Distal Probe Research Articles

Esophageal Mucosal Sensitivity: Possible Links with Clinical Presentations in Patients with Erosive Esophagitis and Laryngopharyngeal Reflux

The goal of this study was to assess whether mucosal sensitivity is related to different combinations of symptoms and lesions in laryngopharyngeal reflux (LPR) and erosive esophagitis and to determine whether reflux pattern is important in the development of the symptoms and lesions of gastroesophageal reflux disease (GERD) or LPR. We conducted a prospective study of 55 unselected new patients: 27 erosive esophagitis patients and 28 LPR patients. The erosive esophagitis group had a significantly higher rate of Bernstein test positivity than the LPR group. The proportions of patients with pathologic acid reflux at the proximal and distal probe were similar in the erosive esophagitis group and in the LPR group. These results were inconsistent with the endoscopic findings. Both retrosternal heartburn and regurgitation symptoms were higher in erosive esophagitis patients. The paucity of classical GERD symptoms and lesions in LPR patients could be attributable to mucosal insensitivity but not to reflux pattern.

Endoscopic Grading of Atrophic Gastritis is Inversely Associated with Gastroesophageal Reflux and Gastropharyngeal Reflux

BackgroundReflux esophagitis is inversely associated with the presence of atrophic gastritis, and endoscopic grading of atrophic gastritis correlates with histological evaluation. The aim of this study was to investigate the association of the endoscopic grade of atrophic gastritis with gastroesophageal and gastropharyngeal reflux.MethodsA total of 627 patients, who underwent endoscopy and ambulatory 24-hour dual-probe pH monitoring, were included in this study. The grade of atrophic gastritis was endoscopically classified into 2 types with the atrophic pattern system: the closed-type (C-type) and the open-type (O-type). We compared the findings from endoscopy and ambulatory pH monitoring for these 2 types.ResultsThe O-type was significantly associated with a lower prevalence of reflux esophagitis (p=0.001). All variables showing gastroesophageal reflux in the distal probe were significantly lower in the O-type than in the C-type (p<0.05). Similarly for the proximal probe, all variables, except the supine time of pH<4, were significantly lower in the O-type than in the C-type (p<0.05). The frequency of gastroesophageal reflux disease and gastropharyngeal reflux disease was in significantly lower in the O-type than in the C-type (p<0.001, p=0.012, respectively).ConclusionsEndoscopic grading of atrophic gastritis is easy and is inversely associated with gastroesophageal and gastropharyngeal reflux.

The role of gastric Helicobacter pylori infection in laryngopharyngeal reflux disease

To investigate the role of Helicobacter pylori (H pylori) infection in laryngopharyngeal reflux (LPR). A prospective multidisciplinary clinical study. Forty-four adult patients who applied to our ENT clinic with LPR symptoms were evaluated. Then these patients underwent upper gastrointestinal system endoscopy and double probe pH monitoring. In addition, during the endoscopy multiple biopsies from the stomach were obtained to detect H pylori. Results from 32 LPR positive patients were assessed (10 male and 22 female). There were no statistically significant differences between the presence of H pylori and sex, age, degree of gastritis and esophagitis, and also the number of reflux, fractional acid exposure time regarding proximal probe readings. Similarly for both proximal and distal probe readings, the average score of esophageal acid clearance was not statistically significant (P > 0.05). In addition, no statistically significant difference was found between the presence of H pylori and GERD (P > 0.05). The results of this study demonstrated that there is no relationship between gastric H pylori infection and LPR. B-3b.

Gastroesophageal flap valve is associated with gastroesophageal and gastropharyngeal reflux

The endoscopic grade of the gastroesophageal flap valve (GEFV) is suggested to be a good predictor of reflux status. The aim of this study was to investigate the association of the GEFV and gastroesophageal and gastropharyngeal reflux. A total of 364 patients (151 men and 233 women; mean age, 52.2 years) who underwent endoscopy, esophageal manometry, and ambulatory 24-h dual-probe pH monitoring were included. GEFV was graded I through IV using Hill's classification; then, GEFV was classified into two groups: a normal GEFV group (grades I and II) and an abnormal GEFV group (grades III and IV). Findings of endoscopy, esophageal manometry, and ambulatory pH monitoring were compared between the groups. Increased GEFV grade was significantly associated with an increased prevalence of both reflux esophagitis and Barrett's epithelium (P < 0.001). Lower esophageal sphincter pressure was significantly lower in the abnormal GEFV group than in the normal GEFV group (P < 0.001). All variables showing gastroesophageal reflux in the distal probe were significantly higher in the abnormal GEFV group than in the normal GEFV group (P < 0.001). In addition, all variables, except the supine time of pH < 4, showing gastropharyngeal reflux in the proximal probe were significantly higher in the abnormal GEFV group than in the normal GEFV group (P < 0.001). The frequency of gastroesophageal reflux disease and of gastropharyngeal reflux disease was significantly higher in the abnormal GEFV group than in the normal GEFV group (P < 0.001). Endoscopic grading of the GEFV is easy and provides useful information about the status of gastroesophageal and gastropharyngeal reflux.

Preimplantation genetic diagnosis significantly improves the pregnancy outcome of translocation carriers with a history of recurrent miscarriage and unsuccessful pregnancies

Preimplantation genetic diagnosis (PGD) for translocations has been shown to significantly reduce the risk of recurrent miscarriage, but because the majority of embryos produced are unbalanced, pregnancy rate is relatively low since 20% or more cycles have no normal or balanced embryos to transfer. The purpose of this study was to evaluate whether PGD could improve pregnancy outcome in translocation carriers with a history of two or more consecutive miscarriages and no live births. PGD for translocations was offered to translocation carriers with two or more previous miscarriages (average 3.5) and no live births (0/117 pregnancies) using a combination of distal and proximal probes to the breakpoints. After PGD, only 18.3% of embryos were normal or balanced. Only 5.3% of pregnancies were lost after PGD compared with 100% before PGD ( P < 0.001). The cumulative pregnancy rate was 57.6% and the cumulative ongoing pregnancy rate was 54.5% in the short period of time of 1.24 IVF cycles, or 46.3% and 43.9% respectively per cycle. In conclusion, PGD significantly reduced losses and increased the number of viable pregnancies ( P < 0.001). IVF plus PGD are a faster method of conceiving a live child than natural conception, at least for translocation carriers with recurrent miscarriages and no previous live births.

Typical GERD Symptoms and Esophageal pH Monitoring Are Not Enough to Diagnose Pharyngeal Reflux

Abnormal pharyngeal reflux of acid (PR) (as measured by pH monitoring) is associated with microaspiration, and is a good predictor of airway symptom response to medical and surgical anti-reflux therapy. However, in clinical practice the link between airway disease and Gastroesophageal reflux disease (GERD) is still based on the presence of typical symptoms (e.g., heartburn) and/or standard esophageal function testing (manometry and 24-pH monitoring). PR is rarely measured directly. We undertook this study to determine if typical symptoms and standard testing could reliably predict the presence of PR. The study group consisted of 518 patients with suspected reflux induced airway disease evaluated from December 1998 through January 2002. Each patient completed a standardized symptom questionnaire, underwent esophageal manometry, and 24-h esophageal and pharyngeal pH monitoring. Patients were classified having abnormal pharyngeal reflux (PR+) if they had >1 episode of PR detected during pH monitoring. One hundred eighty-one patients were PR+ and 337 were PR-. The most common symptoms, namely cough (PR +73%, PR- 68%), hoarseness (PR +64%, PR- 66%), and dyspnea (PR +59%, PR- 59%) were present with similar incidence in PR+ and PR- patients. The incidence of heartburn was 54% in the PR+ and 52% in the PR- patients. Logistic regression analysis revealed that abnormal esophageal acid exposure was a predictor of PR+ (P < 0.001). Neither the presence of heartburn or specific respiratory symptoms, the pressure of the lower esophageal sphincter (LES) or upper esophageal sphincter (UES), or amplitude of esophageal contractions predicted PR+. There was substantial variability in esophageal length (UES to LES), thus the placement of the distal pH probe from the LES varied considerably (median = 13 cm, 2-20 cm). Using established normal values of acid exposure at multiple levels of the esophagus, 24% of PR+ patients had normal amounts of esophageal acid exposure. Typical GERD symptoms, such as heartburn, and typical symptoms of aspiration such as hoarseness, cough, or dyspnea are not enough to positively identify PR. While patients with abnormal esophageal acid exposure are three times more likely than those with normal values to have PR, abnormal esophageal acid exposure alone does not identify all patients with PR. Therefore, relying on symptoms and standard diagnostic testing may fail to identify patients with extraesophageal reflux. Pharyngeal pH monitoring should be considered for patients with suspected reflux-induced airway disease.

Prevalence of Gastroesophageal Reflux in Difficult Asthma

Study objectives To determine the prevalence of gastroesophageal reflux disease (GERD)—both symptoms and objective evidence—using 24-h dual-probe pH monitoring in difficult asthma, and the relationship between the presence and treatment of GERD to clinical outcome Design and setting As part of a systematic evaluation protocol, 68 subjects with difficult-to-control asthma attending a difficult asthma clinic were referred for dual-probe ambulatory pH esophageal monitoring Results Esophageal probe data were available in 52 patients (76%) with difficult asthma. The prevalence of GERD/GERD-associated asthma symptoms was 75% (39 of 52 patients; 95% confidence interval [CI], 63 to 84.7%). The prevalence of GERD as evidenced by an abnormal pH profile at the distal esophageal probe was 55% (29 of 52 patients; 95% CI, 40 to 69%). The prevalence of GERD at the proximal probe was 34.6% (18 of 52 patients; 95% CI, 23.6 to 51%). The prevalence of GERD was similar in asthmatic subjects who responded to intervention and those who remained difficult to control (therapy resistant). Asymptomatic GERD was present in 9.6% (5 of 52 patients); 16% of cough episodes correlated with acid reflux Conclusions In difficult-to-control asthma, GERD is common, but identification and treatment of GERD do not appear to relate to improvement in asthma control in this population

Prevalence of Gastroesophageal Reflux in Difficult Asthma*

To determine the prevalence of gastroesophageal reflux disease (GERD)-both symptoms and objective evidence-using 24-h dual-probe pH monitoring in difficult asthma, and the relationship between the presence and treatment of GERD to clinical outcome. As part of a systematic evaluation protocol, 68 subjects with difficult-to-control asthma attending a difficult asthma clinic were referred for dual-probe ambulatory pH esophageal monitoring. Esophageal probe data were available in 52 patients (76%) with difficult asthma. The prevalence of GERD/GERD-associated asthma symptoms was 75% (39 of 52 patients; 95% confidence interval [CI], 63 to 84.7%). The prevalence of GERD as evidenced by an abnormal pH profile at the distal esophageal probe was 55% (29 of 52 patients; 95% CI, 40 to 69%). The prevalence of GERD at the proximal probe was 34.6% (18 of 52 patients; 95% CI, 23.6 to 51%). The prevalence of GERD was similar in asthmatic subjects who responded to intervention and those who remained difficult to control (therapy resistant). Asymptomatic GERD was present in 9.6% (5 of 52 patients); 16% of cough episodes correlated with acid reflux. In difficult-to-control asthma, GERD is common, but identification and treatment of GERD do not appear to relate to improvement in asthma control in this population.

Cricopharyngeal Muscle Electromyography in Laryngopharyngeal Reflux

The objective was to determine whether laryngopharyngeal reflux was associated with an electrophysiological abnormality of the main part of the upper esophageal sphincter, namely, the cricopharyngeal muscle, which could be related to laryngopharyngeal reflux symptoms. A prospective study of 20 patients with symptoms of laryngopharyngeal reflux. The diagnosis was based on clinical, laryngoscopic, and ambulatory 24-hour pH monitoring findings. Double-probe pH monitoring was performed with placement of the distal and proximal probes 5 cm above the proximal border of the lower esophageal sphincter and 15 cm proximal to the distal probe, in or just beneath the upper esophageal sphincter. Electromyographic recordings were obtained simultaneously on submental and cricopharyngeal muscles during water swallowing. The peak of the submental electromyographic amplitude and its duration was measured using bipolar surface electrodes placed under the chin. The electromyographic features of the cricopharyngeal muscle were investigated by means of concentric needle electrodes inserted percutaneously both in 20 normal subjects and in 20 patients with laryngopharyngeal reflux. All electrophysiological parameters were normal in all of the patients. The durations of foreburst revealed significant correlation with the number of reflux episodes and acid exposure time (P = .026 and P = .044, respectively). The duration of the foreburst correlating with acid exposure time and number of reflux episodes suggested that foreburst duration was extended because of the irritation caused by the acid reflux.

Using reflectance phase to estimate the acoustic response at the tympanic membrane

A common problem in ear-canal acoustics is to estimate the SPL and acoustic transfer functions (ATFs) at the tympanic membrane (TM) based on a response measured at a distal probe location, but standing waves complicate interpretation above 1.5 kHz. Transmission is well approximated up to 8 kHz by modeling the ear canal as a rigid-walled cylindrical tube; the model transforms measurements at the probe tip to those at the TM. Based on SPL and ATFs measured at the probe in 42 normal-hearing and 18 conductive-impaired ears from 0.25–8 kHz, the equivalent SPL and ATFs at the TM are calculated for ambient and pressurized conditions in the ear canal. Tube area is calculated based on probe-tip size, while tube length from probe to TM is calculated from the group delay of the reflectance phase averaged from 6 to 8 kHz. In normal-hearing ears, the mean (±standard deviation) of the SPL difference at the TM re: probe has a maximum of 9.2±3.8 dB at 3.7±0.8 kHz. The equivalent TM admittance has a wideband shape similar to in vivo measurements of umbo velocity level at constant SPL at the TM [Ruggero and Temchin, 2003]. [Work supported by NIH.]

Intraoperative ultrasound probe with an integrated acoustic standoff

An ultrasound probe is provided for imaging and diagnosing areas of interest that are in immediate contact with the probe. The probe provides an integrated standoff comprised of a rubber material having optimal acoustic characteristics. The lens is directly applied to the transducer and the standoff is applied to the lens such that the focal zone is placed at the area immediately below the patient contact surface of the probe. The lens material also encapsulates the transducer and provides reliable protection against electrical shock. The standoff is also separated from the surface being examined by a cap comprised of a biocompatible elastomer having high chemical and abrasive resistance that enables the probe to be easily sterilized and disinfected and provides further protection against electrical shock. The use of a standoff with optimal acoustic properties in, combination with the arrangement of the lens, standoff and cap provides a probe with a focal zone placed at the area immediately below the probe. The lens, standoff and cap are spatially arranged to minimize the volume of the distal transducer section and overall probe such that the probe is easy to manipulate.

The effect of 6-hydroxydopamine lesions on the release of amino acids in the direct and indirect pathways of the basal ganglia: a dual microdialysis probe analysis.

The loss of dopaminergic neurons of the substantia nigra in Parkinson's disease and in animal models of Parkinson's disease is associated with an imbalance in the activity of the so-called 'direct' and 'indirect' pathways of information flow through the basal ganglia. The aim of the present study was to determine whether the imbalance is reflected in changes in the release of GABA, aspartate and glutamate in the pathways using dual probe microdialysis in freely moving rats. Control and 6-hydroxydopamine-(6-OHDA)-lesioned rats were implanted with microdialysis probes in the neostriatum and substantia nigra or globus pallidus and the release of amino acids was analysed in the dialysates. Basal levels of amino acids were largely unaltered by the 6-OHDA lesion; however, the levels of GABA in the globus pallidus dialysates were significantly elevated in the lesioned rats, indicating an imbalance in favour of the indirect pathway. Administration of kainic acid to the neostriatum enhanced the release of GABA locally and in the distal probes in the substantia nigra and globus pallidus. In 6-OHDA-lesioned rats, stimulated release of GABA in the substantia nigra was abolished, indicating a reduction in transmission along the direct pathway. Thus, consistent with the direct-indirect pathway model of the basal ganglia, the 6-OHDA lesion results in an elevation of the basal release of GABA in the striatopallidal (indirect) pathway and a reduction in the evoked release of GABA in the striatonigral (direct) pathway. These imbalances may underlie, at least in part, the motor abnormalities of Parkinson's disease and in animal models of Parkinson's disease.

Stimulation of Tat-independent transcriptional processivity from the HIV-1 LTR promoter by matrix attachment regions.

The chromatin environment and the sites of integration in the host genome are critical determinants of human immunodeficiency virus (HIV) transcription and replication. Depending on the chromosomal location of provirus integration within the genome, HIV-1 long terminal repeat (LTR)-mediated transcription may vary from 0- to 70-fold. Cis-elements such as topoisomerase II cleavage sites, Alu repeats and matrix attachment regions (MARs) are thought to be targets for retroviral integration. Here we show that a novel MAR sequence from the T-cell receptor beta locus (MARbeta) and the IgH MAR mediate transcriptional augmentation when placed upstream of the HIV-1 LTR promoter. The effect of transcriptional augmentation is seen in both transient and stable transfection, indicating its effect even upon integration in the genome. MAR-mediated transcriptional elevation is independent of Tat, and occurs synergistically in the presence of Tat. Further, we show that MAR-mediated transcriptional elevation is specific to the HIV-1 LTR and the Moloney murine leukemia virus LTR promoter. In a transient transfection assay using over-expressed IkappaB, the inhibitor of NF-kappaB, we show that MAR-induced processive transcription is NF-kappaB dependent, signifying the role of local enhancers within the LTR promoter. Furthermore, by RNase protection experiments using proximal and distal probes, we show that MAR-mediated transcriptional upregulation is more prominent at the distal rather than the proximal end, thus indicating the potential role of MARs in promoting elongation.

Optimizing the diagnosis of gastroesophageal reflux in children with otolaryngologic symptoms

Objectives: Although many children with otolaryngologic (ENT) symptoms are being treated for gastroesophageal reflux (GER), how to diagnose GER in children with primarily or exclusively ENT symptoms has yet to be determined. This study compares the incidences of pathologic GER in the upper verses the lower esophagus in a cohort of children with ENT symptoms that were screened for GER. Methods: The results of extended dual channel intraesophageal pH probe monitoring obtained from 14 infants and 14 children with ENT symptoms were retrospectively analyzed. The percent of total monitoring time that the pH was less than 4, reflux index (RI) was determined. The upper limits of normal distal and proximal esophageal RI were based on published data. To evaluate our results, upper esophageal reflux (UER) was also determined in 27 infants and children without ENT or pulmonary symptoms, who had normal lower esophageal reflux (LER) values. Results: Mean upper esophageal RIs in the infants and children with normal LER were similar to previously published values for control infants and adults. Four (29%) of the ENT infants, 11 (79%) of the older ENT children, and 54% of the entire cohort had increased esophageal acid exposure. However, nine (60%) of the 15 pediatric ENT patients with GER had pH abnormalities limited to the upper esophagus. Conclusions: Standard distal pH probe monitoring alone gives a false negative result in a substantial proportion of the infants and children with ENT symptoms being evaluated for GER. Beyond its value in clinical practice, UER testing should be employed in research studies that evaluate the impact of GER therapy on ENT symptoms.

HEMODYNAMIC RESPONSES TO CONTINUOUS AND PULSATILE VENTRICULAR ASSIST IN AN ADULT MOCK CIRCULATION

The objective of this study was to investigate hemodynamic responses to continuous (CF) and pulsatile flow (PF) ventricular assist (VAD) in an adult mock circulation. The in vitro preparation consisted of s mock ventricle, systemic vasculature, and coronary network that produce physiologically-equivalent pressures and flows. The mock circulation was instrumented with a ventricular pressure-volume conductance and atrial pressure catheters, and aortic mot, aortic distal, VAD output, and coronary flow probes. CF (BioMedicus, Medtronic) or PF (UVAD85, University of Utah) VAD were connected by ventricular apical and aortic return cannulae. Hemodynamic measurements were recorded for baseline, CF, and PF during simulated normal (CO = 5 L/m), failing (CO = 3 L/m), and partially recovered (CO = 4 L/min) ventricular function with full (VAD output = 5 L/m) and partial (VAD output=2.5 L/m) unloading. PF assist reduced ventricular diastolic elastance (Ed) by providing larger ejection fraction (EF) and reducing ventricular filling pressure (Pd). CF assist slightly increased Ed with d modest increase in EF and a small reduction in Pd. Continuous unloading of the ventricle may result in a smaller ventricular chamber thereby reducing wall stress, but at the possible expense of a stiffer ventricle and redistribution of regional myocardial perfusion. These results may provide important clinical insight into the consequences of assist technique on cardiac mechanics and suggests the potential for unfavorable endocardial perfusion with CF assist.

Oral Corticosteroids Increase Esophageal Acid Contact Times in Patients With Stable Asthma

The prevalence of gastroesophageal reflux disease (GERD) is higher in people with asthma than in control populations. Predisposing factors for GERD development may include asthma medications such as prednisone. The objective of this study was to determine whether prednisone alters GERD parameters in people with asthma. Prospective, single-blinded, placebo-controlled, crossover study. University medical center clinic. Twenty adults with stable, moderate persistent asthma with minimal esophageal reflux symptoms (less than three times a week) who were not receiving antireflux therapy. Prednisone, 60 mg/d, for 7 days. Asthma, esophageal reflux symptoms, and spirometry were measured during baseline, placebo, and prednisone phases, each 7 days in duration. Dual-probe esophageal pH monitoring, esophageal and respiratory manometrics (20 subjects), and basal and stimulated gastric acid secretion (4 subjects) were measured after placebo and prednisone phases. There were significant increases in esophageal acid contact times at the distal and proximal pH probes during the prednisone phase. Total percentage of time that pH was < 4.0 at the distal probe was 2.5 +/- 0.4% for placebo compared with 5.9 +/- 0.9% for prednisone (p < 0.002). Total percentage of time that pH was < 4.0 at the proximal probe was 0.3 +/- 0.1% for placebo and 0.8 +/- 0.2% for prednisone (p < 0.0007). There were no significant changes in subject weight, spirometry, asthma or esophageal reflux symptoms, manometrics, or basal or stimulated gastric acid secretion. Prednisone, 60 mg/d for 7 days, increased esophageal acid contact times in this small population of people with stable asthma; however, the mechanism for this finding is unclear.

Symptom predictability of reflux-induced respiratory disease.

Gastroesophageal reflux disease (GERD) often is associated with pulmonary problems such as asthma as well as recurrent and nocturnal cough. Dual-probe 24-hr pH monitoring may assist in establishing a correlation between these symptoms and GERD-related symptoms. To determine if any specific symptom was predictive of aspiration, this study was undertaken. Ambulatory dual-probe esophageal pH monitoring was performed on 133 patients who had upper airway and additional symptoms for GERD. All patients had esophageal manometric studies of the lower esophageal sphincter (LES), the upper esophageal sphincter (UES), and the esophageal body before dual-probe pH monitoring was performed. Using two assembled glass probes, the distal and the proximal sensors were placed 5 cm above the proximal border of the LES and 1 cm below the lower border of the UES, respectively. Patients were classified into three groups: proximal and distal probe positive (group I), proximal probe negative and distal probe positive (group II) and proximal and distal probe negative (Group III) Upper airway and additional symptoms plus manometry results of the LES, body and UES study were compared between groups. In addition, positive distal probe patients (groups I and II) were compared for distal fraction of time at pH < 4 and number of reflux episodes at each probe position. A positive distal probe result was defined as an abnormal DeMeester score (> 14.8). A proximal probe test result was considered positive if percent time pH < 4.0 was > 1.1 for total, 1.7 for upright, and 0.6 for supine positions. The ages of the subjects ranged from 18 to 83 years (mean age: 50.5 +/- 1.5 years). Groups I, II, and III included 16 patients, 38 patients, and 79 patients, respectively. Group I had a significantly higher incidence of nocturnal cough than the other two groups. (P < 0.05). The manometric data revealed between groups that LES pressure (LESP) for groups I and II was significantly lower than LESP for group III (P = 0.003). Cricoid pressure, pharyngeal pressure, length, and relaxation of UES were not different between groups. Fraction of reflux time for group I was significantly higher than for group II in the supine position and at mealtime (P < 0.05). The number of reflux episodes for group I was significantly higher at meal time (P < 0.01). In conclusion, nocturnal cough is strongly predictive of proximal esophageal reflux. Proximal reflux episodes are significantly more frequent in the supine position and correlate well with the high predictive value of nocturnal cough.

Ambulatory 24-hour double-probe pH monitoring: the importance of manometry.

Historically, manometry has been used for sphincter localization before ambulatory 24-hour double-probe pH monitoring to ensure accurate placement of the probes. Recently, direct-vision placement (DVP), using transnasal fiberoptic laryngoscopy (TFL), has been offered as an alternative technique. Presumably, DVP might be used to precisely place the proximal (pharyngeal) pH probe; however, using DVP, there appears to be no way to accurately position the distal (esophageal) probe. The purpose of this study was to evaluate the accuracy of DVP for pH probe placement using manometric measurement as the gold standard. Thirty patients undergoing pH monitoring participated in this prospective study. Each subject underwent manometric examination of the esophagus to determine the precise location of the upper and lower esophageal sphincters (UES and LES). In addition, external anatomic landmarks were used to estimate interprobe distances. A physician blinded to the manometry results then placed a pH catheter using DVP so that the proximal probe was located just above the UES. The results were recorded and compared with those obtained by manometry. Accurate DVP of the proximal pH probe was achieved in 70% (23 of 30) of the subjects. The use of external anatomic landmarks to estimate interprobe distance resulted in accurate positioning of the distal probe in only 40% (12 of 30) of the subjects. Using fixed interprobe distances of 15 cm and 20 cm, distal probe position accuracy was 3% (1 of 30) and 40% (12 of 30), respectively. Therefore, using DVP, the distal esophageal probe was in an incorrect position in 60% to 97% of subjects. For double-probe pH monitoring, the proximal probe can be accurately positioned by DVP; however, there is no precise way to determine the interprobe distance required to correctly position the distal pH probe. Failure to accurately position the distal probe results in grossly inaccurate esophageal acid-exposure times. Thus, manometry is needed to ensure valid double-probe pH monitoring data.

Preimplantation genetic diagnosis of structural abnormalities

Preimplantation genetic diagnosis (PGD) of translocations can be achieved through a variety of methods. For female carriers, a possibility is by polar body biopsy and analysis of its metaphase chromosomes using painting probes. For male carriers or female carriers with terminal breakpoints, metaphase chromosomes can also be studied by fusing blastomeres to enucleated oocytes. Otherwise, interphase analysis of the translocation can be performed using distal, subtelomeric or breakpoint spanning probes. The results obtained after PGD of translocations indicate a significant decrease in spontaneous abortions after the procedure, a good selection against unbalanced oocytes and embryos, and pregnancy rates that depend on the type of translocation involved. Balanced translocations occur in 0.2% of the neonatal population, but at a higher rate among infertile couples and patients with recurrent abortions. In a recent report, balanced translocations were found in 0.6% of infertile couples, 3.2% of couples that failed over ten IVF cycles, and 9.2% among fertile couples experiencing three or more consecutive first-trimester abortions (Hum. Reprod. 14 (1999) 2097). They were also found in 2–3.2% of males requiring ICSI (Hum. Reprod. 11 (1996) 2609; Hum. Reprod. 13 (1998) 576). PGD can be offered to carriers of balanced translocations as an alternative to prenatal diagnosis and pregnancy termination of unbalanced fetuses. In recent years, PGD for structural chromosome abnormalities has been attempted by a variety of approaches. The aims of PGD for translocations are to reduce the rate of spontaneous abortions that this population suffers and to minimize the risk of conceiving an unbalanced baby.

Detection of translocations involving the HOX11/TCL3-locus in 10q24 by interphase fluorescence in situ hybridization

The t(10;14)(q24;q11) and its variant t(7;10)(q35;q24), which are recurrent in acute T-cell leukemia, lead to activation of the HOX11/TCL3-gene in chromosomal region 10q24 by juxtaposing this gene to one of the T-cell receptor loci. In the present study, we established a diagnostic assay for detecting these translocations by interphase fluorescence in situ hybridization (FISH). BAC clones flanking the HOX11/TCL3-locus were obtained from a fingerprinted BAC-contig of chromosomal region 10q24. BAC clones located proximal and distal of the HOX11/TCL3-locus were differently labeled and applied to interphase-FISH in seven normal controls and eight T-cell neoplasms with t(10;14)(q24;q11) or t(7;10)(q35;q24). In over 1600 nuclei of controls, a considerable split defined as separation of each one signal for the proximal and distal probe by more than three times the signal diameter was observed in only one cell. In contrast, all T-cell neoplasms with t(10;14) or t(7;10) contained at least 47% of nuclei with a signal split indicating a breakpoint in the HOX11/TCL3-locus. Thus, the established double-color FISH approach provides a new reliable and routinely applicable tool for diagnosing breakpoints in the HOX11/TCL3-locus.