Helicobacter pylori binds von Willebrand factor and interacts with GPIb to induce platelet aggregation

BACKGROUND & AIMS: Clinical studies have suggested an association between cardiovascular disease and infection with Helicobacter pylori. We examined the effect of H. pylori on platelets and the mechanism of the interaction. METHODS: Three of 5 strains of H. pylori induced platelet aggregation with a lag time of 5 +/- 2 minutes that was independent of the toxigenic genes cagA and vacA. Aggregation was inhibited completely by aspirin and a glycoprotein (GP) IIb/IIIa antagonist. Aggregation also was inhibited by monoclonal antibodies that prevented the von Willebrand factor (vWF) interaction with GPIb. vWF-coated H. pylori bound to cells transfected with GPIbalpha but not to mock transfected cells and this was inhibited by an antibody to GPIb. RESULTS: The interaction with platelets appeared to be mediated by vWF because platelet aggregation was blocked by an antibody to vWF. Moreover, a strain of H. pylori that induced platelet aggregation bound vWF to a greater extent than a nonaggregating strain. Aggregation also required IgG and could be inhibited by an antibody to the platelet IgG receptor (FcgammaRIIA). CONCLUSIONS: Some strains of H. pylori induce platelet activation mediated by H. pylori-bound vWF interacting with GPIb, and supported by IgG. These platelet-H. pylori interactions may contribute to the pathogenesis of H. pylori-associated peptic ulcer disease and to the association between H. pylori infection and cardiovascular disease, whereas local platelet effects may contribute to the pathogenesis of H. pylori-associated peptic ulcer disease.     

Assessment of quality of life in the treatment of patients with neuropathic fecal incontinence

INTRODUCTION: Development of quality-of-life measures has been the focus of research in colorectal disorders in recent years. The assessment of quality of life for fecal incontinence should be more important than quantitative measurement of soiling. PURPOSE: This study assesses specific patient quality-of-life objectives, categorizes objectives, and correlates these objectives with continence scores. METHODS: One hundred eighteen patients entered into a randomized, controlled trial of biofeedback were assessed using the Direct Questioning of Objectives quality-of-life measure. All objectives were documented, categorized, and correlated with continence scores and analog scales. RESULTS: In patients with neuropathic fecal incontinence, the most frequent quality-of-life group concerned the ability to get out of home, to socialize outside of home, to go shopping, and not to have to worry about the location of the nearest toilet while out of home (34 percent; 123/364). At least one of these four objectives was stated by 72 percent of patients (85/118). Only 31 percent of patients (37/118) nominated an objective related to the physical act of soiling. The ability to travel (29 percent), exercise including walking (25 percent), perform home duties (19 percent), family and relationships (22 percent), and job (13 percent) were less frequently cited by patients. CONCLUSION: Continence scores focus heavily on the physical aspects of incontinence such as soiling and hygiene, aspects which seem to be less important to the patients themselves. It is important, therefore, that assessments of fecal incontinence should include reference to quality of life, and in particular to its impact on activities relating to getting out of the house.     

Role of oxidative stress in cardiac remodelling after myocardial infarction

Recovery from myocardial infarction is associated with a series of alterations in heart structure and function, collectively known as cardiac remodelling, which play a major role in the subsequent development of heart failure. Early remodelling involves infarct scar formation in the ischaemic zone whereas subsequent ventricular remodelling affects mainly the viable non-infarcted myocardium with especially profound alterations in the extracellular matrix. There is growing evidence for a role of oxidative stress and redox signalling in the processes underlying cardiac remodelling. Reactive oxygen species are a group of highly reactive molecules which have the potential to modulate several biological processes as well as cause tissue damage and dysfunction. Their effects can be beneficial or deleterious, depending on the concentrations produced, the site of production, and the overall redox status of the cell. Reactive oxygen species can be generated by all cardiovascular cell types. Under pathophysiological conditions, major enzymatic sources appear to be mitochondria, xanthine oxidase and the non-phagocytic NADPH oxidases. In this review, we outline the mechanisms underlying the progression of early and late cardiac remodelling with particular focus on the role of oxidative stress and the potential sources of reactive oxygen species which may be involved.     

Neoatherosclerosis in Patients With Coronary Stent Thrombosis: Findings From Optical Coherence Tomography Imaging (A Report of the PRESTIGE Consortium)

Objectives

The purpose of this study was to assess neoatherosclerosis in a registry of prospectively enrolled patients presenting with stent thrombosis using optical coherence tomography.

Ischemic diseases of the bowel

Summary The incidence of acute ischemia of the small bowel is increasing. Although occasionally it is secondary to occlusion of major vessels and amenable to direct surgical attack, it is more often secondary to a perfusion problem without occlusions of large vessels. The diagnosis of ischemia should be considered for any elderly patient with abdominal pain and gastrointestinal bleeding which is not secondary to some overt cause. Early diagnosis requires a differentiation of occlusive from nonocclusive disease, and arteriography appears to be the only reasonable approach. Supportive therapy, including fluid replacement, cardiac support and control of sepsis, is necessary in all these cases. It is applied preoperatively over the course of several hours when the patients have perfusion problems; however, in the cases of patients with largevessel occlusion, the supportive therapy is applied during the intraoperative and postoperative periods. The patient with chronic mesenteric ischemia should have elective surgical correction of the occlusion to the splanchnic flow, not only for relief of pain and correction of weight loss but also to prevent progression to an acute complete occlusion. Editor’s note: This paper and the three following it represent the contributions to a panel discussion presented at the meeting of the American Proctologic Society, June 1969. The articles by Drs. Williams and Byrne have been written from remarks made during the discussion; those of Drs. Donaldson and Wittenberg are segments of the discussion essentially as presented. Presented at the meeting of the American Proctologic Society, Boston, Massachusetts, June 16–18, 1969. Supported in part by National Institutes of Health Grants AMO 8694 and 7-915-468.     

A novel method using formamide for the elution of antibodies from erythrocytes

BACKGROUND AND OBJECTIVES: Accurate identification of antibodies that sensitize red blood cells (RBCs) involves dissociating them from RBCs using an in vitro elution method that does not alter their antigen-binding properties, and analysis of the eluates against a panel of RBCs. MATERIALS AND METHODS: A method was developed that allowed efficient RBC antibody elution. Human polyclonal anti-D was used to sensitize Rh-positive RBCs, and known antigen-antibody disruptive reagents were tested using these RBCs. The best reagent conditions were optimized. Eluates made were tested and compared to results obtained with a glycine-acid-based commercial elution kit to determine efficacy. Patient samples that were positive with direct antiglobulin tests (DATs), and in vitro commercial antisera-sensitized RBCs representing clinically significant antibodies, were used for evaluating the new method. RESULTS: The formamide method was efficient at removing antibodies from RBCs. The patient samples with a positive DAT had antibodies recovered with the same specificity when compared to the acid-based technique. The length of preparation time was similar for both formamide and acid-based methods. Results of testing the eluates made from reagent RBCs sensitized with commercial antisera were distinct with antigen-positive and -negative erythrocytes. CONCLUSIONS: The formamide method compares well with acid techniques and may be an alternative choice of elution method.     

Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder

CONTEXT: Hypoactive sexual desire disorder (HSDD) is one of the most common sexual problems reported by women, but few studies have been conducted to evaluate treatments for this condition. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of a testosterone patch in surgically menopausal women with HSDD. DESIGN: The design was a randomized, double-blind, parallel-group, placebo-controlled, 24-wk study (the Intimate SM 1 study). SETTING: The study was performed at private or institutional practices. PATIENTS: The subjects studied were women, aged 26-70 yr, with HSDD after bilateral salpingo-oophorectomy who were receiving concomitant estrogen therapy. Placebo (n = 279) or testosterone 300 microg/d (n = 283) was administered. There were 19 patients who withdrew due to adverse events in the placebo group and 24 in the 300 mug/d testosterone group. INTERVENTION: Testosterone (300 microg/d) or placebo patches were applied twice weekly. MAIN OUTCOME MEASURE(s): The primary end point was the change in the frequency of total satisfying sexual activity at 24 wk. Secondary end points included other sexual functioning end points and safety assessments. RESULTS: At 24 wk, there was an increase from baseline in the frequency of total satisfying sexual activity of 2.10 episodes/4 wk in the testosterone group, which was significantly greater than the change of 0.98 episodes/4 wk in the placebo group (P = 0.0003). The testosterone group also experienced statistically significant improvements in sexual desire and a decrease in distress. The overall safety profile was similar in both treatment groups. CONCLUSION: In the Intimate SM 1 study, the testosterone patch improved sexual function and decreased distress in surgically menopausal women with HSDD and was well tolerated in this trial.     

Chlamydial virulence determinants in atherogenesis: the role of chlamydial lipopolysaccharide and heat shock protein 60 in macrophage-lipoprotein interactions

Data from a spectrum of epidemiologic, pathologic, and animal model studies show that Chlamydia pneumoniae infection is associated with coronary artery disease, but it is not clear how the organism may initiate or promote atherosclerosis. It is postulated that C. pneumoniae triggers key atherogenic events through specific virulence determinants. C. pneumoniae induces mononuclear phagocyte foam cell formation by chlamydial lipopolysaccharide (cLPS) and low-density lipoprotein oxidation by chlamydial hsp60 (chsp60). Thus, different chlamydial components may promote distinct events implicated in the development of atherosclerosis. Data implicating cLPS and chsp60 in the pathogenesis of atherosclerosis are discussed and novel approaches are presented for attempting to elucidate how these putative virulence determinants signal mononuclear phagocytes to modulate lipoprotein influx and modification.     

Antibacterial resistance and their genetic location in MRSA isolated in Kuwait hospitals, 1994-2004

Background  

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major cause of serious infections in hospitals and in the community worldwide. In this study, MRSA isolated from patients in Kuwait hospitals were analyzed for resistance trends and the genetic location of their resistance determinants.     

Associative conditioning analog selectively increases cAMP levels of tail sensory neurons in Aplysia.

Bilateral clusters of sensory neurons in the pleural ganglia of Aplysia contain cells involved in a defensive tail withdrawal reflex. These cells exhibit heterosynaptic facilitation in response to noxious skin stimulation that can be mimicked by the application of serotonin. Recently it has been shown that this facilitation can be selectively amplified by the application of a classical conditioning procedure to individual sensory neurons. We now report that an analog of this classical conditioning paradigm produces a selective amplification of the cAMP content of isolated sensory neuron clusters. The enhancement is achieved within a single trial and appears to be localized to the sensory neurons. These results indicate that a pairing-specific enhancement of cAMP levels may be a biochemical mechanism for associative neuronal modifications and perhaps learning.