CD1d-restricted NKT cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses

CD1d-restricted NKT cells are a novel T cell lineage with unusual features. They co-express some NK cell receptors and recognize glycolipid antigens through an invariant T cell receptor (TCR) in the context of CD1d molecules. Upon activation through the TCR, NKT cells produce large amounts of IFN-gamma and IL-4. It has been proposed that rapid cytokine output by activated NKT cells may induce bystander activation of other lymphoid lineages. The impact of CD1d-restricted NKT cell activation in the induction of B cell-mediated immune responses to infection is still unclear. We show here that CD1-restricted NKT cells contribute to malarial splenomegaly associated with expansion of the splenic B cell pool and enhance parasite-specific antibody formation in response to Plasmodium berghei infection. The increased B cell-mediated response correlates with the ability of NKT cells to promote Th2 immune responses. Additionally, antibody responses against the glycosylphosphatidylinositol (GPI)-anchored protein merozoite surface protein 1 (MSP-1) were found to be significantly lower in CD1(-/-) mice compared to wild-type animals. P. berghei-infected MHC class II (MHCII)(-/-) mice also generated antibodies against MSP-1, suggesting that antibody production against GPI-anchored antigens in response to malaria infection can arise from both MHCII-dependent and independent pathways.     

Success Rates of Debridement,Antibiotics, and Implant Retention in 230 Infected Total Knee Arthroplasties: Implications for Classification of Periprosthetic Joint Infection

BackgroundProsthetic joint infection (PJI) is the most common cause of failure following total knee arthroplasty (TKA). This study aimed to determine the success of debridement, antibiotics, and implant retention (DAIR) in a large cohort of TKA PJIs and assess the utility of current classification systems in predicting DAIR outcomes in early postoperative, late hematogenous, and chronic PJIs.MethodsIn a multicenter review over 15 years, 230 patients underwent DAIR for first episode PJI following primary TKA. Patient demographics, disease and surgical factors, treatment regime, and outcomes were identified. Univariate and multivariate survival analyses were performed to identify factors associated with successful DAIR. Continuous variables with predictive value were further analyzed using receiver operating characteristic curves. The ability to predict DAIR outcomes of multiple classification systems was also assessed.ResultsPatients were followed for an average of 6.9 years. The overall success rate of DAIR was 53.9%. On receiver operating characteristic analysis, 3 months (area under the curve = 0.63) and 1-year age (area under the curve = 0.66) of implant cut-offs was similarly predictive of outcomes. On multivariate survival analysis, DAIR was successful in 64% of “early” PJIs (implant <1 year) vs 38% of “late hematogenous” PJIs (implant >1 year; odds ratio [OR] 1.78, P = .01). For late PJIs (implant >1 year), Staphylococcus aureus (OR 4.70, P < .001) and gram-negative infections (OR 2.56, P = .031) were risk factors for DAIR failure.ConclusionDAIR has a high failure rate in all PJIs occurring more than a year post primary TKA, particularly when caused by S aureus or gram-negative bacteria. The age of implant is an important predictor of DAIR outcomes.     

Making use of official statistics in research on gender and health status: recent British data

Macintyre et al. [Macintyre, S., Hunt, K., Sweeting, H., 1996. Gender differences in health: are things really as simple as they seem? Social Science and Medicine 42, 617-624] stated that the "whole topic of gender differences in health warrants periodic re-examination". In this paper we begin by presenting an overview of the main sources of national data that are available for monitoring patterns and trends in health by gender. We then give examples of a selection of indicators which contribute to the debate on the nature of differences between men and women in terms of their mortality. morbidity and health service utilisation. We conclude by urging readers to make more use of these sources of data to throw further light on the reasons for the differences and similarities in women's and men's experiences of health.     

Clinical pharmacy services in a community hospital

An example is given of the implementation of clinical pharmacy service program in a community hospital. The need for establishing an efficient drug distribution system is discussed, and the feasibility of utilizing clinically motivated staff pharmacists is presented. A method of limiting the number of patients admitted to the clinical pharmacy service program is also given.     

Serum protein profiles to identify head and neck cancer.

PURPOSE: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. The purpose of this study was to determine whether a new proteomic technology could correctly identify protein expression profiles for cancer in patient serum samples. EXPERIMENTAL DESIGN: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ProteinChip system was used to screen for differentially expressed proteins in serum from 99 patients with HNSCC and 102 normal controls. Protein peak clustering and classification analyses of the surface-enhanced laser desorption/ionization spectral data were performed using the Biomarker Wizard and Biomarker Patterns software (version 3.0), respectively (Ciphergen Biosystems, Fremont, CA). RESULTS: Several proteins, with masses ranging from 2778 to 20800 Da, were differentially expressed between HNSCC and the healthy controls. The serum protein expression profiles were used to develop and train a classification and regression tree algorithm, which reliably achieved a sensitivity of 83.3% and a specificity of 100% in discriminating HNSCC from normal controls. CONCLUSIONS: We propose that this technique has potential for the development of a screening test for the detection of HNSCC.     

Attenuation of Neomycin Ototoxicity by Iron Chelation

Increasing evidence suggests that aminoglycoside ototoxicity is mediated by the formation of an aminoglycoside-iron complex and that the creation of this complex is a preliminary step in generation of free radical species and subsequent hair cell death. In this study we have assessed the ability of the iron chelator deferoxamine to attenuate the hearing loss induced by an ototoxic dose of the aminoglycoside neomycin (100 mg/kg per day for 14 days). Experiments were carried out on pigmented guinea pigs weighing 250 to 300 g. Changes in auditory sensitivity were characterized by monitoring shifts in compound action potential(CAP) thresholds, recorded through indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results show that animals receiving neomycin alone suffered a mean threshold shift exceeding 35 dB at all test frequencies (2.0, 4.0, and 8.0 kHz) 30 days after initiation of treatment. In comparison, all animals receiving cotherapy of neomycin and deferoxamine (150 mg/kg twice daily for 14 days) maintained their CAP threshold, suggesting significant protection from neomycin ototoxicity. A statistical comparison of treatment groups showed that in the animals receiving cotherapy with neomycin and deferoxamine, deferoxamine produced a significant protective effect against neomycin-induced ototoxicity (P < 0.001). These results provide further evidence of the intrinsic role of iron in aminoglycoside ototoxicity and suggest that deferoxamine may have a therapeutic role in attenuating the cytotoxic action of aminoglycoside antibiotics.     

Local synthesis of IgA in the cerebrospinal fluid of patients with neurological diseases

To date qualitative studies of IgA in the cerebrospinal fluid in neurological disease, particularly multiple sclerosis, have been few and given mixed results. The aim of this study was to identify local synthesis of IgA by detection of clonal IgA bands, in a large cohort of patients with a variety of neurological disorders, using polyacrylamide gel electrophoresis, transfer of protein to nitrocellulose membranes and specific staining. Of 2,097 sequentially analysed patients with suspected neurological disease 54 (2.6%) had locally synthesised IgA; most notably, IgA was present in 39 of 291 (13%) patients with suspected multiple sclerosis. The latter group also had a significant excess of light-chain production, particularly free kappa, when compared to multiple sclerosis patients without local synthesis of IgA. Locally synthesised IgA was also demonstrated in inflammatory, infectious and autoimmune diseases of the central nervous system. This qualitative technique is simple and suitable for routine analysis of cerebrospinal fluid, and further qualitative studies of IgA may be useful in investigating the pathophysiology of certain neurological disorders.