Fourier Phase Analysis of Dynamic Antral Contraction Scintigraphy: New Software, Reference Values, and Comparisons to Conventional Gastric Emptying.

Dynamic antral contraction scintigraphy (DACS) has been used to evaluate for gastric dysmotility by measuring antral contraction frequency and ejection fraction (EF). Fourier phase image analysis has the potential to assess gastric antral contractions for dyssynchrony as has been used for analyzing nuclear cardiology ventriculography (multigated acquisition studies) for cardiac dyssynchrony. The aims of this study were to determine whether Fourier phase analysis helps to characterize antral motility physiology, whether Fourier phase analysis correlates with conventional gastric emptying scintigraphy (GES), and which DACS parameters may aid in diagnosing gastric dysmotility, particularly delayed gastric emptying (GE). Methods: DACS and GES of healthy volunteers (n = 22) were compared with patients (n = 99) with symptoms of gastroparesis. New DACS Fourier phase analysis software was developed. Results: GE was delayed (n = 53) or normal (n = 46) in patients. There was a linear correlation between the time for the stomach to empty 50% of the meal and the percentage total proximal and distal in-phase antral pixels at 30 min (r = 0.37, P = 0.0001) and 60 min (r = 0.26, P = 0.007). In healthy volunteers, the mean proximal-to-distal ratio of in-phase antral pixels increased from 1.67 (30 min) to 2.65 (120 min) (P = 0.035), and EF increased from 23% (30 min) to 32% (120 min) (P = 0.022). Multivariable regressions of percentage total proximal and distal in-phase antral pixels (30 min) and EF (60 min) were the best predictors of abnormal GE (adjusted odds ratio, 3.30 [95% CI, 1.21-9.00] and 2.97 [95% CI, 1.08-8.21], respectively). Conclusion: This study used Fourier phase analysis to analyze DACS in healthy volunteers and patients with symptoms of gastroparesis. In addition to establishing reference values, new physiologic information on antral motility was obtained. In healthy volunteers, there was an increasing proximal-to-distal ratio of in-phase antral pixels and antral EF over time after meal ingestion. The percentage total proximal and distal in-phase antral pixels at both 30 and 60 min correlated well with GE values for the time for the stomach to empty 50% of the meal. For symptomatic patients, the percentage total proximal and distal in-phase antral pixels at 30 min and the EF at 60 min after meal ingestion correlated with delayed GE on conventional GES. Thus, Fourier phase analysis of DACS appears to have potential to further aid in diagnosing gastric dysmotility in GES.

Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis.

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD0)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD0 and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis underwent GES to obtain gastric retention and IMD0, WLST, and filled out patient assessment of upper GI symptoms. A total of 234 patients with symptoms of gastroparesis were assessed (86 patients with diabetes, 130 idiopathic, 18 postfundoplication) and 175 (75%) delayed gastric emptying. Low IMD0 <0.568 suggesting initial rapid transit to the distal stomach was present in 8% and correlated with lower gastric retention, less heartburn, and lower volumes consumed during WLST. Low WLST volume (<238 mL) was present in 20% and associated with increased severity of early satiety, postprandial fullness, loss of appetite, and nausea. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.NEW & NOTEWORTHY IMD0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.

Buspirone for early satiety and symptoms of gastroparesis: A multi-centre, randomised, placebo-controlled, double-masked trial (BESST).

BACKGROUND: Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5-HT1 receptor agonist, may improve fundic accommodation. AIM: To determine if buspirone treatment improves early satiety and postprandial fullness in patients with symptoms of gastroparesis. METHODS: This 4-week multi-centre clinical trial randomised patients with symptoms of gastroparesis and moderate-to-severe symptoms of fullness (Gastroparesis Cardinal Symptom Index [GCSI] early satiety/postprandial fullness subscore [ES/PPF]) to buspirone (10 mg orally) or placebo three times per day. The primary outcome was a change in the ES/PPF from baseline to 4 weeks. The primary analysis was per protocol intention-to-treat ANCOVA of between-group baseline vs. 4-week differences (DoD) in ES/PPF adjusted for baseline ES/PPF. Results are reported using both nominal and Bonferroni (BF) p values. RESULTS AND CONCLUSIONS: Ninety-six patients (47 buspirone, 49 placeboes; 92% female, 50% delayed gastric emptying, 39% diabetic) were enrolled. There was no between-groups difference in the 4-week ES/PPF primary outcome: -1.16 ± 1.25 (SD) on buspirone vs -1.03 ± 1.29 (SD) on placebo (mean DoD: -0.11 [95% CI: -0.68, 0.45]; p = 0.69). Buspirone performed better than placebo in patients with severe-to-very severe bloating at baseline compared to patients with none to moderate: (ES/PPF DoD = -0.65 vs. 1.58, pTX*GROUP  = 0.003; pBF  = 0.07). Among individual GCSI symptoms, only bloating appeared to improve with buspirone vs. placebo. CONCLUSIONS: Patients with moderate-to-severe early satiety/postprandial fullness and other symptoms of gastroparesis did not benefit from buspirone treatment to improve the ES/PPF primary outcome compared with placebo. There was a suggestion of the benefit of buspirone in patients with more severe bloating. TRIAL REGISTRATION: ClinicalTrials.gov NCT0358714285.

Hair Loss in Patients with Gastroparesis: A Sign of Nutritional Deficiency in Gastroparesis?

INTRODUCTION: Some patients with gastroparesis (Gp) report hair loss. The aim of this study was to investigate the prevalence of patient-reported hair loss in Gp patients, analyze hair loss association to severity of Gp and nutritional deficiencies, and study effects of multivitamin treatment on hair loss. METHODS: Patients with Gp were questioned about hair characteristics, Gp symptoms, and diet. Patients with hair loss had blood drawn for vitamin levels. Patients with hair loss were treated with daily multivitamin and assessed 8 weeks later. RESULTS: Hair loss was reported in 65 of 143 patients with Gp (45.5%), occurring similarly in idiopathic and diabetic Gp. Hair loss was most commonly noticed while washing and/or combing hair. Patients with hair loss had more severe nausea, abdominal pain, stomach fullness, loss of appetite, abdominal discomfort, bloating, retching, stomach distension, vomiting, early satiety, postprandial fullness, and constipation. Hair loss patients lost more weight over prior 6 months. Patients with hair loss had similar gastric retention on gastric emptying scintigraphy. Overall, 29 of 61 (47.5%) patients with hair loss had at least one abnormal bloodwork result. After 8 weeks of treatment with a daily multivitamin, 17 of 41 (41%) patients had improvement in hair loss. CONCLUSION: Hair loss occurred in 46% of patients with Gp, being associated with more severe symptoms, loss of weight, and several vitamin deficiencies, although not a specific one. Treatment with multivitamins improved hair loss in 40% of patients. Presence of hair loss in patients with Gp should prompt nutritional evaluation and supplementation.

Proximal and distal intragastric meal distribution during gastric emptying scintigraphy: Relationships to symptoms of gastroparesis.

BACKGROUND: Total gastric retention (TGR) from gastric emptying scintigraphy (GES) is used for diagnosing gastroparesis (Gp), but correlates poorly with patients' symptoms. Regional intragastric meal distribution (RIMD) can also be assessed from GES. This study classified patients' meal distribution as proximal or distal to relate RIMD to symptoms of Gp. METHODS: GES studies in patients (n = 193) and control subjects (n = 21) were selected for RIMD analysis. Patients completed Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM) for symptom severity before GES. TGR was analyzed using % TGR, and RIMD used a proximal/distal gastric count ratio (PDCR). Results were classified as proximal or distal RIMD at 0, 1, 2, and 4 h postprandially based on their PDCR being above or below the median value of the patients. RESULTS: Patients with delayed GE and immediate post-meal ingestion distal distribution had more severe early satiety and regurgitation. Distal distribution at 1 h had more severe early satiety and loss of appetite compared to proximal distribution. Patients with delayed GE and proximal distribution at 4 h had more severe nausea, retching, and vomiting compared to 4 h distal distribution. Severely delayed 4 h proximal distribution had more nausea than severely delayed 4 h distal distribution. CONCLUSIONS: Increased early distal IMD in patients with delayed GE was associated with regurgitation and early satiety whereas increased late proximal IMD was associated with nausea, retching, and vomiting. Differentiating proximal from distal meal distribution patterns helps to relate symptoms to gastric dysfunction and may be helpful for directing therapy.

Gastric half emptying time (T½ ) for 4-h gastric emptying scintigraphy simplifies reporting but reduces detection of gastroparesis.

BACKGROUND: Gastric emptying scintigraphy (GES) reports percent retention at 1, 2, and 4 h. Time to empty half the meal (T½ ) could simplify GE reporting. AIMS: To compare the performance of GES T½ to 1-, 2-, and 4-h retention. METHODS: GES studies were reviewed; results determined according to retention at 1, 2, and 4 h. T½ was determined using 3 methods: (1) GES curve fitting using 0, 0.5, 1, 2, 3, and 4 h data; (2) linear interpolation using 0, 0.5, 1, 2, 3, and 4 h data; and (3) linear interpolation using only 0, 1, 2, and 4 h data. RESULTS: Of 495 patients, 265 had normal GE, 4 rapid GE (<30% retention at 1 h), and 226 delayed GE: 17 delayed only at 2 h (>60% ret); 94 delayed only at 4 h (>10% ret); and 115 delayed at both 2 h and 4 h. Strong correlations were seen between each T½ method and 1, 2, 3, and 4 h %-empty values: curve-fit T½ (r = -0.851, -0.942, -0.864, -0.744), linear T½ using all imaging times (r = -0.848, -0.972, -0.878, -0.763), and linear T½ using standard imaging times (r = -0.853, -0.974, -0.868, -0.760). The 132 min cutoff for delayed GE captures 99.1% to 100% of delayed GE at both 2 h and 4 h, 76.5% to 94.1% delayed at 2 h only, but only 36.7% to 39.4% delayed at 4 h only; 3.5 to 11.3% of patients with normal GE miscategorized as delayed. CONCLUSIONS: GES T½ correlates more strongly with retention at 2 h than at 4 h. T½ alone may misclassify patients, particularly those with late-phase (4 h only) delays, reducing its utility for diagnosing gastroparesis.

Role of patent foramen ovale in migraine etiology and treatment: a review.

An increased prevalence between patent formen ovale (PFOs) and migraine exists but there is conflicting data regarding causal relationship between these two conditions. It is controversial whether cardiac screening and intervention like PFO closure provides any benefit in this population and so this area still remains under intense investigation. The management of migraine lies at the intersection between the practice of primary care physicians, neurologists, and cardiologists. There is no consensus as to what is the best practice for the evaluation of these patients with difficult to control migraine given the millions of dollars spent on physician visits and pharmacotherapy. This review seeks to summarize the current literature on this association and studies that have investigated PFO closure in this population.

Remote triggering of fault-strength changes on the San Andreas fault at Parkfield.

Fault strength is a fundamental property of seismogenic zones, and its temporal changes can increase or decrease the likelihood of failure and the ultimate triggering of seismic events. Although changes in fault strength have been suggested to explain various phenomena, such as the remote triggering of seismicity, there has been no means of actually monitoring this important property in situ. Here we argue that approximately 20 years of observation (1987-2008) of the Parkfield area at the San Andreas fault have revealed a means of monitoring fault strength. We have identified two occasions where long-term changes in fault strength have been most probably induced remotely by large seismic events, namely the 2004 magnitude (M) 9.1 Sumatra-Andaman earthquake and the earlier 1992 M = 7.3 Landers earthquake. In both cases, the change possessed two manifestations: temporal variations in the properties of seismic scatterers-probably reflecting the stress-induced migration of fluids-and systematic temporal variations in the characteristics of repeating-earthquake sequences that are most consistent with changes in fault strength. In the case of the 1992 Landers earthquake, a period of reduced strength probably triggered the 1993 Parkfield aseismic transient as well as the accompanying cluster of four M > 4 earthquakes at Parkfield. The fault-strength changes produced by the distant 2004 Sumatra-Andaman earthquake are especially important, as they suggest that the very largest earthquakes may have a global influence on the strength of the Earth's fault systems. As such a perturbation would bring many fault zones closer to failure, it should lead to temporal clustering of global seismicity. This hypothesis seems to be supported by the unusually high number of M >or= 8 earthquakes occurring in the few years following the 2004 Sumatra-Andaman earthquake.

Preseismic velocity changes observed from active source monitoring at the Parkfield SAFOD drill site.

Measuring stress changes within seismically active fault zones has been a long-sought goal of seismology. One approach is to exploit the stress dependence of seismic wave velocity, and we have investigated this in an active source cross-well experiment at the San Andreas Fault Observatory at Depth (SAFOD) drill site. Here we show that stress changes are indeed measurable using this technique. Over a two-month period, we observed an excellent anti-correlation between changes in the time required for a shear wave to travel through the rock along a fixed pathway (a few microseconds) and variations in barometric pressure. We also observed two large excursions in the travel-time data that are coincident with two earthquakes that are among those predicted to produce the largest coseismic stress changes at SAFOD. The two excursions started approximately 10 and 2 hours before the events, respectively, suggesting that they may be related to pre-rupture stress induced changes in crack properties, as observed in early laboratory studies.

The subduction zone flow field from seismic anisotropy: a global view.

Although the morphologies of subducting slabs have been relatively well characterized, the character of the mantle flow field that accompanies subduction remains poorly understood. To analyze this pattern of flow, we compiled observations of seismic anisotropy, as manifested by shear wave splitting. Data from 13 subduction zones reveal systematic variations in both mantle-wedge and subslab anisotropy with the magnitude of trench migration velocity |V(t)|. These variations can be explained by flow along the strike of the trench induced by trench motion. This flow dominates beneath the slab, where its magnitude scales with |V(t)|. In the mantle wedge, this flow interacts with classical corner flow produced by the convergence velocity V(c); their relative influence is governed by the relative magnitude of |V(t)| and V(c).

Intermittent plate tectonics?

Although it is commonly assumed that subduction has operated continuously on Earth without interruption, subduction zones are routinely terminated by ocean closure and supercontinent assembly. Under certain circumstances, this could lead to a dramatic loss of subduction, globally. Closure of a Pacific-type basin, for example, would eliminate most subduction, unless this loss were compensated for by comparable subduction initiation elsewhere. Given the evidence for Pacific-type closure in Earth's past, the absence of a direct mechanism for termination/initiation compensation, and recent data supporting a minimum in subduction flux in the Mesoproterozoic, we hypothesize that dramatic reductions or temporary cessations of subduction have occurred in Earth's history. Such deviations in the continuity of plate tectonics have important consequences for Earth's thermal and continental evolution.

Migration of seismic scatterers associated with the 1993 Parkfield aseismic transient event.

The time-varying deformation field within a fault zone, particularly at depths where earthquakes occur, is important for understanding fault behaviour and its relation to earthquake occurrence. But detection of this temporal variation has been extremely difficult, although laboratory studies have long suggested that certain structural changes, such as the properties of crustal fractures, should be seismically detectable. Here we present evidence that such structural changes are indeed observable. In particular, we find a systematic temporal variation in the seismograms of repeat microearthquakes that occurred on the Parkfield segment of the San Andreas fault over the decade 1987-97. Our analysis reveals a change of the order of 10 m in the location of scatterers which plausibly lie within the fault zone at a depth of approximately 3 km. The motion of the scatterers is coincident, in space and time, with the onset of a well documented aseismic transient (deformation event). We speculate that this structural change is the result of a stress-induced redistribution of fluids in fluid-filled fractures caused by the transient event.