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Bromadiolone, commonly known as super warfarin, is a long-acting coumarin dicoumarin rodenticide. The mechanism of bromadiolone is mainly to inhibit vitamin K1 epoxide reductase and affect the synthesis of coagulation factors Ⅱ, Ⅶ, Ⅸ and Ⅹ, which causes blood coagulation dysfunction and systemic multiple organ hemorrhage. Here, we report of a case of bromadiolone poisoning patient who had digestive tract, abdominal hemorrhage, as well as secondary paralytic ileus. After blood product transfusion and vitamin K1 supplementation, the patient was discharged after the physical condition was improved. It's suggestied that clinicians should pay attention to rare complications to prevent missed diagnosis when treating other bromadiolone poisoning.

Immune checkpoint inhibitors have revolutionized the management of patients with cancer. The increasing use of these agents has brought up a new set of adverse events which are widely heterogenous and potentially life-threatening. Rare immune-related adverse events associated with nervous system have not been described thoroughly, but their early recognition and management may be crucial. Immune-related autonomic neuropathy may be presented with a constellation of symptoms ranging from gastrointestinal and urinary complaints, to sweating and hypotension. Intestinal pseudo-obstruction as consequence of immune-related myenteric autonomic neuropathy is an under-recognized, not-well described and potentially fatal adverse event. We herein, present a unique case of enteric plexus neuropathy induced by PD-L1 blockade in a patient with small-cell lung cancer.

Acute gastrointestinal (GI) immune-related adverse events (irAE) are commonly reported by patients with cancer undergoing treatment with immune checkpoint inhibitors (CPI); however chronic irAEs are rare. We present a case of a 71-year-old woman with metastatic gastro-oesophageal junction (GOJ) adenocarcinoma who developed delayed-onset chronic intestinal pseudo-obstruction (CIPO) while receiving second-line pembrolizumab. Repeated CT scans of the abdomen/pelvis found no small bowel obstruction, and evaluations for bowel inflammation, infection and paraneoplastic syndrome were negative. Bowel rest and glucocorticoids were associated with transient symptom resolution; however, symptoms recurred within 1 month. The patient was ultimately supported with total parenteral nutrition and intestinal motility agents. After 4 months, the GOJ cancer remained stable with no signs of progression. As CPI use expands, the incidence of rare irAEs, such as CIPO, may increase., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Immune checkpoint inhibitors (ICIs) are the treatment of choice for several cancers and can be associated with remarkable clinical benefit, but can also cause serious immune-related adverse events (irAEs). Management of rare and severe irAEs is challenged by an incomplete knowledge of their natural history and pathogenetic mechanisms. We report a case of fatal acute-onset gastro-intestinal (GI) hypomotility from myenteric plexus neuropathy following a single dose of ipilimumab plus nivolumab given for treatment of Merkel cell carcinoma (MCC)., Case Presentation: A 66-year-old man with recurrent metastatic MCC involving several organs (liver, bones and disseminated retroperitoneal lymphadenopathy) developed profound pharyngeal dysphagia and ileus that started 7 days after receiving a single administration of combination immune checkpoint blockade consisting of nivolumab (3 mg/kg) and low-dose ipilimumab (1 mg/kg). A swallowing study showed oropharyngeal dysfunction and aspiration. Imaging studies were consistent with diffuse intestinal paresis. An extensive work-up did not reveal obvious causes of these symptoms, and enteric plexopathy was suspected. Empiric immune suppressive therapy was initiated urgently. Despite an escalating immunosuppressive regimen that included high dose steroids, tacrolimus and therapeutic plasma exchange, no improvement in GI motility was seen and the patient suffered repeated episodes of aspiration. Seven weeks after the onset of GI hypomotility, the patient succumbed to sepsis from intestinal perforations. At autopsy, histologic specimens obtained from the entire GI tract (pharynx to rectum) showed near complete loss of ganglion cells within the myenteric and submucosal plexuses. An associated inflammatory infiltrate was not seen, suggesting a 'burned out' phase of illness. C4d complement deposition was found at the ganglionic sites, suggesting antibody-mediated pathogenesis. Remarkably, at sites of previously suspected Merkel cell metastases, no residual viable Merkel cell carcinoma was identified., Conclusions: GI-tract paresis due to myenteric neuritis is a rarely reported toxicity of ICIs. Because the window of reversibility is likely to be very brief, quick and decisive interventions are warranted. Subtle functional and anatomic perturbations of the myenteric nervous system from the use of ICIs may be more prevalent than realized and should be suspected and addressed in both clinical and investigational settings.

Postoperative analgesia after primary total knee arthroplasty (TKA) and revision knee arthroplasty (RKA) can be reliant on the use of opioids and may lead to opioid-related adverse events (ORAEs). This study evaluated the risk of ORAEs following TKA and RKA using the 5% Medicare claims (2010-2013) database. There were 41,702 TKA and 3817 RKA patients who met the inclusion criteria. At 90 days, respiratory complications were the most common complication (TKA: 6.12%; RKA: 8.01%), followed by postoperative nausea and vomiting (TKA: 2.86%; RKA: 3.95%), and urinary retention complications (TKA: 2.79%; RKA: 3.20%). For TKA, risk factors for respiratory complications included older age, lower socioeconomic status, more comorbidities, obesity, chronic obstructive pulmonary disease, white race, and patients in the Midwest and West (vs. South) (p 002). The average Medicare payment for treating complications within 90 days of a TKA was $6206 and $6222 following RKA. Awareness risks for ORAEs in select patients can assist in developing a multimodal postoperative pain control and patient education protocols. (Journal of Surgical Orthopaedic Advances 27(2):148-154, 2018).

Background and Purpose: Gastrointestinal side effects of chemotherapy are an under-recognized clinical problem, leading to dose reduction, delays and cessation of treatment, presenting a constant challenge for efficient and tolerated anti-cancer treatment. We have found that oxaliplatin treatment results in intestinal dysfunction, oxidative stress and loss of enteric neurons. BGP-15 is a novel cytoprotective compound with potential HSP72 co-inducing and PARP inhibiting properties. In this study, we investigated the potential of BGP-15 to alleviate oxaliplatin-induced enteric neuropathy and intestinal dysfunction., Experimental Approach: Balb/c mice received oxaliplatin (3 mg·kg -1 ·day -1 ) with and without BGP-15 (15 mg·kg -1 ·day -1 : i.p.) tri-weekly for 14 days. Gastrointestinal transit was analysed via in vivo X-ray imaging, before and after treatment. Colons were collected to assess ex vivo motility, neuronal mitochondrial superoxide and cytochrome c levels and for immunohistochemical analysis of myenteric neurons., Key Results: Oxaliplatin-induced neuronal loss increased the proportion of neuronal NO synthase-immunoreactive neurons and increased levels of mitochondrial superoxide and cytochrome c in the myenteric plexus. These changes were correlated with an increase in PARP-2 immunoreactivity in the colonic mucosa and were attenuated by BGP-15 co-treatment. Significant delays in gastrointestinal transit, intestinal emptying and pellet formation, impaired colonic motor activity, reduced faecal water content and lack of weight gain associated with oxaliplatin treatment were restored to sham levels in mice co-treated with BGP-15., Conclusion and Implications: Our results showed that BGP-15 ameliorated oxidative stress, increased enteric neuronal survival and alleviated oxaliplatin-induced intestinal dysfunction, suggesting that BGP-15 may relieve the gastrointestinal side effects of chemotherapy., (© 2017 The British Pharmacological Society.)

In the area of Bielefeld there occurred a striking accumulation of four cases of death as a consequence of a paralytic ileus within a period of two years. All four patients suffered from a psychotic disorder and had taken psychotropic medication for many years. After exclusion of other causes, the anticholinergic effect of the psychotropic medication must be taken as the cause of death. A review of literature and pharmacological receptor profiles are presented. Therapeutic consequences are described in order to prevent more cases of death., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Purpose: Oxaliplatin is a platinum-based chemotherapeutic drug used as a first-line therapy for colorectal cancer. However, its use is associated with severe gastrointestinal side-effects resulting in dose limitations and/or cessation of treatment. In this study, we tested whether oxidative stress, caused by chronic oxaliplatin treatment, induces enteric neuronal damage and colonic dysmotility., Experimental Approach: Oxaliplatin (3 mg·kg -1 per day) was administered in vivo to Balb/c mice intraperitoneally three times a week. The distal colon was collected at day 14 of treatment. Immunohistochemistry was performed in wholemount preparations of submucosal and myenteric ganglia. Neuromuscular transmission was studied by intracellular electrophysiology. Circular muscle tone was studied by force transducers. Colon propulsive activity studied in organ bath experiments and faeces were collected to measure water content., Key Results: Chronic in vivo oxaliplatin treatment resulted in increased formation of reactive oxygen species (O 2 -), nitration of proteins, mitochondrial membrane depolarisation resulting in the release of cytochrome c, loss of neurons, increased inducible NOS expression and apoptosis in both the submucosal and myenteric plexuses of the colon. Oxaliplatin treatment enhanced NO-mediated inhibitory junction potentials and altered the response of circular muscles to the NO donor, sodium nitroprusside. It also reduced the frequency of colonic migrating motor complexes and decreased circular muscle tone, effects reversed by the NO synthase inhibitor, Nω-Nitro-L-arginine., Conclusion and Implications: Our study is the first to provide evidence that oxidative stress is a key player in enteric neuropathy and colonic dysmotility leading to symptoms of chronic constipation observed in oxaliplatin-treated mice., (© 2016 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

While bortezomib is known to cause adverse effects involving the autonomic nervous system, gastrointestinal side effects are typically mild. We describe herein a series of patients with myeloma and impaired renal function who developed severe paralytic ileus secondary to bortezomib use. Our patients had other risk factors for paralytic ileus including electrolyte abnormalities and opiate use. The striking commonality in our patients is the development of paralytic ileus with intravenous bortezomib in the setting of reduced renal function, followed by ileus resolution with bortezomib dose reduction. We discuss the existing literature on this subject and propose a strategy in order to reduce the risk of paralytic ileus in these patients. Upfront bortezomib dose reduction to 1 mg/m 2 intravenously in patients with myeloma with a glomerular filtration rate (GFR) of <30 mL/min may prevent paralytic ileus, while not compromising the clinical outcomes. Our conclusions will have to be validated in larger studies., Competing Interests: Conflicts of Interest: None declared., (2016 BMJ Publishing Group Ltd.)

Vincristine (VCR) is an important drug used in the treatment of acute lymphoblastic leukemia (ALL). VCR-induced neurotoxicity can manifest as peripheral neuropathy, constipation, or paralytic ileus. While there are some case reports describing VCR-induced paralytic ileus (VIPI) in pediatric ALL, there are fewer publication on adult ALL patients. Therefore, we retrospectively investigated VIPI during induction therapy of treatment protocols for ALL in 19 adult patients. The incidence of VIPI was 32%. VIPI was significantly increased in patients receiving concomitant itraconazole (ITCZ) (p = 0.04). We recommend avoidance of the combination of VCR and ITCZ.

We retrospectively analyzed the medical history of 19 elderly myeloma patients treated with the "novel subcutaneous formulation of bortezomib." In our experience, two patients (10 %) discontinued treatment for paralytic ileus. The exact pathogenetic mechanisms of toxic megacolon and paralytic ileus due to "novel subcutaneous formulation of bortezomib" are unclear. Probably, it may be related to possible damage of the autonomic nerve fibers that control organ functions. Adequate prevention and management of the gastrointestinal (GI) toxicities with the use of fluid intake and prokinetic and laxative drugs (at least two types of agents in a suboptimal dose) especially in patients with risk factors for GI side effects (anti-myeloma novel agents, opioids or antiemetics, iron supplements, spinal and cord compression, immobility, history of constipation) can decrease the possibility of interruption of administration of drug and increase adherence to treatment. Clearly this complication must be borne in mind whenever a patient develops acute abdominal pain and distension.

Background: Glucagon-like peptide-2 (GLP-2) is a pleiotropic hormone synthesized and secreted by the enteroendocrine 'L' cells able to exert intestine-trophic and anti-inflammatory effects. The antineoplastic drug cisplatin causes gastrointestinal alterations with clinical symptoms (nausea and vomiting) that greatly affect the therapy compliance. Experimentally, it has been reported that chronic cisplatin treatment caused mucosal damage and enteric neuropathy in the rat colon., Methods: We investigated, through a combined immunohistochemical and functional approach, whether [Gly(2) ]GLP-2, a GLP-2 analog, was able to counteract the detrimental effects of long-term cisplatin administration in the mucosa and myenteric neurons of mouse gastric fundus., Key Results: Morphological experiments showed a reduction in the epithelium thickness in cisplatin-treated mice, which was prevented by [Gly(2) ]GLP-2 co-treatment. Immunohistochemistry demonstrated that cisplatin caused a significant decrease in myenteric neurons, mainly those expressing neuronal nitric oxide synthase (nNOS), that was prevented by [Gly(2) ]GLP-2 co-treatment. In the functional experiments, [Gly(2) ]GLP-2 co-treatment counteracted the increase in amplitude of the neurally induced contractions observed in strips from cisplatin-treated animals. The NO synthesis inhibitor L-N(G) -nitro arginine caused an increase in amplitude of the contractile responses that was greater in preparations from cisplatin+[Gly(2) ]GLP-2 treated mice compared to the cisplatin-treated ones., Conclusions & Inferences: The results demonstrate that in cisplatin long-term treated mice [Gly(2) ]GLP-2 is able to counteract both the mucosal gastric fundus damage, by preventing the epithelium thickness decrease, and the neuropathy, by protecting the nNOS neurons. Taken together, the present data suggest that [Gly(2) ]GLP-2 could represent an effective strategy to overcome the distressing gastrointestinal symptoms present during the anti-neoplastic therapy., (© 2015 John Wiley & Sons Ltd.)

Background: Women treated with gonadotropin-releasing hormone (GnRH) analogs may develop enteric neuropathy and dysmotility. Administration of a GnRH analog to rats leads to similar degenerative neuropathy and ganglioneuritis. The aim of this study on rat was to evaluate the early GnRH-induced enteric neuropathy in terms of distribution of neuronal subpopulations and gastrointestinal (GI) function., Methods: Forty rats were given the GnRH analog buserelin (20 μg, 1 mg/ml) or saline subcutaneously, once daily for 5 days, followed by 3 weeks of recovery, representing one treatment session. Two weeks after the fourth treatment session, the animals were tested for GI transit time and galactose absorption, and fecal weight and fat content was analyzed. After sacrifice, enteric neuronal subpopulations were analyzed. Blood samples were analyzed for zonulin and antibodies against GnRH and luteinizing hormone, and their receptors., Results: Buserelin treatment transiently increased the body weight after 5 and 9 weeks (p < 0.001). Increased estradiol in plasma and thickened uterine muscle layers indicate high estrogen activity. The numbers of both submucous and myenteric neurons were reduced by 27%-61% in ileum and colon. The relative numbers of neurons containing calcitonin gene-related peptide (CGRP), cocaine- and amphetamine-related transcript (CART), galanin, gastrin-releasing peptide (GRP), neuropeptide Y (NPY), nitric oxide synthase (NOS), serotonin, substance P (SP), vasoactive intestinal peptide (VIP) or vesicular acetylcholine transporter (VAchT), and their nerve fiber density, were unchanged after buserelin treatment, but the relative number of submucous neurons containing somatostatin tended to be increased (p = 0.062). The feces weight decreased in buserelin-treated rats (p < 0.01), whereas feces fat content increased (p < 0.05), compared to control rats. Total GI transit time, galactose absorption, zonulin levels in plasma, and antibody titers in serum were unaffected by buserelin treatment., Conclusions: A marked enteric neuronal loss with modest effects on GI function is found after buserelin treatment. Increased feces fat content is suggested an early sign of dysfunction.

Balanced pools of deoxyribonucleoside triphosphate precursors are required for DNA replication, and alterations of this balance are relevant to human mitochondrial diseases including mitochondrial neurogastrointestinal encephalopathy. In this disease, autosomal recessive TYMP mutations cause severe reductions of thymidine phosphorylase activity; marked elevations of the pyrimidine nucleosides thymidine and deoxyuridine in plasma and tissues, and somatic multiple deletions, depletion and site-specific point mutations of mitochondrial DNA. Thymidine phosphorylase and uridine phosphorylase double knockout mice recapitulated several features of these patients including thymidine phosphorylase activity deficiency, elevated thymidine and deoxyuridine in tissues, mitochondrial DNA depletion, respiratory chain defects and white matter changes. However, in contrast to patients with this disease, mutant mice showed mitochondrial alterations only in the brain. To test the hypothesis that elevated levels of nucleotides cause unbalanced deoxyribonucleoside triphosphate pools and, in turn, pathogenic mitochondrial DNA instability, we have stressed double knockout mice with exogenous thymidine and deoxyuridine, and assessed clinical, neuroradiological, histological, molecular, and biochemical consequences. Mutant mice treated with exogenous thymidine and deoxyuridine showed reduced survival, body weight, and muscle strength, relative to untreated animals. Moreover, in treated mutants, leukoencephalopathy, a hallmark of the disease, was enhanced and the small intestine showed a reduction of smooth muscle cells and increased fibrosis. Levels of mitochondrial DNA were depleted not only in the brain but also in the small intestine, and deoxyribonucleoside triphosphate imbalance was observed in the brain. The relative proportion, rather than the absolute amount of deoxyribonucleoside triphosphate, was critical for mitochondrial DNA maintenance. Thus, our results demonstrate that stress of exogenous pyrimidine nucleosides enhances the mitochondrial phenotype of our knockout mice. Our mouse studies provide insights into the pathogenic role of thymidine and deoxyuridine imbalance in mitochondrial neurogastrointestinal encephalopathy and an excellent model to study new therapeutic approaches.

A 22-year-old woman presented with high fever, chest tightness and cough in January 20XX. Since CT scans revealed an anterior mediastinal mass, percutaneous needle biopsies of the mass were performed and she was diagnosed with T-cell lymphoblastic lymphoma (T-LBL). After the immunophenotype of lymphocytes in her pleural effusion had been identified, she received CHOP therapy because her dyspnea worsened, and induction therapy for acute lymphoblastic leukemia was subsequently performed after confirmation of her diagnosis as T-LBL. During this induction therapy, she developed paralytic ileus. One week thereafter, she suddenly exhibited visual disturbance, headache and nausea. Her cerebrospinal fluid was normal. Magnetic resonance imaging showed symmetrical high signal intensities on T2-weighted and fluid-attenuated inversion recovery images, and low signal intensities on T1-weighted images in the cortical and subcortical white matter of the posterior parietal and occipital lobes. Based on these findings, she was diagnosed as having posterior reversible encephalopathy syndrome (PRES). During chemotherapy for hematologic malignancies, some patients with PRES reportedly develop paralytic ileus or tumor lysis syndrome. PRES should be considered in patients with neurological abnormalities following such complications during chemotherapy.

Paralytic ileus is a recognised side effect of the oral agent capecitabine. We present this report on a patient with metastatic colorectal cancer who was treated with capecitabine and presented with persistent paralytic ileus which did not respond to standard conservative measures. Neostigmine was administered safely, resulting in resolution of the paralytic ileus. This approach merits further investigation.

We herein report two patients (70- and 45-year-old men) with refractory multiple myeloma who developed paralytic ileus shortly after starting bortezomib therapy. Bortezomib (1.3 mg/m(2)) was given on days 1, 4, 8, and 11 with daily oral solution itraconazole or voriconazole. Twelve and 15 days after beginning the therapy, each patient developed paralytic ileus. Interestingly, no other signs of peripheral neuropathy such as fingertip numbness were observed at the onset of ileus. Sporadic cases of paralytic ileus after bortezomib therapy have been reported, most of which developed ileus after several courses of bortezomib therapy. Our cases developed paralytic ileus shortly after initiating bortezomib, strongly suggesting that autonomic neuropathy due to bortezomib was induced by the concomitant use of itraconazole or voriconazole.

A 74-year-old female with relapsed multiple myeloma was treated with twice-weekly bortezomib plus dexamethasone (BD)therapy, but severe gastrointestinal adverse events(grade 3 paralytic ileus and constipation)developed. After changing to once-weekly BD therapy, ≥ grade 3 gastrointestinal adverse events did not develop, and she was able to continue BD therapy. A complete response and a treatment-free interval ≥ 2 years were obtained by 8 courses of BD therapy. This case report suggests that once-weekly BD therapy may reduce severe gastrointestinal adverse events without decreasing the clinical efficacy for multiple myeloma.

Methamphetamine abuse has become a significant problem in the United States with recent surveys reporting that nearly 10 million Americans have tried methamphetamine at least once. Methamphetamine is a stimulant drug that causes the release of monoamine neurotransmitters. Among its most deleterious effects are its ability to produce tachycardia, hypertension, and ischemia. However, it also has the potential to cause clinically significant effects outside of the cardiovascular system although a case of paralytic ileus caused by methamphetamine use has not been described before in the literature. Described is a case in which a patient presented with chest and abdominal pain after methamphetamine use. The patient was ultimately diagnosed with a methamphetamine-induced paralytic ileus.

Purpose: A case of paralytic ileus in a patient receiving oral diltiazem therapy for atrial fibrillation is reported., Summary: A 64-year-old man with a history of multiple serious comorbidities, poly-pharmacy, and a recent hospital stay for acute cardiac problems was readmitted to the hospital for gastrointestinal (GI) bleeding. On day 2 of the readmission, he suffered a myocardial infarction complicated by atrial fibrillation with a rapid ventricular response. After initial treatment with oral metoprolol for ventricular rate control was discontinued (due to ineffective rate control and patient complaints of respiratory symptoms), oral diltiazem hydrochloride therapy (30 mg every six hours) was initiated on day 7; the dose was adjusted to a maximum of 120 mg every six hours on day 10. On day 12, the patient complained of nausea, abdominal pain and tenderness, and infrequent bowel movements; imaging studies on day 13 indicated paralytic ileus. Pursuant to a surgical consultation, a nasogastric tube was inserted and nothing was given by mouth except medications. After initial improvement of the GI symptoms, the feeding tube was removed; however, the symptoms worsened over the next two to three days, requiring reinsertion of the tube on day 16. On day 18, after other potential causes of ileus were ruled out, diltiazem therapy was withdrawn. The man experienced rapid symptomatic improvement, with no further GI symptoms, and was discharged four days later., Conclusion: A 64-year-old man receiving high-dose diltiazem to treat atrial fibrillation developed paralytic ileus, which quickly resolved after the medication was discontinued.

Aim: To highlight some problems that may occur when investigating clozapine-associated deaths including (i) that death may be related to gastrointestinal hypomotility and (ii) that post-mortem blood clozapine and norclozapine concentrations may not reflect ante-mortem concentrations., Case Reports: A 41-year-old male died 40 min after admission to hospital as a result of aspiration complicating severe, clozapine-induced constipation. At post-mortem the small bowel was dilated and contained bloodstained mucus, particularly within the jejunum. The large bowel was considerably dilated and contained large quantities of foul-smelling, bloodstained fluid and a small amount of stool. Its lining was focally congested, but there was no other obvious abnormality. Analysis of serum obtained on admission revealed clozapine and norclozapine concentrations of 0.56 and 0.43 mg/L, respectively, whereas post-mortem femoral whole blood obtained <34 h after death showed clozapine and norclozapine concentrations of 3.73 and 1.75 mg/L, respectively. In 6 out of a further 12 clozapine-associated deaths investigated 2002-9 there were reports of gastrointestinal tract problems of varying severity., Conclusions: Severe constipation or paralytic ileus in clozapine-treated patients may lead to intestinal necrosis and/or perforation, or pulmonary aspiration. In some such cases the immediate cause of death may be obvious, but in others only careful assessment of the clinical course of the terminal illness may reveal gastrointestinal hypomotility as a likely underlying cause of death., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Ileus can result from the combined activity of antipsychotic and anticholinergic medications. Despite frequent use, case reports in the literature are sparse. We present a patient who developed a paralytic ileus requiring extended hospitalization. Providers should minimize antipsychotic and concurrent anticholinergic medications, consider prophylactic bowel regimens and monitor for constipation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Transient impairment of bowel function is a frequent and distressing problem in neonates on opioid-induced analgesia. Methylnaltrexone, a peripheral-acting μ-opioid receptor antagonist, has been studied in adults for the treatment of opioid-induced constipation in advanced illness and has been suggested as a promising therapeutic concept for reducing postoperative ileus. Here, we report on a newborn infant on fentanyl analgesia after major abdominal surgery with aggravated ileus. After 8 days of quiescent bowel, the patient's intestinal dysmotility resolved within 15 minutes after intravenous administration of methylnaltrexone (0.15 mg/kg body weight). Methylnatrexone was repeated daily until cessation of fentanyl administration. There were no signs of pain or opioid withdrawal., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Ileus states are serious conditions that may lead to pathophysiological changes which in turn can result in perforation of bowel, peritonitis, sepsis or death. Our paper discusses paralytic ileus states, which can be caused by psychopharmaceutics with anticholinergic side effects., Methods and Results: Retrospective analysis of cases of paralytic ileus in mentally ill patients admitted to Mental Hospital Kromeriz., Conclusion: Although some old psychopharmacs have a much higher potential for anticholinergic side effects than the new ones, there are still some of the new modern antipsychotics which also have anticholinergic side effects which could cause paralytic ileus. Both psychiatrists and surgeons should pay attention to atypical or changed signs of ileus states in mentally ill patients and should be aware of the confounding factors which could make the diagnosis of ileus difficult in mentally ill patients.

Summary: Intestinal pseudo-obstruction is a rare complication resulting from a variety of disorders. Symptoms include abdominal pain, nausea, vomiting, diarrhea, constipation, and malnutrition. Vincristine-related pseudo-obstruction has been reported in the literature, but its description in children and recommendations for management are lacking. A review of the literature revealed 21 reported pediatric cases of vincristine-related pseudo-obstruction. Most have, however, been attributed to a drug interaction with itraconazole, accidental vincristine overdose, or liver failure. Potential genetic causes are rarely addressed. We present here 5 cases of pseudo-obstruction related to vincristine without any identifiable predisposing factors, and a suggested algorithm for management.

Case Description: A French Caucasian man aged 39 with HIV infection was treated with abacavir/lamivudine and ritonavir/lopinavir. The patient (normal renal and liver functions) was diagnosed with a Burkitt lymphoma for which he was treated with cyclophosphamide day 1 to 5; doxorubicin day 1; methotrexate day 10; and vincristine day 1 and 8. At day 12, he suffered from abdominal pain associated with constipation. Paralytic ileus was diagnosed by study imaging. Ileus lasted 10 days necessitating parenteral feeding. Later on, a further cycle of chemotherapy with etoposide replacing vincristine was given and was well tolerated., Conclusion: We speculate that an interaction between ritonavir/lopinavir and vincristine was responsible for this severe toxicity. Vincristine is transported by P-gp and is metabolized via CYP3A5. Ritonavir is a potent CYP3A5 isoenzyme and P-gp inhibitor. Lopinavir is also a P-gp inhibitor. Ritonavir and lopinavir might have delayed vincristine elimination. Clinicians should be aware of this possible interaction.

Paralytic ileus is a temporary arrest of intestinal peristalsis. We report on two patients with breast cancer who developed paralytic ileus following treatment with capecitabine. The pathophysiology of this disorder and its possible connection to capecitabine are described with the aim of promoting the early recognition of the clinical picture so that unnecessary surgery can be avoided.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is most commonly associated with a mitochondrial DNA A to G point mutation at nucleotide 3243 (A3243G) and individuals with the disorder present a wide range of multisystemic symptoms. Seizures in MELAS patients are often intractable and require multiple antiepileptic drugs. Here we report a MELAS patient who presented with acute intestinal pseudo-obstruction following the administration of phenytoin (PHT) as an antiepileptic treatment. She presented with the first stroke-like episode at the age of 6 years and mitochondrial DNA analysis revealed A3243G with 94% mutation load in skeletal muscle. Despite treatment with phenobarbital and clobazam at the age of 16 years, she developed status epilepticus which ceased following PHT infusion. Thereafter, she was started on PHT treatment. One month later, however, she was readmitted because of remarkable abdominal distention. Although abdominal CT showed acute ileus with hepatic portal venous gas mimicking surgical emergency, the abdominal distention gradually recovered over several days following the discontinuation of PHT. Our clinical observations suggest the possibility that intestinal pseudo-obstruction in this patient related to PHT therapy. Careful clinical observation including gastrointestinal symptoms is required in the management of epilepsy in MELAS patients.

Arsenic trioxide (As(2)O(3)) is an effective agent for the treatment of relapsed acute promyelocytic leukemia (APL). We report a patient with intestinal pseudo-obstruction, which occurred while treating relapsed APL with As(2)O(3). A 6-year-old female with relapsed APL developed paralytic ileus, hyperleukocytosis, and a high fever while being treated with As(2)O(3). Although As(2)O(3) was discontinued and dexamethasone was administered, vomiting and abdominal distension worsened. An ileostomy was performed and diffuse patch-like infiltrations on the bowel surface were noted. Pathologic findings revealed APL cells involving the entire intestinal layers. This case history suggests that As(2)O(3) when used for reinduction therapy for APL may adversely affect the intestine and cause acute intestinal pseudo-obstruction., ((c) 2008 Wiley-Liss, Inc.)

Objective: To report the usefulness of antipsychotic dose-reduction for avoiding paralytic ileus in a patient with chronic schizophrenia and comorbid dementia., Case Summary: A 65-year-old in-patient developed severe paralytic ileus warranting a transfer to the general hospital. Constipation was very troublesome and he often needed enema to prevent intestinal obstruction. He had originally been treated with 24 mg of bromperidol, which was reduced to 4 mg, and other psychotropic treatments were simultaneously simplified. As a result, bowel habits improved and enema is now only rarely necessary. Constipation is a frequent adverse effect of antipsychotics and adjunctive psychotropics, which can be severe and may lead to life-threatening paralytic ileus. Dose-reduction obviated a necessity of enema against persistent constipation, while the patient's mental status remained under control. Assessment using the Naranjo probability scale revealed a definite causal relationship., Discussion: With an increasing number of elderly patients with schizophrenia, more cases of severe gastrointestinal motility problems from antipsychotic medication are to be expected. In this patient population dose-reduction of antipsychotics and simplification of concomitant psychotropics should be seriously considered.

Bortezomib is the first anticancer proteasome inhibitor introduced into clinical practice. It has been recently approved for the treatment of multiple myeloma, an incurable plasma cell tumour that accounts for 10-15% of all haematologic malignancies and for approximately 20% of deaths. Gastrointestinal toxicity associated with the use of this drug is common but generally mild to moderate. Paralytic ileus in patients undergoing bortezomib treatment has been reported, although a definite attribution to bortezomib administration has not been established. We report a myeloma patient who developed severe paralytic ileus during bortezomib therapy, which presented in the context of progressive constipation without other known causes and which regressed promptly with medical management after drug cessation, suggesting a direct causal relationship. Awareness of the various potential gastrointestinal toxic effects of bortezomib is of relevance given the growing number of patients undergoing treatment with this important and effective new cancer drug.