John Kelly Smith

The Effects of HIV Infection on Endothelial Function

Endothelial dysfunction and/or injury is pivotal to the development of cardiovascular and inflammatory pathology. Endothelial dysfunction and/or injury has been described in Human Immunodeficiency Virus (HIV) infection. Elaboration of circulating markers of endothelial activation, such as soluble adhesion molecules and procoagulant proteins, occurs in HIV infection. Certain endothelial cells, such as those lining liver sinusoids, human umbilical vein endothelial cells, bone marrow stromal endothelial cells or brain microvascular endothelial cells, have been shown to be variably permissive for HIV infection. Entry of virus into endothelial cells may occur via CD4 antigen or galactosyl-ceramide receptors. Other mechanisms of entry including chemokine receptors have been proposed. Nevertheless, endothelial activation may also occur in HIV infection either by cytokines secreted in response to mononuclear or adventitial cell activation by virus or else by the effects of the secreted HIV-associated proteins, gp 120 (envelope glycoprotein) and Tat (transactivator of viral replication) on endothelium. Enhanced adhesiveness of endothelial cells, endothelial cell proliferation and apoptosis as well as activation of cytokine secretion have all been demonstrated. Synergy between select inflammatory cytokines and viral proteins in inducing endothelial injury has been shown. In HIV infection, dysfunctional or injured endothelial cells potentiate tissue injury, inflammation and remodeling, and accelerate the development of cardiovascular disease.

Regulation and dysregulation of immunoglobulin E: a molecular and clinical perspective

BackgroundAltered levels of Immunoglobulin E (IgE) represent a dysregulation of IgE synthesis and may be seen in a variety of immunological disorders. The object of this review is to summarize the historical and molecular aspects of IgE synthesis and the disorders associated with dysregulation of IgE production.MethodsArticles published in Medline/PubMed were searched with the keyword Immunoglobulin E and specific terms such as class switch recombination, deficiency and/or specific disease conditions (atopy, neoplasia, renal disease, myeloma, etc.). The selected papers included reviews, case reports, retrospective reviews and molecular mechanisms. Studies involving both sexes and all ages were included in the analysis.ResultsBoth very low and elevated levels of IgE may be seen in clinical practice. Major advancements have been made in our understanding of the molecular basis of IgE class switching including roles for T cells, cytokines and T regulatory (or Treg) cells in this process. Dysregulation of this process may result in either elevated IgE levels or IgE deficiency.ConclusionEvaluation of a patient with elevated IgE must involve a detailed differential diagnosis and consideration of various immunological and non-immunological disorders. The use of appropriate tests will allow the correct diagnosis to be made. This can often assist in the development of tailored treatments.

Mixed Streptococcus pneumoniae and gram-negative bacillary pneumonia in the elderly.

Of 24 elderly patients with Streptococcus pneumoniae pneumonia confirmed by transtracheal aspiration, six had concomitant infection with gram-negative aerobic bacilli. All six patients were elderly men with underlying cardiopulmonary disease. Three had had recent prior episodes of gram-negative pneumonia and four had previously received antibiotics. The clinical, laboratory, and epidemiologic characteristics of these six patients with mixed bacterial pneumonia are reported.

A patient with persistent wheezing, sinusitis, elevated IgE, and eosinophilia.

HISTORY OF PRESENTING ILLNESS A 76-year-old Caucasian male, with a past medical history of severe steroiddependent asthma, presented with a 4-day history of worsening shortness of breath and a productive cough. His medical records documented four admissions to the hospital in the last few months for similar complaints. In spite of aggressive therapy for his asthma, including triamcinalone, albuterol, and ipratropium inhalers plus oral prednisone (20 mg daily), his dyspnea worsened progressively. He was now using nebulized albuterol every few hours, with minimal relief. The patient also had symptoms compatible with persistent rhinosinusitis but denied fever, chills, sweats, or recent infectious contacts. He had no symptoms of orthopnea, postural nocturnal dyspnea, or hemoptysis. The patient also denied epistaxis, arthritis, unusual skin eruptions, hematuria, or abdominal pain. There was no history of recent travel. His other routine long-term medications were nitroglycerin, 0.2 mg transdermal patch daily; Adalat, CC 30 mg PO daily; enteric-coated aspirin, 325 mg PO daily; cimetidine, 800 mg PO twice daily; lorazepam, 1 mg PO twice daily; and calcium carbonate 500 mg PO daily.

Transtracheal aspiration in the severely ill elderly patient with bacterial pneumonia.

ABSTRACT: Transtracheal aspiration was performed in 32 elderly hypoxic patients with bacterial pneumonia. No morbidity or mortality was associated with the procedure. Gram stains of the transtracheal aspirate provided rapid, accurate delineation of the etiologic pneumonic agent, and were particularly valuable in indicating mixed bacterial infections. These included 5 cases of Streptococcus pneumoniae plus Gram‐negative bacillary pneumonia. The safety and value of transtracheal aspiration in the severely ill elderly patient are discussed.

Persistent Urticarial Eruption in an Asthmatic Patient

This case demonstrates the importance of recognizing urticarial vasculitis in patients with chronic urticarial eruptions. The salient points in history that point towards the diagnosis of urticarial vasculitis include the presence of painful urticarial lesions that last longer than 24 hours and that heal leaving residual pigmentation. In some cases the urticaria may evolve into palpable purpura. An associated systemic illness that may resemble systemic lupus erythematosus should also suggest the diagnosis, which is established by skin biopsy. Histopathology reveals a leukocytoclastic vasculitis involving postcapillary venules. When associated with systemic vasculitis, the urticaria is likely to be of the hypocomplementemic variety, with immunoglobulin and complement deposition on biopsies, and with serum complement studies demonstrating classical pathway activation, low C1q levels, and anti-C1q precipitins. A variety of agents have been used in the management of urticarial vasculitis, including aspirin, nonsteroidal anti-inflammatory agents, corticosteroids, colchicine, dapsone, hydroxychloroquine, and cytotoxic agents such as cyclophosphamide and azathioprine.