Comparison of Western immunoblotting and the C6 Lyme antibody test for laboratory detection of Lyme disease

Three commercial Lyme disease Western immunoblotting (WB) kits and the C6 Borrelia burgdorferi (Lyme) enzyme-linked immunosorbent assay (ELISA) kit were compared using two commercially available performance panels from the Centers for Disease Control and Prevention (CDC) and Boston Biomedica (BBI). Combined, the panels consisted of 52 characterized specimens. Immunoglobulin G (IgG) sensitivity was similar for the three WB products. The BBI and Marblot WBs were more specific for IgG antibodies, while the Virablot was the most sensitive for IgM antibody. The BBI WB was 100% specific for IgM, while Marblot was 97% and Virablot was 77% specific for IgM. The C6 ELISA was found to be 100% sensitive. Four false-positive C6 results were identified in patients that had clinically and microbiologically confirmed Lyme disease but were not detected by the CDC reference methods. No one WB product showed overall superiority. The C6 ELISA shows promise as the first ELISA for Lyme disease that would not require a supplemental test such as a WB.     

Efficacy and safety of ciclesonide, 200 microg once daily, for the treatment of perennial allergic rhinitis.

BACKGROUND: Ciclesonide is an intranasal corticosteroid approved for the treatment of allergic rhinitis (AR). OBJECTIVE: To evaluate the efficacy, safety, and quality-of-life benefits of intranasal ciclesonide, 200 microg once daily, for the treatment of perennial AR (PAR). METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, adults and adolescents with at least a 2-year history of PAR received intranasal ciclesonide, 200 microg, or placebo once daily for 6 weeks. Patient-evaluated total nasal symptom scores (TNSSs), physician-assessed overall nasal signs and symptoms severity scores, and Rhinoconjunctivitis Quality of Life Questionnaire scores were evaluated. RESULTS: Patient baseline characteristics were similar in the ciclesonide (n = 238) and placebo (n = 233) groups and were consistent with moderate PAR severity. Ciclesonide therapy significantly reduced average morning and evening reflective TNSSs compared with placebo (P < .001) and significantly reduced average morning and evening instantaneous TNSSs (P = .001) over 6 weeks of treatment. At the end point, a greater decrease from baseline was observed in physician-assessed overall nasal signs and symptoms severity for the ciclesonide group compared with the placebo group (P = .051). An appreciable improvement in combined Rhinoconjunctivitis Quality of Life Questionnaire scores at the end point was also observed in the ciclesonide group (P = .01 vs placebo). The frequency of adverse events was similar between treatment groups. CONCLUSIONS: In this study, intranasal ciclesonide treatment was associated with significant reductions in nasal symptoms and appreciable improvements in health-related quality of life in adult and adolescent patients with PAR. Ciclesonide was well tolerated, with a safety profile comparable with that of placebo.     

Optimal management of community-acquired acute bacterial rhinosinusitis: the allergist's perspective.

OBJECTIVES: To characterize the antibiotic resistance seen in community-acquired respiratory tract infections (RTIs) and determine which characteristics to look for in an antibiotic to improve clinical outcomes and decrease the potential for development of resistance. DATA SOURCES: Using MEDLINE, we performed a search of articles published from 1966 to 2004 to evaluate the current literature on the subject of antibiotic resistance and strategies to overcome it. Additional cited references, such as abstracts, were also identified. STUDY SELECTION: Relevant original research articles, reviews, and published abstracts were selected for inclusion in this review. RESULTS: Several factors were identified that should be considered when choosing empiric antibiotic therapy for community-acquired RTIs with the goal of improving clinical outcomes while minimizing the risk of resistance. These factors include spectrum of activity, bactericidal vs bacteriostatic activity, chemical structure, elimination half-life, and potency. CONCLUSIONS: The results of these studies support the use of targeted antibiotic agents that, based on structural and chemical properties, are optimized to have a low potential to induce resistance. This approach to antimicrobial therapy appears to be the most suitable for patients with acute bacterial rhinosinusitis and other community-acquired RTIs.     

Efficacy and safety of clemastine-pseudoephedrine-acetaminophen versus pseudoephedrine-acetaminophen in the treatment of seasonal allergic rhinitis in a 1-day, placebo-controlled park study.

BACKGROUND: Allergic rhinitis afflicts more than 40 million people in the United States and is a leading cause of reduced productivity at work and in school. Patients with allergic rhinitis have a wide range of symptoms that are often treated with oral combination products that contain antihistamines, decongestants, and analgesics. OBJECTIVE: To evaluate the onset of action and the extent of efficacy and safety of a combination (CPA) of clemastine (0.68 mg), pseudoephedrine (60 mg), and acetaminophen (1,000 mg) versus a combination (PA) of pseudoephedrine and acetaminophen versus placebo in the treatment of seasonal allergic rhinitis (SAR). The primary goal was to evaluate the benefit of adding clemastine to the PA combination product to treat the symptoms of SAR. METHOD: A 1-day, multicenter, double-blind, double-dummy, randomized, parallel-group park study was organized, and medication was given at 9:00 AM and 3:00 PM. RESULTS: A total of 298 subjects participated at two outdoor facilities. The primary efficacy outcome was the major symptom complex score averaged over the period of 2 to 5 hours after each dose. Mean absolute and percentage reduction in major symptom complex averaged over the period of 2 to 5 hours in the CPA group was significantly superior to those of either the PA (P < 0.01) or placebo (P < 0.03) groups. Somnolence, fatigue, and nausea were the most common volunteered adverse events; only somnolence was significantly greater after CPA than after either PA or placebo. CONCLUSIONS: Treatment with CPA was safe and highly effective in reducing symptoms associated with SAR. It was more effective than either PA or placebo over most of the postdose observation period.     

Formulation considerations of intranasal corticosteroids for the treatment of allergic rhinitis.

OBJECTIVE: To examine how various aspects of an intranasal corticosteroid (INS) formulation may influence the efficacy, tolerability, and patient preference and adherence to INS therapy. DATA SOURCES: A PubMed search of the literature was conducted for studies on allergic rhinitis published between January 1977 and January 2006 using the keywords intranasal corticosteroid, preservatives, benzalkonium chloride, and tonicity. STUDY SELECTION: Prospective studies, retrospective studies, and case reports were selected for inclusion in this review. RESULTS: Currently available INSs are effective first-line treatments for allergic rhinitis. Differences in patient preference for a particular INS are largely attributable to sensory attributes of the nasal spray, which arise from characteristics of the formulation. Additives and preservatives can cause tolerability issues by irritating the mucosal membranes and causing nasal drying, or they can confer an unpleasant odor or taste to an INS formulation. The relative osmotic pressure, or tonicity, of an INS can modulate nasal absorption and retention, thereby potentially influencing the clinical efficacy. Characteristics such as delivery device and spray volume can affect a patient's perception and experience with a particular INS. Newer INSs, such as ciclesonide, are in development for the treatment of allergic rhinitis, and consideration of the formulation characteristics of these agents is an important part of the development process. CONCLUSIONS: INSs are an effective treatment option for patients with allergic rhinitis; however, there is room for formulation improvement. Optimization of formulation may increase the efficacy, tolerability, and patient preference and adherence to INSs.     

The haematopoietic specific signal transducer Vav1 is expressed in a subset of human neuroblastomas

Vav1 is a signal transducer protein expressed exclusively in the haematopoietic system, where it plays a pivotal role in growth factor-induced differentiation and proliferation. Vav1 couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, leading to cell differentiation and/or proliferation. Vav1 was originally detected as an oncogene, but its involvement in human malignancies has not been reported thus far. We report here that Vav1 is expressed in a neuroblastoma cell line, SK-N-MC. Molecular analysis indicated that there are no gross rearrangements or mutations in the Vav1 gene in SK-N-MC cells. Vav1 protein from SK-N-MC cells was similar to wild-type Vav1 in apparent molecular weight, phosphorylation state, and ability to associate with active EGFR. We also analysed the expression of Vav1 in 42 specimens of human neuroblastoma. Vav1 was expressed in the majority of these tumours. Our results suggest that Vav1 may play a role in the neoplastic process in a subset of neuroblastomas.     

Reduced interleukin-2 (IL-2) production in common variable immunodeficiency is due to a primary abnormality of CD4+ T cell differentiation

Common variable immunodeficiency (CVI) is a condition characterized by hypogammaglobulinemia and impaired antibody responses, resulting in recurrent bacterial infections in untreated patients. In addition, affected individuals exhibit an increased incidence of autoimmunity, malignancy, and certain viral infections, suggesting the presence of an underlying generalized immune dysregulation. We have previously described a subgroup of CVI patients in whom T cells within PBMC populations exhibit a selective defect in lymphokine production. IL-2, IL-4, and IL-5 mRNA production was impaired in these patients, while proliferation, IL-2R expression, and c-myc mRNA production were normal. In the present series of experiments, using highly purified CD4+ T cells prepared by negative selection, we show that this lymphokine production defect is a primary abnormality of CVI CD4+ T cells: whereas CD4+ T cells from CVI patients proliferate normally in response to stimulation by PHA, staphylococcal enterotoxin B (SEB), or anti-CD2 antibodies, these stimuli induce significantly less IL-2 production than observed with CD4+ T cells from normal individuals. Furthermore, we show that this IL-2 production defect is not due to an accessory cell abnormality, since it was seen in the presence of normal (allogeneic) accessory cells, and patient accessory cells supported normal amounts of IL-2 production by PHA-stimulated CD4+ T cells obtained from normal individuals. Of interest, we also found that while IL-2 production by CD4+ T cells from CVI patients induced by stimulation with immobilized anti-CD3 antibody was reduced compared to CD4+ T cells from normal control individuals, this reduction was not statistically significant. Furthermore, stimulation of both CVI patient and normal CD4+ T cells with either ionomycin + phorbol myristate acetate or a combination of immobilized anti-CD3 antibody plus anti-CD28 antibody resulted in a 50-fold increase in IL-2 production compared to stimulation with immobilized anti-CD3 antibody alone, and, under these conditions, CVI and normal CD4+ T cells produced equivalent amounts of IL-2. Finally, minor defects in interferon- production by CD4+ T cells from CVI donors were observed, but these were less severe than the IL-2 production defects and were not statistically significant. We conclude that a primary abnormality of lymphokine production exists in the CD4+ T cells of a subset of patients with CVI. The fact that the IL-2 production defect is more severe upon stimulation with superantigen as opposed to anti-CD3 antibody, and could be overcome by stimulation with ionomycin + phorbol myristate acetate or by costimulation with immobilized anti-CD3+ anti-CD28 antibodies, implies that this defect is due to impairment of a specific signaling pathway.     

Identification of a unique BK virus variant in the CNS of a patient with AIDS

Human polyomavirus BK (BKV; GenBank or EMBL or DDBJ accession no. NC001538) is often reactivated in immunosuppressed patients. Reactivation has been associated primarily with excretion of the virus in the urine, and there have been few reports of renal and/or neurological disease caused by BKV in patients with acquired immunodeficiency syndrome (AIDS). Polymerase chain reaction, Southern blotting, and sequencing were used to detect and identify the noncoding control region (NCCR) of BKV in different tissues in an AIDS patient with meningoencephalitis, retinitis, and nephritis. An undescribed reorganized NCCR variant of the virus, completely different from the variants detected in peripheral blood leukocytes (PBLs) and urine, was identified in the cerebrospinal fluid (CSF) and CNS tissues. These results suggest that rearrangements in the NCCR of the virus have resulted in a BKV variant, which is better adapted to the host cell machinery of the cells in CNS tissue. The rearranged variant (BKV CNS) might have been involved in the initiation and/or development of the pathological lesions observed in the CNS-related tissues of this patient.     

Efficacy and safety of loratadine plus pseudoephedrine in patients with seasonal allergic rhinitis and mild asthma

Background: Antihistamines have been shown to have a variety of therapeutic effects in asthma. Although nasal obstruction may play an important role in modulating lower airway function, no prior trial has used a decongestant in combination with an antihistamine in patients with allergic rhinitis and concomitant asthma.Objective: We sought to determine the efficacy and safety of loratadine (5 mg) plus pseudoephedrine (120 mg) (L/P) twice daily in patients with seasonal allergic rhinitis and mild asthma.Methods: We conducted a randomized, double-blind, placebo-controlled trial of L/P in 193 subjects during the fall allergy season. Nasal and chest symptoms, albuterol use, and peak expiratory flow rates were recorded daily for 6 weeks. Spirometry was measured at baseline and after 1, 2, 4, and 6 weeks of therapy, and health-related quality of life was rated at the beginning and end of the study.Results: Total rhinitis and asthma symptom severity scores were significantly reduced in patients receiving active therapy compared with those receiving placebo throughout the 6-week study. Peak expiratory flow rates improved significantly in patients treated with L/P during weeks 2 through 6 (peak effect [mean ± SEM]: L/P, 26.23 ± 4.64 L/min vs placebo, 8.52 ± 3.53 L/min, p = 0.002) as did FEV₁ (peak effect [mean ± SEM]: L/P, 170 ± 53 ml vs placebo, 20 ± 40 ml, p = 0.01) at all clinic visits. In addition, select measures of asthma-specific quality of life improved significantly relative to placebo.Conclusions: L/P significantly improved nasal and asthma symptoms, pulmonary function, and quality of life in patients with seasonal allergic rhinitis and concomitant mild asthma. (J Allergy Clin Immunol 1997;100:781-8)     

A CdZnTe slot-scanned detector for digital mammography

A new high-resolution detector has been developed for use in a slot-scanned digital mammography system. The detector is a hybrid device that consists of a CCD operating in time-delay integration mode that is bonded to a 150-microm-thick CdZnTe photoconductor array. The CCD was designed with a detector element pitch of 50 microm. Two devices were evaluated with differing crystalline quality. Incomplete charge collection was a source of reduction in DQE. This occurs in both devices due to characteristically low mobility-lifetime products for CdZnTe, with the greatest losses demonstrated by the multicrystalline sample. The mobility-lifetime products for the multicrystalline device were found to be 2.4 x 10(-4) and 4.0 x 10(-7) cm2/V for electrons and holes, respectively. The device constructed with higher quality single crystal CdZnTe demonstrated mobility-lifetime products of 1.0 x 10(-4) and 4.4 x 10(-6) cm2/V for electrons and holes. The MTF and DQE for the device were measured at several exposures and results were compared to predictions from a linear systems model of signal and noise propagation. The MTF at a spatial frequency of 10 mm(-1) exceeded 0.18 and 0.56 along the scan and slot directions, respectively. Scanning motion and CCD design limited the resolution along the scan direction. For an x-ray beam from a tungsten target tube with 40 microm molybdenum filtration operated at 26 kV, the single crystal device demonstrated a DQE(0) of 0.70 +/- 0.02 at 7.1 x 10(-6) C/kg (27 mR) exposure to the detector, despite its relatively poor charge collection efficiency.