Evaluation of a home-delivery service for HIV-infected patients attending an inner London HIV treatment centre.

Home delivery (HD) of medication is a goal of the Department of Health's Pharmacy in the Future; Implementing the NHS Plan. We evaluated the safety and effectiveness of an HD service for antiretroviral therapy (ART). Patients on ART with stable viral load (VL) <50 were identified. Comparison was made between patients using HD and those using the clinic-based pharmacy (CP). The primary endpoint was HIV virological failure (VF) (HIV VL >400 copies/mL on two consecutive occasions). Secondary endpoints included frequency of outpatient attendances (OPA) and an incidence of adverse events. Cumulative incidences (CulmIn) for each outcome event were calculated. Incidence-rate ratios (IRR) were obtained using Poisson regression. Of 1663 patients identified; 450 received HD and 1213 used CP. CuImIn of VF was =4% in those using HD and =7% in those using CP (IRR [95% confidence intervals, CI] =0.53, 0.32-0.90). HD patients had fewer OPA, less frequent blood test monitoring and less frequent abnormal liver function results (IRR [95% CI]= 0.63 [0.59-0.67] and 0.59 [0.53-0.67], 0.68 [0.65-0.71] and 0.64 [0.53-0.78], respectively). Patients deemed stable enough on social, psychological and medical grounds to receive HD of ART had a lower risk of VF, fewer OPA and no increase in adverse events when compared with patients using CP.

Topical H2 antagonist prevents periodontitis in a rabbit model.

Cimetidine is a powerful H2 receptor antagonist that eliminates histamine's effects on chemotaxis, phagocytosis, and superoxide anion production by phagocytes. The purpose of this study was to analyze the clinical and histopathological changes associated with experimental periodontitis in rabbits in response to topically applied cimetidine. Experimental periodontitis was induced in 21 New Zealand White rabbits using Porphyromonas gingivalis (10(9) CFU) topically applied three times a week for a 6-week period to previously ligatured teeth. Topical application of cimetidine in a liposome carrier for the prevention of periodontitis was evaluated in four groups of four animals each: 1, 10, and 100 mg/ml and no treatment (positive control). In addition, there was a vehicle group (n = 3) that received liposome preparation (carrier) only, and two animals with ligature application alone served as negative controls. Periodontal disease was quantified by direct visualization and radiographical evaluation of bone loss on defleshed skulls and by histological analyses of sections stained with hematoxylin-eosin and tartrate-resistant acid phosphatase. In the no-treatment (positive control) and liposome (vehicle) groups, direct visualization and radiological measurements revealed statistically significant bone loss compared to the negative control. Application of cimetidine at all concentrations tested inhibited inflammation and bone loss by >90%. Histological findings revealed that ligated sites of the positive control and vehicle groups showed significant reduction in bone level (P < 0.05) compared to the three cimetidine groups, with a marked decrease in inflammation. The findings of this study provide morphological and histological evidence that topically active cimetidine is a potent inhibitor of P. gingivalis-elicited periodontal inflammation, arresting and/or preventing tissue destruction and influencing cell populations present in the inflammatory cell infiltrate.

Enhanced superoxide release and elevated protein kinase C activity in neutrophils from diabetic patients: association with periodontitis.

Inflammation and oxidative stress are important factors in the pathogenesis of diabetes and contribute to the pathogenesis of diabetic complications. Periodontitis is an inflammatory disease that is characterized by increased oxidative stress, and the risk for periodontitis is increased significantly in diabetic subjects. In this study, we examined the superoxide (O(2)(-))-generating reduced nicotinamide adenine dinucleotide phosphate-oxidase complex and protein kinase C (PKC) activity in neutrophils. Fifty diabetic patients were grouped according to glycemic control and the severity of periodontitis. Neutrophils from diabetic patients with moderate [amount of glycated hemoglobin (HbA(1c)) between 7.0% and 8.0%] or poor (HbA(1c) >8.0%) glycemic control released significantly more O(2)(-) than neutrophils from diabetic patients with good glycemic control (HbA(1c) <7.0%) and neutrophils from nondiabetic, healthy individuals upon stimulation with 4beta-phorbol 12-myristate 13-acetate or N-formyl-Met-Leu-Phe. Depending on glycemic status, neutrophils from these patients also exhibited increased activity of the soluble- and membrane-bound forms of PKC, elevated amounts of diglyceride, and enhanced phosphorylation of p47-phox during cell stimulation. In addition, we report a significant correlation between glycemic control (HbA(1c) levels) and the severity of periodontitis in diabetic patients, suggesting that enhanced oxidative stress and increased inflammation exacerbate both diseases. Thus, hyperglycemia can lead to a novel form of neutrophil priming, where elevated PKC activity results in increased phosphorylation of p47-phox and O(2)(-) release.

Presentation of the Goodpasture autoantigen to CD4 T cells is influenced more by processing constraints than by HLA class II peptide binding preferences.

Class II molecules are believed to influence immune responses by selectively binding antigen-derived peptides for recognition by T cells. In Goodpasture's (anti-glomerular basement membrane) disease, autoimmunity to the NC1 domain of the alpha3-chain of type IV collagen (alpha3(IV)NC1) is strongly associated with HLA-DR15. We have examined the influence of the peptide binding preferences of DR15 molecules on the selection of alpha3(IV)NC1-derived peptides displayed bound to DR15 molecules on the surface of alpha3(IV)NC1-pulsed DR15-homozygous Epstein-Barr virus-transformed human B cells. The preferences of DR15 molecules were investigated using a panel of 24 overlapping peptides spanning the sequence of alpha3(IV)NC1. The alpha3(IV)NC1-derived peptides selected for display to T cells were determined by biochemical analysis as reported previously (Phelps, R. G., Turner, A. N., and Rees, A. J. (1996) J. Biol. Chem. 271, 18549-18553). Three nested sets of naturally presented alpha3(IV)NC1 peptides were detectable bound to DR15 molecules. Peptides representative of each nested set bound to DR15 molecules, but almost two-thirds of the alpha3(IV)NC1 peptides studied had as good or better DR15 affinity than those identified as naturally processed. Thus alpha3(IV)NC1 presentation to T cells is determined more by "processing factors" than by the preferences of relatively indiscriminate DR15 molecules. The results have important implications for the use of class II peptide binding data to aid identification of potential T cell epitopes, especially for antigens which, like alpha3(IV)NC1, contain many sequences able to bind class II molecules.

Effect of lactose derivatives on metastatic potential of B16 melanoma cells.

The effects of various sugars and sugar derivatives on lung colonization (i.e., metastatic deposition) of the highly metastatic BL6 clone of B16 mouse melanoma cells in syngeneic mice were studied, based on the assumption that carbohydrate structures, particularly those with a Gal terminus, play a crucial role in defining the metastatic potential of B16 cells. After incubation with sugar compounds (usually at 0.1 M concentration), tumor cells were injected via the tail vein into 8-week old female mice. Mice were sacrificed after 18-21 days, and tumor cell colonies in lung were counted under a dissecting microscope. Only methyl beta-D-lactoside and lacto-N-tetraose caused significant reduction (35-45% and 36%, respectively) of metastatic deposition compared to controls. Methyl beta-D-lactoside did not exhibit a growth inhibitory effect on BL6 tumor cells, as determined by several methods: in vitro [3H]thymidine incorporation assay, in vitro plating in RPMI-1640 medium culture under physiological conditions followed by cell counting, and in vivo subcutaneous inoculation of age-matched C57/BL mice followed by tumor measurement. These results indicate that the inhibitory effect of methyl beta-D-lactoside on tumor deposition was not related to its effect on tumor cell growth.