心血管危险因素对高血压患者心血管危险分层的影响

目的评估心血管危险因素对高血压患者心血管危险分层的影响。方法据中国高血压防治指南（基层板）对于高血压患者,按血压水平和总心血管危险因素进行危险分层,观察总心血管危险因素对高血压患者危险分层的影响。结果如果忽视危险因素的影响,中低危患者占52．5％,高危占29．7％。加上对危险因素的评估,低危及中危的患者明显减少,而高危（包括极高危）患者明显增加,比较差异有极显著性（户〈0．01）。影响心血管危险分层的危险因素中,比例最大的为血脂异常,在高危险组中占到40％,其次为早发心血管病家族史及吸烟史,分别占到24％和22％,然后是血糖异常和腹型肥胖,占18％和16％。结论心血管危险因素对高血压患者总心血管危险分层有着决定性的影响,治疗策略应根据初始危险分层进行。     

Steady‐state amprenavir and tenofovir pharmacokinetics after coadministration of unboosted or ritonavir‐boosted fosamprenavir with tenofovir disoproxil fumarate in healthy volunteers

Objective

An open‐label, three‐period pharmacokinetic study was conducted to investigate the drug interaction potential between fosamprenavir (FPV) and tenofovir disoproxil fumarate (TDF).

Methods

Thirty‐six healthy subjects received TDF 300 mg once daily (qd) for 7 days (period 1), and then were randomized to 14 days of either FPV 1400 mg twice daily (bid) or FPV/ritonavir (RTV) 700/100 mg bid alone or with TDF (period 2). Subjects continued their randomized dose of FPV for 14 more days, adding or removing TDF based upon its receipt in period 2 (period 3). Twenty‐four‐hour pharmacokinetic sampling was carried out on day 7 of period 1 and on day 14 of periods 2 and 3. Steady‐state plasma amprenavir (APV) and tenofovir (TFV) pharmacokinetics were assessed by noncompartmental analysis and parameter values observed with each regimen were compared using geometric mean ratios with 90% confidence intervals.

Results

After TDF coadministration, APV geometric mean minimum concentration (C_min), maximum concentration (C_max), and area under the plasma concentration–time curve (AUC) increased by 31, 3 and 7% above values observed with unboosted FPV alone; they also increased by 31, 4 and 16% above values observed with FPV/RTV alone. TFV C_min, C_max and AUC decreased by 12, 25 and 15% after FPV coadministration and by 9, 18 and 7% after FPV/RTV coadministration. No significant changes in RTV pharmacokinetics were observed. No differences were noted in adverse events among dosing periods.

Conclusions

In this evaluation of the interaction between FPV and TDF, increases in APV exposures and modest decreases in TFV exposures were observed. These were unlikely to be clinically significant.

     

阴茎折断4例报告并文献复习

目的：报告4例阴茎折断,并对其诊断、治疗和预后进行文献复习,以提高对阴茎折断的认识水平。方法：回顾性分析4例阴茎折断患者的临床资料,结合国内、外文献对其病理、临床表现、诊断、治疗和预后进行探讨。其中3例通过临床表现确诊,1例通过超声波检查确诊。4例均急诊行阴茎血肿清除加白膜修补术。结果：术后随访2—120月,平均81个月,阴茎外观正常,性生活满意,无阴茎弯曲、痛性勃起、尿道狭窄等并发症。结论：阴茎折断临床罕见,粗暴性交为其主要病因,多伴有典型病史,急诊手术效果佳,并发症低,为阴茎折断的最佳治疗方法。     

Dendritic cell generation and CD4+CD25HIGHFOXP3+ regulatory T cells in human head and neck carcinoma during Radio-chemotherapy

Background

Regulatory T cells (Treg) and dendritic cells (DC) play an important role in tumor immunity and immune escape. However, their interplay and the effects of anti-cancer therapy on the human immune system are largely unknown.

Methods

For DC generation, CD14⁺ monocytes were enriched by immunomagnetic selection from peripheral blood of advanced head and neck squamous cell carcinoma (HNSCC) patients and differentiated into immature DC using GM-SCF and IL-4. DC maturation was induced by addition of TNFα. The frequency of CD4⁺CD25^highF0XP3⁺ Treg in HNSCC patients was analyzed before and after radio-chemotherapy (RCT) by four-color flow cytometry.

Results

In HNSCC patients, the frequency of Treg (0.33 ± 0.06%) was significantly (p = 0.001) increased compared to healthy controls (0.11 ± 0.02%), whereas RCT had variable effects on the Treg frequency inducing its increase in some patients and decrease in others. After six days in culture, monocytes of all patients had differentiated into immature DC. However, DC maturation indicated by CD83 up-regulation (70.7 ± 5.5%) was successful only in a subgroup of patients and correlated well with lower frequencies of peripheral blood Treg in those patients.

Conclusion

The frequency of regulatory T cells is elevated in HNSCC patients and may be modulated by RCT. Monocyte-derived DC in HNSCC patients show a maturation deficiency ex vivo. Those preliminary data may have an impact on multimodality clinical trials integrating cellular immune modulation in patients with advanced HNSCC.     

PARP inhibition in atherosclerosis and its effects on dendritic cells,T cells and auto-antibody levels

Objective

Atherosclerosis is a chronic inflammatory process. Poly(ADP-ribose) polymerase-1 (PARP), a nuclear enzyme linked to DNA repair, has been shown to be involved in atherogenesis; however, the effects on dendritic cells, T cells and serum auto-antibody levels are not fully understood.

Methods

Male Apoe^-/- mice on a western diet were treated with the PARP inhibitor 1NO-1001 (n = 15), while the control group (n = 15) received 5% glucose solution for 10 weeks.

Results

Inhibition of PARP markedly reduced atherosclerotic lesion development (p = 0.001). Immunohistochemistry and mRNA analysis revealed a reduced inflammatory compound inside the lesion. Focusing on dendritic cells, INO-1001 reduced number of cells (p = 0.04), grade of activation, represented by I/12 (p = 0.04) and Cd83 (p = 0.03), and grade of attraction, represented by Mip3α (p = 0.02) in the plaque. Furthermore, INO-1001 decreased number of T lymphocyte (p = 0.003) in the lesion and grade of activation after stimulation with oxLDL in vitro. Moreover, serum IgM antibody levels to oxLDL were significantly lower in INO-1001 treated mice (p = 0.03).

Conclusions

Functional blockade of PARP by INO-1001 reduces atherosclerotic lesion development. The anti-atherogenic effect is beside already known mechanisms also moderated due to modulation of DC and T cell invasion and activation, DC attraction as well as IgM antibody levels to oxLDL.     

神经内镜辅助眶上锁孔入路早期夹闭前交通动脉瘤

目的 探讨应用神经内镜辅助眶上锁孔入路早期手术夹闭前交通动脉瘤的疗效.方法中南大学湘雅医学院附属海口医院神经外科自2002年1月至2010年1月采用神经内镜辅助眶上锁孔入路在出血早期(72 h内)手术治疗前交通动脉瘤(Hunt-Hess分级1～3级)患者35例,回顾性分析患者的临床资料和疗效.结果 35例患者均顺利完成动脉瘤夹闭.2例患者术中动脉瘤破裂,经临时阻断载瘤动脉快速解剖瘤颈后夹闭;患者均无入路相关的严重并发症;术后复查DSA或CTA证实动脉瘤夹闭完全,载瘤动脉无狭窄,远端动脉通畅良好.术后3个月复诊时,30例(85.7%)患者恢复良好(GOS评分4～5分),所有患者切口美容效果良好.结论 出血早期(72 h内)经神经内镜辅助眶上锁孔入路手术处理Hunt-Hess分级Ⅰ～Ⅲ级前交通动脉瘤患者安全、有效.

Abstract：

Objective To evaluate the effectiveness of the endoscope-assisted supraorbital keyhole approach in the early surgical treatment of patients with ruptured anterior communicating artery aneurysms (AcoA). Methods Thirty-five patients with ruptured AcoA, admitted to our hospital from January 2002 to January 2010, adopted clipping via endoscope-assisted supraorbital keyhole approach within 72 h of onset. The neurostatus of these patients were ranged from grade 1 to 3 (Hunt-Hiss Scale scores). The surgical details were described, and the clinical results were assessed according to the scores of Glasgow Outcome Scale.Results Operations were successfully finished in all patients; the endoscope-assisted supraorbital keyhole approach offered sufficient exposure of neurovascular structures for clipping AcoA. Intraoperative accidental aneurysm rupture occurred in 2 patients, but these events were managed successfully by blocking-up the parent artery and performing quick aneurysm neck dissection; no serious complications caused by the surgical approach occurred; postoperative DSA or CTA indicated that the aneurysm was totally clipped and the parent artery appeared no stenosis, and distal artery was unobstructed. Three months after the operation, 30 patients (85.7%) achieved very good outcomes (GOS:4-5 scores). All the patients achieved good cosmetic results. Conclusion In selected AcoA patients with grade 1-3, the endoscope-assisted supraorbital keyhole approach is safe and effective for gaining access to and treating the aneurysms on early hemorrhage stage.     

Trafficking and signalling of gonadotrophin-releasing hormone receptors: an automated imaging approach

Gonadotrophin-releasing hormone (GnRH) is a neuropeptide that mediates central control of reproduction by stimulating gonadotrophin secretion from the pituitary. It acts via 7 transmembrane region (7TM) receptors that lack C-terminal tails, regions that for many 7TM receptors, are necessary for agonist-induced phosphorylation and arrestin binding as well as arrestin-dependent desensitization, internalization and signalling. Recent work has revealed that human GnRH receptors (GnRHR) are poorly expressed at the cell surface. This apparently reflects inefficient exit from the endoplasmic reticulum, which is thought to be increased by pharmacological chaperones (non-peptide GnRHR antagonists that increase cell surface GnRHR expression) or reduced by point mutations that further impair GnRHR trafficking and thereby cause infertility. Here, we review recent work in this field, with emphasis on the use of semi-automated imaging to interrogate compartmentalization and trafficking of these unique 7TM receptors.This article is part of a themed section on Imaging in Pharmacology. To view the editorial for this themed section visit http://dx.doi.org/10.1111/j.1476-5381.2010.00685.x     

True T-cell chronic lymphocytic leukemia: a morphologic and immunophenotypic study of 25 cases [see comments]

We studied 25 T-cell chronic lymphocytic leukemia (T-CLL) cases collected over a 15-year period. Immunophenotypic analysis was performed in each case; 12 cases were evaluated by cytogenetics, and gene rearrangement studies were performed in 14 cases. The median age was 57 years with a male predominance (M:F, 15:10). The median presenting lymphocyte count was 36.3 x 10(9)/L (range, 3.9 to 438 x 10(9)/L). Fourteen patients (56%) had shotty adenopathy and ten (40%) had mild-to-moderate splenomegaly at presentation; four (16%) had erythematous skin lesions. The lymphocytes were predominantly small; some cases had a minor component of medium-sized cells (< 10%). The nuclear: cytoplasmic ratios were uniformly high with round to oval nuclei; however, a wide spectrum of nuclear outlines could be found, ranging from minimally to markedly convoluted. Nucleoli were either absent or small and inconspicuous. These lymphocytes did not have the morphology of prolymphocytes and did not contain cytoplasmic granules. Bone marrow infiltration was generally in an interstitial pattern; the degree of involvement ranged from 15% to 90%. Immunophenotyping showed that the lymphocytes were mature T-cells with a predominant CD4+ immunophenotype. Three cases displayed a CD8+ immunophenotype. The patients were treated with a variety of chemotherapeutic regimens with only a minimal response observed in two of 20 patients. We conclude that T-CLL is an uncommon chronic lymphoproliferative disorder (CLPD) that can be morphologically similar to B-CLL, is distinct from T- prolymphocytic leukemia, and has an aggressive clinical course that is refractory to therapy. It may also be difficult to distinguish T-CLL from other T-CLPD, especially the leukemic phase of peripheral T-cell lymphoma and some cases of Sezary syndrome.     

Effects of normal mouse serum on the IL-3-induced proliferation of bone marrow cells

Normal mouse serum (NMS) devoid of colony-stimulating factor (CSF) was found to enhance the interleukin 3 (IL-3)-driven colony formation of bone marrow in vitro. Inclusion of NMS in bone marrow colony-forming assays resulted in greatly increased numbers of colonies and clusters following seven days incubation; however, incubation of bone marrow with NMS before the colony-forming assay had no effect on resultant colony number. The levels of serum-enhancing activity (SEA) did not appear to vary significantly with age and in part was species restricted, in that human and guinea pig serum did not enhance mouse bone marrow colony formation. Conversely, NMS had no effect on human bone marrow colony formation. Levels of SEA were found to vary between strains, as did the degree to which bone marrow from various strains was enhanced by the serum. Serum fractionation studies indicated three active fractions with molecular weights of 800-900 Kd, 60-70 Kd, and 20- 30 Kd. The fraction at 800-900 Kd inhibited colony formation at high concentrations and enhanced colony formation on dilution, whereas the two other active fractions contained enhancing activity at all concentrations tested. These results would indicate that normal serum can play a greater role in colony-forming assays than nutritional supplements. The relationship of the SEA factors to other factors that have been reported to modulate bone marrow colony formation is discussed.