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PubMed1986

Oscillometry and direct blood pressure: a comparative clinical study during deliberate hypotension.

Oscillometry using an automatic monitor was compared with invasive blood pressure monitoring in 21 patients scheduled for surgery under general anaesthesia with deliberate hypotension. Six ranges of mean blood pressure measurements were studied, two of which were hypotensive. An excellent correlation was found between the two methods (systolic: r = 0.94; mean: r = 0.93; diastolic: r = 0.88) but there was a large variability among individual subjects. For systolic, diastolic and mean intra-arterial readings above an approximative value of 10.64 KPa (80 mmHg), the oscillometric monitor was found to underestimate blood pressure. Inversely, it was found to overestimate blood pressure for intra-arterial readings under the approximative value of 10.8 KPa (80 mmHg). We conclude that the non-invasive monitor represents a good trend estimation of the invasive radial blood pressure technique, but that wide inter-individual variability and the overestimation of blood pressure below an approximative value of 10.64 KPa (80 mmHg) precludes interchange of techniques when absolute values are considered, especially during controlled hypotension. However, oscillometry could represent a better estimate of central aortic pressure.

Adult↗
PubMed2006

Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not.

BACKGROUND: Initiation of phenprocoumon therapy is associated with a variable individual response. The CYP2C9 genotype has been shown to influence the response to warfarin therapy, but such an effect on phenprocoumon therapy remains uncertain. METHOD: Two hundred sixty hospital patients started on phenprocoumon were recruited for this study. Body mass index (BMI), waist and hip circumference, dietary habits, comorbidity, and comedication were initially assessed. A 5' exonuclease assay (TaqManR) was used to analyze the presence of five polymorphisms of the CYP2C9 gene in each of the study patients. Study endpoints included the time necessary to achieve the international normalized ratio (INR) target (INR >2) and the total drug amount required to attain target INR. For 250 of 260 patients, the subsequent required daily maintenance dose of phenprocoumon was also recorded. RESULTS: Both the necessary time and total dose required to attain target INR correlated significantly with BMI. The leaner the patient, the shorter the required time interval [BMI <22 (n=31), 5.48+/-2.49 days; BMI 22-25 (n=70), 6.09+/-2.40; BMI 25-30 (n=113), 6.76+/-3.61; BMI >30 (n=46), 8.50+/-5.75; p=0.001] and the lower the required dosage until the therapeutic range was achieved [BMI <22 (n=31), 23.8+/-12.1 mg; BMI 22-25 (n=70), 25.9+/-11.4 mg; BMI 25-30 (n=113), 29.6+/-25.2; BMI >30 (n=46), 35.8+/-19.7; p=0.027]. Overweight and waist circumference as a surrogate marker for abdominal fat were also associated significantly with these two parameters. Moreover, obesity was associated with a lower body-weight-adjusted maintenance dosage. All CYP2C9 genotypes that were tested failed to reveal an association with individual response variability. CONCLUSION: Patient obesity appears to directly correspond to the amount of phenprocoumon required during initiation of therapy. The CYP2C9 genotype was not shown to influence the necessary therapeutic dosage.

Aged↗
PubMed1989

Noninvasive and angiographic evaluation of coronary artery disease in patients with peripheral vascular disease.

The accuracy of exercise testing for detection of coronary artery disease in a population with a high incidence of claudication was evaluated in 58 consecutive patients with abdominal aortic aneurysms or lower extremity occlusive disease. Each patient was evaluated by history and physical examination, symptom-limited testing with exercise treadmill, arm ergometry and exercise radionuclide ventriculography. An algorithm was designed that retrospectively examined the results of each test in a stepwise fashion to simulate a clinical decision-making process. The results of the clinical examination, each of the exercise tests and the noninvasive diagnostic algorithm were compared with the results of coronary arteriography. The predictive accuracy of the clinical evaluation was 36%, treadmill stress testing 57%, treadmill stress plus arm ergometry 74%, exercise radionuclide ventriculography 57% and the noninvasive diagnostic algorithm 89%. When discriminant analysis was applied to all of the exercise variables, no individual test improved the accuracy of the noninvasive diagnostic algorithm. When the analysis considered only individual variables without the algorithm, the model correctly classified only 67% of the patients. Thus, accurate noninvasive evaluation of coronary artery disease is possible in patients with severe peripheral vascular disease when care is taken to design exercise protocols that allow adequate stress on the cardiovascular system.

Adult↗
PubMed1993

Metabolites of dietary (soya) isoflavones in human urine.

This study was undertaken to better understand the metabolic fate of dietary isoflavones in humans. Twelve volunteers were challenged with soya flour and urinary diphenol levels were then determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The presence of previously described urinary diphenols was confirmed, i.e. the isoflavones, daidzein and genistein; the isoflavonoid metabolites, equol, dihydrodaidzein (Int-O-D), O-desmethyl-angolensin (O-Dma); the lignan, enterolactone. Diphenols detected for the first time were the isoflavone, glycitein and five novel isoflavonoid metabolites which are tentatively identified as 6'-hydroxy-O-desmethylangolensin (6' OH-O-Dma), dihydrogenistein (Int-O-G), dehydro-O-desmethylangolensin (dehydro-O-Dma) and two isomers of tetrahydrodaidzein. Urinary excretion rates of the three isoflavones (daidzein, genistein, glycitein) over a 3-day period following soya challenge showed moderate variation (4x, 6x and 12x, respectively) between the 12 individuals suggesting some individual variabilities in ability to deconjugate and to absorb dietary isoflavones. However, urinary excretion rates of each of three major isoflavonoid metabolites (equol, O-Dma, 6' OH-O-Dma) showed more marked variation (922x, 17x, 15x, respectively); while some of this variability may reflect varying individual ability to ferment dietary isoflavones per se, an inverse relationship was found between urinary levels of equol and both O-Dma and 6' OH-O-Dma suggesting individual variability in the preferred metabolic pathways of dietary isoflavones.

Adult↗
PubMed1993

Characterization of alveolar macrophage eicosanoid production in a non-human primate model of mineral dust exposure.

The relative activation of eicosanoid production which results from the exposure of the alveolar macrophage (AM) to mineral dusts is thought to be a key factor in the pathophysiology of occupational lung disease. We compared in vitro basal and silica-stimulated production of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) by AM from normal humans and non-human primates (Macaca nemestrina). In addition, we instilled mineral dusts directly into one lung of the non-human primate and evaluated AM eicosanoid production at two week intervals following dust instillation. Unstimulated AM from humans produce more PGE2 and TXA2 than do AM from M. nemestrina. However, in vitro exposure of AM from both species to silica dust produced a qualitatively similar increase in TXA2 production accompanied by no change in PGE2 production. Sequential analysis of AM eicosanoid production following a single bolus exposure to bituminous or anthracite coal dusts, titanium dioxide (TiO2) dust or crystalline silica showed marked variability among individual non-human primates in qualitative and quantitative aspects of dust-induced eicosanoid production. However, the rank order of potency of the different dusts (silica > anthracite > bituminous) correlated with epidemiological evidence relating the type of dust mined to the incidence of pneumoconiosis. These studies suggest that the non-human primate may serve as a model for the study of both the role of eicosanoids in the etiology of dust-induced occupational lung disease and the biochemical basis for individual variability in the response of lung cells to mineral dust exposure.

Adult↗
PubMed1992

Radiosensitivity measurement of keratinocytes and fibroblasts from radiotherapy patients.

Genetic diversity is believed to influence cellular radiosensitivity and individual variability in normal tissue reactions to radiotherapy. To measure normal cell radiosensitivity in vitro, we investigated a culture technique that yields keratinocyte and fibroblast cell cultures from small skin biopsy samples (average weight 32 mg). This technique uses 3T3 NIH cells as feeder cells, culture medium containing dialyzed fetal calf serum, low calcium, and various growth factors for keratinocyte growth. A calcium concentration of 4 x 10(-3) M and the use of lethally irradiated NIH 3T3 feeder cells were critical to the success of this method. Primary keratinocyte cultures were successfully obtained from nine biopsy specimens, and radiosensitivity measurements were obtained in six of the resulting strains. Keratinocytes were, in general, more radioresistant than fibroblasts derived from the same specimen. We conclude that radiosensitivity assessment of keratinocyte and fibroblast cultures derived from small punch biopsy specimens is feasible. Further studies can now be carried out to determine the degree of variability between individuals and the relationship between in vitro keratinocyte and fibroblast radiosensitivity and their value in predicting normal tissue responses to radiotherapy.

Cell Survival↗
PubMed2004

Arterial versus venous sampling for activated coagulation time measurements during cardiac surgery: a comparative study.

OBJECTIVE: Activated coagulation times (ACTs) are widely used for monitoring anticoagulation during cardiac surgery. Significant variability of this test is well known. Variability in test results was studied, which may arise from the sample drawing site. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Sixty-five patients scheduled for surgery requiring cardiopulmonary bypass were enrolled in the study. INTERVENTION: ACTs were assessed using the Hemochron 801 ACT machine. Samples were collected (1) baseline I from the arterial catheter before anesthetic induction, (2) baseline II from the arterial and venous collection sites after pulmonary artery catheterization, (3) after heparin administration, (4) 10 minutes after blood collection number 3, and (5) after protamine administration. MEASUREMENTS AND MAIN RESULTS: At the baseline II, the ACT measures using venous blood were significantly higher than that obtained using an arterial sample (p = 0.001). There was no significant difference in ACT measures obtained using either arterial or venous blood samples at the other time points. After heparin administration, the ACT variability in individual patients was quite striking, with ranges of up to 600 seconds in repeated measures. CONCLUSION: During the period of systemic anticoagulation, there is great individual variability between ACT measures obtained from venous and arterial samples. Further studies are required to analyze the cause of differences at the baseline and the source of variable coagulation times after heparin.

Adult↗
PubMed2004

Relationships between rigging set-up, anthropometry, physical capacity, rowing kinematics and rowing performance.

The general aim of this study was to examine the relations between rigging set up, anthropometry, physical capacity, rowing kinematics and rowing performance. Fifteen elite single scullers participated in the experiment. Each sculler's preferred rigging set-up was quantified using measurements that included oar length, inboard, span, gearing ratio, swivel-seat height, footstretcher-seat height and distance, and footstretcher angles. Rowing performance was assessed using 2000 m race times from the Australian National Selection trials. Selected anthropometric, physical capacity and kinematic variables were also quantified. Several rigging variables were significantly correlated with each other, and with various anthropometric, physical capacity and kinematic variables. The individual variables that had the highest correlations with race time were 2 km ergometer time (r=0.90), mass (r=-0.87), height (r=-0.86), oar length (r = -0.85) and strength (r = -0.84). Overall results of this study indicated that the fastest rowers tend to be the largest and strongest, and that these larger body dimensions are reflected in the choice of rigging settings. Rigging set-up by itself should not be considered to be a primary determinant of rowing performance, but rather a consequence of faster rowers being larger and stronger and scaling their rigging set-up accordingly. To maximise rowing performance it appears important to tune the rigging of the boat to match the rower's size and strength.

Adult↗
PubMed2005

Effect of audiometric configuration on threshold and suprathreshold auditory steady-state responses.

OBJECTIVE: The purpose of this study was to examine the correlation between auditory steady-state response (ASSR) thresholds and behavioral thresholds in hearing-impaired adults with two common audiometric configurations. A second goal was to compare suprathreshold ASSR growth functions in these two subject groups and to determine whether these growth functions could be used clinically to improve threshold estimation. DESIGN: Thirty adults participated, including 10 subjects with normal hearing, 10 subjects with flat moderately severe sensorineural hearing loss, and 10 subjects with sloping high-frequency sensorineural hearing loss. The accuracy of ASSR threshold estimations for the frequencies of 500, 1000, 2000, and 4000 Hz was compared across groups. In addition, ASSRs were recorded at multiple suprathreshold intensity levels, and the growth of the response was compared across subject groups. RESULTS: ASSR and behavioral thresholds were strongly correlated across all subjects, with no significant difference by audiometric configuration. Slightly poorer correlations were obtained in the normal-hearing subjects than in hearing-impaired subjects and for the 500-Hz test frequency compared with the higher stimulus frequencies. Subtraction and regression methods for predicting behavioral thresholds from ASSR thresholds were equally accurate. Suprathreshold amplitude growth was variable among individuals, but mean growth functions showed steeper slopes in hearing-impaired subjects than in normal-hearing subjects, particularly for the higher frequencies (2000 to 4000 Hz). However, there was not a significant difference in the slopes of amplitude growth functions between subjects with sloping versus flat audiometric configurations for these frequencies, and estimation of threshold from suprathreshold ASSR amplitude growth functions was not advantageous. CONCLUSIONS: ASSR thresholds accurately predicted behavioral threshold equally well for flat or sloping audiometric configurations. The accuracy of threshold estimation for either audiometric configuration and the similar growth function slopes may suggest that there is little spread of activation to neighboring regions of the cochlea when using multiple 100% AM stimuli in subjects with moderately sloping losses. The small amplitude of the ASSR response and individual variability may make threshold estimation based on extrapolation from suprathreshold ASSR responses impractical.

Acoustic Stimulation↗
PubMedDate not supplied

The progress of developmentally delayed pre-school children in a home-training scheme.

The present study compared the rates of development of a group of 35 pre-school children in a home-training scheme. The children entered the service at different ages and suffered from different disabilities. The families received weekly visiting from a home advisor, who was specially trained to develop skills in the parents to help their children. Those who developed most rapidly were the group of environmentally deprived children. The non-specific developmentally delayed and Down's syndrome children progressed well during the study period. The children who suffered from cerebral palsy and those with visual handicaps developed at a very slow rate, despite the training that they were receiving. This finding may reflect the severity of their handicaps but also it suggests that the needs of these particular groups should be further examined. The age of entry to the scheme did not seem to be an important variable. The individual variability within each specified group was wide.

Child Development↗
PubMed1999

Relationship between motion of coronary arteries and diaphragm during free breathing: lessons from real-time MR imaging.

OBJECTIVE: Diaphragmatic navigators are frequently used in free-breathing coronary MR angiography, either to gate or prospectively correct slice position or both. For such approaches, a constant relationship between coronary and diaphragmatic displacement throughout the respiratory cycle is assumed. The purpose of this study was to evaluate the relationship between diaphragmatic and coronary artery motion during free breathing. SUBJECTS AND METHODS: A real-time echoplanar MR imaging sequence was used in 12 healthy volunteers to obtain 30 successive images each (one per cardiac cycle) that included the left main coronary artery and the domes of both hemidiaphragms. The coronary artery and diaphragm positions (relative to isocenter) were determined and analyzed for effective diaphragmatic gating windows of 3, 5, and 7 mm (diaphragmatic excursions of 0-3, 0-5, and 0-7 mm from the end-expiratory position, respectively). RESULTS: Although the mean slope correlating the displacement of the right diaphragm and the left main coronary artery was approximately 0.6 for all diaphragmatic gating windows, we also found great variability among individual volunteers. Linear regression slopes varied from 0.17 to 0.93, and r2 values varied from .04 to .87. CONCLUSION: Wide individual variability exists in the relationship between coronary and diaphragmatic respiratory motion during free breathing. Accordingly, coronary MR angiographic approaches that use diaphragmatic navigator position for prospective slice correction may benefit from patient-specific correction factors. Alternatively, coronary MR angiography may benefit from a more direct assessment of the respiratory displacement of the heart and coronary arteries, using left ventricular navigators.

Adult↗
PubMedDate not supplied

[Exposure to carcinogens in work environment today. State of the art, problems and prospects raised by the Law 626/94].

The implementation in our country of recent legislation on carcinogenic risk assessment and management (VIIth title of Law 626/94) is considered. The authors describe potentialities and limits of the new legislation and of the derived Guidelines issued by the Regions. The health policy in this field and possible evolution in the near future are outlined, bearing in mind the experience of other countries. A short list of questions is suggested as a contribution to the discussion on the future scenario: whether exposure to carcinogens should be lower in the working environment than in the general environment; what is the relative importance of multifactoriality, individual biological variability, individual life-style in the genesis of cancers; whether medical health surveillance is worthwhile in terms of primary prevention; is it always true that there is no threshold limit value for carcinogens; what is the role of individual attitudes to prevention in exposure to carcinogens compared to "objective" protection; which balance between costs and benefits should be aimed at.

Carcinogens, Environmental↗
PubMed2002

Sheep as a mammalian model of genetic variability in melatonin.

Large inter-individual variability in plasma melatonin concentration at night is a common mammalian trait. In sheep, it varies from < 50 pg ml(-1) to > 800 pg ml(-1) but is very consistent within individuals. This inter-individual variability is under strong genetic control, which depends on melatonin secretion from the pineal gland, but not on melatonin catabolism. This genetic variability does not originate from differences in the synthetic enzymes or from a difference in melatonin secretion per mg of tissue, but from a difference in pineal size, which is highly variable among lambs of the same age and live weight. The genetic difference among lambs is already expressed at birth and is due to a difference in the number of pinealocytes rather than in their size. Pineal size and number of pinealocytes correlate strongly with plasma melatonin concentrations. The variability in pineal mass is not associated with the variability in any other organ (for example, the pituitary). The identification of genetic markers in the genome associated with the size of the pineal gland may lead to identification of genes involved in development of the mammalian pineal gland. Divergent selection of sheep on the basis of plasma melatonin concentrations could be used to constitute a mammalian model for extreme plasma concentrations.

Animals↗
PubMed2005

Analysis of biogenic amine variability among individual fly heads with micellar electrokinetic capillary chromatography-electrochemical detection.

Neurochemical variability among individual Drosophila heads has been examined with the sensitivity of electrochemical detection and the selectivity of micellar electrokinetic capillary chromatography. Homogenization of single Drosophila heads in volumes as small as 100 nL has been accomplished. Here we demonstrate reproducible separations for single fly heads in 250-nL volumes providing a 4-fold increase in sensitivity without overloading the electrochemical detector. This increase in sensitivity allows detection of previously undetected analytes, such as N-acetyltyramine (naTA) and octopamine (OA). Analytes including L-3,4-dihydroxyphenylalanine, N-acetyl octopamine, N-acetyldopamine, naTA, N-acetylserotonin, OA, dopamine, tyramine, and serotonin also have been consistently identified in single-head homogenates and observed with homogenates representing populations of Drosophila. Neurochemical variation between individual flies as well as the consistency within a population indicates varying amounts of neurotransmitter turnover. The inception, design, and fabrication of a miniature tissue homogenizer has enabled the separation of biogenic amines and metabolites from these severely volume-limited single Drosophila head homogenates.

Animals↗
PubMed1993

Variability of the main sequence.

PURPOSE: This study investigated the relationship between amplitude and peak velocity of saccadic eye movements (the so-called main sequence) and the intra-individual variability of the main sequence. METHODS: Saccadic amplitudes and peak velocities were measured twice in 58 healthy subjects with an infrared reflection technique. RESULTS: Considerable intra-individual variability was found between the first and second recordings. CONCLUSIONS: Intra-individual variability of saccadic peak velocity affects the interpretation of changes in repeated recordings of peak velocities, such as before and after medication is administered. Furthermore, considerable intra-individual variability decreases the probability that statistically significant differences between patients and control subjects can be detected, especially when groups are small. Calculating the intraclass correlation coefficient allows the number of subjects in comparative studies to be determined.

Adult↗
PubMed2006

Influence of high-dose ketoconazole on the pharmacokinetics of docetaxel.

OBJECTIVE: The pharmacokinetics (PK) of docetaxel are characterized by large inter-individual variability in systemic drug exposure (AUC) and drug clearance. The PK variability is thought to be largely related to differences in the catalytic function of CYP3A, involved in docetaxel metabolism and elimination. As variability in efficacy and toxicity is associated with variability in docetaxel AUC and clearance, reducing inter-individual PK variability may help improve the risk-benefit ratio of docetaxel therapy. We investigated if high-dose ketoconazole, a potent CYP3A inhibitor, could result in a uniform reduction of docetaxel clearance and reduce the inter-individual variability in docetaxel AUC and clearance. METHODS: Seven patients were treated in a randomized-cross over design with intravenous docetaxel (100 mg/m(2)) followed 3 weeks later by docetaxel (15 mg/m(2)) given in combination with orally administered ketoconazole (400 mg 3 times daily, up to 47 hours after docetaxel infusion) or vice versa. Docetaxel plasma concentration-time data were described by a three-compartment PK model. Ketoconazole plasma concentration-time data were described by a one-compartment PK model. RESULTS: Docetaxel clearance was reduced by 50% (P = .018) from 32.8 +/- 13.7 L/hr to 16.5 +/- 8.15 L/hr upon ketoconazole coadministration, albeit with large inter-individual variability (fractional change in clearance, range 0.31 - 0.66). In the presence of ketoconazole, inter-individual variability in clearance and AUC, expressed as coefficient of variation, was increased from 41.6 to 49.5% and from 28.0 to 35.1%, respectively, and not, as we had hypothesized, reduced. CONCLUSION: Inhibition of CYP3A by concomitant high-dose ketoconazole administration does not result in a uniform reduction of docetaxel clearance and does not reduce the inter-individual variability in docetaxel AUC or clearance. This approach is unsuitable as method to achieve a uniform docetaxel PK profile.

Adult↗
PubMedDate not supplied

Matrix metalloproteinase expression in normal skin associated with basal cell carcinoma and in distal skin from the same patients.

OBJECTIVE: To obviate the difficulty of ruling out confounding variables (eg, age, individual variability) as the source of differences seen when comparing tumor tissue and control tissue from unrelated individuals, we examined the expression of matrix metalloproteinase (MMP)-1 (interstitial collagenase) and MMP-9 (92-kDa gelatinase B) in histologically normal skin immediately adjacent to basal cell carcinomas (peritumoral tissue) after Mohs micrographic surgery and postauricular skin from the same patients. DESIGN: Peritumoral and postauricular skin samples were obtained from 17 patients undergoing Mohs surgery. Expression of MMP-1 and MMP-9 was examined in these specimens using a combination of approaches including zymography, collagen-degradation assays, and immunohistology. RESULTS: The expression levels of MMP-1 and MMP-9 were consistently elevated in the peritumoral tissue compared with skin from the distal site. CONCLUSION: This finding indicates that even when potentially important variables such as age and individual variability are controlled for, tumor-specific effects on the expression of MMP-9 and MMP-1 remain.

Basal Cell Carcinoma↗
PubMed2000

Balance control near the limit of stability in various sensory conditions in healthy subjects and patients suffering from vertigo or balance disorders: impact of sensory input on balance control.

The large inter-individual variability within the normal population, the limited reproducibility due to habituation or fatigue, and the impact of instruction and the subject's motivation, all constitute a major problem in posturography. These aspects hinder reliable evaluation of the changes in balance control in the case of disease and complicate objectivation of the impact of therapy and sensory input on balance control. In this study, we examine whether measurement of balance control near individualized limits of stability and under very challenging sensory conditions might reduce inter- and intra-individual variability compared to the well-known Sensory Organization Test (SOT). To do so, subjects balance on a platform on which instability increases automatically until body orientation or body sway velocity surpasses a safety limit. The maximum tolerated platform instability is then used as a measure for balance control under 10 different sensory conditions. Ninety-seven healthy subjects and 107 patients suffering from chronic dizziness (whiplash syndrome (n = 25), Meniere's disease (n = 28), acute (n = 28) or gradual (n = 26) peripheral function loss) were tested. In both healthy subjects and patients this approach resulted in a low intra-individual variability (< 14.5(%). In healthy subjects and patients, balance control was maximally affected by closure of the eyes and by vibration of the Achilles' tendons. The other perturbation techniques applied (sway referenced vision or platform, cooling of the foot soles) were less effective. Combining perturbation techniques reduced balance control even more, but the effect was less than the linear summation of the effect induced by the techniques applied separately. The group averages of healthy subjects show that vision contributed maximum 37%, propriocepsis minimum 26%, and labyrinths maximum 44% to balance control in healthy subjects. However, a large inter-individual variability was observed. Balance control of each patient group was less than in healthy subjects in all sensory conditions. Similar to healthy subjects, patients also show a large inter-individual variability, which results in a low sensitivity of the test. With the exception of some minor differences between Whiplash and Meniere patients, balance control did not differ between the four patient groups. This points to a low specificity of the test. Balance control was not correlated with the outcome of the standard vestibular examination. This study strengthens our notion that the contribution of the sensory inputs to balance control differs considerably per individual and may simply be due to differences in the vestibular function related to the specific pathology, but also to differences in motor learning strategies in relation to daily life requirements. It is difficult to provide clinically relevant normative data. We conclude that, like the SOT, the current test is merely a functional test of balance with limited diagnostic value.

Adolescent↗