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991.
992.
Houghton TJ Tanaka KS Kang T Dietrich E Lafontaine Y Delorme D Ferreira SS Viens F Arhin FF Sarmiento I Lehoux D Fadhil I Laquerre K Liu J Ostiguy V Poirier H Moeck G Parr TR Far AR 《Journal of medicinal chemistry》2008,51(21):6955-6969
Osteomyelitis is an infection located in bone and a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered antibiotics. Targeting antibiotics to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. By taking advantage of the affinity of the bisphosphonate group for bone mineral, we have prepared a set of 13 bisphosphonated antibacterial prodrugs based on eight different linkers tethered to the free amino functionality on fluoroquinolone antibiotics. While all but one of the prodrugs were shown in vitro to be effective and rapid bone binders (over 90% in 1 h), only eight of them demonstrated the capacity to significantly regenerate the parent drug. In a rat model of the disease, a selected group of agents demonstrated their ability to prevent osteomyelitis when used in circumstances under which the parent drug had already been cleared and is thus inactive. 相似文献
993.
994.
JOHNSTON PA; BROWN JS; BRAUMHOLTZ DA; DAVISION AM 《QJM : monthly journal of the Association of Physicians》1992,84(1):619-627
The Medical Research Council's Glomerulonephritis Registry wasused to study clinicopathological correlations and renal survivalin patients with IgA nephropathy reported between 1978 and 1985.IgA nephropathy was the histological diagnosis in 9.3 per centof all renal biopsies reported to the registry during this period,and in 18.1 per cent of those with a primary glomerulonephritis.The 10-year cumulative renal survival rate accounting for censoreddata (Kaplan-Meier) was 83.3 per cent. Univariate analysis ofsurvival curves (log-rank test) found the following parametersto be significantly correlated with poor renal survival: serumcreatinine >120 µmol/l (p<0.001), hypertension(p<0.001), serum albumin <40 g/l (p<0.005), proteinuria>1 g (p<0.025), age >30 years (p<0.025), and focalmesangial proliferation (p<0.05). There was no significantdifference in renal survival between males and females. Multivariateanalysis (Cox's proportional hazards model) revealed that onlya serum creatinine of > 120 µmol/l and a serum albuminof <40 g/l were independently predictive of outcome. These findings indicate marked similarities between the UK experienceof IgA nephropathy and the published European experience. IgAnephropathy is not a benign condition in the UK and patientswith impaired renal function and/or those with a reduced serumalbumin are significiantly more likely to progress to end-stagerenal failure within 10 years. 相似文献
995.
996.
Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease 总被引:5,自引:0,他引:5
McNeil AJ; Yap PL; Gore SM; Brettle RP; McColl M; Wyld R; Davidson S; Weightman R; Richardson AM; Robertson JR 《QJM : monthly journal of the Association of Physicians》1996,89(3):177-185
We examined how HLA types A1-B8-DR3 and B27 were related to progression of
clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City
Hospital cohort of HIV-positive patients, mainly injection drug users.
Patients (n = 692) were prospectively followed from 1985 through March
1994. Accurately estimated seroconversion times were determined
retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were
fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34
patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to
AIDS and 20 died. Twelve patients were typed positive for B27; six of these
progressed to CDC stage IV, one to AIDS and none died. In a proportional
hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3
was significantly associated with covariate-adjusted relative risks of 3.7
(95% CI 1.9- 7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from
seroconversion to death, AIDS and CDC stage IV, respectively. Events for
B27 were too rare to include B27 in analyses to death and AIDS, but B27 was
significantly associated with slower progression to CDC stage IV (0.3, CI
0.1-0.9). Random effects growth curve models were used to estimate
individual rates of loss of square root CD4 count and loss of CD4
percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was
associated with rapid loss of both markers (p = 0.02 and p = 0.01,
respectively); B27 was associated with slow loss of both markers (p = 0.04
and p < 0.005).
相似文献
997.
998.
999.
MN Boomgaard ; AM Joustra-Dijkhuis ; CW Gouwerok ; I Steneker ; HW Reesink ; JA Loos ; RN Pietersz ; D de Korte 《Transfusion》1994,34(4):311-316
BACKGROUND: Posttransfusion complications can be prevented by pretransfusion removal of donor white cells from platelet concentrate. The filtration used for this removal seems to have little effect on platelet function and activation, but more information is needed on its effect on function during subsequent long-term storage of concentrate. STUDY DESIGN AND METHODS: The effect of prestorage filtration of buffy coat-prepared platelet concentrates (PCs) on platelet function, metabolism, and activation was investigated. A pool of three PCs, each made of four buffy coats, was split into three equal volumes; two were filtered over two different filters and the third served as a control. Variables monitored immediately after filtration and during the subsequent 8-day storage period at 22 degrees C included aggregation upon stimulation with collagen and/or ADP, platelet adhesion capacity to collagen and fibrinogen in flowing blood, nucleotide content of and nucleobase release by the platelets, expression of activation-dependent antigens, and beta-thromboglobulin release by the platelets. RESULTS: No differences were observed between the PCs filtered over two different filters and the nonfiltered control PCs immediately after filtration and during storage, except for a selective removal (20%) of beta-thromboglobulin by one filter. CONCLUSION: PCs prepared from a pool of four buffy coats can be filtered and subsequently stored for 8 days (starting +/− 24 hours after whole blood collection) without detriment to platelet function, metabolism, or activation. 相似文献
1000.
RYAN FP; WARD AM; HOLDSWORTH CD 《QJM : monthly journal of the Association of Physicians》1991,78(1):59-63
The presence or absence of nine autoantibodies were assessedin 44 patients with ulcerative colitis (17 with hyposplenism)and 22 patients with Crohn's disease (eight with hyposplenism).The purpose of the study was to determine whether hyposplenismin inflammatory bowel disease is associated with an increasedtendency to autoimmunity, or whether autoimmunity is linkednot to hyposplenism itself but to the underlying bowel disease.The results strongly suggest that the latter hypothesis is correct.There was a much higher frequency of autoantibodies in patientswith ulcerative colitis than in those with Crohn's disease (P0.01),suggesting that autoimmune factors are more important in thepathogenesis of ulcerative colitis than in Crohn's disease. 相似文献