Association of Early Kidney Allograft Failure with Preformed IgA Antibodies to β2-Glycoprotein I

In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti–β₂-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in pretransplant serum was examined retrospectively. Of 269 patients, 89 patients were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were negative (67%; group 2). Graft loss at 6 months post-transplant was significantly higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The most frequent cause of graft loss was thrombosis of the vessels, which was observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04). Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an independent risk factor for early graft loss (P=0.04) and delayed graft function (P=0.04). There were no significant differences regarding patient survival between the two groups. Graft survival was similar in both groups after 6 months. In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of early graft loss caused by thrombosis and a high risk of delayed graft function. Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early clinical outcomes after renal transplantation.     

Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

Tuberculosis trends in Madrid, 1994-2003: impact of immigration and HIV infection.

SETTING: Tuberculosis (TB) cases reported from nine districts of Madrid, where the percentage of immigrant population varied from 1.9% in 1996 to 12.2% in 2003. OBJECTIVE: To describe the trends in TB incidence from 1994 to 2003. DESIGN: Observational study. RESULTS: Between 1994-1995 and 2002-2003, the TB rate decreased from 48.5 (95% CI 45.8-51.1) to 23.3 per 100000 population (95% CI 21.5-25.1) (P < 0.001). The percentage of TB cases co-infected with HIV decreased from 55.9% in 1994 to 14.3% in 2003 (P < 0.001), whereas TB cases in foreigners increased from 2.6% in 1994 to 33.7% in 2003 (P < 0.001). CONCLUSION: Although the TB rates showed a marked decrease in the study period, the increasing impact of immigration contributed to slowing down the trend.     

Composite prostheses for the repair of abdominal wall defects: effect of the structure of the adhesion barrier component

The component of a composite prosthesis, which makes contact with the visceral peritoneum, can be reabsorbable or non-reabsorbable, and laminar or reticular. This study was designed to determine whether the composition of this second, barrier component could improve its behavior at this interface. Abdominal wall defects in rabbits were repaired using a polypropylene prosthesis (PP), or the composites Sepramesh (PP+h) or Vicryl (PP+v). Fourteen days after surgery, the implants were evaluated by light and scanning electron microscopy, and immunohistochemistry. Prosthetic areas occupied by adhesions (PP: 71.08±5.09, PP+h: 18.55±4.96, P+v: 69.69±16.81%), neoperitoneal thickness (PP: 256.17±21.68, PP+h: 83.11±19.63, PP+v:213.72±35.90 μm) and macrophage counts (PP: 8.73±1.16, PP+h: 27.33±4.13, PP+v: 31.24±3.08%) showed significant differences (P<0.05). The tested biomaterials induced an optimal recipient tissue infiltration. Least adhesion formation was observed on the PP+h implants. This suggests that the second component, although reabsorbable, should be smooth in structure.     

Endothelial and smooth muscle properties of coronary and mesenteric resistance arteries in spontaneously hypertensive rats compared to WKY rats

Summary— To investigate if the functional alterations observed in resistance arteries of spontaneously hypertensive rats (SHRs) were also present at the coronary level, in vitro experiments were performed in mesenteric resistance arteries (MRA) and in right (RIC) and left interventricular coronary (LIC) arteries taken from 15–25-week-old SHR and age-matched Wistar Kyoto rats WKYs. Using a passive extension protocol, internal diameters corresponding to 100 mmHg intraluminal pressure (D₁₀₀) were determined and vessels were set up to a normalized internal diameter (0.9 D₁₀₀). SHR mesenteric resistance arteries had a significantly smaller diameter compared to WKY arteries, whereas both types of SHR coronary arteries had a greater diameter compared to those of WKY rats. In arteries in the absence of contracting agonist, nitro-L-arginine (NOLA, 100 μM) induced a progressive rise in basal tone, which could be reversed by subsequent addition of L-arginine (100 μM) but not D-arginine (100 μM). When expressed as percent of maximal contractions induced by agonists (noradrenaline, NA [10 μM] in MRA; serotonin, 5-HT [10 μM], in RIC and LIC), these contractions were significantly stronger in WKY compared to SHR coronary and mesenteric resistance arteries. In NA-precontracted MRA and 5HT-precontracted coronary arteries in the presence of indomethacin (10 μM), the magnitude of acetylcholine-induced maximal relaxations (expressed as percent of maximal contractions induced by agonists) was greater in WKY compared to SHR arteries. After a 30-min incubation period, NOLA (100 μM) completely inhibited relaxations induced by acetylcholine (0.01–10 μM) in all types of precontracted arteries. Subsequent additions of sodium nitroprusside, (SNP, 10 μM) induced complete relaxations in all preparations. These results show that a basal release of NO or NO-like compound by endothelial cells is present in isolated mesenteric resistance and coronary arteries of WKY rats and SHRs. The contribution of endothelium-derived relaxing factor-nitric oxide (EDRF-NO) to arterial tone was lower in MRA compared to coronary arteries in both strains and in SHR compared to WKY arteries. In the SHR preparations, the impaired relaxation induced by acetylcholine appeared to be due to a functional alteration of the endothelium in the presence of normal reactivity of the smooth muscle cells.     

麦冬类中药组织切片计算机三维重建图鉴

利用计算机技术实现麦冬类中药组织连续切片三维重建与动态显示,为计算机辅助生药学鉴定和教学提供了新的三维图像技术和研究资料。     

表小檗碱对α受体的作用

表小檗碱(epiberberine,EB)是从湖北产黄连(Coptis chinensis Franch)中提取的一种生物碱,属苯喹嗪类原小檗碱,对其药理作用的研究资料甚少,未见其对α肾上腺素体作用的报道。资料表明,许多原小檗碱类化合物有α受体阻滞作用,为从该类化合物中选择     

Surgical treatment of active prosthetic valve endocarditis. Results in 66 patients

The results of combined medical and surgical management of 66 patients with active prosthetic valve endocarditis (APVE) are analyzed. Between 1970 and 1985, 3510 patients were operative survivors of mitral, aortic or double mitral-aortic valve replacement. Cumulative follow-up was 15,640 patient-years (mean 4.4 years). The overall annual incidence of reoperation for APVE was 0.42 +/- 0.05% (0.34 +/- 0.08% for biological and 0.46 +/- 0.06% for mechanical prostheses, p = n.s.). Early APVE occurred in 21 patients and 45 patients had late APVE. Indications for surgery were heart failure in 92%, systemic emboli in 5% and persistent sepsis in 3% of patients. Overall operative mortality (less than 30 days) was 38% (25/66). (Early APVE 52% and late APVE 31%). Anatomical location, valve design and number of prostheses implanted did not correlate with a higher operative risk. Overall endocarditis-related mortality was 56% (37/66). Uni and multivariate stepwise logistic regression analysis identified: 1) date of surgery (p = 0.01), 2) renal failure (p = 0.03) and 3) early APVE (p = 0.03) as predictors of endocarditis-related death. Actuarial survival at 1, 5 and 10 postoperative years was 41 +/- 6%, 30 +/- 6% and 24 +/- 7% respectively. This study confirms the high lethality of APVE. However, with adequate and aggressive combined medical and surgical management, some patients can be saved.