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- Refractory gastroesophageal reflux disease: advances and treatment. [JOURNAL ARTICLE]
- Expert Rev Gastroenterol Hepatol 2014 Apr 19.
'Refractory gastroesophageal reflux disease' is one of the most common misnomers in the area of gastroesophageal reflux disease. The term implies reflux as the underlying etiology despite unresponsiveness to aggressive proton pump inhibitor therapy. The term should be replaced with 'refractory symptoms.' We must acknowledge that in many patients symptoms of reflux often overlap with non-GERD causes such as gastroparesis, dyspepsia, hypersensitive esophagus and functional disorders. Lack of response to aggressive acid suppressive therapy often leads to diagnostic testing. In majority of patients these tests are normal. The role of non-acid reflux in this group is uncertain and patients should not undergo surgical fundoplication based on this parameter. In patients unresponsive to acid suppressive therapy GERD is most commonly not causal and a search for non-GERD causes must ensue.
- Relationship of Gastrointestinal Symptoms and Psychosocial Distress to Gastric Retention in Children. [JOURNAL ARTICLE]
- J Pediatr 2014 Apr 11.
To determine whether gastrointestinal (GI) symptoms (abdominal pain, nonpain GI symptoms, nausea) and/or psychosocial distress differ between children with/without gastroparesis and whether the severity of GI symptoms and/or psychosocial distress is related to the degree of gastroparesis.Children aged 7-18 years (N = 100; 63 female patients) undergoing a 4-hour gastric emptying scintigraphy study completed questionnaires evaluating GI symptoms, anxiety, and somatization for this prospective study. Spearman correlation, Mann-Whitney, t-test, and χ(2) tests were used as appropriate for statistical analysis.Children with gastroparesis (n = 25) were younger than those with normal emptying (12.6 ± 3.5 vs 14.3 ± 2.6 years, P = .01). Because questionnaire responses from 7- to 10-year-old children were inconsistent, only patient-reported symptoms from 11- to 18-year-olds were used. Within this older group (n = 83), children with gastroparesis (n = 17) did not differ from children with normal emptying in severity of GI symptoms or psychosocial distress. In children with gastroparesis, gastric retention at 4 hours was related inversely to vomiting (r = -0.506, P = .038), nausea (r = -0.536, P = .019), difficulty finishing a meal (r = -0.582, P = .014), and Children's Somatization Inventory score (r = -0.544, P = .024) and positively correlated with frequency of waking from sleep with symptoms (r = 0.551, P = .022).The severity of GI symptoms and psychosocial distress do not differ between children with/without gastroparesis who are undergoing gastric emptying scintigraphy. In those with gastroparesis, gastric retention appears to be inversely related to dyspeptic symptoms and somatization and positively related to waking from sleep with symptoms.
- Duplication at Xq28 involving IKBKG is associated with progressive macrocephaly, recurrent infections, ectodermal dysplasia, benign tumors, and neuropathy. [JOURNAL ARTICLE]
- Clin Dysmorphol 2014 Apr 9.
Duplications on Xq28 are common, although quite variable in size, but usually include the MECP2 gene. Here, we present a patient with a unique, small, 167-kb duplication at Xq28, not including MECP2. The most important gene in the duplicated region was IKBKG, mutations in which can cause a variety of distinct syndromes. Our patient's symptoms overlapped with different IKBKG-associated phenotypes, including hypohidrotic ectodermal dysplasia, incontinentia pigmenti, immunodeficiency, recurrent isolated invasive pneumococcal disease and anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, and lymphedema. In addition, she also had peripheral neuropathy, gastroparesis and various benign tumors, but no intellectual disability. Mixed syndromal presentation in several patients with IKBKG defect implies that IKBKG-related phenotypes are more like a spectrum, rather than distinct syndromes. We also suggest our patient's multisystem phenotype to be a novel contiguous gene syndrome, in which the key features include immune deficiency, macrocephaly, skin abnormalities, gastroparesis, peripheral small-fiber neuropathy, and benign tumors.
- From Ischochymia to Gastroparesis: Proposed Mechanisms and Preferred Management of Dyspepsia Over the Centuries. [JOURNAL ARTICLE]
- Dig Dis Sci 2014 Apr 9.
Dyspeptic symptoms are common with most patients suffering functional disorders that remain a therapeutic challenge for medical practitioners. Within the last three decades, gastric infection, altered motility, and hypersensitivity have gained and lost traction in explaining the development of functional dyspepsia. Considering these shifts, the aim of this review was to analyze changing understanding of and approaches to dyspepsia over a longer time period. Monographs, textbooks, and articles published during the last three centuries show that our understanding of normal gastric function has improved dramatically. With increased insight came new ideas about disease mechanisms, diagnostic options, and treatments. Despite shifts over time, the importance of functional abnormalities was recognized early on and explained in the context of societal influences and stressors, anxieties, and biological influences, thus resembling the contemporary biopsychosocial model of illness. Symptoms were often attributed to changes in secretion, motility, and sensation or perception with technological innovation often influencing proposed mechanisms and treatments. Many of the principles or even agents applied more than a century ago are still part of today's approach. This includes acid suppression, antiemetics, analgesics, and even non-pharmacologic therapies, such as gastric decompression or electrical stimulation of the stomach. This historical information does not only help us understand how we arrived at our current state of knowledge and standards of care, it also demonstrates that enthusiastic adoption of various competing explanatory models and the resulting treatments often did not survive the test of time. In view of the benign prognosis of dyspepsia, the data may function as a call for caution to avoid the potential harm of overly aggressive approaches or treatments with a high likelihood of adverse effects.
- The effects of comprehensive mental intervention on the recovery time of patients with postsurgical gastroparesis syndrome. [JOURNAL ARTICLE]
- J Clin Nurs 2014 Apr 5.
To explore the effects of comprehensive mental intervention on the recovery time and symptoms of depression in patients with postsurgical gastroparesis syndrome.Postsurgical gastroparesis syndrome may occur after abdominal surgery. The development of postsurgical gastroparesis syndrome is believed to be influenced by neuropsychiatric factors, manifest as psychological dysfunction and distress.Randomised controlled trial.A total of 120 patients with postsurgical gastroparesis syndrome were randomly divided into a mental intervention group (n = 60) and a control group (n = 60) by odd or even numbers. The mental intervention group received comprehensive mental intervention including support, counselling, music and massage plus all aspects of conventional therapy. The control group received only conventional therapy, including a three-cavity gastric tube, fasting, parenteral/enteral nutrition, routine care and health guidance. Pre intervention and postintervention depression levels were assessed in both groups by the Center for Epidemiological Survey Depression Scale. Gastric function recovery was assessed in all patients.Postintervention depression scores were significantly reduced in the mental intervention group, and pre-/postdifferences were significantly greater compared to control group scores. The mental intervention group had significantly shorter times for symptom disappearance (nausea, vomiting, abdominal distention), extubation duration, eating recovery, gastric drainage volume >600 ml/day, gastroparesis recovery, as well as shorter hospital stays and lower hospital expenses.Comprehensive mental intervention improved negative emotions and depression and shortened recovery time of patients with postsurgical gastroparesis syndrome.Mental intervention is important to postsurgical recovery, and primary nurses are encouraged to understand how to care for postsurgical patients physically and psychologically, with at least one nurse in the postsurgical setting trained to provide mental intervention.
- Nasogastric tube insertion followed by intravenous and oral erythromycin in refractory nausea and vomiting secondary to paraneoplastic gastroparesis: A case report. [JOURNAL ARTICLE]
- Palliat Med 2014 Mar 31.
Background:Gastroparesis is an under-recognised cause of refractory nausea and vomiting in patients with malignancy. The most common aetiologies are paraneoplastic and postsurgical dysmotility. There are little data on the efficacy of treatment to direct the management of patients with this symptom. We present a case and brief summary of current literature.Case presentation:We present the case of a 72-year-old patient with metastatic neuroendocrine carcinoma of the pancreas with dehydration and renal impairment secondary to nausea and vomiting. Replacement of duodenal stent, gastroscopy, endoscopic retrograde cholangiopancreatogram and gastric motility studies revealed gastroparesis rather than mechanical obstruction.Case management:The patient was transferred to an inpatient palliative care unit for symptom management where a nasogastric tube was inserted, followed by intravenous erythromycin with excellent improvement in symptoms and oral intake. He was switched to oral erythromycin with ongoing effect.Case outcome:With stabilisation of symptoms and renal function, the patient was able to be discharged with maintenance of good symptomatic control.Conclusions:Further research is needed into the management of gastroparesis in palliative care patients. In particular, we suggest that initial drainage with a nasogastric tube followed by a course of erythromycin warrants further study.
- Gastrointestinal motility problems in critical care: A clinical perspective. [JOURNAL ARTICLE]
- J Dig Dis 2014 Mar 27.
Advances in surgery, anesthesia and intensive care have led to a dramatic increase in the number of patients who spend time in our intensive care units (ICUs). Gastrointestinal (GI) motility disorders are common complications in the intensive care setting and are predictors for increased mortality and length of the stay in the ICU. Several risk factors for the development of GI motility problems in the ICU setting have been identified and include sepsis, being on mechanical ventilation, and the use of vasopressors, opioids or anticholinergic medications. Our focus is on the most common clinical manifestations of GI motor dysfunction in the ICU patient: gastroesophageal reflux, gastroparesis, ileus and acute pseudo-obstruction of the colon.
- Emerging drugs for the treatment of gastroparesis. [JOURNAL ARTICLE]
- Expert Opin Emerg Drugs 2014 Mar 26.
Introduction: Gastroparesis presents with symptoms of gastric retention with findings of delayed gastric emptying on diagnostic testing. Manifestations of gastroparesis are disabling in severe cases and lead to significant health resource utilization. Current therapies often are ineffective, may exhibit tolerance on chronic administration or produce prominent side effects in large patient subsets. Areas covered: This review assessed literature on drugs with theoretical efficacy in gastroparesis including medications that accelerate gastric emptying, reduce nausea and vomiting, or act as neuromodulators to reduce gastric sensitivity. Numerous agents exhibit diverse actions to modify gastric sensorimotor function in animal models; however, few medications are in controlled testing in gastroparesis. Prokinetic drugs with promise for this condition include investigational serotonin 5-HT4 agonists, motilin agonists, dopamine D2 antagonists, ghrelin agonists and an agent with combined muscarinic antagonist and acetylcholinesterase inhibitory effects. Other antiemetics and complementary and alternative formulations may be effective for some symptoms. Expert opinion: Development of effective novel therapies of gastroparesis without the neurotoxicity and cardiac arrhythmogenic effects of current agents will mandate a better definition of the gastric and extragastric factors responsible for the pathogenesis of the varied clinical manifestations of this disorder.
- Rumination Syndrome: A Review of Current Concepts and Treatments. [JOURNAL ARTICLE]
- Am J Med Sci 2014 Mar 17.
: Rumination is a normal and common phenomenon among ruminant animals; but in humans, it is always regarded as symptom indicative of abnormal function of the upper gastrointestinal tract, and understanding of the mechanisms explaining this event are still evolving. Learning-based theories, organic factors such as gastroesophageal reflux disease and psychological disturbances (eg, depression, anxiety) and the role of life stresses have been postulated as potential mechanisms of rumination. In this review, we take the approach that rumination syndrome is a distinct and discrete functional gastroduodenal disorder. We review current concepts of the pathophysiology of this entity and diagnostic approaches, then detail the treatment paradigms that have been pursued in rumination syndrome in adults. Patients with rumination syndrome have a very distinct set of symptoms. It was focused on the immediate postprandial period, but recently, there is an awareness of an expanding spectrum of the clinical presentation. This includes the concept of "conditioned vomiting" occurring in the setting of delayed gastric emptying (gastroparesis). Physicians' awareness of rumination syndrome is essential in the diagnosis and management of this disorder. Stress and psychological aspects in rumination syndrome are invariably in the background and have to be addressed. The crucial steps in the treatment strategy for rumination syndrome rely on reassurance, education and a physiologic explanation to the patient and family that this is not a "disease," followed by behavioral and relaxation programs and addressing stress factors.
- Domperidone interacts with pioglitazone but not with ondansetron via common CYP metabolism in vitro. [JOURNAL ARTICLE]
- Xenobiotica 2014 Mar 18.
Abstract 1. Domperidone (prokinetic agent) is frequently co-administered with pioglitazone (anitidiabetic) or ondansetron (antiemetic) in gastroparesis management. These drugs are metabolized via cytochome P-450 (CYP) 3A4, raising the possibility of interaction and adverse reactions. 2. The concentration-dependent inhibitory effect of pioglitazone and ondansetron on domperidone hydroxylation was monitored in pooled human liver microsomes (HLM). Pioglitazone was further assessed as a mechanism-based inhibitor. Microsomal binding was evaluated in our assessment. 3. In HLM, Vmax/Km estimates for monohydroxy domperidone formation decreased in presence of pioglitazone. Diagnostic plots indicated that pioglitazone inhibited domperidone in a partial mixed-type manner. The in vitro Ki was 1.52 µM. Predicted in vivo AUCi/AUC ratio was 1.98. 4. Pioglitazone also exerted time-dependent inhibition on the metabolism of domperidone and the average remaining enzymatic activity decreased significantly upon preincubation with pioglitazone over 0-40 min. 5. Diagnostic plots showed no inhibitory effect of ondansetron on domperidone hydroxylation. 6. In conclusion, pioglitazone inhibited domperidone metabolism in vitro through different complex mechanisms. Our in vitro data predict that the co-administration of these drugs can potentially trigger an in vivo drug-drug interaction.