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Size quantification of liver metastases in patients undergoing cancer treatment: reproducibility of one-, two-, and three-dimensional measurements determined with spiral CT.

PURPOSE: To assess the reproducibility of one-, two-, and three-dimensional measurements of the size of liver metastases. MATERIALS AND METHODS: The sizes of 10 liver metastases were determined 200 times: Ten observers measured each lesion by using images obtained at two different CT studies and with five different measurement techniques (maximum diameter, product of diameters, area, volume, and product of three diameters). They repeated each measurement in a separate session. The influence of measurement technique and lesion type (size and morphologic appearance) on measurement reproducibility was assessed. RESULTS: Three-dimensional measurements proved to be as reproducible as one- and two-dimensional measurements. Measurement reproducibility was influenced mainly by the size (P < .0001) and morphologic appearance (P < .01) of the lesions. CONCLUSION: Three-dimensional size measurements obtained with spiral CT are reproducible and could therefore replace the two-dimensional measurements of tumor size currently obtained with follow-up CT studies.

Humans↗

Doppler perfusion index: an interobserver and intraobserver reproducibility study.

PURPOSE: To assess the potential of Doppler perfusion index (DPI) measurement as a routine diagnostic tool in the detection of occult colorectal liver metastases. MATERIALS AND METHODS: By using color doppler ultrasound, two independent sonologists performed DPI measurements blindly in 20 patients aged 30-82 years; interobserver reproducibility was assessed. A second group of 20 patients aged 37-88 years were examined to assess the level of intraobserver reproducibility of DPI measurements attained by one sonologist. For each patient in this group, the DPI was measured three times in succession, and the variability between measurements was analyzed. Calculations of the intraclass correlation coefficient and the coefficient of variation (CV) were used to determine the levels of reproducibility. The data were also analyzed by using the Student paired t test, with significance established at P less than .05. RESULTS: The interobserver CV and intraobserver CV were 20% and 16%, respectively. The two sonologists who examined the first group of patients agreed independently on the DPI status in 18 of 20 (90%) patients. CONCLUSION: In this study, both the intraobserver reproducibility and the interobserver reproducibility of DPI measurements were clinically acceptable.

Adult↗

Reproducibility of the Finn chamber nickel patch test in two different phases of the ovulatory menstrual cycle.

BACKGROUND: Studies on nickel patch test reactivity and reproducibility of positive tests at different points of the menstrual cycle are heterogeneous. OBJECTIVE: To investigate if non-reproducibilities of positive nickel sulphate patch tests in the two different phases of ovulatory menstrual cycles with the endocrine evidence of luteal phase adequacy are statistically different. METHODS: 15 women (group 1) with positive Finn chamber(R) nickel patch test results in the follicular phase of the ovulatory cycle and 13 women (group 2) with positive Finn chamber nickel patch test results in the luteal phase of the ovulatory cycle were tested again in the counter-phases of their ovulatory cycle, with a scheduled interval of 6 weeks following the first tests. Reproducibilities of the tests in the two groups were evaluated statistically. RESULTS: 3 of the positive test results in group 1 (20%) and 2 of the positive test results in group 2 (15.4%) were non-reproducible. The difference was not statistically significant. CONCLUSION: The reproducibility of positive Finn chamber nickel patch tests does not seem to be affected by the changes in the follicular and luteal phases of the ovulatory cycle.

Adult↗

Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography in silicone oil-filled eyes.

PURPOSE: To evaluate the reproducibility of nerve fiber layer (NFL) thickness measurements by optical coherence tomography (OCT) in individuals with silicone oil-filled eyes. METHODS: Eighteen patients who had undergone pars plana vitrectomy and silicone oil tamponade for retinal detachment were enrolled in a prospective, case-controlled clinical study. Each patient underwent OCT measurement of NFL thickness. Five repetitions of a series of scans on five separate occasions within a 0.5-month period were performed. Each eye was scanned at two different nerve head programs [radius (R) = 1.5 and R = 1.73]. The contralateral healthy eye was used as control. For each option (R = 1.5 and R = 1.73) and region (superior, inferior, temporal, nasal and overall mean), variance components and intraclass correlation coefficients (ICCs) were determined using repeated-measures regression. In these models, NFL thickness, as measured by OCT, was considered to have three variance components: intersubject, intervisit (within subject, between dates), and intravisit (within subject, within date). The ICC (intersubject variance/total variance) was used as a measure of reliability. RESULTS: The contralateral healthy eye provided a higher degree of reproducibility than the silicone oil-filled eye (p = 0.0001). Reproducibility was higher in a given eye on a given visit than from visit to visit. Reproducibility as measured by ICCs was as follows: R = 1.5, 0.54/0.30 (control eyes/silicone oil-filled eyes); R = 1.73, 0.51/0.30. CONCLUSIONS: Reproducibility results for OCT measurement of NFL thickness are different in healthy eyes and silicone oil-filled eyes. NFL thickness measurement is not reliable in silicone oil-filled eyes.

Case-Control Studies↗

Reproducibility of measurements of coronary narrowings by videodensitometry and by digital calipers.

Computer-assisted videodensitometry has been shown to be a reliable and reproducible method of measuring absolute and relative coronary narrowings. Using a commercially available analyzer (Vanguard XR70) we confirmed intra- and interobserver reproducibilities in 34 narrowings in 9 patients. Analyses were performed on normal area and diameter, stenotic area and diameter, percent area stenosis and percent diameter stenosis. For all 6 analyses, excellent intra- and interobserver correlations were found (r = 0.93-0.98), with slopes close to 1 and intercepts close to zero. Caliper measurements (Mitutoyo Digimatic) of the same lesions by the same observers showed good inter- and intraobserver reproducibility for percent diameter stenosis (r = 0.90 and 0.86), with mean interobserver difference of 1.67 +/- (SD) 6.4% and intraobserver difference of 2.97 +/- (SD) 7.9%. However, less good correlations were found between caliper and videodensitometric measurements of percent diameter stenosis; r = 0.61 and 0.76 for the two observers. These data suggest that videodensitometry is a highly reproducible quantitative angiographic method, suitable for documenting changes in the severity of coronary artery lesions, both spontaneous or related to interventions. Caliper measurements do not provide the same degree of accuracy, but they have acceptable reproducibility in measuring diameter stenosis. As such, they are also suitable for assessing changes in severity of coronary artery lesions in individual patients.

Angioplasty, Balloon, Coronary↗

Reproducibility studies with the Zeiss SLC system and animal cataract models.

Scheimpflug photography has become the basic method for documentation of lens transparency changes in clinical and experimental ophthalmology, due to its high reproducibility. In animal cataract studies, the reproducibility is strongly influenced by the handling characteristics of the camera used, due to limited cooperation of the animal. The reproducibility of the Zeiss SLC system, which offers a direct quality control of the image on the video screen, was tested with 2 animal cataract models, the ultraviolet B (UVB)-induced cataract and the true diabetic cataract in the Brown-Norway rat. 10 rats each of the 2 cataract models and of an untreated control group were photographed in a random order on 3 occasions on the same day by the same photographer. Quality control and densitometry were performed by the same system operator, the measurement window was positioned standardly, coincident with the optical axis of the eye. Statistical comparison was carried out in the capsular layer, that is the area of initial cataract development in both models, and in the cortical layer, into which the diabetic cataract progresses during its later stages of development. The nuclear layer was also evaluated, but has no direct relation to one of the models employed. The results clearly indicate that the reproducibility is predominantly influenced by the homogeneity or inhomogeneity of the cataract model employed. The system operator and the photographer provided that they are well trained, have minor influence on the reproducibility of the Zeiss SLC system.

Animals↗

Reproducibility of ultrasound assessment of carotid plaque occurrence, thickness, and morphology. The Tromsø Study.

BACKGROUND AND PURPOSE: Ultrasonography is increasingly used in vascular research, but there is limited information about the reproducibility of the ultrasound method for screening purposes. In this study the reproducibility of ultrasound assessment of carotid plaque occurrence, thickness, and morphology was examined within the setting of a population health survey. METHODS: In 1994/1995, 6720 participants in the Tromsø Study, Norway, underwent B-mode ultrasound scanning of the right carotid artery. The between- and within-sonographer reproducibility of ultrasound assessment of plaque occurrence and thickness was estimated by repeated scanning of a random sample of 107 participants. The between- and within-sonographer reproducibility of plaque morphology classification (echogenicity, four categories and heterogeneity, two categories) was determined by repeated reading of videotaped images of 119 randomly selected arteries with plaques. RESULTS: Between- and within-sonographer agreement on plaque occurrence was substantial with kappa values (95% CI) of 0.72 (0.60 to 0.84) and 0.76 (0.63 to 0.89), respectively. Reproducibility of plaque thickness measurements was moderate, with mean absolute differences ranging between 0.25 and 0.55 mm (coefficients of variation between 13.8% and 22.4%). Agreement on plaque morphology classification was high, with kappa values ranging between 0.54 and 0.73. CONCLUSIONS: Population screening using B-mode ultrasound provides a valuable means for the detection and morphological evaluation of carotid plaques, whereas measurements of plaque thickness are subject to considerable measurement error.

Aged↗

A protocol for performing reproducible methacholine inhalation tests in children with moderate to severe asthma.

Reproducibility of methacholine inhalation tests (MIT) over a 2-wk period has been established in adult populations, but similar studies demonstrating reproducibility in children are lacking. We set out to establish the reproducibility of MIT in children as a prerequisite for a study of the natural history of airway hyperreactivity in asthmatic children. Most inhalation testing is done in persons with mild asthma because the recommended time interval for the withholding of medications prior to bronchial challenge is poorly tolerated by more labile asthmatics. In order to evaluate asthmatics with more severe disease, we modified a standardized method of methacholine inhalation to include a three-tier pretest medication regimen and investigated the reproducibility of this MIT protocol in 11 children as young as 6 yr of age. The three tiers were designed to keep baseline FEV1 greater than or equal to 70% predicted since diminished baseline airway caliber may affect MIT results. Eight of the 11 children were bronchodilator-dependent, and two of the eight also required inhaled steroids. Eleven children (6 to 13 yr of age) underwent MIT, between December and March, 1 day, 1 wk, and 1 month after an initial test. The PD20FEV1 using cumulative breath units (BU) were compared. The range of PD20FEV1 in the 11 children was 0.27 to 14.4 BU, with nine subjects classified as severe (PD20FEV1 less than 2.5 BU). We found a high degree of reproducibility of MIT. The interest correlation coefficient (r) was 0.98 after 1 day, 0.95 after 1 wk, and 0.96 after 1 month.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Six-minute walk, maximal exercise tests: reproducibility in fibrotic interstitial pneumonia.

Resting pulmonary function and exercise variables are widely used to stage and monitor idiopathic interstitial pneumonia (IIP). However, the variability of exercise data (maximal exercise and the 6-minute walk test) has not been evaluated definitively. We have prospectively quantified the reproducibility of resting and exercise functional data in fibrotic IIP (idiopathic pulmonary fibrosis, fibrotic nonspecific interstitial pneumonia) and have evaluated interrelationships between variables. Thirty consecutive patients with fibrotic IIP underwent serial resting pulmonary function tests, 6-minute walk (n = 29), and maximal exercise (n = 24) at an interval of 1 week, with all testing performed in accordance with American Thoracic Society standards. Within-subject reproducibility was excellent for 6-minute walk distance (SD/mean = 4.2%) and clinically acceptable for resting pulmonary function indices and VO(2)max on maximal exercise testing. However, the amplitude of oxygen desaturation at the end of exercise was poorly reproducible in both 6-minute walk and maximal exercise testing (SD/mean > 25%). There was a highly significant relationship between VO2max on maximal exercise testing and 6-minute walk distance (r(s) = 0.78, p < 0.0001). In fibrotic IIP, the excellent reproducibility of the 6-minute walk distance is a major advantage in routine staging and monitoring, whereas maximal exercise variables are poorly reproducible.

Aged↗

Reproducibility of visual analog scale (VAS) pain scores to mechanical pressure.

This study tested the reproducibility of visual analog scale (VAS) pain scores to measure changes in masseter muscle pain evoked by maximally tolerable mechanical stimulation over a short time period in healthy subjects. This study also evaluated gender differences in reproducibility of VAS scores to mechanical stimulation. Ten healthy female and eight healthy male individuals participated in this study. The recordings of VAS pain scores to an identical mechanical pressure on the masseter muscle were performed at three different sessions (T1, T2, and T3). The subjects rated their pain on a VAS to a maximally tolerable stimulus that was recorded on an algometer at the first session. The algometer pressure reading was recorded for each subject and then used to duplicate the same identical mechanical stimulus at each of the three sessions. This identical pressure was repeated in the same marked spot at six minutes and after 30 minutes. The subjects rated the pain on a VAS to this identical stimulus at each session. There was no significant difference in VAS pain scores of all subjects at T1, T2, and T3. There was no significant difference in reproducibility of VAS pain scores in females compared to males. Intraclass correlation coefficients were 0.811 on the right masseter and 0.844 on the left masseter. VAS pain scores to mechanical stimulation were reproducible over a short time period. Gender did not affect the reproducibility. This previously unreported method of measuring pain to repeated identical mechanical stimulation appears to have potential for both clinical and research application.

Adult↗

Reproducibility of twitch mouth pressure, sniff nasal inspiratory pressure, and maximal inspiratory pressure.

Twitch mouth pressure (Pmo,tw) during magnetic phrenic nerve stimulation and sniff nasal inspiratory pressure (SNIP) were recently proposed as alternative noninvasive methods for assessing inspiratory muscle strength. This study aimed to compare their reproducibility with maximal inspiratory pressure (MIP) in normal subjects. Ten healthy subjects were studied at functional residual capacity in semirecumbent position. Cervical magnetic phrenic nerve stimulation was performed during gentle expiration against an occlusion incorporating a small leak. Constancy of stimulation was controlled by recording diaphragmatic electromyogram. Within and between-session reproducibility of pressure were studied for Pmo,tw, SNIP, and MIP. The subjects were studied during a session of 10 manoeuvres repeated after 1 day and 1 month. The mean values were 16 cmH2O for Pmo,tw, 118 cmH2O for SNIP, and 115 cmH2O for MIP. For the three tests, the within subject variation was small in relation to between-subject variation, with the intraclass correlation coefficient ranging 0.79-0.90 for Pmo,tw, 0.85-0.92 for SNIP, and 0.88-0.92 for MIP. At 1 day interval, the coefficient of repeatability (2 SD of differences) was 3.6 cmH2O for Pmo,tw, 32 cmH2O for SNIP and 28 cmH2O for MIP. At 1 month interval, the coefficient of repeatability was 5.8 cmH2O for Pmo,tw, 23 cmH2O for SNIP and 21 cmH2O for MIP. We conclude that the within session reproducibility of the new tests twitch mouth pressure and sniff nasal inspiratory pressure is sufficient to be clinically useful. For sniff nasal inspiratory pressure, the between session reproducibility established after 1 day was maintained after 1 month. For twitch mouth pressure, the between session reproducibility declined slightly after 1 month. These characteristics should be considered when using these methods to follow an individual patient over time.

Adult↗

Reproducibility of cervical range of motion in patients with neck pain.

BACKGROUND: Reproducibility measurements of the range of motion are an important prerequisite for the interpretation of study results. The aim of the study is to assess the intra-rater and inter-rater reproducibility of the measurement of active Range of Motion (ROM) in patients with neck pain using the Cybex Electronic Digital Inclinometer-320 (EDI-320). METHODS: In an outpatient clinic in a primary care setting 32 patients with at least 2 weeks of pain and/or stiffness in the neck were randomly assessed, in a test- retest design with blinded raters using a standardized measurement protocol. Cervical flexion-extension, lateral flexion and rotation were assessed. RESULTS: Reliability expressed by the Intraclass Correlation Coefficient (ICC) was 0.93 (lateral flexion) or higher for intra-rater reliability and 0.89 (lateral flexion) or higher for inter-rater reliability. The 95% limits of agreement for intra-rater agreement, expressing the range of the differences between two ratings were -2.5 +/- 11.1 degrees for flexion-extension, -0.1 +/- 10.4 degrees for lateral flexion and -5.9 +/- 13.5 degrees for rotation. For inter-rater agreement the limits of agreement were 3.3 +/- 17.0 degrees for flexion-extension, 0.5 +/- 17.0 degrees for lateral flexion and -1.3 +/- 24.6 degrees for rotation. CONCLUSION: In general, the intra-rater reproducibility and the inter-rater reproducibility were good. We recommend to compare the reproducibility and clinical applicability of the EDI-320 inclinometer with other cervical ROM measures in symptomatic patients.

Adult↗

Interbreath-hold reproducibility of lung tumour position and reduction of the internal target volume using a voluntary breath-hold method with spirometer during stereotactic radiotherapy for lung tumours.

The purpose of this study was to evaluate the interbreath-hold reproducibility of the tumour (gross tumour volume, GTV) position and relative reduction of the internal target volume (ITV) using a voluntary breath-hold method with a spirometer in a clinical setting of stereotactic radiotherapy (SRT) for lung tumours 11 patients with 14 lung tumours were enrolled in this study. CT scans were performed once at the free breathing phase and five times at the breath holding phase before the first treatment day. Patients held their breath at the end-expiration phase under spirometer-based monitoring. All GTVs were delineated by a physician and the GTV centroid was calculated automatically. To evaluate the interbreath-hold reproducibility of the tumour position, we measured the distance of three dimensions (craniocaudal, CC; left-right, LR; anteroposterior, AP) and vectors between the GTV centroid and bony landmark. The reproducibility was defined as the average of the differences between the GTV centroid and bony landmark from the second to fifth CT scans with regard to that from the first CT scans. We also evaluated the relative reduction of ITV between the free breathing and breath-holding phase. The interbreath-hold reproducibility of the tumour position was 1.3+/-1.3 mm, 1.4+/-1.8 mm, 2.1+/-1.6 mm and 3.3+/-2.2 mm in CC, LR and AP directions and vectors, respectively. ITV at the breath-holding phase was significantly smaller than that at the free breathing phase (P<0.01). In conclusion, the voluntary breath-hold method with a spirometer is feasible, with relatively good reproducibility of the tumour position for SRT in the clinical setting.

Aged↗

[Reproducibility of a self-administered questionnaire for dietary habits, smoking, and drinking].

Reproducibility of results from a self-administered questionnaire on dietary habits (the frequency of taking various foods and eating habits), smoking and drinking was examined to study the reliability of the questionnaire, stability of lifestyle, and the validity of the questionnaire in assessing lifestyle as a risk factor in chronic diseases. The study sample included 120 males and 173 females in a rural town in Kyoto Prefecture, who participated in a series of three health examinations in 1988, 1989, and 1992. A survey using the same questionnaire was performed before each health examination. Reproducibility was assessed by correlation (Spearman's rank correlation coefficient or kappa coefficient), exact agreement of category answered, and comparison of mean frequency. An attempt was made to separate reliability and stability from reproducibility using the data from the questionnaire obtained in the three years. Good reproducibility for one-year and four-year intervals was found for foods taken habitually or often (boiled rice, cooked rice gruel with tea, milk, coffee, fruits and bread), and habits (eating breakfast, some eating habits, smoking and drinking). The same was also found for cigarette or alcohol consumption among current consumers except that cigarette consumption over a four-year interval was more likely to change. The reliability of the questionnaire and stability of these items were considered satisfactory, suggesting that the questionnaire was a valid method of assessing long-term lifestyle. Poor reproducibility of results regarding consumption of green-yellow and other vegetables indicated both poor reliability and a change in consumption over four years, and suggested poor validity. However, disagreement in more than one category of vegetables was not large and misclassification in assessing them as risk factors and changes in frequency of consumption may not be large either. Although correlation coefficients for the items of dairy food and eating snacks were fair, disagreement in more than one category was relatively large which may have caused misclassification. The mean frequency of consumption of pickles and fishpaste, ham or sausage significantly decreased over the four year interval. This may reflect the influence of health education on reducing salt intake.

Adult↗

Effect of injectate temperature and thermistor position on reproducibility of thermodilution cardiac output determinations.

STUDY OBJECTIVE: The purpose of this study was to evaluate the effect of thermistor position with varying injectate temperatures on the reproducibility of thermodilution cardiac output determination. The key hypothesis to be tested was that the positioning of the proximal thermistor at the right atrial port would improve the reproducibility of thermodilution cardiac output determination, independent of injectate temperature. DESIGN: Prospective randomized trial. SETTING: The study was performed in the cardiac catheterization laboratory of the West Haven Veterans Affairs Medical Center. PARTICIPANTS: Twenty consecutive patients undergoing right and left heart catheterizations were enrolled in the study. INTERVENTIONS: Each patient underwent triplicate determination of thermodilution cardiac output measurements under four experimental conditions: (1) ambient or room temperature injectate using an external thermistor in the injectate reservoir; (2) iced injectate using an external thermistor; (3) room temperature injectate using an internal right atrium (RA) thermistor; and (4) iced injectate using an RA thermistor. Reproducibility was assessed by the coefficient of variation (CV) and standard error of the mean percent (SEM%), of the triplicate measurements. MEASUREMENTS AND RESULTS: Using an internal RA thermistor improved the reproducibility of cardiac output determinations independent of injectate temperature. Using room temperature injectate, the CV was 12.8 percent using an external thermistor and 7.9 percent using an internal RA thermistor (p < 0.05). Using iced injectate, the CV was 10.2 percent using an external thermistor and 5.5 percent using an internal RA thermistor (p < 0.05). CONCLUSIONS: Reproducibility of thermodilution cardiac output determinations is improved when injectate temperature is measured internally, at the RA, as opposed to externally in the reservoir. This has clinical implications for determining significant changes in serial cardiac output determinations.

Analysis of Variance↗

Acceptability, reproducibility, and sensitivity of forced expiratory volumes and peak expiratory flow during bronchial challenge testing in asthmatic children.

OBJECTIVES: To compare the acceptability, reproducibility, and sensitivity of spirometric outcome measures of airway caliber during challenge testing in children. DESIGN: FEV(1), forced expiratory volume in 0.75 s, forced expiratory volume in 0.5 s, and peak expiratory flow (PEF) were recorded during stepwise dosimetric histamine challenge tests. The responses were compared, and the reproducibility at baseline and from duplicate measurements at each challenge step was determined. PATIENTS: One hundred five children with newly diagnosed asthma, aged 5 to 10 years. RESULTS: Compared to PEF, FEV(1) showed better baseline reproducibility (p = 0.002) and higher sensitivity (p < 0.0001) during challenge testing, determined as the change normalized to the baseline variation, while the forced expiratory volumes were not significantly different in these respects. During challenge testing in subjects with acceptable flow-volume tracings, paired recordings of FEV(1) agreed within 0.1 L in 85% and within 0.2 L in 93% of measurements. During challenge testing, the reproducibility of FEV(1) measurements was not better than that of the other indexes. Failure to exhale long enough precluded the use of FEV(1) in 16 of the children, particularly the youngest children. CONCLUSIONS: The results demonstrated that the recently published guidelines for FEV(1) measurements during challenge tests can be applied to children. During challenge tests in asthmatic children, the advantage of the shorter fractions of forced expiratory volume was that they were more often acceptably recorded than FEV(1), while they showed as good reproducibility and were also equally sensitive in assessing changes in airway obstruction.

Asthma↗

Long-term reproducibility of respiratory gas exchange measurements during exercise in patients with stable cardiac failure.

Present-day technology has greatly facilitated the monitoring of respiratory gas exchange in the clinical exercise laboratory. Despite the growing use of these techniques to assess the severity and progression of disease or therapeutic response in patients with heart failure, the long-term reproducibility of oxygen uptake (VO2), carbon dioxide production, minute ventilation, heart rate (HR), and blood pressure at rest and during incremental exercise in such patients, to our knowledge, has not been evaluated. Therefore, the purpose of this study was to quantify the reproducibility of these variables along with exercise duration, maximum VO2 (VO2max) and anaerobic threshold in a group of 16 patients (61 +/- 7 years, 14 male) with chronic, stable cardiac failure of varying severity and etiology who had five or more incremental treadmill exercise tests over a period of time that ranged from 3 to 22 months. For each variable, reproducibility was represented by the coefficient of variation (CVAR). Except for exercise duration, CVAR was not a function of the severity of heart failure and, for all variables, patient-to-patient variation in CVAR was approximately 9 percent. The maximum CVAR for HR, systolic blood pressure, VO2, and VO2max was generally below 10.5 percent and for exercise duration and anaerobic threshold it was less than 12.5 percent. Based on this retrospective analysis, it is concluded that reproducible respiratory gas exchange and HR exercise responses are obtainable over extended periods of time in patients with stable, chronic cardiac failure. Exercise duration, however, is less reproducible in patients with moderate to severe failure.

Aged↗

Reproducibility of the growth hormone response to stimulation with growth hormone-releasing hormone plus arginine during lifespan.

The reliability and reproducibility of provocative stimuli of growth hormone (GH) secretion in the diagnosis of GH deficiency are still controversial both in childhood and in adulthood. The combined administration of GH-releasing hormone (GHRH) and arginine (ARG), which likely acts via inhibition of hypothalamic somatostatin release, is one of the most potent stimuli known so far and has been proposed recently as the best test to explore the maximal somatotrope capacity of somatotrope cells. However, it is well known that, usually, provocative stimuli of GH secretion suffer from poor reproducibility and that of the GHRH + ARG test has still to be verified. We aimed to verify the between- and within-subject variability of the GH response to the GHRH + ARG test in normal subjects during their lifespan as well as in hypopituitaric patients with GH deficiency (GHD). In 10 normal children (C: six male and four female, age 12.3 +/- 0.9 years, body mass index (BMI) = 16.6 +/- 0.7 kg/m2, pubertal stages I-III), 18 normal young adults (Y: ten male and eight female, age 31.1 +/- 1.3 years, BMI = 21.4 +/- 0.4 kg/m2), 12 normal elderly subjects (E: two male and ten female, age 74.4 +/- 1.8 years, BMI= 22.6 +/- 0.6 kg/m2) and 15 panhypopituitaric GH-deficient patients (GHD: nine male and six female, age 40.9 +/- 4.1 years, BMI= 22.7 +/- 1.0 kg/m2), we studied the inter- and intra-individual variability of the GH response to GHRH (1 microg/kg i.v.) + ARG (0.5 g/kg i.v.) in two different sessions at least 3 days apart. The GH responses to GHRH + ARG in C (1st vs 2nd session: 61.6 +/- 8.1 vs 66.5 +/- 9.4 microg/l), Y (70.4 +/- 10.1 vs 76.2 10.7 microg/l) and E (57.9 14.8 vs 52.1 +/- 8.0 microg/l) were similar and reproducible in all groups. The somatotrope responsiveness to GHRH + ARG also showed a limited within-subject variability (r = 0.71, 0.90 and 0.89 and p < 0.02, 0.0005 and 0.0005 for C, Y and E, respectively). Similarly in GHD, the GH response to the GHRH + ARG test showed a good inter- (1st vs 2nd session: 2.3 +/- 0.5 vs 2.2 +/- 0.6 microg/l) and intra-individual reproducibility (r = 0.70, p < 0.005). The GHRH + ARG-induced GH responses in GHD were markedly lower (p < 0.0005) than those in age-matched controls and no overlap was found between GH peak responses in GHD and normal subjects. In normal subjects, the GH response to GHRH + ARG is very marked, independent of age and shows limited inter- and intra-individual variability. The GH response to the GHRH + ARG test is strikingly reduced in panhypopituitaric patients with GHD, in whom the low somatotrope responsiveness is reproducible. Thus, these findings strengthen the hypothesis that GHRH + ARG should be considered the most reliable test to evaluate the maximal secretory capacity of somatotrope cells and to distinguish normal subjects from GHD patients in adulthood.

Adult↗