GI Sites Research Articles

Mo1225 Factors Associated With C. difficile Negative Gastrointestinal Symptoms After Intestinal Microbiome Restoration

5-ASA levels increased after 1 h for Pentasa and Apriso and 3 h for Lialda. Prominent 5ASA and Ac-5-ASA release after Pentasa was observed at all GI sites (including gastric). Gastric 5-ASA levels were >170-fold higher after Pentasa vs. Lialda. Peak small bowel GI 5-ASA (Figure 1) and Ac-5-ASA (not shown) levels were 15 to 1000+ fold lower for Lialda vs. Pentasa and Apriso, emphasizing greater colon release for Lialda. In addition, peak GI Ac-5-ASA levels were seen earlier with Pentasa (4.0+2.0 h) vs. Apriso (7.0+0.0 h) and Lialda (6.0+1.4 h). Plasma 5-ASA and Ac-5-ASA levels were lower vs. GI fluids consistent with luminal actions (Table 1). As in GI fluids, plasma 5-ASA and Ac-5-ASA appeared earliest for Pentasa and latest for Lialda. Peak plasma levels occurred 12 h after Lialda, reflecting again mostly colon absorption. Conclusions: Using novel multiport catheters to aspirate GI fluids for regional drug release analysis, we showed variable time-dependent appearance and absorption of 3 mesalamine products. Release of 5-ASA and its metabolite occurred earliest and most proximally with Pentasa (including gastric release). Small bowel release and absorption were slower and more distal with Apriso and were minimal with Lialda. Such innovative in vivo techniques will be used to validate in vitro dissolution methods and support computational models for future processes that are applicable to developing luminally-acting and extended-release drugs. This research was funded by FDA grants HHSF223201000082C and HHSF223201300460A.

Mo1227 Cathelicidin Mimic Ceragenin CSA13 Modulates Clostridium difficile Associated Colitis and Toxin a Mediated Enteritis in Mice

5-ASA levels increased after 1 h for Pentasa and Apriso and 3 h for Lialda. Prominent 5ASA and Ac-5-ASA release after Pentasa was observed at all GI sites (including gastric). Gastric 5-ASA levels were >170-fold higher after Pentasa vs. Lialda. Peak small bowel GI 5-ASA (Figure 1) and Ac-5-ASA (not shown) levels were 15 to 1000+ fold lower for Lialda vs. Pentasa and Apriso, emphasizing greater colon release for Lialda. In addition, peak GI Ac-5-ASA levels were seen earlier with Pentasa (4.0+2.0 h) vs. Apriso (7.0+0.0 h) and Lialda (6.0+1.4 h). Plasma 5-ASA and Ac-5-ASA levels were lower vs. GI fluids consistent with luminal actions (Table 1). As in GI fluids, plasma 5-ASA and Ac-5-ASA appeared earliest for Pentasa and latest for Lialda. Peak plasma levels occurred 12 h after Lialda, reflecting again mostly colon absorption. Conclusions: Using novel multiport catheters to aspirate GI fluids for regional drug release analysis, we showed variable time-dependent appearance and absorption of 3 mesalamine products. Release of 5-ASA and its metabolite occurred earliest and most proximally with Pentasa (including gastric release). Small bowel release and absorption were slower and more distal with Apriso and were minimal with Lialda. Such innovative in vivo techniques will be used to validate in vitro dissolution methods and support computational models for future processes that are applicable to developing luminally-acting and extended-release drugs. This research was funded by FDA grants HHSF223201000082C and HHSF223201300460A.

Multiple sporadic gastrointestinal stromal tumors concomitant with ampullary adenocarcinoma: A case report with KIT and PDGFRA mutational analysis and miR-221/222 expression profile

GISTs originating multifocally at different GI sites, in patients lacking familial syndromes, could be interpreted as recurrent/metastatic disease. MiR-221/222 have recently been identified as regulators of KIT expression in GISTs. We report the first case of synchronous GISTs in the stomach and duodenum concomitant with an ampullary adenocarcinoma. Different CD117 expression patterns could be related to different KIT mutational status in the two lesions: gastric GIST showed a dot-like pattern and lacked KIT mutations; duodenal GIST had a strong membranous expression pattern, likely due to KIT exon 9 duplication, which is associated with lower response to imatinib. MiR-221/222 were downregulated in GISTs as compared with normal tissue (p<0.05) and expressed increased levels in the gastric GIST as compared with duodenal one (p<0.05). Our data support an independent origin of the two GISTs. Determining whether these tumors are multiple primaries or recurrencies is helpful to predict their malignancy and to select proper treatment.

Breast cancer biomarker discordance between primary and sites of metastasis: A systematic review.

e11574 Background: Systemic treatment choices for breast cancer patients with recurrent disease are usually based on the ER/PR/Her2 biomarker status of the primary cancer. Biomarker discordance between the primary and metastatic sites is well recognised and could have important therapeutic implications. A systematic review was conducted to assess the extent of biomarker discordance between the primary cancer and metastasis, and whether is influenced by the site of metastasis. Methods: An electronic search of multiple literature databases implemented by an information scientist was conducted to identify studies reporting outcomes of ER/PR/Her2 receptor stability between primary site and recurrent disease. Seven reviewers independently screened the 5034 abstracts and full text articles, which were identified according to pre-defined selection criteria. The same reviewers performed data collection from all included studies. Studies that were identified reported on receptor conversion between primary sites of breast cancer and various sites of metastasis including lymph node, liver, brain, lung, skin, GI sites and bone marrow. Results: Preliminary results from 385 eligible studies consistently demonstrated discordance between the primary and metastatic sites. When discordance occurred, the general trend was for loss of hormone receptor. ER hormone status was more stable (discordance 10.2-32.5%) than PR (discordance 25.5-40.7%). HER2 was found to have lower rates of discordance (2.6-14.5%). In general, higher ER/PR discordance was found in bone (40-68%) and liver (0-54%) when compared to other sites brain (36%), lung (9-18%), skin (6-22%), GI (15-40%). In the prospective studies, biomarker discordance led to change in patient management in up to 20% of the patient population. Conclusions: Our results demonstrate that biomarker discordance between primary and distant metastases does occur in breast cancer, occurs more frequently with PR, and the extent of discordance is influenced by the site of metastasis. Further research is required to have a better explanation about the pathophysiology of the biomarker status change and its clinical implications.

Pediatric Duodenal Mucosal Biopsies with Eosinophilic Infiltrates: A Clinicopathologic Study

Aims: To describe the clinicopathologic features of children with Duodenal eosinophilic infiltrates (DEI). Study Design: Retrospective. Place and Duration of Study: Pediatric Gastroenterology Division, Texas Children’s Hospital over 24 months (Jan 1, 1998 –Dec 31, 1999). Methodology: Children with DEI at Texas Children’s Hospital over 24 months were identified. Clinical symptomatology was analyzed by a retrospective medical record review. Two pediatric pathologists re-evaluated all biopsies. Follow-up was done by contacting the patients 12-36 months after the initial diagnosis. Results: Total number of GI biopsies that included duodenum over the study period was 1145 biopsies. Out of 1145 cases, 780(68%) cases indicated eosinophilic infiltrates (EI) at some GI site. Out of these, 287(37%) cases had DEI. Mean age was 10.4 years. (F: M .2:1). Race: 197(79%) Caucasians, 37(15%) Latin Americans, 9(4%) African Americans and 6(2%) Arabs. Clinical symptomatology: 249 records were available for Short Communication British Journal of Medicine & Medical Research, 3(3): 555-565, 2013 556 evaluation. 69.9% complained of abdominal pain, 55% had vomiting, 34.9% with diarrhea and 32.9% had weight loss. 105 patients were available for follow up; 38% continued to have abdominal pain, 15.2% with vomiting, 10.5% diarrhea and 7.6% had a persistent weight loss. Peripheral eosinophilia was present in 35.2%. Medical treatment included proton pump inhibitors (57.0%), H2-blockers (55.4%), steroids (26.5%), and elemental diet (9.6%). Histopathology: 6% had 20 eos/hpf. There were no significant differences in the number of eos/hpf between those with or without a specific symptom. Fourteen children (5.6%) subsequently developed IBD; their histopathological data did not differ from the rest. Conclusion: 1) children with DEI present with variable chronic symptoms 2) symptoms persisted in a significant number of patients despite therapy, 3) Close observation is warranted since a small number of patients may develop IBD.

Are Proton Pump Inhibitors a True Risk Factor of HIP and Spine Fractures?: A Longitudinal Cohort Study

G A A b st ra ct s rectum 38% and cancer stage was in situ/local 62%, regional 17%, distant metastasis 13%, unknown or missing stage 9%. Twenty percent of patients with NET were diagnosed in the period 1995-1999, 35% in 2000-2004 and 45% in 2005-2009. Unadjusted 5 year survival rates from time of diagnosis by site were: stomach 56%, duodenum 66%, small intestine 52%, colon 67%, rectum 84%. Factors associated with shorter survival were increasing age, hazard ratio (HR) 1.05 (95% CI 1.04-1.06), not being married HR 1.41 (95% CI 1.201.65), NET location [compared to rectum: stomach HR 2.26 (95% CI 1.68-3.05), duodenum HR 1.70 (95%CI 1.26-2.28), small intestine HR 1.85 (95% CI 1.42-2.42), colon 1.83 (95% CI 1.41-2.39)], stage [compared to in situ/local: regional HR 1.15 (95% CI 0.90-1.47), distant HR 2.38 (95% CI 1.87-3.05), unknown stage HR 1.67 (95% CI 1.29-2.17)], and earlier period of diagnosis [compared to 1995-1999: 2000-2004 HR 0.70 (95% CI 0.590.85) 2005-2009 HR 0.43 (95% CI 0.34-0.54)]. Conclusions: Two-thirds of patients diagnosed with GI NET in the VA system had local disease and three quarters underwent resection. As in other studies, more patients were diagnosed in recent time periods versus earlier time periods. In adjusted analysis, worsened survival was associated with older age, not being married, tumor site, advanced stage, and older year of diagnosis. There was no difference in survival between local and regional disease. Rectal NET has been previously shown to be associated with male gender and minority race which may explain the high proportion of rectal NET in the VA. We found that rectal NET had better survival compared to survival in veterans with NET from other GI sites.

Extra Nodal Marginal Zone Lymphoma of MALT Type: Radiotherapy is Potentially Curative for Localized Disease

Extra Nodal Marginal Zone Lymphoma of MALT Type: Radiotherapy is Potentially Curative for Localized Disease

Microscopic Gastrointestinal Stromal Tumors in Esophageal and Intestinal Surgical Resection Specimens

Microscopic gastrointestinal stromal tumors (GISTs) (synonyms: sporadic interstitial cell of Cajal hyperplasia, seedling GISTs, minimal GISTs) are common incidental findings in gastroesophageal resections (9% to 35%). To our knowledge, their frequency, clinicopathologic features, and molecular pathogenesis from nongastroesophageal sites have so far not been sufficiently analyzed. We studied 19 lesions from distal esophagus (n=8), gastroesophageal junction (n=2), sigmoid colon (n=5), and vermiform appendix, cecum, rectum, and small intestine (1 each). Microscopic GISTs were detected in 0.2%, 0.1%, and 0.01% of routinely processed resection specimens from sigmoid colon, vermiform appendix, and rectum, respectively. Patients were 11 men and 8 women with a mean age of 66 years (range, 57 to 86 y). Thirteen patients had GI cancers and 5 had diverticular disease. None has a family history of GIST or features of neurofibromatosis 1. Lesions were 0.5 to 4 mm in size (mean, 1.12 mm), were all spindled and had noncircumscribed infiltrating borders. All arose in the muscularis propria and 2 were predominantly subserosal. Immunohistochemistry revealed a CD117/CD34/smooth muscle actin-negative phenotype in 18/19 lesions. Three KIT exon 11 mutations (2 point mutations and 1 deletion, all involving W557) were detected in 3/12 lesions with successful molecular analysis. In conclusion, incidental microscopic GISTs are uncommon in intestinal resections (< or =0.1%), contrasting with their gastroesophageal counterparts (> or =9%). Somatic KIT mutations are early initiating molecular events in a subset of them. The remarkable variation in the incidence of microscopic GISTs at different GI sites suggests an origin from heterogeneous subsets of interstitial cells of Cajal with varying potentials for neoplastic transformation.

847 Effect of Multi-Point Gastric Electrical Pacing (MGP) On Symptoms, Gastric Emptying and Electrical Activity in Diabetic Gastroparesis

other sites (incidental TICs) were excluded from this analysis. Daily fiber & abstinence from ASA & NSAIDs were recommended. Outcomes were analyzed for PRES vs. DEF subgroups & by baseline treatment groups (MED, ENDO, SURG) post-60 days after initial diagnosis & treatment. Data were recorded on standard forms by research coordinators & SAS was used for data management & analysis. RESULTS: Patients were similar in all demographics, except for more RBC's & ENDO treatments in the DEF group. The mean age was 72 yrs, 29% were female, 16% took anticoagulants & all had co-morbidities. 43 pts (37.7%) had definitive & 71 pts (62.3 %) presumptive TIC Bleeds. Mean F/U was 1195±77 days. Compliance with fiber & ASA/NSAIDs was low. The rates of rebleeds & other TIC COMPL for DEF (N=43) vs. PRES (N=71); & MED (N=74), ENDO (N=32) & SURG (N=8) are shown in the Table. No differences were significant (p> 0.05). The cumulative death rate was 16.7% & no one died of TIC bleed or TIC-COMPL. CONCLUSIONS: For patients with documented diverticular hemorrhage followed long-term: 1. Rebleeding rates were low, but as likely to be from TICs as other GI sites. 2. No one died of TIC bleeds or TIC complications, which were also very rare. 3. There were no significant outcome differences after medical, endoscopic, or surgical therapies. Based upon these data, the recommendation of surgery for an index diverticular bleed should be revised. Partially supported by NIH grants (K24DK002650) & CURE (P30-DK040301) Human Studies Core.

Traitement chirurgical de l’endométriose rectale

Intestinal endometriosis accounts for 8-12% of all endometriosis and rectal involvement is most often encountered in the context of deep pelvic infiltration. Intestinal symptoms, often nonspecific, are most typically seen as painful defecation or constipation worsening in the premenstrual period associated with pelvic pain, dysmenorrheal, dyspareunia, and infertility. Physical examination should include a pelvic exam under anesthesia. Endorectal ultrasound best evaluates rectal muscle invasion, while pelvic MRI and CT will evaluate the full extent of pelvic involvement and other GI sites of implantation. Only radical extirpative surgery of all intestinal, urologic, deep pelvic, and adnexal sites of endometriosis will permit relief of pain, prevent recurrence, and hopefully preserve fertility. In view of the frequency of extra-intestinal sites of involvement and technical difficulties augmented by previous surgical interventions, open laparotomy remains the preferred approach. A laparascopic approach would be reserved only for well-selected patients presenting with isolated colorectal involvement.

A Large Pedunculated Rectal Carcinoid Tumor Resected by Endoscopic Snare Polypectomy

A 53 y/o asymptomatic black female with a history of HTN underwent a routine screening colonoscopy which revealed a 18mm pedunculated rectal polyp as well as a 10mm pedunculated transverse colon polyp. Both were removed by snare cautery. The rectal polyp was grossly atypical. It was pale, firm and nodular with irregular borders on a wide stalk. Pathology reported a rectal carcinoid tumor and a transverse colon tubular adenoma and. An endoscopic rectal ultrasound was performed three weeks later which revealed no invasion of the submucosa. Multiple jumbo biopsies were obtained from the polypectomy site all were negative for any residual carcinoid tumor tissue. Computed tomography of the chest, abdomen and pelvis were negative for metastasis. Discussion: Carcinoid tumors are derived from the neuroendocrine system. They have the capbility of secreting an array of biologically active agents. The incidence of carcinoid tumors has been estimated to be 8.4 per 100,000. 74% of carcinoid tumors are located in the gastrointestinal tract, the ileum, appendix and the rectum are the most common GI sites. The Bronchopulmonary system is responsible for the majority of the other sites. Grossly they are usually submucosal. They are usually yellow/tan or pale/gray secondary to a high lipid content, as well as firm and rubbery. Histologically they appear as nests, cords or rossettes of uniform round cells with rare mitotic figures. Immunohistochemically, they may be differentiated from other neuroendocrine tumors with chromogranins A, B, C, synaptophysin and enolase stains. They are best visualized endoscopicaly using EUS and by Somatostatin scintography, PET scans and CT scans. Tumors less than 1cm < 2% chance of mets, 1–1.9cm 10–15%, >2cm 60–80%. The overall survival rate of rectal carcinoid tumors is 72%. Their prognosis and treatment depend on a variety of factors including: location, size, degree of invasion and possibly by whether they are sessile or pedunculated. Pedunculated rectal carcinoid tumors are extremely rare. This may be the tenth reported case in medical literature. There have been recommendations regarding endoscpopic resection of flat, sessile rectal carcinoid tumors, however in our case of a pedunculated carcinoid tumor, more studies are needed to determine the prognosis and the most appropriate treatment.

A Systematic Review Evaluating the Addition of Radiation Therapy to Chemotherapy for Localized Aggressive Non-Hodgkin's Lymphoma: What Is the Role for Radiotherapy?.

Purpose/Objective: We performed a systematic review and meta-analysis of chemotherapy alone compared to chemotherapy plus radiation in the management of adult early stage aggressive non-Hodgkin's lymphoma (NHL). Overall survival (OS) and disease-free survival (DFS) at 5 years were evaluated.Materials/Methods: Randomized trials published after 1990 comparing chemotherapy alone to chemotherapy plus radiation therapy in the management of adult aggressive NHL were identified through searches of MEDLINE and CANCERLIT databases. In addition, a search of ASTRO, ASCO, and ASH Proceedings from 1999 to the present was performed to identify updates of published articles and abstracts. Studies that were limited to GI sites only were excluded. Only studies employing CHOP or CHOP-like regimens and radiation therapy to a minimum dose of 30 Gy were deemed acceptable. Chemotherapy alone regimens had to consist of a minimum of 4 cycles of therapy. All trials reported OS and DFS at 5 years. A meta-analysis was performed using STATA statistical software, including tests for homogeneity and publication bias. Trials were analyzed by risk ratio (RR) method.Results: Five randomized trials (n = 1933, range for individual studies 215 to 647) were identified that met all inclusion criteria. The 5-yr OS and DFS RRs for the addition of radiation therapy to chemotherapy are presented in Figures 1 and 2, respectively. Three studies suggested an OS and DFS benefit with the addition of radiation to chemotherapy and two suggested an improved OS and DFS among patients treated with chemotherapy alone. Only two of the studies reported patterns of relapse (Aviles et al and Horning et al). These studies showed improved local control with combined modality therapy (16 – 23% vs. 4 – 5%). Risk ratios for OS ranged from 0.90 to 1.56. DFS estimates range from 0.89 to 1.82. A meta-analysis was conducted to estimate the overall treatment effects for this group of studies for both OS and DFS. Due to the high degree of heterogeneity among these trials (p-value for heterogeneity <0.001 for both OS and DFS), summarizing these results with a pooled estimate of effect would be inappropriate. Heterogeneity was decreased only marginally with the exclusion of any individual study from the pooled estimate.Conclusions: It remains unclear whether early stage aggressive NHL patients benefit from the addition of radiation to CHOP-based chemotherapy. However, at this time we are not able to delineate those patients who will benefit from radiotherapy from those who will not. Currently CHOP-based chemotherapy plus radiation remains a standard of care in the US for early stage aggressive NHL. However, controversy remains regarding the role of radiation in light of conflicting results. Our ability to draw firm conclusions based on this review is limited due to the study heterogeneity. Differences among study populations may largely account for this heterogeneity. [Display omitted]

Cessation of activity in red nucleus neurons during stimulation of the medial medulla in decerebrate rats.

The pontine oral reticular nucleus, gigantocellular reticular nucleus (Gi) and dorsal paragigantocellular nucleus (DPGi) of the medulla are key elements of a brainstem-reticulospinal inhibitory system that participates in rapid eye movement (REM) sleep atonia. Our recent study has shown that excitation of these brainstem nuclei in decerebrate rats inhibits locus coeruleus cells and the midbrain locomotor region neurons related to muscle tone facilitation. In the present study we have examined the influences of electrical and chemical stimulation of Gi and DPGi inhibitory sites on the activity of neurons located in the magnocellular part of the red nucleus (RMC), a cell group that participates in both the tonic and phasic regulation of motor output. A total of 192 RMC neurons were recorded in precollicular-premammillary decerebrate rats with muscle rigidity and induced locomotion. Thirty-three RMC neurons were identified antidromically as rubrospinal (RMC-spinal) cells by stimulation of the contralateral dorsolateral funiculus at the L2 level. A total of 141 RMC neurons (88.7 %) and all RMC-spinal neurons were inhibited during electrical stimulation of Gi and DPGi inhibitory sites. This cessation of activity was correlated with bilateral muscle atonia or blockage of locomotion. Six RMC cells (3.8 %) were excited (224 +/- 50 %, n = 6, minimum = 98, maximum = 410, P < 0.05) and 11 cells (7 %) gave no response to Gi and DPGi stimulation. Microinjections of kainic acid (100 microM, 0.2 microl) into Gi and DPGi inhibitory sites, previously identified by electrical stimulation, produced a short-latency (35 +/- 3.5 s, n = 11) decrease of rigid hindlimb muscle tone and inhibition of all tested RMC (n = 7) and RMC-spinal (n = 5) neurons. These results, combined with our recent published data, suggest that inhibition of motor function during activation of the brainstem inhibitory system is related to both the descending inhibition of spinal motoneurons and suppression of activity in supraspinal motor facilitatory systems. These two mechanisms acting synergistically may cause generalized motor inhibition during REM sleep and cataplexy.

Muscle tone facilitation and inhibition after orexin-a (hypocretin-1) microinjections into the medial medulla.

Orexins/hypocretins are synthesized in neurons of the perifornical, dorsomedial, lateral, and posterior hypothalamus. A loss of hypocretin neurons has been found in human narcolepsy, which is characterized by sudden loss of muscle tone, called cataplexy, and sleepiness. The normal functional role of these neurons, however, is unclear. The medioventral medullary region, including gigantocellular reticular nucleus, alpha (GiA) and ventral (GiV) parts, participates in the induction of locomotion and muscle tone facilitation in decerebrate animals and receives moderate orexinergic innervation. In the present study, we have examined the role of orexin-A (OX-A) in muscle tone control using microinjections (50 microM, 0.3 microl) into the GiA and GiV sites in decerebrate rats. OX-A microinjections into GiA sites, previously identified by electrical stimulation as facilitating hindlimb muscle tone bilaterally, produced a bilateral increase of muscle tone in the same muscles. Bilateral lidocaine microinjections (4%, 0.3 microl) into the dorsolateral mesopontine reticular formation decreased muscle rigidity and blocked muscle tone facilitation produced by OX-A microinjections into the GiA sites. The activity of cells related to muscle rigidity, located in the pedunculopontine tegmental nucleus and adjacent reticular formation, was correlated positively with the extent of hindlimb muscle tone facilitation after medullary OX-A microinjections. OX-A microinjections into GiV sites were less effective in muscle tone facilitation, although these sites produced a muscle tone increase during electrical stimulation. In contrast, OX-A microinjections into the gigantocellular nucleus (Gi) sites and dorsal paragigantocellular nucleus (DPGi) sites, previously identified by electrical stimulation as inhibitory points, produced bilateral hindlimb muscle atonia. We propose that the medioventral medullary region is one of the brain stem target for OX-A modulation of muscle tone. Facilitation of muscle tone after OX-A microinjections into this region is linked to activation of intrinsic reticular cells, causing excitation of midbrain and pontine neurons participating in muscle tone facilitation through an ascending pathway. Moreover, our results suggest that OX-A may also regulate the activity of medullary neurons participating in muscle tone suppression. Loss of OX function may, therefore, disturb both muscle tone facilitatory and inhibitory processes at the medullary level.

Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987–1997: incidence, causes, and outcome

OBJECTIVE: Severe GI bleeding after hematopoietic cell transplantation is commonly due to lesions that are unusual in nontransplant patients. The frequency of GI bleeding appears to have decreased over the last decade, but the reasons have not been readily apparent. We sought to determine the incidence of severe bleeding during two time periods, to describe the causes and outcomes of bleeding, and to analyze the reasons behind an apparent decline in severe bleeding over the decade covered. METHODS: During 1986–1987 and 1996–1997, we followed all patients with and without severe bleeding at our institution, a marrow transplant center. RESULTS: Over this decade, the incidence of severe bleeding declined from 50/467 (10.7%) to 15/635 (2.4%) ( p < 0.0001). Overall mortality from intestinal bleeding declined from 3.6% to 0.9% ( p = 0.002), but mortality in those with bleeding remained high (34% vs 40%). The onset (day 42 vs 47) and platelet counts (35,994 vs 37,600/μl) were similar, but the sites and causes of bleeding were different. During 1986–1987, 27/50 patients bled from multiple GI sites, viral and fungal ulcers, or graft- versus-host disease (GVHD). Over the decade, bleeding from GVHD had decreased 80% ( p < 0.0001), and bleeding from viral ( p < 0.0001) and fungal ( p = 0.023) ulcers almost disappeared. CONCLUSIONS: The incidence of severe GI bleeding has declined significantly over the last decade because of prevention of viral and fungal infections and severe acute GVHD. However, severe bleeding after transplant remains a highly morbid event, particularly among patients with GVHD.

Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987-1997: incidence, causes, and outcome.

Severe GI bleeding after hematopoietic cell transplantation is commonly due to lesions that are unusual in nontransplant patients. The frequency of GI bleeding appears to have decreased over the last decade, but the reasons have not been readily apparent. We sought to determine the incidence of severe bleeding during two time periods, to describe the causes and outcomes of bleeding, and to analyze the reasons behind an apparent decline in severe bleeding over the decade covered. During 1986-1987 and 1996-1997, we followed all patients with and without severe bleeding at our institution, a marrow transplant center. Over this decade, the incidence of severe bleeding declined from 50/467 (10.7%) to 15/635 (2.4%) (p < 0.0001). Overall mortality from intestinal bleeding declined from 3.6% to 0.9% (p = 0.002), but mortality in those with bleeding remained high (34% vs 40%). The onset (day 42 vs 47) and platelet counts (35,994 vs 37,600/microl) were similar, but the sites and causes of bleeding were different. During 1986-1987, 27/50 patients bled from multiple GI sites, viral and fungal ulcers, or graft-versus-host disease (GVHD). Over the decade, bleeding from GVHD had decreased 80% (p < 0.0001), and bleeding from viral (p < 0.0001) and fungal (p = 0.023) ulcers almost disappeared. The incidence of severe GI bleeding has declined significantly over the last decade because of prevention of viral and fungal infections and severe acute GVHD. However, severe bleeding after transplant remains a highly morbid event, particularly among patients with GVHD.

Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced emesis.

The theoretical basis for and clinical experience with using oral serotonin type 3 (5-HT3)-receptor antagonists for preventing chemotherapy-induced emesis are discussed. Evidence supports the idea that antineoplastic drugs and irradiation can initiate emesis by releasing serotonin from enterochromaffin cells in the gut mucosa, which activates peripheral vagal afferent nerves. In view of the GI site of serotonin release and vagal afferent activation, the proximity of neuronal 5-HT3 receptors, and the pharmacologic properties of 5-HT3-receptor antagonists, the oral use of these agents is rational. Oral granisetron 2 mg once daily or 1 mg twice daily has been evaluated in more than 4500 patients receiving highly or moderately emetogenic chemotherapy. Rates of total control of emesis ranged from 44% to 60%, and complete-response rates ranged from 70% to 94%. Oral ondansetron 8 mg three times daily has proven effective in patients receiving antineoplastics with moderate or moderately high emetogenic potential. Two double-blind studies demonstrated the efficacy of a single 24-mg oral dose of ondansetron administered approximately 30 minutes before cisplatin-based chemotherapy. Patients randomized to oral ondansetron had higher total-control and complete-response rates than patients receiving intravenous granisetron or ondansetron. Oral dolasetron 100 or 200 mg once daily also prevented emesis. Oral administration of 5-HT3-receptor antagonists for the prevention of acute emesis associated with chemotherapy is rational and appears to be effective.

Parenteral ketorolac-risks of GI and operative site bleeding are small

Parenteral ketorolac-risks of GI and operative site bleeding are small

Parenteral ketorolac ??? risks of GI and operative site bleeding are small

Parenteral ketorolac ??? risks of GI and operative site bleeding are small

Reticulospinal and reticuloreticular pathways for activating the lumbar back muscles in the rat.

These experiments tested hypotheses about the logic of reticulospinal and reticuloreticular controls over deep back muscles by examining descending efferent and contralateral projections of the sites within the medullary reticular formation (MRF) that evoke EMG responses in lumbar axial muscles upon electrical stimulation. In the first series of experiments, retrograde tracers were deposited at gigantocellular reticular nucleus (Gi) sites that excited the back muscles and in the contralateral lumbar spinal cord. The medullary reticular formation contralateral to the Gi stimulation/deposition site was examined for the presence of single- and double-labeled cells from these injections. Tracer depositions into Gi produced labeled cells in the contralateral Gi and Parvocellular reticular nucleus (PCRt) whereas the lumbar injections retrogradely labeled cells only in the ventral MRF, indicating that separate populations of medullary reticular cells project to the opposite MRF and the lumbar cord. In the second series of experiments the precise relationships between the location of neurons retrogradely labeled from lumbar spinal cord depositions of the retrograde trace, Fluoro-Gold (FG) and effective stimulation tracks through the MRF were examined. The results indicate that the Gi sites that are most effective for activation of the back muscles are dorsal to the location of retrogradely labeled lumbar reticulospinal cells. To verify that cell bodies and not fibers of passage were stimulated, crystals of the excitatory amino acid agonist, N-methyl-D-aspartate (NMDA) were deposited at effective stimulation sites in the Gi. NMDA decreased the ability of electrical stimulation to activate back muscles at 5 min postdeposition, indicating a local interaction of NMDA with cell bodies at the stimulation site. In the third series of experiments, electrical thresholds for EMG activation along a track through the MRF were compared to cells retrogradely labeled from FG deposited into the cervical spinal cord. In some experiments, Fast Blue was also deposited into the contralateral lumbar cord. Neurons at low threshold points on the electrode track were labeled following cervical depositions, indicating a direct projection to the cervical spinal cord. The lumbar depositions, again, labeled cells in MRF areas that were ventral to the locations of effective stimulation sites, primarily on the opposite side of the medulla. In addition, the lumbar depositions back-filled cells in the same cervical segments to which the Gi neurons project. These results suggest that one efferent projection from effective stimulation sites for back muscle activation is onto propriospinal neurons in the cervical cord, which in turn project to lumbar cord levels.(ABSTRACT TRUNCATED AT 400 WORDS)