Low dose melphalan in the treatment of myelofibrosis: a single centre experience.
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Biomedical subjects
Publications and source records attributed to L Chee.
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OBJECTIVE: To examine the contribution of the primary immunodeficiency states, which are uncommon in the general population, to refractory sinusitis. STUDY DESIGN: We retrospectively reviewed the charts of 316 patients with sinusitis who were referred to the Allergy and Immunology Clinic for immunological evaluation from 1991 to 1997. METHODS: Of the 316 patients, 79 were selected for further study. Inclusion criteria included at least one sinus surgery and/or sinusitis diagnosed by endoscopy and/or computed tomography (CT) scan at least three times in the previous year. Patients with human immunodeficiency virus (HIV), allergic fungal sinusitis, cystic fibrosis, and primary ciliary dyskinesia were excluded. The results of their immunological evaluation for atopy, T-lymphocyte function, and immunoglobulin levels were examined. RESULTS: The average age of these 79 patients was 44 years (+/- 14.5 standard deviation [SD]). They had, on average, 2.94 (+/- 2.19 SD) previous operations and had mean sinus CT scores (Lund-McKay) of 11.2 (+/- 5.0 SD). Forty of 79 (50.6%) patients had at least one positive result on skin test to an aeroallergen. Delayed hypersensitivity skin testing revealed that 22 of 55 patients (40%) were anergic. Of the 60 patients with in vitro T-lymphocyte function testing, 54.8% showed abnormal proliferation in response to recall antigens, 11.3% had decreased response to alloantigen, and 26.3% demonstrated decreased response to T-cell mitogens. Determination of quantitative immunoglobulins showed low immunoglobulin G in 14 of 78 patients (17.9%), low immunoglobulin A in 13 of 78 (16.7%), and low immunoglobulin M in 4 of 78 (5.1%). Common variable immunodeficiency (CVID) was diagnosed in 9.9% of patients, and selective IgA deficiency was found in 6.2%. CONCLUSIONS: This retrospective review reveals an unexpectedly high incidence of immune dysfunction. These results suggest that immunological testing should be an integral part of the evaluation of patients with refractory sinusitis.
Certain cases of thyroid-related orbitopathy may require surgical decompression of the orbit. The purpose of this paper is to highlight new techniques of orbital decompression in thyroid-related orbitopathy. We present two illustrative cases selected from our recent surgical experience. The techniques of combined-approach decompression, transcaruncular approach to the medial orbital wall, drilling reduction of the greater wing of sphenoid and lateral wall lag-screw fixation after lateralization by greenstick fracture are presented. The relative utility of each technique is examined. These techniques expand the surgical repertoire for this condition and allow individualization of treatment for a specific patient's needs.
Elucidation of the changes in gene expression associated with biological processes is a central problem in biology. Advances in molecular and computational biology have led to the development of powerful, high-throughput methods for the analysis of differential gene expression. These tools have opened up new opportunities in disciplines ranging from cell and developmental biology to drug development and pharmacogenomics. In this review, the attributes of five commonly used differential gene expression methods are discussed: expressed sequence tag (EST) sequencing, cDNA microarray hybridization, subtractive cloning, differential display, and serial analysis of gene expression (SAGE). The application of EST sequencing and microarray hybridization is illustrated by the discovery of novel genes associated with osteoblast differentiation. The application of subtractive cloning is presented as a tool to identify genes regulated in vivo by the transcription factor pax-6. These and other examples illustrate the power of genomics for discovering novel genes that are important in biology and which also represent new targets for drug development. The central theme of the review is that each of the approaches to identifying differentially expressed genes is useful, and that the experimental context and subsequent evaluation of differentially expressed genes are the critical features that determine success.
The characteristic CXC chemokine disulfide core of interleukin-8 (IL-8) has been rearranged in a variant replacing the 9-50 disulfide with a 9-38 disulfide. The new variant has been characterized by its binding affinity to IL-8 receptors A and B and the erythrocyte receptor DARC. This variant binds the three receptors with affinities between 500- and 2,500-fold lower than wild-type IL-8. Binding affinity results are also reported for the variant with alanine substituted for both cysteines 9 and 50. The Glu38-->Cys/Cys50-->Ala IL-8 crystallizes in space group P2(1)2(1)2(1) with cell parameters a = 46.4, b = 49.2, and c = 69.5 A, and has been refined to an R-value of 19.4% for data from 10 to 2 A resolution. Analysis of the structure confirms the new disulfide arrangement and suggests that changes at Ile10 may be the principal cause of the lowered affinities.
Histoplasmosis is a fungal infection which when disseminated can be potentially fatal, especially in the immunocompromised patient. Disseminated histoplasmosis can present with orolaryngeal manifestations which often mimic carcinoma or tuberculosis. A high index of suspicion and diagnosis with biopsy is needed. Two recent cases are presented and the literature reviewed. As the number of immunocompromised patients increases, more cases of histoplasmosis in the head and neck will be encountered. Early treatment can reduce morbidity and mortality.