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Biomedical subjects

P G Mulder

Publications and source records attributed to P G Mulder.

At least 37 records · Page 2Linked to original sources

In vivo antibody response and in vitro CTL activation induced by selected measles vaccine candidates, prepared with purified Quil A components.

Semipurified Quil A and purified Quil A were used to prepare well-characterized subunit vaccine candidates against measles. Variation in the relative amounts of the measles virus (MV) fusion (F) protein, Quil A-components and lipids did not influence induction of antibody responses in mice, but had a pronounced effect on the capacity to induce cytotoxic T cell (CTL) activity of a CD8(+) MV F-protein specific human T cell clone in vitro. A characteristic MV iscom preparation based on the combined use of HPLC-purified Quil A-components QA-3 and QA-22 (QA-3/22) efficiently induced CTL activity in vitro. Comparable results were obtained by mixing beta-propiolactone inactivated MV with iscom-matrix QA-3/22 or free QA-22. On the basis of the data presented it was concluded that these three preparations are interesting MV vaccine candidates for further evaluation in pre-clinical experiments in a primate model.

Adjuvants, Immunologic↗

Cholesterol as an independent predictor of outcome after renal transplantation.

BACKGROUND: The debate on the role of high serum cholesterol levels in cardiovascular disease or chronic vascular rejection in kidney-transplanted patients has not yet been settled. METHODS: We studied the influence of serum cholesterol at 1 year after transplantation on the failure risk in all 676 kidney graft recipients who survived with a functioning graft. Other variables included in this analysis were donor/recipient age and gender, original disease, race, number of HLA-A and -B mismatches, previous transplants, postmortal or living-related transplantation, and transplantation year. At 1 year after transplantation, we included: serum cholesterol, serum creatinine, proteinuria, and hypertension. RESULTS: In the Cox proportional hazards analysis, serum cholesterol at 1 year after transplantation turned out to be an important, independent variable influencing all end points (adjusted for all other variables in the model). The influence on graft failure censored for death was log-linear, and there was interaction with serum creatinine at 1 year. The adverse effect of elevated serum cholesterol levels on the graft failure rate decreased with increasing serum creatinine levels. The influence of serum cholesterol on the rate ratio (RR) for patient failure was linear too, and here there was interaction with recipient age. The negative influence of serum cholesterol on the RR for patient failure decreased with increasing recipient age. The risk for over-all graft failure was influenced by increasing serum cholesterol levels, and there was interaction with recipient age. Because recipient age had interaction with donor age and serum creatinine, the influence of all four variables together on the RR was estimated. It is shown that whereas the RR for over-all graft failure in young recipients of a renal transplant increases significantly with higher cholesterol levels, there is very little influence on the RR of elderly recipients. The risk increases proportionally with increasing serum creatinine levels. CONCLUSION: Serum cholesterol levels have an independent influence on graft, patient, and over-all graft failure.

Adult↗

Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma.

When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment.

Administration, Inhalation↗

The influence of cholesterol on mortality after transplantation is age dependent.

There is still no consensus on the treatment of elevated serum cholesterol in patients with a renal transplant. In the general population treatment is age dependent. We studied the influence of serum cholesterol 1 year after transplantation in all 676 recipients of a kidney graft transplanted in Rotterdam that survived and functioned for at least 1 year. The other variables included in this analysis are: donor and recipient age and gender, original disease, race, number of HLA A and B mismatches, number of previous transplantations, postmortal or living related transplantation and transplantation year. At 1 year after transplantation the following variables were included: serum cholesterol, serum creatinine, proteinuria and hypertension. In the Cox proportional hazards analysis, serum cholesterol at 1 year after transplantation turned out to be an important, independent variable influencing patient failure. The influence was linear but there was interaction with recipient age. The negative influence of serum cholesterol on the RR for patient failure decreased with increasing recipient age. For example, the proportional increase in RR of a 20-year-old with a serum cholesterol of 12 mmol/l compared with that of a cholesterol of a patient with serum cholesterol of 6 mmol/l was 6. In a 60-year-old with a cholesterol of 12 mmol/l the proportional increase in RR was only 1.2 compared with a contemporary with a cholesterol of 6 mmol/l. Serum cholesterol levels have an independent influence on patient failure. The RR is influenced by recipient age, so that the negative effect of increasing cholesterol levels in the elderly is overruled by the RR of age and disappears.

Adult↗

Outcome after hemi-arthroplasty for displaced intracapsular femoral neck fracture related to mental state.

This study was performed to assess mortality and functional outcome after hemi-arthroplasty for displaced intracapsular femoral neck fractures in relation to mental state. Between 1991 and 1995, 202 consecutive patients over 70 years of age were followed for at least two years or until death. Thirty-nine patients were known with senile dementia at the time of admission. The four-month mortality rate was 11.7% for the mentally normal patients and 33.3% for the mentally impaired patients. After one year the mortality rate was 19. 6% for the mentally normal patients and 43.6% for the mentally impaired patients. This difference is statistically significant (p<0. 001). Of the 141 surviving mentally normal patients, who had been mobile before operation, 16 (11.3%) were not mobile four months after operation. Of the 24 surviving mentally impaired patients, who had been mobile before operation, 18 (75.0%) were not mobile four months after operation. This difference is statistically significant (p<0.001). The conclusion of our study is that mental state has a statistically significant effect on mortality and functional outcome after hemi-arthroplasty for displaced intracapsular femoral neck fractures. For demented patients, hemi-arthrplasty is a too major operation and less invasive methods of internal fixation should be considered.

Activities of Daily Living↗

Doppler imaging of vibrations as a tool for quantifying first tarsometatarsal joint stiffness.

OBJECTIVE: To assess whether first tarsometatarsal joint stiffness can be measured by Doppler imaging of vibrations and if so, to assess reference values. DESIGN: Repeated in vivo Doppler imaging of vibrations measurements at the first tarsometatarsal joint in healthy persons. BACKGROUND: Clinical hypermobility of the first tarsometatarsal joint is an important factor in a hallux valgus deformity. No objective and non-invasive test is available to quantify first tarsometatarsal joint mobility. Doppler imaging of vibrations, a technique recently developed to measure joint stiffness, might be an effective tool to quantify stiffness of this joint. METHODS: Vibrations were applied to the head of the first metatarsal in 46 feet of 23 healthy subjects and picked up by a transducer at both sides of the first tarsometatarsal joint. A pilot study was performed on three patients with hypermobility of the first tarsometatarsal joint. Measurements are expressed in threshold units related to colour Doppler imaging. RESULTS: The values of the threshold units were found to be very similar in healthy persons, with a good repeatibility; 95% of the healthy persons had a threshold unit below 3.4. No significant difference was found between the left and right foot, or between male and female subjects. Also there was no significant correlation with age or weight of the subjects. In the three patients with first tarsometatarsal hypermobility we found threshold units above 5. CONCLUSIONS: With Doppler imaging of vibrations first tarsometatarsal joint stiffness can be measured in healthy persons in a non-invasive and objective way. In a pilot study, three patients with first tarsometatarsal hypermobility showed lower stiffness values than the healthy subjects. Relevance This study presents a new method for quantification of first tarsometatarsal joint stiffness and provides reference values in healthy persons. First measurements on patients gave promising results to future use of this method for assessment of clinical hypermobility in hallux valgus patients.

Adolescent↗

Upper limb tension tests as tools in the diagnosis of nerve and plexus lesions. Anatomical and biomechanical aspects.

OBJECTIVE: To analyse the validity of nerve tension tests used in the diagnosis of nerve (root) and plexus lesions of the upper extremity. DESIGN: In six arms of embalmed human bodies, in situ measurements were performed to assess the effect of nerve tension tests on the median, ulnar and radial nerves and the cords of the brachial plexus. BACKGROUND: In clinical practice it is useful to have fast, easy and cheap tests for the diagnosis of nerve (root) lesions of the upper extremity, analogous to Lasègue's Straight Leg Raising test.Methods. The Upper Limb Tension Tests for the median, ulnar and radial nerves, as well as the Upper Limb Tension Tests combined with contralateral rotation and lateral bend of the cervical spine (Upper Limb Tension Test+) were used to generate tension to these nerves. Buckle force transducers were used to assess tensile forces in the nerves and in the medial, lateral and posterior cords of the brachial plexus. RESULTS: Nerve tension introduced in the distal part of the median, ulnar and radial nerves was transmitted upward to the cords of the brachial plexus. Exclusively the median nerve Upper Limb Tension Test and Upper Limb Tension Test+ turned out to be sensitive and specific tension tests. Mechanical tension caused by the Upper Limb Tension Test+ was not significantly higher than that caused by the Upper Limb Tension Tests. The Upper Limb Tension Tests cannot be used to selectively stress cervical nerve roots. The findings justify investigation of exclusively the median nerve Upper Limb Tension Test and Upper Limb Tension Test+ on their clinical validity. RELEVANCE: Before nerve tension tests for the median, ulnar and radial nerves can be introduced to clinical practice it is necessary to assess their validity quantitatively.

Arm↗

The effect of retrobulbar irradiation on exophthalmos, ductions and soft tissue signs in Graves' ophthalmopathy: a retrospective analysis of 90 cases.

PURPOSE: Retrospective analysis of the effect of retrobulbar irradiation on exophthalmos, ductions and soft tissue signs in patients with Graves' ophthalmopathy. METHODS: We analysed the charts of 111 consecutive patients who were treated with retrobulbar irradiation according to standardised intake criteria between 1992 and 1997. After exclusion of patients who underwent other treatment (with steroids or orbital decompression) shortly before or within 6 months after irradiation, and on whom insufficient data were available, 90 patients were included. For these 90 patients, we analysed the exophthalmometry, ductions, soft tissue signs and visual acuity shortly before irradiation and after 3 and 6 months, respectively. RESULTS: In the whole group, the Hertel value was on average 22 mm (SD 2.9) both before irradiation and after 3 and 6 months of follow-up. Separate analysis of data on 25 patients with bilateral exophthalmos of more than 24 mm also revealed no change in exophthalmos at follow-up. In the whole group, both abduction and elevation had improved by about 1 degree (SD 6.6 degrees; p = 0.05) after 3 months. This improvement has little clinical significance. In a subgroup of 14 patients who showed more than 10 degrees of restricted eye motility in one or more directions, both abduction and elevation had increased by about 4 degrees (SD 10 degrees; p = 0.02) at 3 and 6 months follow-up. Soft tissue signs had improved at 6 months after irradiation. We found no change in visual acuity after irradiation. CONCLUSION: Retrobulbar irradiation in Graves' ophthalmopathy does not seem to reduce exophthalmos. It probably improves eye motility in patients with severe restrictions. The late improvement in soft tissue signs may either be a late effect of irradiation or be related to the natural history of the disease.

Adult↗

Pharmacodynamics and kinetics of omeprazole MUPS 20 mg and pantoprazole 40 mg during repeated oral administration in Helicobacter pylori-negative subjects.

BACKGROUND: Omeprazole has become available in a tablet formulation, a Multiple Unit Pellet System (MUPS) containing a large number of small individually enteric-coated micropellets. AIM: To compare the acid-inhibitory effect of omeprazole MUPS 20 mg with pantoprazole 40 mg and to describe the pharmacokinetics of both drugs following administration on day 1 and day 6. METHODS: Randomized, two-way crossover study. Sixteen Helicobacter pylori-negative healthy subjects, whose gastric acidity fell below pH 4 for 70% of a 24-h baseline period were included. Intragastric pH was measured continuously. RESULTS: On day 1 both drugs significantly raised median 24-h gastric pH compared to baseline. Median pH and percentages of time above pH 3 and 4 on day 1 and day 6 of administration were not significantly different, with the exception of median daytime pH on day 6, which was significantly higher with omeprazole (4.65 vs. 4.05). AUC and Cmax of omeprazole were significantly increased on day 6. AUC and Cmax of pantoprazole were not significantly increased. CONCLUSIONS: No significant difference in acid-inhibitory effect on day 1. On day 6 median daytime pH was significantly higher with omeprazole MUPS, but the percentages of time spent above pH 3 and 4 were not significantly different. The significant increase in bioavailability of omeprazole may contribute to the increased effect on day 6.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Efficacy and safety of wet-wrap dressings in children with severe atopic dermatitis: influence of corticosteroid dilution.

BACKGROUND: The wet-wrap treatment involves emollients or corticosteroid dilutions under occlusive wet dressings, and has been reported to be highly effective in severe refractory atopic dermatitis (AD). OBJECTIVES: To investigate the influence of different corticosteroid dilutions on the efficacy and hypothalamic-pituitary-adrenal (HPA) axis suppression in children with severe refractory AD having wet-wrap dressings. METHODS: Eighteen children were treated with a 50% dilution of fluticasone propionate (FP) 0.05% cream for 2 weeks. In another five children a side-to-side comparison was conducted with 10%, 25% and 50% dilutions of FP cream under wet wrap. A third group of eight children was treated with 0% (= emollient), 5%, 10% or 25% dilutions of FP cream applied on the whole body under wet wrap. RESULTS: After 1 week, a major improvement averaging 74% was observed, without apparent differences between 5%, 10% or 25% dilutions of FP cream under wet wrap, with less improvement in the second week of treatment. The first and second group of children showed HPA axis suppression in only three of 23 children using measurements of 09.00 h serum cortisol after 2 weeks. The third group of children showed HPA axis suppression, as indicated by 06.00 h serum cortisol levels, which was related to the absolute amount of FP applied. CONCLUSIONS: This suggests that weaker corticosteroid dilutions had comparable high efficacy, but lower risk of HPA axis suppression.

Administration, Topical↗

Preventive treatment of intranasal fluticasone propionate reduces cytokine mRNA expressing cells before and during a single nasal allergen provocation.

BACKGROUND: The local production and release of a number of cytokines regulate allergic upper airway inflammation. Medication is usually used at the presentation of the first symptoms. There are, however, clues that it is advisable to start taking the corticosteroid before the grass pollen season begins. METHODS: This single allergen provocation study was conducted in autumn, out of the hay fever season. Nasal mucosa biopsies were taken twice before provocation (before and after 4 weeks of preventive treatment) and three times after allergen provocation (1 h, 24 h and 1 week). The preventive treatment used was fluticasone propionate aqueous nasal spray (FPANS) (n = 10) or a placebo (n = 9). Eosinophils and mRNA positive cells (in situ hybridization for IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IFNgamma, RANTES and TNFalpha) were counted in the biopsies. RESULTS: Preventive treatment with FPANS out of season resulted in a decrease in eosinophils and mRNA positive cells for IL-5 and IL-6. After allergen provocation, levels of most of the measured cytokines (IL-3, IL-5, IL-6, IL-13, IFNgamma, RANTES and TNFalpha) and eosinophils were reduced using corticosteroids. The numbers of cells (eosinophils, IL-3, IL-6 and IL-8) correlated with nasal symptoms. Significant correlations in the early and late allergic phase were found between eosinophils and cytokines (IL-3, IL-10 and IL-13). CONCLUSION: These results indicate that preventive treatment with FPANS prior to contact with grass pollen is effective in reducing the increase of cytokine mRNA positive cells in reaction to grass pollen contact.

Administration, Intranasal↗

Intranasal capsaicin is lacking therapeutic effect in perennial allergic rhinitis to house dust mite. A placebo-controlled study.

In a recent placebo-controlled study we demonstrated that capsaicin is an efficacious substance in the treatment of non-allergic non-infectious rhinitis. In this study the therapeutic effect lasted more than 9 months. This effect was not based on modulation of inflammation. To evaluate the effect of repeated application of capsaicin to patients with a nasal allergy to house dust mites (HDM), using the same treatment protocol as recently introduced in the treatment of non-allergic patients. Twenty-six patients with rhinitis, 15 females and 11 males (range: 20-46 years; mean 30.5), allergic to HDM were treated with either capsaicin or placebo in a double-blind, placebo-controlled, parallel group design. Nasal reactivity to HDM expressed as nasal symptoms, albumin and leukotriene levels in nasal lavage fluid and responsiveness to histamine, assessed as symptoms before and 6 weeks after treatment, were used to compare both treatment groups. In addition, visual analogue scales and rhinitis quality of life (RQL) assessment before, 6 weeks after and 3 months after treatment were used as outcome variables. No significant effect of capsaicin on nasal challenge tests with HDM (nasal symptoms, albumin and leukotriene levels), on VAS or RQL outcome 6 weeks or 3 month's after treatment, was demonstrated. Capsaicin did have a small effect on the area of the curve (AUC) of histamine dose response curves (P = 0.03). Desensitization with capsaicin in doses sufficient to control symptoms in patients with severe non-allergic rhinitis is lacking therapeutic effect in perennial allergic rhinitis.

Administration, Inhalation↗

Psychosocial sequelae in 29 children with giant congenital melanocytic naevi.

Giant congenital melanocytic naevus (GCMN) may be expected to affect psychosocial functioning of children and their parents due to deviant appearance and painful treatment. To obtain insight into clinical aspects and psychosocial functioning of those suffering from GCMN, 29 children diagnosed with GCMN syndrome or single GCMN received a dermatological examination, were interviewed, and their mothers and teachers completed standardized questionnaires on the child's competence and behavioural/emotional problems and their own adjustment. Social problems were reported for 30% of the patients and behavioural/emotional problems for 25.9%. There was no correlation between visibility of the naevus, treatment or child age and psychological problems. Mothers reported considerable psychosocial burden. It is concluded that children with GCMN are at increased risk of social and behavioural/emotional problems, and mothers suffer considerable psychological impact of their child's condition.

Adaptation, Psychological↗

Body proportions during 6 years of GH treatment in children with short stature born small for gestational age participating in a randomised, double-blind, dose-response trial.

The aim of this study was to assess body proportions in children with short stature born small for gestational age (SGA) before and during 6 years of growth hormone (GH) treatment. A prospective randomised double-blind dose-response study comparing the effects of 3 vs. 6 IU GH/m2/day. Seventy-nine children with short stature (height SD-score < -1.88) born small for gestational age (birth length SD-score < -1.88). Before and during GH treatment, height, sitting height (SH), hand (Hand) and foot length (Foot), biacromial (Biac) and biiliacal diameter (Biil) were measured. All results were adjusted for age and sex, and expressed as SD-scores (SDS) using reference values for healthy Dutch children. To describe the size of SH, Hand, Foot, Biac, and Biil in relation to height, these values were adjusted for the SDS of height. At baseline, these short children had small hands and feet and narrow shoulders and pelvis compared to healthy peers. Height and SH, were, however, even more affected. Consequently, on average, these children had relatively large hands and feet, and relatively broad shoulders and pelvis compared to their height, but a normal sitting height in proportion to height. In most of the individuals, the values for body proportions were, however, within the normal range. During 6 years of GH treatment the SD-scores of all measurements increased significantly towards values more close to zero. The mean size of Hand, Foot, and Biil decreased in proportion to height. The mean SH increased relatively more than height, however, to values well within the normal range. The mean Biac in relation to height had not changed after 6 years of GH treatment. No differences in the 6-year changes in body proportions were found between the two GH dosage groups. Untreated short children born small for gestational age have, on average, relatively large hands and feet, and broad shoulders and pelvis, but a normal sitting height compared to height. The increase in height during 6 years of GH treatment is accompanied by an improvement of the proportions of the size of hands, feet, and biiliacal diameter, in relation to height. The increase in height appeared to be the result of the increase in sitting height as well as leg length, but the sitting height SD-score increased slightly more than that of leg length. The changes in body proportion during GH treatment were dose-independent. Thus, 6-year continuous GH treatment with either 3 or 6 IU/m2/day in children with short stature born small for gestational age does not negatively influence body proportions.

Anthropometry↗

Fetal transverse cerebellar diameter measurements in normal and reduced fetal growth.

OBJECTIVES: To establish the increase in fetal transverse cerebellar diameter (TCD) relative to gestational age during normal and restricted fetal growth; to determine the significance of TCD and TCD/AC relationship in predicting fetal outcome as expressed by perinatal mortality. DESIGN: A retrospective cross-sectional study. SUBJECTS: Three hundred and sixty normally developing fetuses between 17 and 34 weeks of gestation and 73 growth-restricted fetuses between 24 and 34 weeks of gestation. METHODS: Ultrasonographic measurements included head circumference (mm), abdominal circumference (mm) and transverse cerebellar diameter (mm). A gestational age-related normal reference chart was produced for TCD. RESULTS: Statistically significant relationships between transverse cerebellar diameter and gestational age, abdominal circumference and head circumference were found. The normal fetal TCD exhibited a more than twofold increase in size during the second half of pregnancy. Twenty-six per cent of the small-for-gestational age (SGA) fetuses displayed a reduced TCD and 82% of the SGA fetuses demonstrated raised TCD/AC values. No statistically significant difference in perinatal mortality or birth weight was found between the subsets of growth-restricted fetuses with reduced or normal TCD; or between the subsets with normal or raised TCD/AC values. CONCLUSIONS: In the normally developing fetus the TCD increases with advancing gestational age. Increased TCD/AC values are suspicious of fetal growth restriction. The perinatal mortality in growth-restricted fetuses with a small cerebellum is increased twofold over that of other fetuses.

Abdomen↗

The optimal stimulus to elicit suppression in small-angle convergent strabismus.

PURPOSE: To determine the optimal stimulus duration as well as the most appropriate luminance profile to elicit suppression in small-angle convergent strabismus. METHODS: In 10 subjects with small-angle convergent strabismus, using a device allowing binocular viewing and peripheral fusion, we determined what the optimal stimulus would be to elicit suppression. Three control subjects were also included in the study. Stimuli were shown randomly in the central 3 degrees of the visual field of either eye. Stimulus durations were varied in seven steps from 50 to 1000 ms and three luminance-time profiles were used: square wave, triangle and half-sinus, thus yielding 21 different stimuli. The peak light intensity was the same for all stimuli. RESULTS: Suppression, defined as the difference in the threshold sensitivities under monocular vs. binocular viewing, was found with our test device in five of the ten subjects, and ranged between 3 and 33 dB. Suppression was deepest with triangular or half-sinusoidal stimuli of 400 ms duration. Square wave stimuli elicited the smallest amount of suppression. CONCLUSION: Stimuli with a gradual increment and decrement, like triangular or half-sinusoidal stimuli, with a duration of 400 ms are the most effective to elicit suppression

Adolescent↗

Reproducibility of measurements with the nerve fiber analyzer (NfA/GDx).

PURPOSE: To determine the reproducibility of measurements with the Nerve Fiber Analyzer, a scanning laser polarimeter designed for quantifying glaucoma in healthy patients and patients with glaucoma. The authors also assessed the variance of measurements between instruments. METHODS: Measurements were made with the third generation Nerve Fiber Analyzer, the GDx. The study consisted of three parts. In the first part, the authors measured the right eyes of 10 healthy volunteers on 5 consecutive days. In the second part, 45 patients with glaucoma underwent Nerve Fiber Analyzer measurements of one randomly selected eye on two separate days in a 5-week period. For all 14 available parameters, reproducibility of measurements was expressed in terms of 95% limits of agreement and as the intraclass correlation coefficient. The Nerve Fiber Analyzer software has an option of creating a mean image from a selection of single images; for both parts of the study, the reproducibility of measurements was calculated for a "single image," and a "mean-of-three" image. In the third part of the study, 17 volunteers underwent repeated Nerve Fiber Analyzer measurement sessions on each of three different instruments. Using multivariate analysis of variance, the authors determined the variance of measurements between instruments. RESULTS: The reproducibility of measurements varied considerably across parameters. Limits of agreement in mean images for superior maximum and inferior maximum were 7.2 microm and 7.7 microm, respectively in the healthy volunteers, and 8.7 microm and 7.9 microm, respectively in the patients with glaucoma. For healthy patients, the intraclass correlation coefficient was greater than 90% in 10 of 14 parameters. In patients with glaucoma, the intraclass correlation coefficient was greater than 90% in 13 of 14 parameters. Some parameters reproduced better in a mean than in a single image; these differences, however, were small and generally not statistically significant. The between-instruments component also varied across parameters and was highest in ratio-based parameters. CONCLUSIONS: The reproducibility of measurements varied across parameters. In general, the reproducibility of measurements with the Nerve Fiber Analyzer was high. The reproducibility of measurements was similar between healthy patients and patients with glaucoma. Any measured change in nerve fiber layer thickness would be statistically significant if it exceeded approximately 7 or 8 microm in the superior maximum or inferior maximum parameter in healthy patients. Reproducibility of measurements hardly differed between single images and mean images. The reproducibility of measurements among the three instruments we used was highest for straight parameters.

Adult↗