Abnormally-fucosylated serum haptoglobins in patients with inflammatory joint disease

The fucosylation of haptoglobins is altered in rheumatoid arthritis. In order to investigate the clinical usefulness of this finding, serum levels of abnormally-fucosylated haptoglobins (FHp) have been assessed in defined and matched groups of patients with different inflammatory joint diseases. FHp was elevated in 16/17 patients with active rheumatoid arthritis (RA); 1/20 patients with inactive rheumatoid arthritis; 1/11 patients with osteoarthritis; and 4/10 patients with seronegative polyarthritis. Raised FHp levels, therefore, are not disease-specific. There was no relationship between the duration of RA and the FHp level. The FHp expression in RA was also compared with other biochemical indices of disease activity. The degree of correlation between FHp and articular index, joint score and early-morning stiffness was very similar to that obtained for C reactive protein (CRP), and better than that obtained for erythrocyte sedimentation rate and haemoglobin. FHp, however, gives fewer false-positives than CRP in cases of inactive disease. until FHp can be measured more easily and cheaply, CRP estimation is still the biochemical test of choice in RA.     

Pharmacokinetics of rosiglitazone in patients with end-stage renal disease

The pharmacokinetics and tolerability of a single 8-mg oral dose of rosiglitazone, an anti-diabetic agent, were compared in 10 long-term haemodialysis patients and 10 healthy volunteers. Haemodialysis patients received rosiglitazone 4 h after haemodialysis (non-dialysis day) and 3 h before haemodialysis (dialysis day). Haemodialysis did not influence rosiglitazone pharmacokinetics, and dialytic clearance was low (0.10 1/h). The mean area under the concentration-time curve (AUC(0-infinity)), the maximum observed plasma concentration (Cmax) and the half-life for rosiglitazone were similar in haemodialysis patients (non-dialysis day) and healthy individuals (2192 +/- 598 ng.h/ml versus 2388 +/- 494 ng.h/ml, 338 +/- 114 ng/ml versus 373 +/- 95 ng/ml, and 3.70 +/- 0.75 h versus 3.81 +/- 0.86 h, respectively). AUC(0-infinity) and Cmax were not markedly influenced by haemodialysis. Rosiglitazone dose adjustments are not warranted in patients with type 2 diabetes with end-stage renal failure on haemodialysis.     

Pharmacokinetics of cefoperazone in patients with neoplastic disease.

The pharmacokinetics of cefoperazone, a new semisynthetic cephalosporin, were studied in 34 patients with neoplastic disease. This compound was administered in a variety of doses and schedules without observable toxicity in any patient. The mean peak serum concentration after a 15-min intravenous infusion of 2 g was 264 microgram/ml after the first dose; the serum half-life was 2.1 h. There was no significant change in half-life or serum concentrations after 4 or 7 days of therapy. The mean peak serum concentration after infusion of 1 g over 15 min was 133 microgram/ml, with a mean of 10.7 microgram/ml at 6 h. The serum half-life was 2 h. The mean peak serum concentration after infusion of 1 g over 0.5 h was 101 microgram/ml. When 8 g was subsequently administered daily by a continuous infusion schedule, levels were maintained at 80 microgram/ml. When the dose was increased to 16 g daily, serum concentrations were maintained at an average of 153 microgram/ml. Only 37% of cefoperazone was recovered in the urine in a 12-h period after the initial dose, suggesting the importance of other mechanisms of excretion; however, serum concentrations in one patient with renal insufficiency were significantly higher than serum concentrations in patients with normal renal function.     

临床护理路径在老年髋关节置换术患者中的应用

目的:探讨临床护理路径在老年髋关节置换术患者中的应用效果。方法:将90例髋关节置换患者随机等分成观察组与对照组,对照组给予常规护理,观察组采用临床护理路径护理。比较两组患者遵医行为、Harris髋关节评分、并发症发生率、平均住院日数及对护理服务满意度情况。结果:观察组患者遵医行为、髋关节功能评分、患者对护理服务满意度均优于对照组(P0.05),并发症发生率低于对照组(P0.05),平均住院日短于对照组(P0.05)。结论:临床护理路径提高了髋关节置换术患者及其家属的遵医行为和满意度,确保各项护理措施有效实施,从而缩短住院时间,降低术后并发症发生率,进而促进髋关节功能恢复。     

Pharmacokinetics of rimantadine hydrochloride in patients with chronic liver disease

Six patients with chronic liver disease and six sex-, age (+/- 5 years)-, and weight (+/- 5 kg)-matched healthy control subjects received a single dose of two 100 mg tablets rimantadine HCl. Eight additional patients with chronic liver disease who were not matched to healthy subjects received a single dose of two 100 mg tablets of rimantadine HCl. Blood and urine samples were collected and rimantadine concentrations were determined by a GCMS method. The values for maximum plasma concentration, AUC, elimination half-life, and renal clearance were not significantly different between patients and control subjects, independent of the statistical analyses (parametric and nonparametric) used. The mean apparent elimination half-life, volume of distribution, and total clearance in the matched patients with liver disease were 32 hours, 24 L/kg, and 676 ml/min, respectively. Renal clearance and the amount excreted in the urine unchanged were 63 ml/min and 10%, respectively. In conclusion, rimantadine pharmacokinetics were not appreciably altered in patients with less severe chronic liver disease.     

Pharmacokinetics of metronidazole in patients with alcoholic liver disease.

The pharmacokinetics of metronidazole was evaluated in eight patients with alcoholic liver disease. Metronidazole (7.5 mg/kg) was administered to each patient intravenously. Serial blood samples were obtained after the dose. Serum metronidazole concentrations were determined by high-performance liquid chromatography. The following pharmacokinetic parameters (mean +/- standard deviations) were obtained: half-life, 18.31 +/- 6.06 h; elimination rate constant, 0.042 +/- 0.013 h-1; volume of distribution, 0.77 +/- 0.16 liters/kg; and total body clearance, 0.51 +/- 0.11 ml/min per kg. Compared with subjects with normal liver function, patients with liver disease showed a reduction in drug elimination rate and total body clearance. The half-life of metronizadole in serum and volume of distribution were increased. Large variations of these parameters were also observed among the patients. On the basis of these observations, a reduced dose of metronidazole should be given to patients with alcoholic liver disease to avoid accumulation of metronidazole and its metabolites. Monitoring of drug concentration in serum may also be necessary to optimize therapy.     

Surgical strategies in patients with inflammatory bowel disease

Crohn's disease and ulcerative colitis are specific inflammatory bowel diseases. Quality of life can be considerably limited. It does not depend on the form of therapy that Crohn's disease is highly recurrent, whereas colitis ulcerosa is curable by proctocolectomy. For both forms of disease surgery is an important option. It has to be included early in the therapy concept and not as last choice. Quality of life in patients with Crohn's disease can be raised significantly by surgery. Meticulous selection of the patients are essential to the policy of surgery as well as a regular aftercare. Best profit for those patients are treatment with an interdisciplinary team, consisting of gastroenterologists, nutrition advisers, psychologists, surgeons and radiologists.     

Biotransformation of sulindac in end-stage renal disease

In normal humans sulindac, a prodrug, undergoes two major biotransformations: irreversible oxidation to the inactive sulfone metabolite and reversible reduction to the pharmacologically active sulfide metabolite. To assess any effect of end-stage renal failure on sulindac biotransformation, six patients were given 200 mg sulindac orally. Plasma was sampled over 24 hours. Protein binding of sulindac and metabolites was determined by equilibrium dialysis. Results were compared with historic controls. AUC(0-12) for sulindac and the sulfone were similar to controls. AUC(0-12) for the sulfide was significantly reduced to 4.85 micrograms X hr/ml from 13.1 micrograms X hr/ml (P less than 0.02). Protein binding of all three compounds was significantly reduced by renal failure. When corrected for protein binding, the AUC(0-12) for sulindac and the sulfone was twice that of controls whereas that of the sulfide was 42 ng X hr/ml compared with 83 ng X hr/ml in normal individuals (P less than 0.001). This suggests that end-stage renal failure impairs the reduction of sulindac to the active sulfide whereas oxidation to the sulfone is intact.     

Anti-alpha-enolase antibodies in patients with inflammatory Bowel disease

BACKGROUND: Patients with inflammatory bowel disease (IBD) carry autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies (pANCA). alpha-Enolase has been proposed as a target antigen in IBD. We evaluated the prevalence and diagnostic value of anti-alpha-enolase antibodies in IBD and related disorders. METHODS: We used a classic proteomic approach with extracts from granulocytes and pANCA-positive ulcerative colitis (UC) sera to confirm alpha-enolase as a target antigen. By means of Western blot analysis, we screened a cohort of 525 subjects for the presence of anti-alpha-enolase antibodies. We performed GeneArray experiments on RNA extracted from colonic mucosal biopsies from 35 IBD and 6 control patients. RESULTS: We detected anti-alpha-enolase antibodies 49.0% of patients with UC, 50.0% of patients with Crohn's disease, 30.5% of patients with primary sclerosing cholangitis, 37.8% of patients with autoimmune hepatitis, 34.0% of patients with ANCA-positive vasculitis, 31.0% of non-IBD gastrointestinal controls, and 8.5% of healthy controls. Gene array experiments showed a significant upregulation of alpha-enolase mRNA in colonic mucosal biopsies from patients with IBD, but not from controls. There was no association between the presence of pANCA and anti-alpha-enolase antibodies. Preabsorption with alpha-enolase did not eliminate the pANCA pattern on indirect immunofluorescence. CONCLUSIONS: Anti-alpha-enolase antibodies are present in a substantial proportion of patients with IBD, patients with various inflammatory/autoimmune disorders, and non-IBD gastrointestinal controls. Therefore, anti-alpha-enolase antibodies are of limited diagnostic value for the diagnosis of IBD.     

炎症性肠病患者脊柱关节炎的表现特点

目的 探讨炎症性肠病(IBD)患者的肠外表现—脊柱关节炎的发生情况,为后续炎症性肠病患者的诊断治疗提供借鉴.方法 分析2016年9月至2020年9月本院收治的210例炎症性肠病患者(其中溃疡性结肠炎/UC组138人,克罗恩病/CD组72人)肠道病变分布情况,并分析UC组及CD组患者脊柱关节炎各种分型的发生率及两组之间表...     

Alpha-tocopherol, lipids and lipoproteins in knee-joint synovial fluid and serum from patients with inflammatory joint disease.

1. We have determined the antioxidant status of synovial fluid and serum of patients with inflammatory joint disease in terms of the biologically active lipid-soluble antioxidant, alpha-tocopherol. Synovial fluid concentrations of alpha-tocopherol were significantly lower relative to those of paired serum samples (P < 0.001). Serum levels of alpha-tocopherol in these patients did not differ significantly from those in control serum. 2. Lower concentrations of cholesterol, triacylglycerol and low-density lipoprotein were also observed in patients' synovial fluid compared with matched serum samples. However, multiple regression analysis of the data indicated that there remained a significant depletion of alpha-tocopherol, which was largely independent of these co-variables, in inflammatory synovial fluid. These findings are consistent with the consumption of alpha-tocopherol within the inflamed joint via its role in terminating the process of lipid peroxidation. 3. Nuclear magnetic resonance spectroscopic analysis of matched inflammatory synovial fluid and serum confirmed lower concentrations of triacylglycerol in synovial fluid together with evidence of a shortened mean triacylglycerol chain length. The latter metabolic difference suggests an increased utilization of triacylglycerols for energy within the inflamed joint.     

Lifelong control with inflammatory bowel disease patients

The benefits and the burden of a lifelong control scheme for patients with chronic inflammatory bowel disease are discussed. The benefits cover physical, psychologic, and social conditions. Valuable scientific gains can be yielded secondarily from the data collection.     

Pharmacokinetics of cefotaxime and desacetylcefotaxime in patients with liver disease.

The dispositions of cefotaxime and its metabolite desacetylcefotaxime were investigated in patients with different forms of chronic parenchymal liver disease (CPLD). A total of 31 subjects (27 patients and 4 controls) received a single 2-g dose of cefotaxime by infusion, and serial blood samples were drawn. The area under the concentration-time curve ranged from 176 to 241 micrograms.h/ml, the apparent half-life ranged from 1.49 to 2.42 h, and clearance ranged from 2.06 to 3.10 ml/min/kg in patients with four different forms of CPLD. The area under the concentration-time curve and the apparent half-life of desacetylcefotaxime ranged from 72 to 128 micrograms.h/ml and 7.1 to 13.4 h, respectively. Pharmacokinetic parameters were significantly different in patients with CPLD compared with those in control subjects and were related to clinical indices of hepatic impairment. Modest accumulation of cefotaxime in patients with severe hepatic impairment is unlikely to produce toxicity because of its high therapeutic index, and dosing modifications may not be required.     

Pharmacokinetics of panipenem/betamipron in patients with end-stage renal disease

Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of panipenem/betamipron. In this study, the pharmacokinetics of panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of panipenem/betamipron (500mg/500mg). The in vitro extraction ratios of panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of panipenem in patients were 9.53 ± 1.26l/h with hemodialysis, and 2.92 ± 0.238l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643l/h and 0.615 ± 0.511l/h, respectively. The clearance of panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500mg/500mg of panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.     

不同剂量阿托伐他汀对老年冠心病合并心房颤动患者炎症因子及预后的影响

目的 观察不同剂量阿托伐他汀对老年冠心痛合并心房颤动患者炎症因子及预后的影响,探讨阿托伐他汀抗心房颤动的可能机制.方法 将100例老年冠心痛合并心房颤动患者随机分为10 mg阿托伐他汀组(n=50)和20 mg阿托伐他汀组(n=50),观察两组患者治疗前后血清炎症因子高敏C反应蛋白(hsCRP)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、左心房内径(LAD)及心房利尿钠肤(ANP)的变化,同时记录治疗6个月后两组患者实性心律维持率及栓塞事件发生率.结果 治疗后,两组hsCRP、IL-6、TNF-a、ANP水平及LAD内径均较治疗前降低,20mg组:hsCRP(4.10±1.85)mg/L vs (6.42±1.71)mg/L,IL-6(11.71±1.69)ng/L vs (14.61±2.47)ng/L,TNF-α(18.07±2.67)ng/L vs (22.32±3.51)ng/L,ANP(213.10±28.20)ng/L vs (352.10±58.71)ng/L,LAD(38.8±7.1)mm vs (50.2±8.7)mm(P<0.05),且20 mg阿托伐他汀组降低更明显(P<0.05);同时20 mg阿托伐他汀组较10 mg阿托伐他汀组窦性心律维持率高,栓塞事件发生率低(P<0.05).结论 阿托伐他汀能降低老年冠心痛合并心房颤动患者血清炎症因子水平,同时能降低ANP水平及LAD内径,提高窦性心律维持率,降低栓塞事件发生率,且呈剂量依赖性,这可能是阿托伐他汀发挥抗心房颤动作用的机制之一.