Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “pH”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1991

Relationship of cerebral and myocardial intracellular pH to blood pH during hypothermia.

The regulation of tissue pH during hypothermia is important for cellular homeostasis. The present study was undertaken to determine the relationship between blood pH and intracellular pH in the brain and heart during hypothermia in sheep and to compare these data with those in humans. Intracellular pH (pHi) was determined by 31P nuclear magnetic resonance (NMR) spectroscopic data collected from the heart and brain of sheep during cardiopulmonary bypass (CPB). Alpha-stat and pH-stat blood pH management schemes were compared. When the blood pH was held constant (pH stat), the pHi of the heart increased from 7.01 +/- 0.01 at 37 degrees C to 7.18 +/- 0.02 at 26 degrees C, and the pHi of the brain increased from 7.04 +/- 0.02 at 37 degrees C to 7.23 +/- 0.02 at 26 degrees C and to 7.32 +/- 0.04 at 20 degrees C. Alpha-stat pH management resulted in similar increases in pH to that found with pH-stat [heart: 7.00 +/- 0.02 at 37 degrees C to 7.19 +/- 0.03 at 26 degrees C; brain: 7.07 +/- 0.02 at 37 degrees C to 7.29 +/- 0.02 at 26 degrees C, and 7.32 +/- 0.03 at 20 degrees C]. The tissue pH of the heart in humans showed similar findings during blood pH-stat regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

pH-dependent elution profiles of selected proteins in HPLC having a stationary phase modified with pH-sensitive sulfonamide polymers.

An approach to controlling protein interactions with silica (glass) beads grafted with pH-sensitive copolymers of a sulfonamide and N,N-dimethylacrylamide is proposed. The bead surface was modified with poly(N.N-dimethyl acrylamide-co-methacryloyl sulfadimethoxine), which exhibits hydrophobic/hydrophilic switching around pH 7.0. Phase transition in the aqueous solution, the wettability change of the modified surface and surface tension of the polymer-grafted glass surface was characterized by changes in turbidity and the dynamic contact angle as a function of pH. The discontinuous phase transition in the copolymer solution shifted to a higher pH region as the composition of sulfadimethoxine monomer (SDM) was increased. However, the transition pH in continuous wettability changes on the modified surface was not affected by polymer composition due to differences in the dynamic motion. The ionized SDM of the copolymers enhanced wettability. Therefore, the advancing contact angle of the surface decreased by 45 degrees above pH 7.0, whereas wettability at low pH values was low due to the hydrophobic surface. Elution behavior of the selected four model proteins with different pI (bovine serum albumin (pI 5.0), insulin (pI 5.3), fibrinogen (pI 6.1) and myoglobin (pI 7.1)) was investigated by using pH-sensitive copolymer-modified glass beads at four pH values (5.0, 6.0, 7.0 and 8.0). Retention time of the proteins in pH-sensitive aqueous chromatography was easily regulated by eluent pH that controls the proportion of electrostatic and hydrophobic interactions between the stationary phase and the protein. At pH 5.0, hydrophobic interaction on the deionized polymer-grafted surface is an important force in separating the proteins. However, identification of the proteins at pH 7.0 was effectively facilitated due to the electrostatic interaction between the negatively charged polymer support and positive charges on protein.

Biocompatible Materials↗
PubMed1990

Activity of the multidrug transporter results in alkalinization of the cytosol: measurement of cytosolic pH by microinjection of a pH-sensitive dye.

Multidrug-resistant cells contain a plasma membrane efflux pump, the multidrug transporter, which actively expels certain hydrophobic drugs from the cytosol to the cell exterior. These drugs are usually positively charged at physiological pH. Because one might predict that this efflux of positively charged molecules might deplete the cytosol of protons, raising the cytosolic pH, we examined the cytosolic pH of multidrug-resistant cells directly using a pH-sensitive dye coupled to a membrane-impermeable molecule. The dye (SNARF), covalently coupled to 10,000 MW dextran, was mechanically microinjected into the cytosol of cultured multidrug-resistant mouse NIH3T3 cells which express the human multidrug transporter. The fluorescence emission of the dye in living cells was measured using epifluorescence microscopy at different wavelengths to provide a measure of the pH of the cytosolic environment. Multidrug-resistant cells had a higher cytosolic pH than drug-sensitive normal parental cells. As the pH of the culture medium was increased, normal cells maintained their cytosolic pH below 7.0, whereas the cytosolic pH of multidrug resistant cells rose. The difference in cytosolic pH between the two cell types was more than 0.2 pH units at an external culture medium pH of 8.2. Treatment with agents that inhibit multidrug transporter-mediated efflux, such as verapamil and vinblastine, essentially eliminated the elevation of cytosolic pH, presumably because they are good substrates for the pump which overwhelm its capacity to pump other materials. These results suggest that the multidrug transporter is indirectly a proton pump, and that cells may contain an endogenous substrate or substrates for this transporter in the absence of added drugs.

Alkalies↗
PubMed2001

[The pH reaction in aqueous humor to antiglaucoma agents of various concentrations and pH levels].

The authors investigated the effect on pH of the aqueous humour in man (collected before surgery of senile cataract, where the pH of the aqueous humour was within the range of 6.80-7.46 (7.11 +/- 0.11), after administration of antiglaucomatic drugs with a different concentration and pH (0.005% Xalatan--pH 6.43, 0.5% Timoptol--pH 6.80, 1% Pilocarpine--pH 5.87, 2% Trusopt--pH 5.33) under conditions in vitro. All mentioned antiglaucomatic drugs immediately reduced the pH of the aqueous humour towards acid values in the following order: Trusopt-Xalatan-Pilocarpine-Timoptol. pH changes of aqueous humour after addition of Timoptol, Xalatan, Pilocarpine have the same course in time, and shift to alkaline pH values. The pH of aqueous humour after addition of Trusopt reached only during the 240th minute levels of the control aqueous humour. The pH values after all antiglaucomatic drugs did not change between 240 minutes and 24 hours. As regards the rate of activity and extent of effect in conjunction with the time when the pH of the control aqueous humour was attained the authors recorded the following order: Pilocarpine-Timoptol-Xalatan-Trusopt.

Aged↗
PubMed2002

Effects of pH management during deep hypothermic bypass on cerebral microcirculation: alpha-stat versus pH-stat.

OBJECTIVE: There is controversy regarding the optimal pH strategy during deep hypothermic bypass in children. We directly visualized the effects of the pH-stat and alpha-stat strategy on cerebral microcirculation (including leukocyte/endothelial cell interactions) in a piglet model using intravital fluorescence microscopy. METHODS: Two groups of 5 piglets (mean weight 9.6+/-1.3 kg) with a cranial window over parietal cerebral cortex underwent 10-minute normothermic bypass, 40-minute cooling on cardiopulmonary bypass ([CPB] Hct 30%, 100 mL/kg/min), 60-minute circulatory arrest at 15 degrees C, and 40-minute rewarming with alpha-stat (group alpha) or pH-stat (group pH). Plasma was labeled with fluorescein-ITC-dextran for assessment of microvascular diameter. Circulating leukocytes were labeled and observed in postcapillary venules for adhesion before and up to 120 minutes after CPB. Cerebral tissue oxygenation was evaluated by quantification of NADH autofluorescence, which increases during ischemia. RESULTS: At the end of normothermic bypass diameter of cerebrocortical microvessels increased to 116+/-9% (alpha) versus 119+/-10% (pH) of pre-CPB baseline values. During cooling microvascular diameter decreased in group alpha and significantly increased in group pH (89+/-11% (alpha) versus 132+/-13% (pH) at the end of cooling; P<0.001). During the first 10 minutes of rewarming, the cerebral microvascular diameter was significantly larger when the pH stat strategy was used. Tissue oxygenation at the end of cooling was significantly greater in the pH-stat group (P=0.008). On reperfusion, the pH-stat strategy resulted in significantly more rapid return of tissue oxygenation toward baseline although at the end of rewarming the metabolic recovery was complete in both groups. The whole body lactate during early rewarming was significantly less with the pH stat strategy. There was no significant difference between the groups regarding the number of adherent leukocytes throughout the time course of the experiment. CONCLUSIONS: pH-stat management increases tissue oxygenation during deep hypothermic bypass and after circulatory arrest. Leukocyte/endothelial cell interactions during hypothermic bypass are mild with both alpha-stat and pH-stat.

Animals↗
PubMed1988

Intracellular pH of Chinese hamster ovary cells heated at 45.0 degrees C at pH 6.6.

The mechanism by which low pH sensitizes cells to hyperthermic treatments is unknown. In this report we have examined the relationship between the extracellular and intracellular pH of Chinese hamster ovary (CHO) cells after 45.0 degrees C heating. The intracellular pH (pHi) was measured with a fluorescence technique developed for flow cytometric instrumentation using the dye 1,4-diacetoxy-2,3-dicyanobenzene. Cellular esterase activity was modified by heating, requiring 20 min incubation time with the dye to achieve stable intracellular pH measurements. The intracellular pH of CHO cells incubated under normal pH (7.3) conditions was not perturbed significantly with up to 20 min of heating. Heating from 5 to 15 min induced increases in the pHi of CHO cells incubated under low pH (6.6) conditions. Cells heated in either normal pH or low pH medium became acidified with prolonged heating times. However, the distributions of intracellular pH showed that 20 to 30% of the population heated for up to 60 min at either pH 7.3 or 6.6 overlapped with the pHi distributions of normal cells. A decrease in intracellular pH does not seem to be the principal reason for the heat sensitization caused by low extracellular pH.

Animals↗
PubMed1998

Mitochondrial dysfunction and cytoskeletal disruption during chemical hypoxia to cultured rat hepatic sinusoidal endothelial cells: the pH paradox and cytoprotection by glucose, acidotic pH, and glycine.

We investigated mechanisms underlying death of cultured rat liver sinusoidal endothelial cells exposed to chemical hypoxia with KCN (2.5 mmol/L) to simulate the adenosine triphosphate (ATP) depletion and reductive stress of anoxia. During chemical hypoxia, acidotic pH prevented cell death. Glucose (0.3-10 mmol/L) also prevented cell killing. Cytoprotection by glucose but not acidosis was associated with prevention of ATP depletion. After 4 hours of chemical hypoxia at pH 6.2 (simulated ischemia), rapid cell death occurred when pH was restored to pH 7.4 with or without washout of KCN (simulated reperfusion). This pH-dependent reperfusion injury (pH paradox) was prevented after KCN washout at pH 6.2. Glycine (0.3-3 mmol/L) also prevented the pH paradox, but glucose did not. The initial protection by acidotic pH and glycine during simulated reperfusion was lost when pH was later restored to 7.4 or glycine was subsequently removed. Mitochondria depolarized during chemical hypoxia. After washout of cyanide, mitochondrial membrane potential (delta psi) did not recover in cells that subsequently lost viability. Conversely, those cells that repolarized after cyanide washout did not subsequently lose viability. The actin cytoskeleton and focal adhesions became severely disrupted during chemical hypoxia at both pH 6.2 and 7.4 and did not recover after cyanide washout under any condition. Glucose during chemical hypoxia prevented cytoskeletal disruption. In conclusion, endothelial cell damage during simulated ischemia/reperfusion involves mitochondrial dysfunction, ATP depletion, and ATP-dependent cytoskeletal disruption. Glycine and acidotic pH prevented cell killing after reperfusion but did not reverse mitochondrial injury or the profound disruption to the cytoskeleton.

Adenosine Triphosphate↗
PubMed1980

Salt-induced pH changes in spinach chloroplast suspension. Changes in surface potential and surface pH of thylakoid membranes.

A pH decrease in chloroplast suspension in media of low salt concentration was observed when a salt was added at pH values higher than 4.4, while at lower pH values a pH increase was observed. The salt-induced pH changes depended on the valence and concentration of cations of added salts at neutral pH values (higher than 4.4) and on those of anions at acidic pH values (lower than 4.4). The order of effectiveness was trivalent greater than divalent greater than monovalent. The pH value change by salt addition was affected by the presence of ionic detergents depending on the sign of their charges. These characteristics agreed with those expected from the Gouy-Chapman theory on diffuse electrical double layers. The results were interpreted in terms of the changes in surface potential, surface pH and the ionization of surface groups which result in the release (or binding) of H+ to (or grom) the outer medium. The analysis of the data of KCl-induced pH change suggests that the change in the surface charge density of thylakoid membranes depends mainly on the ionization of carboxyl groups, which is determined by the surface pH. When the carboxyl groups are fully dissociated, the surface charge density reaches -1.0 +/- 0.1 . 10(-3) elementary charge/square A. Dependence of the estimated surface potential on the bulk pH was similar to that of electrophoretic mobility of thylakoid membrane vesicles.

Cations↗
PubMed1990

The energy requirements of pH homoeostasis define the limits of pH regulation--a model.

The regulation of intracellular pH of Platymonas subcordiformis cells is investigated with 31P-NMR spectroscopy at various external pH values. The limits of pH homeostasis differ between respiring cells and cells solely glycolyzing. The former retain their normal cytoplasmic pH for external pH values from 5 to more than 12, while in the latter intracellular pH is less stable below external pH 6, and external pH of more than 11 causes hydrolysis of intracellular polyP. The power necessary to maintain a stable intracellular pH is calculated from the electrochemical potential and H+/OH- flux rates across the cell membrane. H+/OH- transport across the membrane by diffusion as well as through hydrogen-bonded chains is considered. Comparison of the minimal power necessary to keep intracellular pH stable at various external pH values by ATP consuming processes with the estimated power available to aerobic and anaerobic cells in the dark shows that different energy turnover may explain the different behaviour of the cells when exposed to extreme pH values.

Adenosine Diphosphate↗
PubMed2001

Females have lower skin surface pH than men. A study on the surface of gender, forearm site variation, right/left difference and time of the day on the skin surface pH.

BACKGROUND/AIMS: It is of great interest to describe the many functions and properties of the skin in order to better understand reactions that result in different skin abnormalities, as a prerequisite in the development of skin products and topical medicines. Skin surface pH is considered a critical parameter of skin wellbeing and is typically studied on the forearm skin. Despite many previous investigations, this is an extensive field that still needs a great deal of research. The aim of our study was to investigate gender related differences, differences between right and left arms, anatomical variation and daytime variation in skin surface pH. METHODS: Skin surface pH was measured on the flexor surface of the forearm on eleven healthy volunteers (6 men and 5 women). A Mettler Toledo pH meter (pH meter 1140) was used. The subjects were measured once every hour from 8 a.m. to 3 p.m. in five areas from the elbow to the wrist. In each of the five areas, three measurements were performed next to each other, and the mean of these was used in subsequent calculations. RESULTS: A statistically significant difference in skin pH between men (mean pH=5.80) and women (mean pH=5.54) was found, with women being more acidic than men (P<0.01). No difference between right and left arm was found. In men, the area closest to the wrist had significantly lower pH values compared with the proximal sites. This was not the case in women. Skin surface pH decreased during normal working hours in both genders. CONCLUSION: Spontaneous skin surface pH was found to be significantly lower in women, as compared to men--albeit, the difference was small and of unknown relevance. Nevertheless, comparative studies on skin surface pH should be balanced with respect to gender. There appeared to be no right/left difference and no systematic change during the working day. Also, measurements should not be conducted close to the wrist.

Female↗
PubMed1996

Objective determination of pH thresholds in the analysis of 24 h ambulatory oesophageal pH monitoring.

In 24 h oesophageal pH monitoring, pH 4 is widely but arbitrarily used as the threshold between reflux and non-reflux pH values. The aim of the study was to define pH thresholds objectively, based on Gaussian curve fitting of pH frequency distributions. Single-channel 24 h oesophageal pH monitoring was performed in 26 healthy volunteers and 26 patients with pathological gastro-oesophageal reflux, and five-channel pH-metry was performed in 14 healthy volunteers and 14 patients. The calculated pH thresholds varied between healthy volunteers from 5 center dot 0 to 6 center dot 4 in the upright position and from 4 center dot 5 to 5 center dot 7 in the supine position, but were constant between different oesophageal recording sites. In 15 and nine patients (single-channel and five-channel pH-metry respectively), pH thresholds could not be determined at the distal oesophageal sites. However, the calculated pH thresholds in the proximal oesophagus were in the same range as in the control subjects. The authors conclude that the use of the conventional threshold of pH 4 leads to underestimation of the extent of gastrooesophageal reflux, but are reluctant to advocate the use of higher thresholds in clinical practice.

Adult↗
PubMed2000

The relationship of raw broiler breast meat color and pH to cooked meat color and pH.

Three replicate trials were conducted to determine the influence of raw breast meat color and pH on subsequent cooked meat color and pH. In each trial, approximately 50 breast fillets were obtained from a commercial processing plant based on being either normal, lighter than normal, or darker than normal. Color (L* = lightness, a* = redness, and b* = yellowness) of each fillet was determined in triplicate on the underside surface of the fillet (to avoid scalding effects), and the pH was determined on a tissue sample removed from the posterior portion of each fillet. Fillets were then cooked in steam at 98 C for 20 min and cooled to room temperature, and a second sample was removed from the posterior section for cooked meat pH. Cooked meat color was measured on an exposed surface, to avoid cooking-related discoloration. The data were subjected to linear regression analysis to determine the relationship between raw and cooked values. Results indicated a significant linear relationship between raw and cooked values for each color parameter as well as pH. Model R2 values were 0.43, 0.40, 0.64, and 0.78 for L*, a*, b*, and pH, respectively. There were also significant linear relationships between raw meat L* and raw muscle pH (R2 = 0.59) as well as cooked meat L* and raw meat pH (R2 = 0.36). These results indicate that raw breast meat color and pH affect cooked breast meat color and pH but that cooking reduces the degree of color variation. Moreover, cooked meat lightness is more closely associated with raw breast meat pH than with cooked meat pH.

Analysis of Variance↗
PubMed1990

Does pH paper accurately reflect gastric pH?

The testing of gastric pH in the ICU has become the standard of care for most critically ill patients. It has been demonstrated that maintaining a gastric pH of greater than 3.5 confers protection from upper GI bleeding, while lesser pH values subject the patient to hemorrhagic risk. We compared nasogastric pH, as measured by pH electrode, to color-scaled pH paper in 16 critically ill patients hospitalized 3 to 10 days in the surgical ICU. Statistical analysis of 370 gastric specimens revealed a sensitivity of 66.7% and specificity of 94.5% when a paper pH (pH[p]) of greater than or equal to 4 was used as the therapeutic end-point. The sensitivity and specificity of the same pH(p) for clear buffered solutions were 100%. We conclude that the use of pH(p) lacks the clinical accuracy for determining the effects of therapy for the prophylaxis of stress gastritis and will lead to a significant degree of undertreatment. This lack of accuracy is not due to observer error or the quality or age of the testing paper. Our results suggest that if the measurement of gastric pH by pH(p) analysis is to be used as a guide for the prevention of stress-related hemorrhage, a more accurate method of monitoring may be warranted.

Critical Care↗
PubMed2000

Dynamic changes of intracellular pH in individual lactic acid bacterium cells in response to a rapid drop in extracellular pH.

We describe the dynamics of changes in the intracellular pH (pH(i)) values of a number of lactic acid bacteria in response to a rapid drop in the extracellular pH (pH(ex)). Strains of Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, and Lactococcus lactis were investigated. Listeria innocua, a gram-positive, non-lactic acid bacterium, was included for comparison. The method which we used was based on fluorescence ratio imaging of single cells, and it was therefore possible to describe variations in pH(i) within a population. The bacteria were immobilized on a membrane filter, placed in a closed perfusion chamber, and analyzed during a rapid decrease in the pH(ex) from 7.0 to 5.0. Under these conditions, the pH(i) of L. innocua remained neutral (between 7 and 8). In contrast, the pH(i) values of all of the strains of lactic acid bacteria investigated decreased to approximately 5.5 as the pH(ex) was decreased. No pronounced differences were observed between cells of the same strain harvested from the exponential and stationary phases. Small differences between species were observed with regard to the initial pH(i) at pH(ex) 7.0, while different kinetics of pH(i) regulation were observed in different species and also in different strains of S. thermophilus.

Hydrogen-Ion Concentration↗
PubMed1991

Effect of changing venoarterial pH difference on in vivo arterial pH.

Plasma pH has been postulated to change slowly in blood leaving the pulmonary capillaries because of the uncatalyzed dehydration of CO2. If so, there could be a difference between in vivo and in vitro arterial pH, the magnitude of which would be dependent on the venoarterial pH difference (v-aDpH). We tested this hypothesis in anesthetized dogs by changing v-aDpH by airway CO2 loading and by comparing arterial pH measured in vivo by a rapidly responding intravascular pH electrode with that measured in vitro by a conventional glass electrode. Using a multiple regression analysis, we found a small but significant contribution of venous pH to in vivo arterial pH, with a regression coefficient of 0.0718 (P less than 0.0001), suggesting a postcapillary increase of in vivo arterial pH. When carbonic anhydrase was inhibited by the administration of acetazolamide, the effect of venous pH on arterial pH was abolished, and a unique relationship between in vivo and in vitro arterial pH was established (regression coefficient 1.02; P greater than 0.05, comparison with unity). These results could be accounted for in a computer simulation of gas exchange among alveolus, plasma, and erythrocyte. We conclude that there exists a small but measurable postcapillary increase in arterial pH.

Acetazolamide↗
PubMed1992

Development of buffer systems for pH control and evaluation of pH effects on fiber digestion in vitro.

An in vitro buffering system capable of pH control between pH 5.8 and 6.8 was developed to examine the effect of media pH on disappearance of NDF at various times of fermentation and to assess initially the effect of media pH on kinetics of NDF digestion. The pH conditions selected for evaluation of these buffer systems were 5.8, 6.2, and 6.8. Use of McIlvaine's solution with sodium bicarbonate was not successful because of rapid drifting of pH downward during fermentation. To evaluate the effectiveness of citric or phosphoric acids as components of phosphate-bicarbonate buffer systems, alfalfa silage and a mixture of alfalfa silage and corn grain (1:1 mixture, dry basis) were fermented for 0, 12, 24, 48, and 72 h. The pH of each flask was measured at 0, 4, 12, 24, 48, and 72 h postinoculation, and pH was readjusted with bicarbonate solution when necessary. Drifting of media pH downward was more noticeable when phosphoric acid was used to adjust the buffer pH than with citric acid. Citric acid had no adverse effects on NDF digestion compared with phosphoric acid when used to adjust a phosphate-bicarbonate buffer system. Alfalfa hay, bromegrass hay, and corn silage were incubated for 0, 12, 24, 48, 72, or 96 h at pH 5.8 or 6.8 using the phosphate-bicarbonate buffer system adjusted with citric acid. Estimation of kinetics of NDF digestion indicated that a decrease in media pH from 6.8 to 5.8 resulted in a marked reduction in NDF digestion; the largest apparent difference was extended digestion lag time.

Animal Feed↗
PubMed2006

In vitro pH analysis of active and arrested dentinal caries in extracted human teeth using a micro pH sensor.

The aim of this study was to evaluate the pH at the surface of active or arrested carious dentin using a micro pH sensor, and to compare the relationship between different pH measurement techniques. Twenty extracted carious teeth were divided into two groups, active or arrested caries, according to predefined clinical criteria before extraction. The surface pH values of carious dentin were measured using three methods: surface pH directly measured using a micro pH sensor (Direct); sectioned teeth measured using a pH-imaging microscope (Imaging) or micro pH sensor (Slice). For all techniques, statistically significant differences in pH values were observed between active and arrested dentinal caries (p<0.05). In addition, positive relations between the three pH measurement methods were found. In conclusion, Direct pH measurement using micro pH sensor might assist in caries lesion assessment and clinical treatment based on the concept of Minimal Intervention.

Adult↗
PubMed1991

Which pH threshold is best in esophageal pH monitoring?

Two questions were examined, namely, 1) whether pH 4 is really the optimal threshold for the definition of acid gastroesophageal reflux, and 2) to what extent shifting of the upper limits of normal affects sensitivity and specificity of 24-h pH monitoring. To answer these questions, we studied 74 patients with proven reflux disease and 37 asymptomatic volunteers, using ambulatory 24-h esophageal pH monitoring. Gastroesophageal reflux was defined as episodes with esophageal pH of less than the threshold values 3.0, 3.5, 4.0, 4.5, or 5.0, respectively. For each of these pH thresholds, the percentage time with esophageal pH below the threshold was calculated separately for periods of upright and supine body position. Two-dimensional receiver-operating-characteristic (ROC) analysis was used to define upper limits of normal. A maximum of sensitivity, specificity, and rate of correct decisions (all 89%) was obtained using pH 4 for the definition of gastroesophageal reflux, although other pH thresholds were not much worse. On the basis of pH 4, the upper limits of normal could be shifted around the "optimal upper limit of normal" within a certain limit without considerable loss of accuracy of pH monitoring. This may explain the divergences between upper limits of normal obtained by different laboratories. In conclusion, 1) the threshold pH 4 should further be used for the definition of acid gastroesophageal reflux, and, 2) within certain limits, shifting of the upper limits of normal has little effect on the accuracy of pH monitoring in gastroesophageal reflux disease.

Adolescent↗