Combined pH and pressure measurement device for oesophageal investigations

A combined pH- and pressure-measurement device for oesophageal investigations has been designed using monocrystalline antimony pH electrodes and perfused polyvinyl catheters. The combined device facilitates pressure measurements simultaneously with pH recording, both distal and proximal to the pH electrode. The device is easier to pass through the nose to the oesophagus than the conventional glass pH electrode. pH and pressure measurements in the oesophagus are therefore simplified and valuable information about the function of the region of the lower oesophageal sphincter is added owing to the simultaneous recording of the two parameters.     

Modified conventional type ofpCO2-electrode with monocrystalline antimony as the pH-sensing element

Rapid determinations of bloodgas parameters are desirable in today's clinical care. This calls for continuousin vivo measurements with miniaturised electrodes. In this study we have replaced the commonly used glass pH sensor in a pCO₂-electrode of the conventional type with a monocrystalline antimony electrode. The disadvantages of the glass electrode, such as instability and fragility when miniaturised, are of minor importance for an antimony electrode. The results, which confirm that the antimony pCO₂-electrode does not need frequent calibration, have been obtained using macroscale electrodes. However, the favourable characteristics of the antimony electrode are known to be maintained even after miniaturisation. Therefore, it seems possible that in the future we shall be able to measure bloodgas parameters such as pCO₂ in vivo with reasonable accuracy.     

New approach for elucidating the oxygen sensitivity and calibration of the antimony electrode

The biomedical use of the polycrystalline antimony pH electrode is hampered by oxygen dependence and low pH resolution (0.1 pH). Although, the pH resolution is improved by using highly purified crystallographically oriented monocrystalline antimony (COMA), the oxygen effect on the electrode remains. In an in vitro examination of the COMA electrode it was found that the oxygen dependence is similar to that of polycrystalline antimony, i.e. nonlinear with an increase in sensitivity below 10 kPa. These findings imply that the oxygen tension in the vicinity of a COMA pH electrode, has to be known or controllable for the pH reading to be at all valid especially at low oxygen levels, such as is often seen in biomedical applications. A calibration procedure using a zero oxygen solution is used in order to obtain absolute pH readings in a measurement solution of pre-set or known oxygen levels. Furthermore, the nonlinear oxygen sensitivity of the antimony electrode suggests that the underlying electrochemical reactions are other than those described by corrosion theory.     

Evaluation of a miniature antimony electrode for measurement of myocardial pH

Myocardial pH reflects the metabolic status of the heart and pH monitoring is an invaluable way to monitor the efficacy of myocardial protection during cardiac surgery. We developed a miniature antimony electrode for pH measurement in the heart. We examined the sensitivity, accuracy and the effects of temperature and oxygen tension on pH readings with this electrode in standard buffers and in anaesthetized dogs. In buffers the antimony electrode exhibited a gradient of -50.3 +/- 1.8 mV pH-1 at 25 degrees C, close to the Nernstian slope and showed a high correlation with conventional glass electrode readings (mean difference 0.027 +/- 0.0035 pH, r2 = 0.97). With increasing temperature the antimony electrode pH readings increased by 0.03 +/- 0.002 pH degree C(-1). With increasing PO2 the pH reading decreased (-0.73 pH/log PO2 mm Hg, r2 = 0.96). In the dog heart the antimony electrode showed a decrease in myocardial pH with increasing PCO2, and an increase in pH when NaHCO3 was given intravenously. Coronary occlusion resulted in paradoxically higher pH readings with the antimony electrode due to the effect of lowered myocardial PO2 interfering with pH measurement. The dissolution of antimony from the electrode in blood plasma was tested and found to be low. These studies suggest that antimony electrodes have low toxicity and provide accurate pH determinations under conditions of constant PO2. For more widespread clinical application, the problem of oxygen interference needs to be solved.     

Accuracy and choice of procedures in 24-hour oesophageal pH monitoring with monocrystalline antimony electrodes

In 24 h pH monitoring, the evaluation is dependent on the absolute accuracy of the pH measurements. Several sources of error exist, such as the chemical composition of calibration buffers and reference electrode gel and the effect of temperature on both the pH and the reference electrodes. We investigated the magnitude of these errors for the monocrystalline antimony electrode. Similar analysis applies to other types of pH electrodes. The errors we found are important when choosing a calibration procedure. We recommend a calibration procedure in which the pH and reference electrodes are both put in a beaker with the calibration buffers prior to and after the 24 h measurements. The calibration buffers and the electrode gel should have a specially selected ion composition where, for example, the Cl-ion concentration is critical. Corrections for differences in temperature between the calibration and the in situ measurements must be added. The pH measurements can be checked by performing in situ calibration.     

Evaluation of a miniature antimony electrode for measurement of myocardial pH

Myocardial pH reflects the metabolic status of the heart and pH monitoring is an invaluable way to monitor the efficacy of myocardial protection during cardiac surgery. We developed a miniature antimony electrode for pH measurement in the heart. We examined the sensitivity, accuracy and the effects of temperature and oxygen tension on pH readings with this electrode in standard buffers and in anaesthetized dogs. In buffers the antimony electrode exhibited a gradient of -50.3±1.8 mV pH_-1 at 25°C, close to the Nernstian slope and showed a high correlation with conventional glass electrode readings (mean difference 0.027+-0.0035 pH, r²=0.97). With increasing temperature the antimony electrode pH readings increased by 0.03±0.002 pH C^-1. With increasing PO₂ the pH reading decreased (-0.73 pH/log PO₂ mm Hg, r²=0.96). In the dog heart the antimony electrode showed a decrease in myocardial pH with increasing PCO₂, and an increase in pH when NaHCO₃ was given intravenously. Coronary occlusion resulted in paradoxically higher pH readings with the antimonyelectrode due to the effect of lowered myocardial PO₂ interfering with pH measurement. The dissolution of antimony from the electrode in blood plasma was tested and found to be low. These studies suggest that antimony electrodes have low toxicity and provide accurate pH2 determinations under conditions of constant PO₂. For more widespread clinical application, the problem of oxygen interference needs to be solved.     

Catheter tip pH electrodes for continuous intravascular recording

A small, flexible catheter-tip pH electrode has been developed for continuous measurement of intravascular pH in man and animals. The electrode utilises a pH sensitive polymer membrane rather than pH glass. The electrode passes through the lumen of a conventional cardiac catheter, by which it may be introduced to any desired site in the circulation. The electrode has no cross-sensitivity to other ions, to osmolality or oxygen tension. It is insensitive to flow and pressure. The response time is less than 300 ms, and the mean drift in vivo is 0.01 pH units/h. Continuous recordings of intravascular pH in animals have been made for up to Th. The electrodes can be sterilised, and have been used in man.     

A method for the manufacture of single barrel liquid ion-selective microelectrodes: an in situ study of ant venom pH

A method for the manufacture of single barrel ion-sensitive microelectrodes, employing liquid ion-selective sensors, is described in detail. This method had proven reliable and repeatable for the manufacture of pH-sensitive microelectrodes using a liquid proton carrier. It is believed that this method has advantages over other published methods since it allows direct visualization and control of major steps during electrode fabrication and overcomes several problems often encountered using more conventional methods. Microelectrodes fabricated using this technique have been used to measure the in situ pH of venom from two myrmicine ants,Tetramorium caespitum (L.) andMyrmica ruginodis (N.).     

Histological changes in the oesophageal squamous mucosa: correlation with ambulatory 24 hour pH monitoring

AIMS: To determine the value of squamous mucosal histology in the assessment of patients with gastro-oesophageal reflux symptoms. METHODS: Sixty six patients with reflux symptoms underwent endoscopy with oesophageal biopsy, manometry, and 24 hour oesophageal pH testing. The following histological features were assessed in squamous mucosa: the degree of basal cell hyperplasia, the degree of papillary zone elongation, and the density of neutrophil and eosinophil infiltration. Comparisons were made between the histological findings and the oesophageal function tests. RESULTS: The correlation between the traditionally accepted histological markers of gastro-oesophageal reflux disease in squamous mucosa and 24 hour pH testing was predominantly negative, with the exception of neutrophil inflammation in the squamous mucosa of patients with complicated reflux disease. CONCLUSIONS: This study was unable to confirm the value of the Ismail-Beigi criteria as histological markers of acid reflux. By inference, biopsy of the oesophageal squamous mucosa is of limited value in the assessment of patients with reflux symptoms.     

Oxygen sensitivity of recessed and unrecessed antimony pH microelectrodes

It is desirable to reduce or eliminate the oxygen sensitivity of antimony pH microelectrodes in physiological applications because it is not possible to determine if changes in the electrode's EMF are associated with changes in pH or pO₂. The oxygen sensitivity of electroplated antimony pH microelectrodes was experimentally determined for a factorial combination of (a) recessing the electrode tip, (b) saturating the medium with antimony axoide and (c) buffering the medium with phosphate. After establishing the baseline pH sensitivity in phosphate buffers, EMF was measured in a flow-through chamber using an electrometer, while the equilibrating gas was varied selectively from 5 per cent to 21 per cent oxygen. The investigation concluded that recessing the antimony pH microelectrode does not eliminate but does reduce the electrode's oxygen sensitivity. Saturating the medium with antimony oxide or buffering with phosphate do not reduce the oxygen sensitivity of the antimony pH microelectrode. Loss of electroplated antimony from the tip of the antimony pH microelectrode was associated with an increase in EMF.     

Multichannel intra-luminal impedance signals variability during gastro-oesophageal activities

Multichannel intra-luminal impedance (MII) technique has been proven to be a successful diagnostic tool in detecting and displaying activities inside the oesophagus. It improves the diagnostic capability of oesophageal disorders since it gives accurate and more in-depth information about the activities inside the oesophagus, especially reflux episodes. A comparison is presented between normal and abnormal adults in terms of variability in MII signals during baselines and reflux episodes. A comparative study of episode duration for normal and abnormal subjects is presented. The characteristics of MII signals during gastro-oesophageal reflux episodes as well as during baselines are investigated. These characteristics show different responses between normal and abnormal individuals which help improving MII analysis capability in evaluating patients with gastro-oesophageal reflux disease and enhances the automatic detection of the oesophageal activities. Baselines from normal and abnormal samples were fitted to gamma distributions as a trial to distinguish between normal and abnormal samples.     

Hydrogel basedin vivo reference electrode catheter

A hydrogel basedin vivo reference electrode catheter has been developed. A simple diffusion model of ion transport was applied to study chloride ion transport through polyhydroxyethylmethacrylate (pHEMA) membranes. Based on an experimentally derived effective diffusion coefficient of D_eff=4·04±0·5×10⁻⁸ cm²s⁻¹, a reference electrode catheter was fabricated featuring a dimensionally appropriate pHEMA porous liquid junction, a gelled Ringer's solution internal electrolyte compartment and a Ag/AgCl internal half cell. The reference electrode potential is not a function of pH from pH6 to pH9 and is linearly related to temperature by 0·33 m V^oC⁻¹. In animal trials, the intravascular catheter electrodes exhibit an average stability of ±0·92mV for 6–8h. Stability in blood can be attributed to the haemocompatibility and transport properties of pHEMA.     

Early adenocarcinoma of the oesophagus and oesophageal cyst

Aims : An increased risk of adenocarcinoma of the oesophagus has been demonstrated in patients with long segments of Barrett's mucosa. The risk of cancer associated with short segments of metaplasia of the oesophagogastric junction is not known. Methods and results : We report a case of early adenocarcinoma of the oesophagus arising on short tongues of Barrett's mucosa associated with an oesophageal cyst. The patient was a 68-year-old man with no previous clinical history of gastro-oesophageal reflux disease. The fortuitous discovery of an oesophageal cyst lead to the diagnosis of short tongues of Barrett's mucosa with high-grade dysplasia. On pathological examination of the resected specimen, an early adenocarcinoma had developed in Barrett's mucosa, localized just above the oesophageal cyst. Conclusions : As oesophageal cysts can cause symptoms suggestive of reflux, we hypothesize that this association may not be fortuitous.     

上消化道动态多点pH监测微型传感器技术的研究

论述了一种新的上消化道动态多点ｐＨ监测传感器导管，导管上集成有多个锑电极和一个Ａｇ－Ａｇｃｌ参比电极管。胃液抽取法和动态监测法对照的动物实验证实了技术的可靠性。将此传感器导管用于临床研究，显示了此技术在非心源性胸痛等消化道功能性疾病和消化生理研究上的重要意义。     

Cytokeratin 7 and 20 expression in intestinal metaplasia of the distal oesophagus: relationship to gastro-oesophageal reflux disease

AIMS: Intestinal metaplasia and gastro-oesophageal reflux disease typify classical Barrett's oesophagus. Cytokeratin (CK) 7 and 20 phenotypes differentiate intestinal metaplasia in long segment Barrett's oesophagus from gastric intestinal metaplasia. This study examines the relationship between CK7/20 phenotypes and reflux disease in intestinal metaplasia of the distal oesophagus. METHODS AND RESULTS: Eighty patients with oesophageal pH studies included 30 with long segment Barrett's, 16 with short segment Barrett's and 34 with intestinal meatplasia of the gastro-oesophageal junction. Representative biopsy specimens were immunostained for CK7 and CK20. All 30 long segment patients demonstrated a Barrett's CK7/20 phenotype. All nine short segment patients with gastro-oesophageal reflux had a Barrett's CK7/20 phenotype, while four of seven short segment patients without reflux had a gastric CK7/20 phenotype (P = 0.019). Of 14 patients with intestinal metaplasia of the gastro-oesophageal junction and reflux, 10 (71%) had a Barrett's CK7/20 phenotype, compared with 11 (55%) of the 20 non-reflux patients. CONCLUSIONS: CK7/20 immunoreactivity for patients with intestinal metaplasia of the distal oesophagus without long segment Barrett's oesophagus suggests a heterogeneous group, with an association between Barrett's CK7/20 pattern and gastro-oesophageal reflux disease in both short segment Barrett's and intestinal metaplasia of the gastro-oesophageal junction.     

Oesophageal adenocarcinoma: The new epidemic in men?

The last decades have witnessed an unprecedented rise in the incidence of oesophageal adenocarcinoma. This rise has mainly affected men, and current male-to-female sex ratio estimates range from 7-10 to 1. Major risk factors for oesophageal adenocarcinoma are gastro-oesophageal reflux disease and obesity, especially in combination. The prevalence of these risk factors has increased during the last decades, but there does not seem to be a marked differential distribution among men and women. However, reflux among men is more often associated with erosive reflux disease than it is among women. There is also evidence that male-type obesity, with a prominent abdominal distribution of fat, confers a greater risk increase for oesophageal adenocarcinoma than the female equivalent. Due to the marked male predominance and the finding that women tend to develop specialized intestinal metaplasia (Barrett's oesophagus) and adenocarcinoma at a later age than men, interest has been directed towards a potential aetiological role of reproductive factors and sex hormones. Breastfeeding has been found to be a protective factor for the development of adenocarcinoma, while no association has hitherto been established with other reproductive factors. Taken together, the male predominance in the incidence of oesophageal adenocarcinoma may partly be explained by the differential effect of the major risk factors reflux disease and obesity, but the mechanisms whereby this occurs need to be elucidated. Moreover, the association with breastfeeding indicates a need for extensive epidemiological studies to clarify a possible role of sex hormonal influence in the aetiology of oesophageal adenocarcinoma.     

The iridium/iridium oxide electrode to in vivo measurement of oesophageal and gastric pH

An iridium-iridium oxide electrode for in vivo pH measurement of the distal oesophagus is described. It is small and flexible so it is well accepted by patients for long-term pH monitoring. The electrode also offers the possibility of including another electrode and/or a pressure sensor for simultaneous detection of two or more parameters—gastric pH or oesophageal pressure for example. A clinical study was performed on 15 healthy volunteers and the results were checked on a DGC Nova 4/s computer, showing less than 0.005% of tension in mV out of the established range in a period of 24 h pH monitoring. The volunteers' results were compared with the normal values obtained by DeMeester using a glass electrode on a similar, healthy group of American patients and no significant differences were observed.

Owing to its small size, reliability, fast response to pH changes, durability and its easy storage, the Ir/IrO₂ electrode is ideal for long-term pH monitoring of the upper gastro-intestinal tract.     

The effect of alginates on deoxycholic-acid-induced changes in oesophageal mucosal biology at pH 4

Long-standing gastro-oesophageal reflux disease (GORD) can give rise to Barrett's oesophagus (BM), a metaplastic condition and precursor to oesophageal adenocarcinoma (AC). Oesophageal cancer was once rare but is now the 5th biggest cancer killer in the U.K. Reflux of bile acids into the oesophagus is implicated in the progression to BM as bile acids at pH 4 have been shown to induce c-myc expression, an oncogene upregulated in BM and AC. In the present study we investigated the role of the biopolymer alginate on bile acid induced molecular changes in oesophageal cell lines. OE21, OE33 and TE-7 oesophageal cell lines were exposed to 100 microM deoxycholic acid at pH 4 in the presence or absence of alginates. Levels of c-myc, E-cadherin, beta-catenin and Tcf signalling were determined by Real-Time PCR, Western blotting, immunofluoresence and reporter assays. All alginates tested were able to prevent the induction of c-myc by acidified deoxycholic acid in vitro. The upstream effects of acidified deoxycholic acid on E-cadherin, beta-catenin and Tcf signalling were also suppressed by alginate. Therefore, we have demonstrated that reflux of bile acids into the oesophagus initiates a potentially damaging molecular cascade of events using an in vitro model and that a biopolymer, alginate, can protect against these effects.     

The isolated hypertensive lower oesophageal sphincter: audit in a specialist unit

The hypertensive lower oesophageal sphincter (HLOS) is a distinct clinical entity defined by a lower oesophageal sphincter (LOS) pressure > or = 30mmHg and normal LOS relaxation and oesophageal peristalsis. The clinical, physiological, and radiological details of 27 patients with HLOS diagnosed in a 3-year period were reviewed. The reasons for referral included: gastro-oesophageal reflux disease (GORD) (33%), dysphagia (18.5%), epigastric discomfort (11%), non-cardiac chest pain (15%), globus (7.5%) and other (15%). All patients had manometric evidence of HLOS (Median LOS pressure 30 mmHg, range 25-50 mmHg) and 6 patients (20.7%) had abnormal pH studies. Less than 22% of contrast studies demonstrated an abnormality. There was no change in manometric findings following pharmacological treatment. Two patients underwent oesophagomyotomy and had normal manometry on follow up. We conclude that HLOS mimics a variety of upper gastrointestinal disorders and oesophageal manometry is the gold standard of diagnosis. There was an unexpectedly high incidence of GORD (22%) in this group. The significance and treatment of HLOS is discussed.