Early diagnosis of osteoarthritis using cathepsin B sensitive near-infrared fluorescent probes

OBJECTIVE: Osteoarthritis is currently diagnosed utilizing X-ray and MRI-techniques, both of which are based on the morphological changes of tissue. However, once changes are detected, the tissue has an irreversible defect. This study investigates early diagnosis of OA on a molecular basis using a recently developed cathepsin B sensitive near-infrared (NIR) fluorescent probe. METHOD: Twelve male nude mice were induced osteoarthritis by intra-articular injection of collagenase (1.0%, w/v) into the right knee joint. The left knee joint served as the negative control. The cathepsin B NIR probe is activated by arthritis-associated cathepsin B, thus resulting in the emission of an intensive NIR fluorescence signal which can be detected in vivo. NIR fluorescence signals were acquired on an optical imaging system using an excitation wavelength of 610-650 nm and an emission wavelength of 680-720 nm. RESULTS: Mild to moderate degenerative cartilage was observed 1 month after collagenase injection. NIR fluorescence imaging of mice showed approximately a 3-fold difference in signal intensity between osteoarthritic and normal joints 24 h after intravenous injection of the reporter probe. Immunohistochemical evaluation also revealed cathepsin B expression in the arthritic lesion of femorotibial joints, and not in the control contra-lateral knee joints. CONCLUSION: As the cathepsin B activatable NIR fluorescent imaging showed a significant difference between the osteoarthritic and normal joints, the cathepsin B activatable NIR fluorescent probe thus offers a potential new imaging technology for early OA diagnosis.     

Computed Tomographic Assessment of the Surgical Risks Associated with Fibrocavernous Pulmonary Tuberculosis

Purpose We evaluated the surgical risks associated with fibrocavernous pulmonary tuberculosis by retrospectively examining chest computed tomography (CT) scans.Methods We reviewed the records of 40 patients who underwent pulmonary resection for fibrocavernous pulmonary tuberculosis, for whom preoperative CT scans were available. The disease was categorized as class I, defined as a cavity within one lobe without remarkable pleural thickness, in 21 patients; class II, defined as a cavity extending beyond one lobe or within one lobe with remarkable pleural thickness, in 10 patients; and class III, defined as bilateral cavities, in 9 patients. Four of the nine patients with bilateral cavities underwent bilateral pulmonary resection and five underwent unilateral pulmonary resection. The study parameters were intraoperative blood loss, operative time, hospital stay, major operative morbidity, and hospital death.Results Intraoperative blood loss and operative time were significantly greater and hospital stay was significantly longer in patients with advanced disease (P = 0.046, P = 0.000, and P = 0.143, respectively). Major surgical morbidity mainly occurred in association with advanced disease (P = 0.028) at the following incidences: class I, 5%; class II, 30%; class III, 44.4%. Two hospital deaths occurred, both following bilateral pulmonary resection for class III disease, accounting for an overall 5% mortality rate.Conclusion The surgical risks associated with fibrocavernous pulmonary tuberculosis were well correlated with anatomic involvement, according to the extent of cavitation and the severity of pleural thickness, as depicted by CT. Staged pulmonary resection or the combination of one-sided resection with other modalities is recommended for the treatment of bilateral cavities.     

Vertebrae adjacent to spinal bone lesion are inconsistent reference markers: a magnetic resonance spectroscopic viewpoint

PURPOSE: To ascertain the suitability of vertebrae adjacent to spinal bone lesions as a signal intensity reference on MRI, and compare the MR spectroscopic appearance of vertebral body compression fractures due to malignant tumor infiltration, bone weakening (e.g., osteoporosis), and/or minor trauma. MATERIALS AND METHODS: Twenty-five patients with spinal compression fractures underwent routine spinal MRI with an additional 1H MRS study protocol to assess the percent fat fraction of the compressed vertebrae as well as the adjacent bony environment. Peak areas for water and total lipid were calculated from short-TE single-voxel 1H MR spectra using the LCModel analyzing tool. RESULTS: There were consistent water-only patterns in the fractured vertebra suggesting either near complete marrow replacement by malignant tissue or local edematous fluid/hemorrhage within the marrow spaces. However, the adjacent vertebrae showed a wide range of patterns from a dominant lipid signal to the inverse of a pronounced water level. These results far exceed the normal variation expected based on age and sex. CONCLUSION: The results suggest that the adjacent vertebrae may not be an accurate reference, especially in diffusion-weighted imaging (DWI), because of the large difference between the two compartments. Furthermore, in the case of gradient-echo measurements, the in-phase vs. opposed-phase effects are significant.     

中晚期肺癌动脉聚乙烯醇栓塞的疗效分析

目的探讨聚乙烯醇(PVA)颗粒动脉灌注栓塞治疗晚期支气管肺癌的近期疗效。方法对31例中晚期肺癌患者进行选择性支气管或肋间动脉造影,造影确定有富肿瘤血供动脉后行灌注栓塞术,先行将5-FU、阿霉素(THP)、顺铂灌注再用PVA颗粒经导管栓塞患侧供血动脉。结果31例患者中供血动脉以支气管动脉为主者21例,以肋间动脉为主者10例。治疗后临床症状改善率100%,且无严重并发症,有效率为80.6%(25/31)。结论PVA颗粒选择性栓塞治疗中晚期支气管肺癌具有较好的临床疗效,安全性高且并发症较少。     

Brief pressure overload of the left ventricle preconditions rabbit myocardium against infarction

Background

Several nonischemic stimuli have been shown to precondition myocardium. We investigated cardioprotective effects and underlying mechanisms of brief pressure overload of the left ventricle in this study.

Methods

Brief pressure overload of the left ventricle was achieved by two 10-minute partial snaring of the ascending aorta so that systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. Ten minutes after different pretreatments, myocardial infarction was induced by a 60-minute coronary artery occlusion followed by 3-hour reperfusion. Area at risk and myocardial infarct was determined by blue dye injection and triphenyl tetrazolium chloride staining.

Results

The myocardial infarct size, expressed as percentage of area at risk, was significantly reduced in the pressure overload group (15.9% ± 2.9%, p < 0.001, n = 9) as well as in the ischemic preconditioning group (14.9% ± 1.9%, p < 0.001, n = 9) versus the control group (30.0% ± 6.9%, n = 10). Pretreatment with a blocker of stretch-activated ion channels (gadolinium, 40 μmol/kg, intravenous) abolished the protection induced by pressure overload and ischemic preconditioning. Gadolinium itself did not alter the extent of infarct. There was no significant difference in hemodynamics, area at risk, and mortality among all groups of animals.

Conclusions

Brief pressure overload of the left ventricle by partial snaring of the ascending aorta preconditioned rabbit myocardium against infarction. The underlying mechanism might be related to activation of stretch-activated ion channels.     

Prospective Study on Lamivudine-Resistant Hepatitis B in Renal Allograft Recipients

The natural history of lamivudine-resistant hepatitis B virus (HBV) infection in renal transplant recipients (RTx) is unclear, despite its increasing incidence. Twenty-nine HBsAg-positive RTx with rising HBV DNA received lamivudine therapy. The course of lamivudine-resistant HBV infection was studied prospectively. During 68.7 +/- 12.5 months of follow-up, 14 (48.3%) patients developed lamivudine resistance, at 10-35 months (mean 16.9 +/- 7.0). All showed mutant sequences at codons 552 and 528 of the YMDD motif, while 13 patients demonstrated wild-type sequence at codon 555. Lamivudine resistance was unrelated to patient demographics, HBeAg status/sero-conversion, or genotype. Following resistance, HBV DNA and alanine aminotransferase showed an initial increase followed by spontaneous gradual reduction. The subsequent peak HBV DNA was lower (1.26 +/- 1.09 x 10(9) vs. 6.26 +/- 12.23 x 10(9) copies/mL, p = 0.011), while that of alanine aminotransferase was higher (196 +/- 117 vs. 77 +/- 47 imicro/l, p = 0.005), compared with pretreatment levels. Post-resistance hepatitic flare occurred in 11 (78.6%) patients. This was transient in four (36.4%), but became chronic in six (54.5%) patients. Decompensation was noted in one patient during this flare, but all survived. We conclude that drug resistance is prevalent in lamivudine-treated RTx. Despite a lower ensuing peak viremia compared with baseline, hepatitic flare is common. While most patients have spontaneous resolution, a minority may develop potentially fatal decompensation during the preceding exacerbation.     

Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation: a protocol with early elimination of steroids and reduction of tacrolimus dosage.

A prospective evaluation was performed to study the potential benefits of the use of interleukin-2 receptor antibody (IL-2Rab) in the induction therapy with early elimination of steroid and reduction of tacrolimus dosage in liver transplant recipients among whom 94% had chronic hepatitis B infection. Thirty-one liver transplant recipients who underwent right-lobe live donor (n = 19) or cadaveric (n = 12) liver transplantation received IL-2Rab, basiliximab 20 mg intravenously within 6 hours of graft reperfusion and on postoperative day 4 (IL-2ab group). Two doses of steroid injection were given intraoperatively and on postoperative day 1. Postoperative immunosuppression was maintained with oral tacrolimus and mycophenolate mofetil without the use of steroids. The operative outcomes were compared with those of 49 patients who received standard immunosuppressive regimen consisting of tacrolimus and corticosteroid (steroid group). The overall postoperative morbidity and hospital stay were comparable between the 2 groups. There were significantly lower incidences of postoperative new-onset diabetes (0% vs 28%, P =.011), acute cellular rejection (6% vs 27%, P =.038), and cytomegalovirus (CMV) antigenemia (0% vs 18%, P =.011) in the IL-2Rab group compared with the steroid group. The blood cholesterol level at 6 months after transplantation was significantly lower in the IL-2Rab group (median, 4.0 vs 4.4 mmol/L, P =.007). On follow-up, none of the patients in the IL-2Rab group had hepatitis B viral breakthrough or hepatocellular carcinoma (HCC) recurrence, whereas 1 and 3 patients in the steroid group developed these complications, respectively. In conclusion, treatment of liver transplant recipients with IL-2Rab with early withdrawal of steroids and reduction of tacrolimus dosage is associated with lower incidences of postoperative new-onset diabetes, acute cellular rejection, and CMV antigenemia, as well as a lower serum cholesterol level. Further studies and long-term follow-up are required to document their potential benefits on hepatitis B and HCC recurrences.     

大脑前动脉近端动脉瘤的显微外科治疗

目的探讨大脑前动脉近端动脉瘤(A1动脉瘤)的临床特征及外科手术技巧。方法1995年6月～2003年12月间共治疗颅内动脉瘤患者362例,其中A1动脉瘤占2．2％(8例),对A1动脉瘤患者的临床资料进行回顾性分析。结果所有动脉瘤均位于A1穿动脉的起始部,起源于内侧远端纹状体动脉的3例,内侧近端纹状体动脉的5例。术中发现后方指向的6例,下方指向的2例。8个动脉瘤均为囊性动脉瘤,其中6例为小动脉瘤,平均直径6．9mm。全组动脉瘤经手术夹闭,患者预后优7例,良1例。结论手术治疗A1动脉瘤保护A1穿动脉和选用合适的瘤夹是预防缺血性并发症的关键。