Bowel infarction as the initial manifestation of disseminated aspergillosis.

Disseminated aspergillosis in the immunocompromised patient most commonly presents with clinically apparent pulmonary involvement and roentgenographic infiltrates. We report a patient with acute myelogenous leukemia who developed bowel infarction due to gastrointestinal invasion of Aspergillus fumigatus as the initial manifestation of widespread fungal disease.     

Should we eradicate Helicobacter pylori infection in patients receiving nonsteroidal anti‐inflammatory drugs or low‐dose aspirin?

Whether Helicobacter pylori infection alters the risk of ulcer disease in patients receiving nonsteroidal anti‐inflammatory drugs (NSAIDs) or low‐dose aspirin is one of the most controversial topics in peptic ulcer research. This is an important management issue, particularly in countries where peptic ulcer disease is common and the prevalence of H. pylori infection is high. Current evidence shows that H. pylori infection increases the ulcer risk associated with NSAIDs or low‐dose aspirin. Eradication of H. pylori reduces the subsequent risk of endoscopic and complicated ulcers in patients who are about to start long‐term NSAIDs. Among patients with H. pylori infection and a history of ulcer bleeding who continue to use low‐dose aspirin, 1 week of eradication therapy prevents recurrent ulcer bleeding. Failure of eradication and concomitant use of NSAIDs, however, account for most cases of recurrent bleeding with low‐dose aspirin. The apparent protective effect of H. pylori in long‐term NSAIDs users reported in some studies was actually the weeding out of susceptible patients who were intolerant to NSAIDs. There is no convincing evidence that eradication of H. pylori has any clinically important adverse effect on the healing and prevention of ulcers in NSAIDs users.     

世界胃肠病学组织(WGO-OMGE)临床指南——发展中国家幽门螺杆菌感染

我非常高兴向大家推荐这份发展中国家幽门螺杆菌（H．priori）临床指南。该指南的编译是由数位在该领域具有丰富临床经验的世界知名专家共同完成的。     

The unmasking of <Emphasis Type="Italic">Pneumocystis jiroveci</Emphasis> pneumonia during reversal of immunosuppression: case reports and literature review

Background  

Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.     

Priming of human neutrophils with N-formyl-methionyl-leucyl- phenylalanine by a calcium-independent, pertussis toxin-insensitive pathway

Resting neutrophils may be "primed" to augmented effector function, eg, superoxide (O2-) production in the respiratory burst, upon a second stimulation with a variety of soluble agonists including formylated methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA). At priming concentrations of FMLP (5 x 10(-9) mol/L) that did not initiate O2- generation, two metabolic activities were noted: (1) approximately a threefold increase in the baseline intracellular calcium (Ca++i) level, that was not dependent on extracellular Ca++, and (2) a rapid rise in intracellular pH that was blocked by 5-(N,N- dimethyl) amiloride (DA), that had no effect on the Ca++i response to priming. Furthermore, there were no significant increases in inositol metabolites in cells primed and stimulated with FMLP compared with cells receiving the stimulating dose of FMLP alone and pretreatment with pertussis toxin (PT) (before the addition of the priming -5 x 10(- 9) mol/L dose of FMLP), whereas abolishing the response to FMLP during the second stage of stimulation, had (1) no effect on FMLP-primed cells subsequently stimulated with PMA, and (2) only partially ablated the rise in Ca++i initiated with FMLP. That FMLP priming involved distinctive processes to those of the well characterized FMLP-coupled Ca++-dependent activation cascade was shown by the full priming effect attained in a Ca++-free buffer, which did not sustain an O2- response to a second-stage FMLP stimulation, but sustained a primed response to PMA. These data demonstrate that FMLP primes human neutrophils by a Ca++-independent and PT-insensitive pathway, offering a functional model for studying heterogeneous FMLP receptor-coupled reactions.     

Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement

OBJECTIVE: Provide explicit expert-based consensus recommendations for the management of adults with primary and secondary spontaneous pneumothoraces in an emergency department and inpatient hospital setting. The use of opinion was made explicit by employing a structured questionnaire, appropriateness scores, and consensus scores with a Delphi technique. The guideline was designed to be relevant to physicians who make management decisions for the care of patients with pneumothorax. OPTIONS: Decisions for observation, chest tube placement, surgical interventions, and radiographic imaging. OUTCOMES: Effectiveness of pneumothorax resolution, duration of and patient tolerance of care, and pneumothorax recurrence. EVIDENCE: Literature review from 1967 to January 1999 and Delphi questionnaire submitted in three iterations to a multidisciplinary physician panel. VALUES: The guideline development group determined by consensus the relevant outcomes to be considered in developing the Delphi questionnaire. Benefits, harms, and costs: The type and magnitude of benefits, harms, and costs expected for patients from guideline implementation. RECOMMENDATIONS: Management decisions vary between patients with primary or secondary pneumothoraces, with observation of small pneumothoraces being appropriate only for primary pneumothoraces. The level of consensus varies regarding the specific interventions indicated, but agreement exists for the general principles of care. VALIDATION: Recommendations were peer reviewed by physician experts and were reviewed by the American College of Chest Physicians (ACCP) Health and Science Policy Committee. IMPLEMENTATION: The guideline recommendations will be published in printed and electronic form with distribution of synopses for patients and health care providers. Contents of the guideline will be incorporated into continuing medical education programs. SPONSORS: The ACCP.     

Management guidelines for uninvestigated and functional dyspepsia in the Asia-Pacific region: First Asian Pacific working party on functional dyspepsia

Dyspepsia is most optimally defined as pain or discomfort centred in the upper abdomen. The symptom complex may be caused by peptic ulcer disease, gastro-oesophageal reflux, or gastric cancer but is most often due to functional (or non-ulcer) dyspepsia. While upper endoscopy is the method of choice to determine the underlying cause of dyspepsia, it is expensive. A more pragmatic approach is needed in the Asia-Pacific region where health services are limited. A detailed treatment algorithm is given for managing patients presenting with new-onset dyspepsia and documented functional dyspepsia after endoscopy, and evidence to support this approach is reviewed. Prompt endoscopy is recommended for patients with alarm features. In patients without alarm features, treatment for 2–4 weeks with an empirical anti-secretory or prokinetic agent, followed by investigation using non-invasive Helicobacter pylori testing and treatment for patients who do not respond or relapse, is recommended. Trials of management strategies are now needed to establish the efficacy and cost-effectiveness of the approaches recommended.     

Early results of a prospective study on the pyrolytic carbon (pyrocarbon) Amandys? for osteoarthritis of the wrist

INTRODUCTION

The preliminary results of a pyrocarbon interpositional radiocarpal implant in a small cohort of patients were reviewed. As it is currently only a limited release product, we describe to potential users early complications and negative outcomes.

METHODS

Patients were assessed using pain levels, ranges of motion, grip strength, type of and time to return to work as well as pre-operative and post-operative DASH (Disabilities of the Arm, Shoulder and Hand) scores. Radiographs were taken and patient satisfaction was recorded.

RESULTS

All six patients were contacted. One was not satisfied. Three had reduced motion. None experienced squeaking. There were no immediate or late post-operative complications. There was one early volar displacement of an implant.

CONCLUSIONS

Although our early results are somewhat encouraging, further and longer studies are warranted before supporting the use of this particular pyrocarbon implant as a primary procedure.     

Potentiating Functional Antigen-specific CD8+ T Cell Immunity by a Novel PD1 Isoform-based Fusion DNA Vaccine

Understanding and identifying new ways of mounting an effective CD8⁺ T cell immune response is important for eliminating infectious pathogens. Although upregulated programmed death-1 (PD1) in chronic infections (such as HIV-1 and tuberculosis) impedes T cell responses, blocking this PD1/PD-L pathway could functionally rescue the “exhausted” T cells. However, there exists a number of PD1 spliced variants with unknown biological function. Here, we identified a new isoform of human PD1 (Δ42PD1) that contains a 42-nucleotide in-frame deletion located at exon 2 domain found expressed in peripheral blood mononuclear cells (PBMCs). Δ42PD1 appears to function distinctly from PD1, as it does not engage PD-L1/PD-L2 but its recombinant form could induce proinflammatory cytokines. We utilized Δ42PD1 as an intramolecular adjuvant to develop a fusion DNA vaccine with HIV-1 Gag p24 antigen to immunize mice, which elicited a significantly enhanced level of anti-p24 IgG1/IgG2a antibody titers, and important p24-specific and tetramer⁺CD8⁺ T cells responses that lasted for ≥7.5 months. Furthermore, p24-specific CD8⁺ T cells remain functionally improved in proliferative and cytolytic capacities. Importantly, the enhanced antigen-specific immunity protected mice against pathogenic viral challenge and tumor growth. Thus, this newly identified PD1 variant (Δ42PD1) amplifies the generation of antigen-specific CD8⁺ T cell immunity when used in a DNA vaccine.