might obscure any threshold for health effects in epidemiological studies. METHODS: Personal air sampling was carried out on two groups of eight traffic wardens for four days on two consecutive weeks in November 1994. These measurements were compared with standard environmental static sampling data that were obtained for the same period. A simulation with log normal distributions of personal exposures was produced, and an arbitrary risk calculated for each exposure, assuming a threshold of 50 micrograms/m3, and an exposure-response curve was calculated. RESULTS: The median concentration for personal samplers in week 1 was 123 micrograms/m3 and 41 micrograms/m3 in week 2. Corresponding area concentrations were 10 micrograms/m3 and 7.5 micrograms/m3. The differences between the personal and area results were significant, as were the differences for personal sampling between weeks 1 and 2. The simulation showed that the variation in individual exposures around an area sampler obscured the threshold. CONCLUSIONS: Area sampling data may be of limited value in the investigation of the biological effects of exposure to pollution and their use may result in real thresholds being obscured. Personal exposure assessment may be crucial in determination of the health effects attributable to different concentrations of air pollutants.

Adult↗

The correlation between negative middle ear pressure and the corresponding conductive hearing loss in children. A 12-month study of 352 unselected 7-year-old children.

An epidemiological study of negative middle ear pressure in children made it possible to test its relationship to conductive hearing loss. About 350 children were subjected to a screening procedure recording audiogram and middle ear pressure five times during a 12-month period. Those children who failed to perceive just one tone or who had a middle ear pressure equal to or worse than -150 mmH2O in one or both ears were referred to the Hearing Clinic for conventional audiometry and middle ear pressure measurement each month. By computing the weighted average of the regressions for each child, a straight linear relationship was found between negative pressure and conductive hearing loss. In addition, a frequency dependence was found, the hearing loss being maximal at about 500 Hz. In general, the study shows that tympanometry is of limited value in predicting hearing loss in a child. The threshold for pathology of about -150 mmH2O, being a predisposing factor in secretory otitis media, corresponds to the upper confidence limit of the normal range of hearing loss found in this series. There is no distinct value of negative pressure that clearly distinguishes between normal and pathological condition, but it is concluded that a middle ear pressure worse than -150 mmH2O should be considered a probable hearing handicap.

Acoustic Impedance Tests↗

[Annoyance due to street traffic and aircraft noise].

Annoyance is an important criterion to assess the health-impairing effects of noise. Affected are especially communications, due to speech interference, as well as relaxation and sleep. The extent of annoyance increases with rising noise load in the street traffic as well as in the air traffic. Air-traffic noise in residential areas should lie below NNI-values of 35; values of above 45 NNI result in a heavy noise load and require sound-protection measures. Street-traffic noise in residential areas should not surpass an Leq value of 60 dB(A) in daytime and 50 dB(A) at night; Leq values of more than 65 dB(A) are qualified as considerable annoyance and are thus critical. In recreation areas the threshold limits should be 5 dB(A) below these values, whereas for shops and offices at main thoroughfares values higher by 5 dB(A) can be tolerated. The noise load should first of all be diminished by stricter regulations for vehicles as well as by measures regarding traffic organization. Furthermore, noise-conscious driving is recommended. Very great traffic noise also requires sound protection measures.

Aircraft↗

Estimating infant head injury criteria and impact response using crash reconstruction and finite element modeling.

A combination of finite element modeling and sled test reconstruction of real-world infant head injury scenarios has been used to investigate infant head impact response and tolerance to skull fracture. Studying the role of cranial sutures on infant skull response was of particular interest. The specific injury scenarios selected for reconstruction involved infants in rear-facing child restraint systems (CRS) who sustained skull fractures and brain injuries from deploying passenger-side frontal airbags. Approximations of the loading conditions for three injury cases, as well as estimates of loading conditions not expected to result in head injury, were produced in the laboratory. A finite element model (FEM) of a six-month-old infant head was developed using available material properties and humanlike geometry. The infant head FEM was used to simulate different injury and no-injury loading conditions based on CRS response data from the reconstruction tests. Acceleration results and stress distributions are consistent with the level of injury in the different real-world cases. Cranial sutures have a negligible effect on stress distribution in the infant skull. Logistic regression analysis was used to estimate threshold stresses associated with skull fracture. The acceleration responses of the infant head FEM and the CRABI ATD were compared for the no-injury and injury-producing conditions. Results suggest that the biofidelic loading range of the CRABI ATD may be limited to impacts at or below injury-producing loading severities. Provisional injury assessment reference values corresponding to the threshold for minor skull fracture over a limited loading range were estimated for the current CRABI ATD, and recommended improvements for the CRABI ATD head are presented.

Journal Article↗

Requirements for improving quality in the measurement of bone markers.

BACKGROUND: A number of biochemical assays readily detect molecules released from the bone matrix and collagen degradation in both serum and urine specimens. The variability of bone biochemical markers is still an issue of practical concern limiting their wider clinical use, and compromising the management of the individual patient. The aim of the present study was to define quality specifications of bone markers measurement in the total testing process. METHODS: The different sources of biological variability of biochemical bone marker were assessed according to the current knowledge and categorized as pre-analytical, intra-analytical and post-analytical. RESULTS: The identification of factors influencing bone marker measurements allowed recommendations to be made for decreasing pre- and intra-analytical variation in order to improve laboratory performance. The assessment of post-analytical sources of variation, moreover, involves the practical use of bone markers in identifying individual women at risk of fractures and the identification of non-responders, providing adequate limit value, least significant change value or optimal threshold of bone marker change. CONCLUSIONS: Laboratory services may improve the potential clinical applications of biochemical markers of bone remodeling by improving method standardization, defining and reducing pre-analytical and analytical variables and providing reports that specify analytical and biological variation or cut-off values, thus facilitating data interpretation or reports.

Analysis of Variance↗

Gold and palladium burden from dental restoration materials.

From 81 volunteers (16 without dental restorations, 65 with gold crowns or inlays) samples of saliva before and after chewing gum, blood, serum, urine and faeces were taken and analysed for gold (Au) and palladium (Pd). The Au concentration in all analysed biomonitors correlates significantly to the number of teeth with gold restorations. For Pd the correlations were still significant, but weaker than for Au. Persons with gold restorations show maximal Au and Pd concentrations, 10(2)-10(3) higher than the background burden. The calculated maximal daily Au load in saliva (1.38 mg Au per day) reaches the range of an oral Au therapy for rheumatoid arthritis with 6 mg Auranofin (= 1.74 mg Au per day). During this therapy severe and frequent side effects are reported. In contrast, the Au concentration in serum maximally reached from Au restorations, amounts to only approximately 1/20 of the Au level during arthritis therapy. But even under subtherapeutic doses of 1 mg Auranofin/day severe side effects have been reported (4 out of 56 cases). The mean Au blood concentration from 1 mg Auranofin daily was only 3 times higher than our maximum value. A toxicological classification of the Pd values is difficult, because no toxicological threshold limit has been established, especially for the low-level long-term burden with Pd.

Adolescent↗