Severe akathisia as a side effect of metoclopramide

Case description A case of severe metoclopramide-induced akathisia in a breast cancer patient being treated with chemotherapy is presented, eventually culminating in hospital admission. In retrospect, this adverse effect was not recognized for several weeks because the prescription had not been properly recorded in the chart, the patient initially denied using the drug, and extensive psychological adjustment difficulties were also present. Conclusion Movement disorders as an adverse effect of metoclopramide have been described on a regular basis over the past decades. Case reports such as this confirm there is under-recognition of adverse effects and emphasize the need to take a comprehensive medication history and recognize well known side effects of medications such as metoclopramide

Transforming growth factor beta induces sensory neuronal hyperexcitability, and contributes to pancreatic pain and hyperalgesia in rats with chronic pancreatitis

Background: Transforming growth factor beta (TGFβ) is upregulated in chronic inflammation, where it plays a key role in wound healing and promoting fibrosis. However, little is known about the peripheral effects of TGFβ on nociception.Methods: We tested the in vitro effects of TGFβ1 on the excitability of dorsal root ganglia (DRG) neurons and the function of potassium (K) channels. We also studied the effects of TGFβ1 infusion on pain responses to noxious electrical stimulation in healthy rats as well as the effects of neutralization of TGFβ1 on evoked pain behaviors in a rat model of chronic pancreatitis.Results: Exposure to TGFβ1 in vitro increased sensory neuronal excitability, decreased voltage-gated A-type K+ currents (IA) and downregulated expression of the Kv1.4 (KCNA4) gene. Further TGFβ1 infusion into the naïve rat pancreas in vivo induces hyperalgesia and conversely, neutralization of TGFβ1 attenuates hyperalgesia only in rats with experimental chronic pancreatitis. Paradoxically, TGFβ1 neutralization in naïve rats results in pancreatic hyperalgesia.Conclusions: TGFβ1 is an important and complex modulator of sensory neuronal function in chronic inflammation, providing a link between fibrosis and nociception and is a potentially novel target for the treatment of persistent pain associated with chronic pancreatitis. © 2012 Zhu et al.; licensee BioMed Central Ltd

Cyclic vomiting syndrome in adults

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72300/1/j.1365-2982.2008.01113.x.pd

Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a non-randomized controlled trial

BACKGROUND: Although lateral internal sphincterotomy is the gold-standard treatment for chronic anal fissure, intrasphincteric injection of botulinum toxin seems to be a reliable new option. The aim of this non-randomized study is to compare the effect of lateral internal sphincterotomy and botulinum toxin injection treatments on the outcome and reduction of anal sphincter pressures in patients with chronic anal fissure. METHODS: Patients with chronic anal fissure were treated with either botulinum toxin injection or lateral internal sphincterotomy by their own choice. Maximal resting pressure and maximal squeeze pressure measurements were performed before and 2 weeks after treatments by anal manometry. Patients were followed for fissure relapse during 14 months. RESULTS: Twenty-one consecutive outpatients with posterior chronic anal fissure were enrolled. Eleven patients underwent surgery and ten patients received botulinum toxin injection treatment. Before the treatment, anal pressures were found to be similar in both groups. After the treatment, the maximal resting pressures were reduced from 104 ± 22 mmHg to 86 ± 15 mmHg in the surgery group (p < 0.05) and from 101 ± 23 mmHg to 83 ± 24 mmHg in the botulinum toxin group (p < 0.05). The mean maximal squeeze pressures were reduced from 70 ± 27 mmHg to 61 ± 32 mmHg (p > 0.05) in the surgery group, and from 117 ± 62 mmHg to 76 ± 34 (p < 0.01) in the botulinum toxin group. The fissures were healed in 70 percent of patients in the botulinum group and 82 percent in the surgery group (p > 0.05). There were no relapses during the 14 months of follow up. CONCLUSION: Lateral internal sphincterotomy and botulinum toxin injection treatments both seem to be equally effective in the treatment of chronic anal fissure

Antispasmodic and vasodilator activities of Morinda citrifolia root extract are mediated through blockade of voltage dependent calcium channels

<p>Abstract</p> <p>Background</p> <p><it>Morinda citrifolia </it>(Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders.</p> <p>Methods</p> <p>Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract of <it>Morinda citrifolia </it>roots (Mc.Cr).</p> <p>Results</p> <p>The Mc.Cr produced a concentration-dependent relaxation of spontaneous and high K⁺induced contractions in isolated rabbit jejunum preparations. It also caused right ward shift in the concentration response curves of Ca⁺⁺, similar to that of verapamil. In guinea-pig right atria, Mc.Cr caused inhibition of both atrial force and rate of spontaneous contractions. In rabbit thoracic aortic preparations, Mc.Cr also suppressed contractions induced by phenylephrine (1.0 μM) in normal- Ca⁺⁺and Ca⁺⁺-free Kerb's solutions and by high K⁺, similar to that of verapamil. In rat thoracic aortic preparations, Mc.Cr also relaxed the phenylephrine (1.0 μM)-induced contractions. The vasodilatory responses were not altered in the presence of L-NAME (0.1 mM) or atropine (1.0 μM) and removal of endothelium.</p> <p>Conclusions</p> <p>These results suggest that the spasmolytic and vasodilator effects of Mc.Cr root extract are mediated possibly through blockade of voltage-dependent calcium channels and release of intracellular calcium, which may explain the medicinal use of <it>Morinda citrifolia </it>in diarrhea and hypertension. However, more detailed studies are required to assess the safety and efficacy of this plant.</p

Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis

To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices, respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance

Species and tissue-specificity of prokinetic, laxative and spasmodic effects of Fumaria parviflora

<p>Abstract</p> <p>Background</p> <p><it>Fumaria parviflora </it>Linn. (<it>Fumariaceae</it>), is a small branched annual herb found in many parts of the world including Saudi Arabia and Pakistan. This study was designed to provide pharmacological basis for the medicinal use of <it>Fumaria parviflora </it>in gut motility disorders.</p> <p>Methods</p> <p>The <it>in-vivo </it>prokinetic and laxative assays were conducted in mice. Isolated intestinal preparations (ileum and jejunum) from different animal species (mouse, guinea-pig and rabbit) were separately suspended in tissue baths containing Tyrode's solution bubbled with carbogen and maintained at 37°C. The spasmogenic responses were recorded using isotonic transducers coupled with PowerLab data acquisition system.</p> <p>Results</p> <p>The aqueous-methanol extract of <it>Fumaria parviflora </it>(Fp.Cr), which tested positive for the presence of alkaloids, saponins, tannins and anthraquinones showed partially atropine-sensitive prokinetic and laxative activities in the <it>in-vivo </it>in mice at 30 and 100 mg/kg. In the <it>in-vitro </it>studies, Fp.Cr (0.01-1 mg/ml) caused a concentration-dependent atropine-sensitive stimulatory effect both in mouse tissues (jejunum and ileum), and rabbit jejunum but had no effect in rabbit ileum. In guinea-pig tissues (ileum and jejunum), the crude extract showed a concentration-dependent stimulatory effect with higher efficacy in ileum and the effect was partially blocked by atropine, indicating the involvement of more than one types of gut-stimulant components (atropine-sensitive and insensitive). This could be a plausible reason for the greater efficacy of Fp.Cr in gut preparations of guinea-pig than in rabbit or mouse.</p> <p>Conclusions</p> <p>This study shows the prokinetic, laxative and spasmodic effects of the plant extract partially mediated through cholinergic pathways with species and tissue-selectivity, and provides a sound rationale for the medicinal use of <it>Fumaria parviflora </it>in gut motility disorders such as, indigestion and constipation. This study also suggests using different species to know better picture of pharmacological profile of the test material.</p

Oral Ondansetron Administration in Emergency Departments to Children with Gastroenteritis: An Economic Analysis

Stephen Freedman and colleagues performed a cost analysis of the routine administration of ondansetron in both the United States and Canada and show that its routine administration to eligible children in such settings could provide substantial benefit

Sulindac targets nuclear β-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines

Nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive potential against colorectal carcinomas (CRCs). Inhibition of cyclooxygenase (COX)-2 underlies part of this effect, although COX-2-independent mechanisms may also exist. Nonsteroidal anti-inflammatory drugs appear to inhibit the initial stages of the adenoma-carcinoma sequence, suggesting a link to the APC/beta-catenin/TCF pathway (Wnt-signalling pathway). Therefore, the effect of the NSAID sulindac on nuclear (nonphosphorylated) beta-catenin and beta-catenin/TCF-mediated transcription was investigated. Nuclear #946;-catenin expression was assessed in pretreatment colorectal adenomas and in adenomas after treatment with sulindac from five patients with familial adenomatous polyposis (FAP). Also, the effect of sulindac sulphide on beta-catenin/TCF-mediated transcription was studied. Adenomas of FAP patients collected after treatment with sulindac for up to 6 months showed less nuclear beta-catenin expression compared to pretreatment adenomas of the same patients. Sulindac sulphide abrogated beta-catenin/TCF-mediated transcription in the CRC cell lines DLD1 and SW480, and decreased the levels of nonphosphorylated beta-catenin. As a result, the protein levels of the positively regulated TCF targets Met and cyclin D1 were downregulated after sulindac treatment. This study provides in vivo and in vitro evidence that nuclear beta-catenin localisation and beta-catenin/TCF-regulated transcription of target genes can be inhibited by sulindac. The inhibition of Wnt-signalling provides an explanation for the COX-2-independent mechanism of chemoprevention by NSAID

Aspirin induces cell death and caspase-dependent phosphatidylserine externalization in HT-29 human colon adenocarcinoma cells

The induction of cell death by aspirin was analysed in HT-29 colon carcinoma cells. Aspirin induced two hallmarks of apoptosis: nuclear chromatin condensation and increase in phosphatidylserine externalization. However, aspirin did not induce either oligonucleosomal fragmentation of DNA, decrease in DNA content or nuclear fragmentation. The effect of aspirin on Annexin V binding was inhibited by the caspase inhibitor Z-VAD.fmk, indicating the involvement of caspases in the apoptotic action of aspirin. However, aspirin did not induce proteolysis of PARP, suggesting that aspirin does not increase nuclear caspase 3-like activity in HT-29 cells. This finding may be related with the ‘atypical’ features of aspirin-induced apoptosis in HT-29 cells. © 1999 Cancer Research Campaig