Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program

An estimated two billion persons are latently infected with Mycobacterium tuberculosis. The host factors that initiate and maintain this latent state and the mechanisms by which M. tuberculosis survives within latent lesions are compelling but unanswered questions. One such host factor may be nitric oxide (NO), a product of activated macrophages that exhibits antimycobacterial properties. Evidence for the possible significance of NO comes from murine models of tuberculosis showing progressive infection in animals unable to produce the inducible isoform of NO synthase and in animals treated with a NO synthase inhibitor. Here, we show that O2 and low, nontoxic concentrations of NO competitively modulate the expression of a 48-gene regulon, which is expressed in vivo and prepares bacilli for survival during long periods of in vitro dormancy. NO was found to reversibly inhibit aerobic respiration and growth. A heme-containing enzyme, possibly the terminal oxidase in the respiratory pathway, likely senses and integrates NO and O2 levels and signals the regulon. These data lead to a model postulating that, within granulomas, inhibition of respiration by NO production and O2 limitation constrains M. tuberculosis replication rates in persons with latent tuberculosis.     

Evaluation of the Appropriateness of Pacemaker Mode Selection in Bradycardia Pacing:

Although guidelines for selection of the appropriate pacing mode have been published, little data is available on how closely these are followed in the clinical setting. All 738 patients (men 412, women 326; age 73.4 +/- 0.46 years; range 19-101 years) who underwent pacemaker implantation from 1996 to 2000 were reviewed to determine if the appropriate mode was selected based on the ACC/AHA guidelines with the data collected prospectively. Demographic, investigational, and implantation data including the presence of sinus disease and/or atrioventricular block, diagnosis, indication for pacing, ACC/AHA class indication for device therapy, recommended ACC/AHA mode, implanted mode, and reason for not using the recommended mode were entered into an SPSS data base. Of 738 patients, 708 were cross-tabulated for a match to the guidelines of which 358 (50.6%) had a mode selected that did not conform. The reasons were advanced physical disability (16%), physician choice without identifiable reason (21%), rate modulation selected without identifiable indication (16%), DDD implanted instead of VDD (25%), advanced age (9%), rare need for pacing (6%), a need for specific device features (5%), and unstable stimulation thresholds or difficult venous access (2%). In the treatment of bradyarrhythmias, deviation from the ACC/AHA indicated mode occurred in a substantial proportion of pacing system implantations. However, in many, the deviation appeared appropriate considering the patient's clinical status. Nevertheless, in a smaller proportion of patients the deviation appeared inappropriate requiring rectification. The two outstanding categories were: (1) elderly denied a dual chamber system with no clinical explanation and (2) selection of rate-modulated devices without any indication of chronotropic incompetence.     

Multiply relapsing hairy cell leukemia responsive to repeated courses of rituximab: A case report

While cladribine is a highly effective therapy for patients with symptomatic hairy cell leukemia (HCL), up to 37% of patients ultimately relapse and incompletely responding patients relapse more frequently. Rituximab is a monoclonal antibody against CD20 that has been shown to be effective in patients with relapsed HCL. We present an unusual case of successful multiple re-treatments with rituximab in a patient with heavily pre-treated HCL and briefly review the relevant literature.     

A decoupler-free simple paper microchip capillary electrophoresis device for simultaneous detection of dopamine,epinephrine and serotonin

This paper demonstrates a new and simplified configuration for capillary electrophoresis-amperometric detection (CE-AD) using a paper microfluidic chip incorporating inexpensive wax printing and screen printing based methods and then used for electrophoretic separation and simultaneous in-channel amperometric detection of three clinically relevant neurochemicals in a single run without using any decouplers. Detection of neurochemicals e.g., dopamine, epinephrine and serotonin is crucial for early prediction of neurological disorders including Parkinson''s, Alzheimer''s, dementia, as well as progressive neuro-psychiatric conditions such as depression, anxiety, as well as certain cardiovascular diseases. The plasma concentrations of such neurochemicals are as important as those present in cerebrospinal fluid (CSF) and can be useful for rapid and convenient biosensing. However, simultaneous detection of such neurochemicals in a complex mixture such as human serum requires their separation prior to detection. With the developed microchip, separation and detection of the neurochemicals were exhibited within 650 seconds without pre-treatment and the procedure was validated with spiked fetal bovine serum samples. Beside this, the developed paper microfluidic chip has potential to be integrated in point-of-care diagnosis with onsite detection ability. Moreover, the use of a straight channel capillary, a screen-printed carbon electrode without decoupler, in-channel amperometric detection and low sample volume requirements (2 μL) are shown as additional advantages.

This paper demonstrates a simplified configuration for capillary electrophoresis-amperometric detection using paper microfluidic chip for separation and simultaneous detection of three clinically relevant neurochemicals without using any decouplers.     

Randomized controlled trial comparing outcomes of video capsule endoscopy with push enteroscopy in obscure gastrointestinal bleeding

BACKGROUND:

Optimal management of obscure gastrointestinal bleeding (OGIB) remains unclear.

OBJECTIVE:

To evaluate diagnostic yields and downstream clinical outcomes comparing video capsule endoscopy (VCE) with push enteroscopy (PE).

METHODS:

Patients with OGIB and negative esophagogastroduodenoscopies and colonoscopies were randomly assigned to VCE or PE and followed for 12 months. End points included diagnostic yield, acute or chronic bleeding, health resource utilization and crossovers.

RESULTS:

Data from 79 patients were analyzed (VCE n=40; PE n=39; 82.3% overt OGIB). VCE had greater diagnostic yield (72.5% versus 48.7%; P<0.05), especially in the distal small bowel (58% versus 13%; P<0.01). More VCE-identified lesions were rated possible or certain causes of bleeding (79.3% versus 35.0%; P<0.05). During follow-up, there were no differences in the rates of ongoing bleeding (acute [40.0% versus 38.5%; P not significant], chronic [32.5% versus 45.6%; P not significant]), nor in health resource utilization. Fewer VCE-first patients crossed over due to ongoing bleeding (22.5% versus 48.7%; P<0.05).

CONCLUSIONS:

A VCE-first approach had a significant diagnostic advantage over PE-first in patients with OGIB, especially with regard to detecting small bowel lesions, affecting clinical certainty and subsequent further small bowel investigations, with no subsequent differences in bleeding or resource utilization outcomes in follow-up. These findings question the clinical relevance of many of the discovered endoscopic lesions or the ability to treat most of these effectively over time. Improved prognostication of both patient characteristics and endoscopic lesion appearance with regard to bleeding behaviour, coupled with the impact of therapeutic deep enteroscopy, is now required using adapted, high-quality study methodologies.     

Resolution of hereditary hemorrhagic telangiectasia and anemia with prolonged alpha-interferon therapy for chronic hepatitis C

Hereditary hemorrhagic telangiectasia is a group of autosomal dominant disorders, characterized by telangiectases that develop in the skin, mucous membranes, and visceral organs. Currently, there is no satisfactory treatment of hereditary hemorrhagic telangiectasia. Interferon has never been used for the treatment of hereditary hemorrhagic telangiectasia. In this case, we report disappearance of hereditary hemorrhagic telangiectasia lesions after 12 months of treatment with interferon-alpha for chronic hepatitis C. Further studies are warranted to evaluate its role and potential use in the treatment of hereditary hemorrhagic telangiectasia.