Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4

Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci.     

The association between Helicobacter pylori infection and functional dyspepsia in patients with irritable bowel syndrome

OBJECTIVE: Irritable bowel syndrome (IBS) is associated with an exaggerated response to a variety of physiological and nonphysiological gastrointestinal stimuli. Many patients with IBS also have functional dyspepsia. Our aim was to examine the hypothesis that Helicobacter pylori (H. pylori) infection may predispose IBS patients to functional dyspepsia. METHODS: In 69 IBS patients, dyspeptic symptoms, H. pylori status, and sociodemographic and psychological variables (perceived stress, trait anxiety, and depression) were assessed. Sociodemographic and psychological variables were also evaluated in 52 control subjects. RESULTS: Mean scores for perceived stress (17.1 +/- 6.0 vs 14.9 +/- 6.0, p = 0.05), trait anxiety (45.6 +/- 9.1 vs 41.1 +/- 7.8, p = 0.004) and depression (9.9 +/- 8.4 vs 5.0 +/- 5.5, p = 0.0002) were higher in IBS patients than in controls. In all, 33 of the 69 patients (47.8%) had H. pylori infection, and this was associated with relevant symptoms of epigastric pain (odds ratio [OR] = 6.77, 95% confidence interval [CI] 1.89-24.3) and postprandial upper abdominal fullness (OR = 4.23, 95% CI 1.38-13.2). H. pylori infection and female gender were independent predictors of the presence of relevant dyspepsia (OR = 8.31, 95% CI 2.35-29.5 and 6.06, 95% CI 1.71-21.5, respectively). Symptom intensity was associated with the level of perceived stress (total relevant symptom number > or =3 vs <3, OR = 1.16 per point on a 40-point perceived stress scale, 95% CI 1.01-1.34). CONCLUSIONS: In IBS patients, the presence of dyspepsia is associated with H. pylori infection, female gender, and perceived stress.     

Suicidal bupropion ingestions in adolescents: increased morbidity compared with other antidepressants

Objective: Bupropion is often categorized as a newer generation antidepressant and assessed with serotonin reuptake inhibitors as a lower risk than older tricyclic antidepressants (TCAs). The objective of this study was to compare outcomes in adolescent suicide from ingestions between bupropion and TCA medications.

Study design: An analysis of the National Poison Data System for exposures coded “suspected suicide” in adolescents (age: 13–19) was undertaken for the years 2013–2016 and included TCAs or bupropion. We compared clinical effects, therapies and medical outcomes.

Results: Over the four-year period there were 2253 bupropion and 1496 TCA adolescent suspected suicide calls. There was a significant linear increase in bupropion ingestions over the four years. Across all years, there were on average 189.2 (95% CI: 58.1–320.4; p?=?.01) more ingestions of bupropion than TCA. When comparing bupropion to a TCA, ingestions of bupropion were significantly more likely to be accompanied by seizure (30.7% vs 3.9%; p?p?p?p?p?Conclusions: Adolescents who overdose on a single medication in a suicide attempt with bupropion have a statistically significant higher incidence of major outcomes and seizures. The risks of bupropion as a potential means of suicidal gesture by overdose must be considered, and weighed against its benefits and side effect profile when choosing an appropriate agent for the treatment of depression in adolescents.     

Relationship between esophageal motility and transit in patients with type I diabetes mellitus

OBJECTIVES: Delayed esophageal transit and abnormal esophageal motility occur frequently in patients with long-standing diabetes mellitus. However, the relationship between transit and motility has not been assessed directly. The aim of this study was to investigate the patterns of esophageal motor function documented previously to have delayed esophageal emptying and esophageal transit in patients with insulin-dependent diabetes mellitus. METHODS: Concurrent esophageal manometry and radionuclide measurement of transit of liquids and solids were performed in 11 patients with insulin-dependent diabetes, 10 age-matched controls, and 11 young normal subjects. RESULTS: Patients with diabetes had a greater frequency of transit hold-up for solids (96%) than did older controls (65%) or young normals (42%) (p < 0.001), whereas the frequency of transit hold-up for liquid boluses was similar among the three groups (diabetics, 36%; older normals, 17%; young normals, 17%). The major mechanism responsible for bolus hold-up in diabetics was peristaltic failure (liquid, 52%; solid, 67%) and the level of hold-up coincided with the level of bolus hold-up for 10/11 liquid and 27/28 solid boluses. CONCLUSIONS: In insulin-dependent diabetes, retarded esophageal transit usually reflects either peristaltic failure or focal low-amplitude pressure waves.     

Detached ciliary tufts mistaken for peritoneal parasites: a warning

Detached ciliary tufts of columnar epithelial cells from the female genital tract may be mistakenly identified as protozoa when examined in wet mounts of fluid specimens in the laboratory because of their appearance and motility, although they are generally identified correctly in fixed specimens prepared for cytologic examination. A case of such mistaken identity in specimens from a gynecologic patient was documented, and the literature on ciliary tufts was reviewed. Infectious disease and gynecology consultants should be alert to the potential confusion arising from the presence of ciliary tufts in body fluids.     

The role of registries in facilitating clinical research in BMT: examples from the Center for International Blood and Marrow Transplant Research

Observational databases, such as those maintained by the Center for International Blood and Marrow Transplant Research (CIBMTR) and the European Blood and Marrow Transplant Group (EBMT), play an important role in facilitating research into hematopoietic SCT (HCT) outcomes. The CIBMTR maintains a large database of the outcome of BMTs performed in 450 centers in 47 countries, including information on 240,000 transplant recipients and adding information on about 14,000 new transplants per year. The database has data for 9000 survivors followed for 10 or more years. The database may facilitate the understanding of outcomes by addressing questions difficult to answer through clinical trials. Clinical databases may also aid the development of optimal designs for prospective clinical trials. Use of the CIBMTR database for trial design and monitoring is an integral part of the US Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The establishment of international outcomes registries was an important component of advances in HCT over the past three decades. Future progress will be further enhanced by inter-registry collaboration through the Worldwide Blood and Marrow Transplant Group (WBMT).