Acoustic rhinometry and lavage biomarkers in relation to some building characteristics in Swedish schools.

It has been suggested that certain building factors can be associated with specific exposures, such as dampness, chemical emissions and dust. The aim of the study was to examine the relationships between some selected building factors, on the one hand, and signs of inflammation or obstruction in the upper airways on the other. Acoustic rhinometry and nasal lavage were used in a field study among 234 school personnel in 12 randomly selected schools (participation rate 84%). Eosinophil cationic protein (ECP), lysozyme, albumin and myeloperoxidase (MPO) were analyzed in the lavage fluid. Building related factors selected for the study were: roof inclination, fundament, building construction, signs of water damage, floor material, building age, ceiling height, bookcases and plants in the classroom. Control was made for potential confounders. The results indicate a pattern of nasal responses: less patent noses and an inflammatory biomarker response could be related to flat roof and a concrete slab fundament, factors that are known risk factors for water leakage, building dampness and possibly microbial growth. A reduced nasal patency without an inflammatory biomarker response was related to factors associated with plasticizers and dust. Positive effects were observed for plants in the classroom and in older buildings.

Influence of personal factors on nasal patency and lavage biomarkers in white-collar workers.

Large biological variability between subjects has been shown for both acoustic rhinometry and nasal lavage biomarker concentrations, but relatively little is known about the influence of personal factors on these techniques. The aim was to evaluate if nasal symptoms, acoustic rhinometric measurements and nasal lavage fluid biomarkers are related to age, gender, smoking, atopy or asthma. A standardized nasal investigation was applied in 411 white-collar workers, belonging to three occupational groups: school personnel (n = 234), office workers (n = 89) and hospital workers (n = 88). Lavage fluid analysis included determination of eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin. Females had smaller nasal dimensions in the anterior part of the nose (p < 0.001), and lower lavage fluid concentrations of ECP (p = 0.004), MPO (p = 0.002), and albumin (p = 0.01). Rhinometric dimensions or lavage fluid biomarker concentrations were not related to age, smoking, atopy or asthma. Some differences in rhinometric and biomarker measurements were observed between the occupational groups, and adjustment was made for occupation. Rhinometric measures and lavage biomarkers were consistently interrelated, which suggests a combined mucosal swelling and inflammatory reaction. This indicates a potential usefulness of a combined use of acoustic rhinometry and lavage biomarkers to study nasal mucosal reactions.

Indoor air pollutants in schools: nasal patency and biomarkers in nasal lavage.

BACKGROUND: There is growing concern about the respiratory health aspects of the indoor air quality in schools. METHODS: A standardized investigation, including nasal lavage (NAL), measurement of the nasal cavity by acoustic rhinometry, and hygienic measurements of airborne pollutants, was performed in classrooms, outside the pollen season. All 279 school personnel working in the main buildings of 12 randomly selected primary schools in an urban community in central Sweden (Uppsala) were invited to enroll in the study; 234 (84%) participated. Eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme, and albumin were analyzed in NAL fluid. Crude statistical analysis, as well as multiple regression analysis, was performed, controlling for room temperature, age, sex, current smoking, and a history of atopy. RESULTS: Most classrooms (83%) did not meet the Swedish ventilation standards. A lower degree of nasal patency was found at higher concentrations of respirable dust, nitrogen dioxide (NO2), formaldehyde, and total molds, and in the presence of Aspergillus spp. in the classroom air. The most consistent findings were observed for formaldehyde, NO2, and Aspergillus spp., related to both decreased nasal patency and increase of ECP and lysozyme in NAL. The presence of yeast was associated with an increase of ECP and lysozyme in NAL, but was not related to nasal patency. CONCLUSIONS: Ventilation flow was below current hygienic standards in the classrooms. Air pollutants in the classroom air may influence nasal patency and inflammatory response in the nasal mucosa.

Embryonic and postnatal accumulation of homogeneous substance in the endolymphatic sac in the guinea pig.

OBJECTIVE: The endolymphatic sac (ES) of vertebrates contains varying amounts of a homogeneous substance (HS) that stains deeply with basic aniline dyes. Histochemically, HS is characterized as a carbohydrate-protein complex, being both neutral and acidic in nature. In the present study, deposition of HS in the ES was studied in the guinea pig from the 3rd week of gestation to 104 weeks postnatally in order to find out if HS accumulates with age, at which point during embryonic development this substance appears, if its presence is correlated to the sense of hearing and if the amount of substance in the left versus right ear of one and the same animal is correlated to any degree. METHODS: Sixty-nine endolymphatic sacs were evaluated in 38 guinea pigs. The ES specimens were sectioned for light and transmission electron microscopy and the amount of HS filling was categorized in four groups: none, low, medium and a high level of substance. RESULTS: The substance was not discerned until after 7 weeks of gestation, when it filled only a minor part of the distal ES lumen. At 9 weeks gestation the nature of the substance altered, becoming homogeneous, as visualized by osmium-toluidine blue staining and approximately filling the distal half of the luminal space. In the postnatal period, 65% of ES specimens were filled with HS to the intermediate or proximal ES, whereas only 6.5% of the ES specimens were devoid of the substance. The extent of filling of the ES in the prenatal temporal bones was significantly less than postnatally (P < 0.0001, chi2-test). The extent of postnatal filling was not correlated with age. Left and right ears were closely correlated in one and the same animal. Phagocytic cells were often found at the border between clear endolymph and stainable substance. CONCLUSION: The appearance of HS seemed to coincide temporally with the onset of hearing during the prenatal period indicating that it could play a part in normal inner ear functioning in the guinea pig. The close correlation regarding the level of the HS in the left and right ear, both pre- and postnatally could reflect a general symmetry in endolymph pressure-volume conditions within the inner ear fluid systems, as well as in the environmental hydrostatic pressure in the posterior cranial fossa.

Acoustic rhinometry in epidemiological studies--nasal reactions in Swedish schools.

A cross-sectional study was performed on the relationships between hygienic measurements and nasal investigations in 234 personnel in 12 primary schools in mid-Sweden. Hygienic data included building characteristics, measurements of indoor air pollutants, air change rate, temperature and humidity. Clinical examinations included symptom reports, acoustic rhinometry and nasal lavage, with the determination of biomarker levels for eosinophil cationic protein (ECP), lysozyme, myeloperoxidase (MPO) and albumin. Subjective nasal obstruction was increased in schools with mechanical ventilation (adjusted prevalence OR = 2.0; 95 CI 1.1-3.7) and subjects reporting nasal obstruction had higher levels of dust in the classroom, compared to those not reporting this symptom (p = 0.008 by Mann-Whitney U-test). Congruently, a decreased nasal patency measured by acoustic rhinometric minimum cross-sectional areas (MCA1 and MCA2) was related to the use of mechanical ventilation (p = 0.008 and p = 0.02 respectively, by Mann-Whitney U-test), dust levels (p = 0.03 and p < 0.001 respectively, by Kendall's tau correlation analysis), a lower cleaning frequency of desks (p < 0.001 and p = 0.02 respectively, by Kendall's tau correlation analysis), the use of wet mopping (p < 0.001 and p = 0.04 respectively, by Mann-Whitney U-test) and PVC floor material (p < 0.001 and p = 0.034 respectively, by Mann-Whitney U-test). The cleaning frequency of floors was positively correlated with MCA1 (p = 0.049 by Kendall's tau correlation analysis). In buildings with signs of water damage, flat roof or a concrete slab fundament the personnel had increased ECP, lysozyme or albumin levels in nasal lavage. A reduced nasal patency and an increased inflammatory biomarker response were seen for higher levels of formaldehyde (MCA1, MCA2, VOL1, VOL2, ECP and lysozyme) and nitrogen dioxide (MCA1, VOL2, ECP and lysozyme) in the classrooms. In conclusion, the results indicate that acoustic rhinometry in combination with the determination of nasal lavage biomarkers can be used to study effects on the upper airways of the indoor environment. Actual exposures to indoor air pollutants in Swedish schools can affect the occurrence of subjective nasal obstruction and give clinical signs of reduced nasal patency together with an inflammatory biomarker response in the nasal mucosa.

Inflammation markers in nasal lavage, and nasal symptoms in relation to relocation to a newly painted building: a longitudinal study.

INTRODUCTION: There is a need to evaluate possible health effects of ventilation improvements and emissions from new buildings, in longitudinal studies. New methods to study biological effects on the eyes and upper airways are now available. MATERIAL AND METHODS: A longitudinal study was performed on 83 trained social workers in two offices in Uppsala, Sweden. The exposed group (n = 57) moved to a newly redecorated building nearby. Low emitting building material had been used, including a new type of solvent-free water-based paint. The control group (n = 26) worked in the same office during the study period (November 1995 to February 1996). Hygiene management was carried out in both offices, at the beginning and the end of the investigation. Tear film stability (BUT) was measured. Nasal patency was measured by acoustic rhinometry, and eosinophilic cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin were analyzed in nasal lavage fluid (NAL). RESULTS: The relocation resulted in an increase in the personal outdoor airflow rate from 11 to 22 l/s. Indoor concentrations of terpenes were higher in the new building, and powdering of the new linoleum floor was observed. Measurements showed low levels of volatile organic compounds (VOC), formaldehyde, carbon dioxide (CO(2)), nitrogen dioxide, respirable dust, and microorganisms in the air of all buildings. The move resulted in an increased nasal patency and an increase of ECP and lysozyme in NAL, after adjusting for changes in the control group. No changes were observed for nasal or ocular symptoms. A seasonal effect, with a decrease of ECP, was observed in the control group. CONCLUSSION A well-ventilated office building can be redecorated without any major ocular or nasal effects, or measurable increase of indoor air pollution if low-emitting building materials are selected. In agreement with previous evidence, the improved ventilation flow may explain the increase of nasal patency. The increase of ECP and lysozyme in NAL suggested an inflammatory effect in the new building. Since this building had increased ventilation flow, increased concentrations of terpenes, and powdering from the polish on the new linoleum floor, identification of causative agents was difficult. The hygiene measures did not give any evidence that emissions from the new type of solvent-free water-based paints or building dampness were responsible for the observed nasal effects. Considering the higher emissions of VOC reported from older types of water-based latex paints and solvent-based wall paints, the new type of solvent-free water-based paint seems to be a good choice from the hygiene point of view.

Nasal patency and lavage biomarkers in relation to settled dust and cleaning routines in schools.

OBJECTIVES: This study determined the relations between settled dust and cleaning routines in classrooms on one hand, and nasal symptoms, nasal cavity dimensions, and the concentration of selected biomarkers of inflammation in nasal lavage on the other. METHODS: Measurements of settled dust via standardized vacuum cleaning and an investigation of the cleaning routines were performed in 12 randomly selected primary schools in the municipality of Uppsala. Clinical examinations including acoustic rhinometry and nasal lavage were performed in the school environment among 279 school personnel working in the main buildings of the schools. Eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme, and albumin were analyzed in the lavage fluid. The relationships between the medical and hygienic data were analyzed both bivariately and with a multiple regression model controlling for age, gender, smoking, atopy, room temperature, and urban vicinity of the school. RESULTS: The amount of settled dust was positively related to subjective nasal obstruction and smaller nasal cavity dimensions measured with acoustic rhinometry. The noses were less patent, and the levels of ECP or lysozyme in the lavage were increased for the subjects in schools with a lower frequency of floor mopping, a lower frequency of desk cleaning, and where wet mopping was used. CONCLUSIONS: Our results indicate that the actual dust levels in Swedish classrooms can affect the occurrence of nasal obstruction among school personnel. A beneficial effect on the clinical signs of the nasal mucosa was observed for a higher frequency of both floor mopping and desk cleaning, whereas the use of wet mopping seemed disadvantageous in comparison with dry mopping. These findings illustrate the need for adequate cleaning procedures to minimize the environmental effects on the airway mucosa.

Nasal patency and biomarkers in nasal lavage--the significance of air exchange rate and type of ventilation in schools.

OBJECTIVES: The aim of the present study was to examine the relationships between the ventilation rate and the type of ventilation system, on the one hand, and objective nasal measures, on the other. METHODS: A standardized investigation, including acoustic rhinometry and nasal lavage, was performed in the school environment. All 279 school personnel working in the main buildings of 12 randomly selected primary schools in the municipality of Uppsala were invited, and 234 (84%) participated. The dimensions of the nasal cavity were measured with acoustic rhinometry. Eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme, and albumin were analyzed in the lavage fluid. The air exchange rate and the room temperature were measured in the classrooms. Relationships between nasal symptoms, nasal patency, and the concentration of biomarkers, on the one hand, and the type of ventilation system, the air exchange rate, and the temperature, on the other, were analyzed by both crude bivariate analysis and multiple regression models, controlling for the type of ventilation, the air exchange rate, room temperature, age, gender, smoking, atopy, and the urban vicinity of the school. RESULTS: A lower degree of nasal patency as measured by acoustic rhinometry and increased levels of ECP and lysozyme in nasal lavage were associated with a lower air exchange rate in the schools. Although mechanically ventilated schools had higher air exchange rates, they were associated with more nasal symptoms, and nasal mucosal swelling and with increased lavage levels of ECP and lysozyme as compared with schools with natural ventilation only. In contrast, 12 subjects working in a school with mechanical displacement ventilation had more patent noses and lower levels of inflammatory markers as compared with the personnel in schools with natural ventilation only. CONCLUSION: Our results indicate that both a low air exchange rate and mechanical ventilation systems based on dilution can be associated with reduced nasal patency and an inflammatory biomarker response of the nasal mucosa among school personnel. The only school with sufficient ventilation according to the current Swedish recommendations had a displacement system and the fewest signs of nasal reactions among the personnel.

Nasal congestion in relation to low air exchange rate in schools. Evaluation by acoustic rhinometry.

Upper airway symptoms are common, but there is little information available on clinical findings in relation to indoor air pollution. This pilot study was conducted to test whether increased levels of indoor air pollutants in schools may correlate to a swelling of the nasal mucosa. The assumption was made that the degree of swelling could be related to the degree of decongestive effect of xylometazoline, and measured by acoustic rhinometry. The study was performed among 15 subjects in a school with low air exchange rate (0.6 air changes/h) and 12 subjects in a school with high air exchange rate (5.2 air changes/h). Hygienic measurements were performed in both schools. Acoustic rhinometry was performed for each individual under standardized forms. Cross-sectional areas and volumes of the nasal cavity were measured before and after decongestion with xylometazoline hydrochloride. Absolute values of the minimal cross-sectional area were lower in the school with poor ventilation. The decongestive effect of xylometazoline was significantly higher in the school with low air exchange, when correction for the influence of age was made. A diminished decongestive effect was seen with increasing age. The exposure measurements showed that indoor concentrations of volatile organic compounds, bacteria and moulds were higher in the school with low ventilation. In conclusion, raised levels of indoor air pollutants due to inadequate ventilation in schools may affect the upper airways and cause a swelling of the nasal mucosa, and acoustic rhinometry could be a useful objective method to measure human nasal reactions to the indoor environment.

Morphological changes in rat submandibular gland mucous cells during fixation with 10% formalin.

The features of mucous cells in 10% formalin (FA)-fixed submandibular glands differ markedly from those fixed in glutaraldehyde (GA). We therefore studied morphological changes in mucous cells during 10% FA fixation. Mucous cells were fixed in either 10% FA, neutral sodium-phosphate-buffered (Na-PBed) 10% FA, ice-cold 10% FA or an ice-cold fixative mixture of 2.0% paraformaldehyde (PA) and 0.5% GA. Two different methods were used: immersion fixation and venous perfusion fixation. The 10% FA-fixed tissues had elliptical or flattened nuclei, a clear cytoplasm and no secretory granules. Tissues fixed with the fixative mixture displayed almost round nuclei, a broad endoplasmic reticulum and abundant secretory granules in the cytoplasm. Tissues immersion-fixed with neutral Na-PBed 10% FA or perfusion-fixed with ice-cold 10% FA had almost the same light microscopic appearance as that of the mixture-fixed tissues. To elucidate the process of morphological changes during 10% FA fixation at room temperature, samples immersed in 10% FA for varying periods of time were postfixed immediately in the fixative mixture and exposed to microwave irradiation. This method produced a variety of findings, even within the same section. There was a significant difference in the findings seen in the center of the section and at the periphery. The initial changes caused by 10% FA were rupture of the secretory granules located in the perinuclear region and destruction of the perinuclear organelles such as Golgi apparatus, mitochondria and endoplasmic reticulum. Absorption of the endoplasmic reticulum progressed so that the perinuclear region became translucent. To obtain a better structure in mucous cells from the fixed submandibular gland tissues, an appropriate fixative such as GA should be used and the fixative should infiltrate into the tissues as quickly as possible.

Origin of sympathetic and sensory innervation of the endolymphatic sac. A retrograde axonal tracing study in the guinea pig.

Lectin-conjugated horseradish peroxidase (WGA-HRP) was used as a retrograde axonal tracer to determine endolymphatic sac (ES) innervation and the nature of such a nervous supply. WGA-HRP placed into the ES of the guinea pig resulted in labelling of neurons in the ipsilateral sympathetic superior cervical ganglion and the sensory trigeminal ganglion. The number of labelled neurons in the cervical superior ganglion varied according to the survival time with peak labelling occurring after 48 h. Sparse labelling of the sensory trigeminal ganglion was also present after 48 h. The results indicate that sympathetic neurons from the superior cervical ganglion and to a certain extent trigeminal somatosensory neurons innervate the ES or perisaccular tissue. If these findings reflect the existence of a sympathetic functional reflex unit remains to be elucidated.

Hyaluronan content in human inner ear fluids.

Histochemical analyses of the luminal contents of the endolymphatic sac in numerous mammalian species have indicated a presence of acid mucopolysaccharides or proteoglycans. In the present study, one of these substances, hyaluronan (hyaluronic acid; HA), in endolymphatic sac endolymph and vestibular perilymph in humans, was biochemically determined with a highly specific radioassay. A considerable variation in HA concentration was noted between the individual ES endolymph samples, with a mean value of 2.50 micrograms/g (range 0.00-10.86). In perilymph the HA concentrations were less variable and the mean concentration was 0.91 micrograms/g (range 0.56-1.51). The difference between endolymph and perilymph HA concentration was not statistically significant (p greater than 0.05). The ability of HA to interact with proteoglycans, thereby forming giant hydrophilic molecules, could be important for ES function. These molecules may create a swelling pressure which is resistant to compressive forces that under conditions of increased intracranial hydrostatic pressure otherwise could cause ES collapse and impaired function.

Uptake of radioactive sulphur in the endolymphatic sac. An autoradiographic study.

Autoradiographic uptake of labelled sulphur (S35) in the endolymphatic sac was analysed after performing surgical labyrinthectomy and after systemic administration of glycerol and ethacrynic acid. Accumulation of radioactive substance was observed after surgical labyrinthectomy and associated with a deposition of stainable substance in the endolymphatic sac lumen. Increased activity was noted in the epithelial layer after administration of ethacrynic acid, whereas glycerol did not increase radioactivity in the endolymphatic sac despite the deposition of stainable substance therein. This fact was believed to depend on a too short time interval between the injection and the sacrifice of the animals, as well as a weaker concentration of the sulphated compound within the endolymphatic sac. The results suggest that the endolymphatic sac may secrete sulphur-containing substances presumably associated with a deposition of a stainable substance in the endolymphatic sac.

Effects of hyperosmolar substances on the endolymphatic sac.

The murine endolymphatic sac (ES) was studied 15 min to 8 hours after intravenous glycerol administration. Initially the ES showed varying degrees of obliteration and this was mostly pronounced at 15-60 min after the injection. After 2 hours the normal volume was regained and after 4 hours the lumen was dilated to 160% of its normal volume. After 6-8 hours the ES had almost regained its normal appearance. The epithelial lining showed an increase in the number of granular cells which, after two hours, reached a peak of 15.8% (p less than 0.01) compared to normal controls which showed 6.1% granular cells of total cell population in the ES. The increase of granular cells was accompanied by filling of the ES lumen with a stainable substance. The epithelial reaction may serve the purpose of counteracting decreases in endolymph pressure either in the ES or in the entire labyrinth.

General effects of hyperosmolar agents on the endolymphatic sac.

The effects of glycerol, urea and mannitol on the structure of the murine endolymphatic sac were investigated at various time intervals after their administration. Within 15 min after administration of glycerol and urea the lumen of the endolymphatic sac was partially collapsed and the density of its contents was increased. At the same time many light epithelial cells displayed abundant intracytoplasmic granules containing floccular and/or lamellar material. A similar type of material was observed in the lumen in close proximity to these cells. This suggested that macromolecular substances were secreted into the endolymphatic sac lumen from these cells. Mannitol induced similar changes, though less pronounced. It is proposed that the changes in the endolymphatic sac following systemic administration of hyperosmolar substances reflect an ability of the endolymphatic sac to compensate for endolymphatic volume and pressure changes caused by these agents.

Subcellular changes in the endolymphatic sac after administration of hyperosmolar substances.

The effects of hyperosmolar substances on the ultrastructure of the endolymphatic sac were studied in mice. Fifteen minutes after intravenous injection of urea or glycerol, subcellular changes in the endolymphatic sac were observed. These consisted of the occurrence of abundant cytoplasmic granules with a floccular or lamellar material, or both, in the light epithelial cells. Similar material was also present in the lumen of the endolymphatic sac, suggesting a common source and increased secretory activity. Mannitol caused similar changes, though less pronounced. The possibility that the alterations in the fine structure of the endolymphatic sac may be associated with a reduction in the hydrostatic fluid pressure in the rest of the labyrinth is discussed.

Degradation of the homogeneous substance in the endolymphatic sac.

The accumulation and degradation of a homogeneous precipitate in the lumen of the endolymphatic sac (ES) was studied in mice. Filling of the endolymphatic sac was induced by surgical labyrinthectomy and the sacs were studied 1-8 weeks postoperatively. The initial phase (1-2 weeks postlabyrinthectomy) was characterized by filling of the ES with the homogeneous precipitate. The number of freely floating cells in the lumen was increased after two weeks. Three weeks postoperatively the ES lumen was generally clear, with apparently no stainable material. Ultrastructural analysis of the ES showed that this clearance of the endolymphatic space resulted from degradational activity in the epithelial cells initiated in the proximal portion of the sac. Breakdown of the homogeneous substance seemed to result from cellular ingestion with concomitant lysosomal digestion. Four weeks postoperatively cell clusters were observed subepithelially and were filled with densely staining precipitate, indicating that these cells or macrophages were involved in the turnover of the homogeneous substance in the ES. The functional significance of a degradational system of this substance in the ES is discussed.

Effects of ototoxic diuretics (loop diuretics) on the endolymphatic sac.

The acute and chronic effects of treatment with ethacrynic acid (EA) and furosemide (FU) on the structure of the murine endolymphatic sac were studied by means of light and transmission electron microscopy. The animals were treated with loop diuretics in doses which are known to cause morphological alterations of the stria vascularis and a significant reduction of the endocochlear potential. A single intravenous injection of either EA or FU resulted in immediate morphological changes such as an increase in cytoplasmic contents of endoplasmic reticulum and more prominent Golgi structures of the light cells. These cells developed membrane-bound granules and a smooth tubular network in the apical cytoplasm. These findings together with the appearance of a precipitate on the luminal aspect of the cell membrane suggested secretory activity. Ten days after daily intraperitoneal injections with loop diuretics in subtoxic doses, the epithelial cytoarchitecture of the endolymphatic sac was altered, with pronounced veiling of the light cells by the dark cells. It is concluded that the changes in the endolymphatic sac epithelium after treatment with ototoxic diuretics may not be a result of a primary toxic effect on the sac per se, but rather be secondary to alterations in fluid and ion homeostasis in the rest of the inner ear.

Reflux esophagitis: assessment of therapy effects and observer variation by video documentation of endoscopy findings.

Twenty-eight patients with endoscopically confirmed erosive or ulcerative esophagitis completed an 8-week placebo-controlled trial evaluating the symptomatic and endoscopic improvement obtained with ranitidine, 150 mg twice daily. Twice daily the patients recorded the number of episodes of retrosternal pain, regurgitation, and pyrosis on a diary card during a trial period of 1 week and during the 1st and 5th study week. Video documentation of endoscopy findings was undertaken before and at the end of the trial. The symptomatic relief obtained with ranitidine was significantly better than that obtained with placebo. The videotapes were assessed blindly and independently by three experienced fiberoptic endoscopists. The tapes were also recoded and reassessed by the same endoscopist. No systematic difference between different observers, either before or after treatment, could be detected. The interobserver variation, expressed as Kendall's tau b correlation coefficient, was 0.44 to 0.74. This coefficient was higher in intra-observer variation (0.63 to 0.91). Corresponding kappa-values for inter- and intra-observer variations were 0.12 to 0.30 and 0.27 to 0.85, respectively. The esophagitis, as judged by all observers, improved more in the ranitidine group than in the placebo group, but the difference did not reach statistical significance.