A multidisciplinary approach to identifying and managing heterotopic gastric inlet patches.

INTRODUCTION: Gastric inlet patches are often incidental, but can also be a treatable cause of laryngo-esophageal symptoms. METHODS: We retrospectively reviewed all patients whose gastric inlet patches were diagnosed following assessment for laryngopharyngeal and swallowing symptoms. Improvement following Argon Plasma Coagulation (APC) was assessed using Minimum Clinically-Important Difference methodology combining voice, throat, and swallowing domains. Correlations between APC response and measures of reflux and mucosal barrier integrity, measured during 24-h pH-impedance manometry, were obtained. Proximal and Distal Mean Nocturnal Baseline Impedance (MNBI) values were separately calculated and the novel variable of Mucosal Impedance Gradient was derived as [((Distal MNBI-Proximal MNBI)/((Distal MNBI + Proximal MMBI)/2)) x 100]. KEY RESULTS: Inlet patches were detected in 57 of 651 patients who had Transnasal Panendoscopy (8.7 ± 2.2%). There were 34 males. Mean age was 58 years. Mean duration of symptoms was 2 years. The commonest symptoms were hoarseness (n = 33), throat symptoms (n = 24), and dysphagia (n = 21), respectively. APC was used to ablate patches in 34 patients. Treatment response was 71% at a mean followup of 5.5 months. MIG > - 25% predicted response to APC, with area under the receiver operating characteristic curve of 0.875 (Sensitivity = 81%; Specificity = 100%; p < 0.0001). CONCLUSIONS: Gastric inlet patches are common and under-recognized. They can cause protracted pharyngo-esophageal symptoms. Patch ablation is an effective treatment for carefully selected patients. Optimal patient selection requires multidisciplinary teamwork. Mucosal Impedance Gradient could further refine patient selection.

Impact of endoscopic laser cricopharyngeal myotomy on lower oesophageal sphincter physiology.

Dysphagia is a watershed symptom that localises poorly. Dividing causes of dysphagia into oropharyngeal and oesophageal does not always best serve the patient. We report the case of a patient whose diagnosis and treatment required three separate specialist referrals to two specialties, with 18 months passing between initial referral and definitive treatment. The predominant pathology was isolated upper oesophageal sphincter dysfunction that responded well to laser cricopharyngeal myotomy. Following surgery, patient symptoms resolved and lost weight was regained. High-resolution manometry showed that the upper sphincter resting pressure had fallen from 117±45 to 21±11mmHg, but the lower sphincter resting pressure had risen, albeit without symptoms, from 16±8 to 44±17mmHg (p<0.001 in both cases). Surgery on upper oesophageal sphincter in the presence of lower oesophageal sphincter incompetence is known to lead to intractable regurgitation and pneumonia, and this novel physiological observation further emphasises the need to holistically consider the patient and to systematically evaluate the entire swallowing system before undertaking invasive interventions.

The effects of proton pump inhibitors on autonomic tone in patients with erosive and non-erosive esophagitis.

BACKGROUND: Reduction in autonomic tone as measured by heart rate variability (HRV) has been associated with various inflammatory conditions including reflux disease. The nature of and permanence of this damage have not been fully assessed. METHODS: Fourteen individuals with non-erosive reflux disease (NERD) and 10 individuals with erosive reflux disease (ERD) as identified on endoscopy were assessed for HRV prior to starting a course of proton pump inhibitor (PPI) therapy and 8 weeks from the start of PPI therapy. KEY RESULTS: Reflux symptoms were significantly improved by PPI therapy (p = 0.001), with no significant difference in reflux symptoms between the NERD and ERD groups either before (p = 0.45) or following therapy (p = 0.17). The ERD group displayed reduced HRV prior to PPI therapy as compared with a non-symptomatic group. There was significant improvement of HRV resulting from PPI therapy in the ERD group as measured by inspiration/expiration ratio on forced breathing (p = 0.02), Valsalva ratio (p = 0.03), and extended metronome-guided breathing at 6 breaths per minute (p = 0.03). While a similar pattern was seen in the NERD group, the effects were not as strong and did not reach statistical significance. CONCLUSIONS & INFERENCES: The results are consistent with a growing body of evidence that cardiac autonomic neuropathy as measured by HRV is associated with gastro-esophageal reflux disease and also suggest that successful treatment of the inflammation can lead to reversal of the deterioration of autonomic tone associated with that inflammation.

Assessment of changes in cardiac autonomic tone resulting from inflammatory response to the influenza vaccination.

A total of 71 healthy volunteers opting to have a routine influenza vaccination were investigated for potential changes in cardiovascular autonomic tone resulting from the temporary inflammatory effects of an influenza vaccination. A number of temporal and frequency domain parameters of heart rate and breathing were assessed 2-5 days prior to vaccination and 1-4 days postvaccination. Three lead electrocardiograph (ECG), beat-to-beat finger blood pressure and chest plethysmography signals were measured. After an extended resting period, patients performed metronome-guided breathing at six breaths per min for a period of 2 min. Standard Ewing tests of autonomic function were also performed. All volunteers completed a vaccine symptom questionnaire. A subgroup of 15 volunteers who reported significant symptomatic reaction to the vaccination for at least 24 h following vaccination were identified based on the results of the questionnaire. A significant reduction in measures of heart rate variability (HRV) obtained during metronome-guided breathing was noted following vaccination in the subgroup of 15 symptomatic volunteers. No significant changes were observed in standard Ewing assessment, fractal dimension analysis, baroreflex sensitivity assessment or resting HRV. There was no evidence of significant reduction in autonomic tone following vaccination in the full sample of 71 volunteers. Results suggest a significant change in HRV response to a small inflammatory provocation and suggest further investigation of the inflammatory causes of dysautonomia is of value.

Proximal acid reflux treated by fundoplication predicts a good outcome for chronic cough attributable to gastro-oesophageal reflux disease.

PURPOSE: The aim for this study is to examine whether proximal, as opposed to distal, oesophageal reflux predicts a good outcome after fundoplication in patients with suspected acid-induced chronic cough. METHOD: Between 1999 and 2007, 81 patients with refractory chronic cough underwent manometry and dual-probe pH studies. In 59 patients, pathological reflux was confirmed, and 21 of these underwent laparoscopic fundoplication by a single surgeon. Proximal reflux was defined as an upper channel time pH <4 of >1.4%. The Chi-square test and Mann-Whitney U test were used in the statistical analysis. RESULTS: All patients with heartburn had their symptoms abolished by surgery. The proximal extent of reflux predicted cough improvement. Eleven of 14 patients with proven proximal reflux had complete symptom relief from surgery as opposed to two of seven with distal only reflux (Chi-square = 4.95; degrees of freedom = 1; p = 0.026). There was no correlation between oesophageal motility (as assessed by per cent abnormal wet swallows) and pathological reflux on outcome of surgery. Correlation of episodes of coughing with episodes of proximal or distal reflux was poor and had no useful predictive value. CONCLUSION: Patients with refractory chronic cough are significantly more likely to benefit from surgery if their pH study shows an upper channel pH time >1%.

Automated identification of peristaltic pressure waves in oesophageal manometry investigations using the rolling correlation technique.

We have implemented the technique of rolling correlation coefficient as proposed by Buttfield and Bolton (2005 Real time measurement of RR intervals using a digital signal processor J. Med. Eng. Technol. 29 8-13) for ECG R-wave detection in the detection and timing of oesophageal peristalsis. 43 sequential patients attending for oesophageal manometry were retrospectively reviewed. Two expert reviewers visually assessed each swallow for normality of peristaltic amplitude and propagation speed. Automatic assessment was performed using rolling correlation, maximum amplitude, threshold and maximum gradient techniques of identifying onset of peristalsis. Rolling correlation was comparable with the maximum amplitude technique at identifying peristaltic pressure waves visually identified as present. Rolling correlation was most effective at correctly identifying propagation velocity as normal (698 out of 845 normally propagating waves) and highest correlation with expert visual assessment of percentage abnormal propagation for each patient (R value 0.918). In a sub-group of 11 studies assessed as displaying normal motility, rolling correlation gave lowest variation of propagation speed and highest consistency with visual assessment. The rolling correlation technique is effective and accurate at identifying oesophageal peristalsis and characterizing peristaltic propagation in manometric studies even in the presence of abnormally weak peristalsis and other confounding pressure perturbations.

Laboratory-free measurement of gait rhythmicity in the assessment of the degree of impairment and the effectiveness of rehabilitation in patients with vertigo resulting from vestibular hypofunction.

A portable system for measurement of stride time rhythmicity was developed using the technique of Hausdorff et al (2001a Arch. Phys. Med. Rehabil. 82 1050-6). Measurement was performed for an extended period of walking of 256 steps for each foot outside of the laboratory on 18 normal individuals and 20 patients referred with symptomatic vestibular impairment. Ten of the patients were reassessed following vestibular therapy. Gait rhythmicity measured by standard deviation (SD) stride time was found to be significantly higher in patients with vestibular impairment than in normal volunteers (mean +/- SD 60.3 +/- 39.8 ms versus 21.9 +/- 4.9 ms respectively, P < 0.001, t-test). The ten patients who returned following a course of vestibular rehabilitation displayed significant improvement in SD stride time following therapy (mean +/- SD 57.3 +/- 44.6 ms prior to and 40.9 +/- 23 ms following therapy, P = 0.01, Wilcoxon signed rank test). Gait rhythmicity measurement, specifically measurement of stride time variability, appears to be a powerful assessment tool for objective measurement of extent of impairment and response to therapy in patients with vestibular hypofunction.

Simultaneous measurement of instantaneous heart rate and chest wall plethysmography in short-term, metronome guided heart rate variability studies: suitability for assessment of autonomic dysfunction.

Instantaneous heart rate and chest wall motion were measured using a 3-lead ECG and an air pressure chest wall plethysmography system. Chest wall plethysmography traces were found to accurately represent the breathing pattern as measured by spirometry (average correlation coefficient 0.944); though no attempt was made to calibrate plethysmography voltage output to tidal volume. Simultaneous measurements of heart rate and chest wall motion were made for short periods under metronome guided breathing at 6 breaths per minute. The average peak to trough heart rate change per breath cycle (AVEMAX) and maximum correlation between heart rate and breathing cycle (HRBRCORR) were measured. Studies of 44 normal volunteers indicated clear inverse correlation of heart rate variability parameters with age (AVEMAX R = -0.502, P < 0.001) but no significant change in HRBRCORR with age (R = -0.115). Comparison of normal volunteers with diabetics with no history of symptoms associated with autonomic failure indicated significant lower heart rate variability in diabetics (P = 0.005 for AVEMAX) and significantly worse correlation between heart rate and breathing (P < 0.001 for HRBRCORR). Simultaneous measurement of heart rate and breathing offers the possibility of more sensitive diagnosis of autonomic failure in a simple bedside test and gives further insight into the nature of cardio-ventilatory coupling.

The use of a two-dimensional ultrasound time-of-flight system for location of the centre of gravity in posturography measurements.

A method has been developed for objective assessment of balance using ultrasound time-of-flight (ToF) posturography measurements to accurately locate the centre of gravity (CoG) of a subject. Two orthogonal 40 kHz ultrasound transmitters are mounted on the subject's waist at the height of the CoG. Anterior/posterior and lateral motions are detected independently by measuring variations in the ToF from the transmitters to appropriately positioned wall-mounted receivers. The motion of the CoG is accurately traced during the course of 20 second assessment periods as the subject stands on a solid surface with eyes open and eyes closed. The tests are repeated with the subject standing on a standardized soft surface. Trials of day-to-day repeatability and repeated tests on patients prior to therapy indicate there is no significant improvement to balance measures with experience of the system. Balance measures are significantly worse in patients suffering vertigo symptoms following traumatic brain injury than for equivalent normal volunteers. Repeated measures post-therapy indicate significant improvement in balance measures following vestibular therapy in patients with vertigo. CoG location using ultrasound ToF is a suitable method of tracking sway and thus assessing balance in normals and balance-compromised patients.

The pulmonary deposition of two aerosol preparations of nedocromil sodium delivered by MDI assessed by single photon emission computed tomography.

The pulmonary deposition and pharmacokinetics of fine and coarse radioactive aerosols of nedocromil sodium, of mass median aerodynamic diameters 16 microns and 24 microns respectively, delivered by metered dose inhaler (MDI) have been investigated. The corresponding geometric standard deviations of the particle size distributions were 5.32 and 3.93. Pulmonary deposition was assessed by both planar radionuclide scintigraphy and multi-modality three dimensional imaging using single photon emission computed tomography (SPECT) and x-ray computed tomography (CT). The three dimensional data were analysed by transformation to a hemispherical shape based on the fractional radial distance of each point in the lung from the centre to the corresponding extrapolated point on the periphery. This enabled parameters on the variation of both concentration of deposition and total amount deposited with penetration distance to be calculated. For both planar and SPECT data the central to peripheral concentration ratio (C/P ratio) was calculated. The three dimensional C/P ratio showed a median value (3.21) which was significantly higher than for the planar imaging (2.03) (p < 0.001). The parameter used to express the variation of total amount deposited was the median dose position. This showed that for both aerosols 50% of the dose was deposited at sites with a percentage central to peripheral distance of greater than 68%. There was a trend for total percentage of the fine aerosol in the lungs to be higher than for the coarse and for its deposition to be more peripheral. In addition the mean concentrations in blood were measured to be greater for the fine aerosol. However these differences were relatively small and none were individually statistically significant. The technique of combined SPECT and CT imaging was shown to be valuable in obtaining more accurate information on pulmonary distribution of inhaled aerosol deposition. The merits, limitations and potential applications of the technique are discussed.

Evaluation of the factors affecting the accuracy and precision of a technique for quantification of volume and activity in SPECT.

The use of the technique of maximization of interclass variance to determine the threshold level defining the volume of an object in single photon emission computed tomography (SPECT) and hence its activity has been evaluated in a variety of conditions. The influence of varying activity on volume assessment and varying volume on activity assessment were shown to be negligible. The effect of object shape for the range of shapes likely to be found in the body was also small. Non-uniformity of activity in the object caused an underestimation of volume and to a lesser extent its activity. However, with activity varying by 100% within the volume, volume was only underestimated by 10% and activity by 3%. The presence of activity surrounding the object caused an overestimation of volume which increased linearly with the relative level of surrounding activity. The object to surrounding activity concentration ratio could be estimated and therefore its effect corrected. The influence of nearby objects and methods of dealing with their effect on the technique are described. Activity concentrations in objects with uniform distribution assessed using total activity divided by total volume were shown to be more accurate than assessments from maximum voxel count rate for objects with a volume below 150 ml.

Measurement of placental volume with real-time ultrasound in mid-pregnancy.

A new method to measure placental volume in mid-pregnancy using real-time ultrasound is described. The method is an adaptation of the B-mode parallel planimetric technique. The mean error of in vitro measurements on 45 balloons (mean volume 186 mL range: 88-485 mL) was -2.24 mL, standard deviation 6.76 mL. The error standard deviation of in vivo placental volume measurements was 16.4 mL (volume range: 173-396.5 mL). Placental measurements were made on 175 women between 14.3 weeks and 21.4 weeks, menstrual age (MA) and a smooth centile curve derived. Median volume increased linearly from 144 to 329 mL. The size of the ultrasound probe limits the technique to use before 20 weeks, MA.

Dosimetric assessment of radiolabelled lipiodol as a potential therapeutic agent in colorectal liver metastases using combined CT and SPECT.

Lipiodol has previously been used as an agent for targeted radiotherapy by selective retention in primary hepatic tumours following direct hepatic arterial infusion. We have considered the potential dosimetry of 131I-labelled lipiodol in treating colorectal liver metastases. Fifteen patients with multiple colorectal liver metastases underwent selective hepatic angiography when 5 ml lipiodol labelled with 40 MBq 131I were infused. All patients underwent planar scintigraphy of the abdomen and thorax, single photon emission computed tomography (SPECT) of the liver and whole body counting on at least two occasions following lipiodol injection. Computed tomographic (CT) images of the liver were also taken typically 7 days postinjection. The lipiodol was found to deposit on the periphery of metastases of less than 10 cm diameter. In one patient a metastasis of diameter greater than 15 cm failed to infuse. In two patients the lobe of the liver containing metastases was not successfully infused. Overlay of CT and SPECT images confirmed concentration in metastases. Quantification of SPECT images indicated that between 55 and 100% (median 86%) of the injected activity was retained in the liver following injection, and tumour to liver ratios of dose delivered ranged from 1.21:1 to 4.7:1 (median 3.1:1). Tumour does ranged from 11.8 to 43.3 mGy MBq-1 injected. Dose to the lungs ranged from 0 to 46% of the liver dose (median 16%). Lipiodol has potential for treatment of colorectal liver metastases in targeted radiotherapy.

A new method of quantification of the pulmonary regional distribution of aerosols using combined CT and SPECT and its application to nedocromil sodium administered by metered dose inhaler.

Aerosols of nedocromil sodium labelled with 99Tcm were delivered on 20 separate occasions to healthy male volunteers. Planar and single photon emission computerized tomography (SPECT) gamma scintigraphy were immediately performed to assess the pulmonary regional distribution of delivered aerosol. On a separate occasion volunteers were imaged using X-ray computed tomography (CT). Alignment of SPECT and CT images was performed using marked anatomical features and the anterior and lateral skin outlines. CT images provided data for attenuation correction and were used to define the anatomical lung volume. Central to peripheral (CP) ratios of deposited activity were calculated from volumes of interest in coronal and transverse sections of the right lung. These were compared with CP ratios obtained from planar images obtained immediately following aerosol inhalation. Volumetric CP ratio correlated significantly with immediate planar CP ratio (p < 0.001). Analysis of deposition in the whole right lung was performed by separating the SPECT lung data into a series of thin concentric shells centred on the entry of the right main bronchus. Measures were defined for describing the variation of deposition density and cumulative total deposition with distance from the lung centre. These showed significant correlation with planar CP ratio (p < 0.001). SPECT analysis using CT is consistent with planar measures of aerosol deposition but offers a more complete quantification of aerosol penetration and absolute deposited activity within the whole lung. It is a valuable new tool for aerosol analysis.

Evaluation of a technique for the quantification of radioactivity and volume of an object using SPECT.

The technique of threshold determination using maximization of interclass variance (MIV) has been evaluated for the assessment of radioactivity and volume in single photon emission computed tomography (SPECT). The SPECT reconstruction incorporated scatter and attenuation correction using an attenuation map from computed tomographic (CT) images. The technique has been examined on a large number of phantom objects with both 99Tcm and 131I. Volume measurement of objects was performed using a variety of methods of applying the MIV technique. The standard error of volume estimation for the optimum method was 7.3 ml for 99Tcm and 15.3 ml for 131I. Activity was measured by expansion of the volume of interest representing the space occupied by the object to make allowance for limited SPECT resolution. The standard errors of the activity measurements were 0.22 MBq for 99Tcm and 0.24 MBq for 131I.

A technique for the absolute quantification of 131I radiopharmaceuticals using SPECT.

A technique is described for the quantification of the three-dimensional distribution of 131I radiopharmaceuticals using single photon emission computed tomography (SPECT). A theoretical discussion of the problems of scatter and septal penetration in 131I SPECT is presented. The correction of these effects using the geometric mean line source scatter subtraction technique and a distance varying counting sensitivity, is described. The volume and activity of objects in the SPECT dataset were assessed by segmentation using the technique of maximization of interclass variance. The technique has been examined in phantom experiments showing that volumes and activities of objects containing a uniform concentration of activity can be assessed to a precision of 7.3% (1 S.D.) and 0.32 MBq (1 S.D.) respectively. The technique has been successfully applied to patient studies using both 131I-metaiodobenzyl guanidine (MIBG) and lipiodol.

Biodistribution of Lipiodol following hepatic arterial injection.

Thirteen patients undergoing selective coeliac angiography before insertion of an indwelling hepatic arterial cannula underwent injection of 3 ml radiolabelled Lipiodol (2 MBq 131I) into the hepatic artery at the end of the procedure. At subsequent laparotomy 1-9 days later, biopsies were taken from normal liver and metastases. The radioactivity of this material was measured to establish the tumour:liver ratios. Two patients with large metastases (> 10 cm in diameter) had low ratios. In the remainder, the median ratio at 24 h was 1.5:1 (range 1.1-2.5:1; n = 5) and 2.6:1 (range 1.5-64.0:1; n = 6) at 3-9 days. Four patients underwent single photon emission computed tomography, which confirmed selective retention of Lipiodol in small metastases, although no activity was detected in a large deposit (> 15 cm) 10 days after injection. The tumour:liver ratio in the other three patients increased from 3.0-5.6:1 on day 1 to 4.5-7.2:1 on day 6. This study suggests that Lipiodol may be a useful therapeutic delivery agent to small colorectal liver metastases.

Humidification as an adjunct to chest physiotherapy in aiding tracheo-bronchial clearance in patients with bronchiectasis.

Humidification of inspired air or oxygen is frequently utilized by respiratory physiotherapists to relieve sputum retention. Cold water, jet nebulizing humidifiers are in widespread use but there has been no previous attempt to investigate the efficacy of this treatment. We have performed a single-blind, cross-over study to quantify the effect of humidification as an adjunct to chest physiotherapy. Seven patients with bronchiectasis completed the trial, with a mean (range) age of 51 years (41-64 years) and mean (range) percent of predicted FEV1 of 46% (29-76%). On 2 days, separated by 1 week, subjects were randomly allocated to humidification or no humidification as a precursor to an optimal chest physiotherapy regimen. A radio-aerosol of human serum albumin millimicrospheres labelled with 99mTechnetium was used to measure sputum clearance by serial gamma camera images. Serial measurements of sputum weight and FEV1 were also recorded. Humidification (30 min) was followed by postural drainage (20 min) with the subject using the forced expiration technique to assist clearance. When humidification was combined with physiotherapy there was a significant increase in total wet weight of sputum (P less than 0.05) with a median (range) increase of 6 g (-9-15.5 g); and a significant increase in total radiolabel clearance (P less than 0.05) with a median (range) increase of 8.7% (1-13%), compared to physiotherapy alone. This study demonstrates that the use of cold water, jet nebulizing humidifiers significantly increases tracheo-bronchial clearance above that of an optimal physiotherapy regimen alone in bronchiectasis.(ABSTRACT TRUNCATED AT 250 WORDS)