血小板衍生生长因子在肺癌中的意义

目的 探讨血小板衍生生长因子(PDGF)在非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)中的表达及意义。方法 采用免疫组织化学法观察了PDGF—A链、PDGF—B链在NSCLC和SCLC中的表达。结果 PDGF—B链的过表达在NSCLC显著增高，PDGF—A链的过表达在两组间无显著性差异。结论 PDGF—A链和PDGF—B链的生物学特征可能有所不同，相比而言，肿瘤微血管的增生与PDGF—B链的关系可能更密切。     

Modulatory effect of pineapple peel extract on lipid peroxidation,catalase activity and hepatic biomarker levels in blood plasma of alcohol-induced oxidative stressed rats

Objective

To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation, changes in catalase activities and hepatic biochemical marker levels in blood plasma.

Methods

Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3 000 rpm for 10 min. The plasma was analyzed to evaluate malondialdehyde (MDA), catalase activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations.

Results

Administration of alcohol caused a drastic increase (87.74%) in MDA level compared with the control. Pineapple peel extract significantly reduced the MDA level by 60.16% at 2.5 mL/kg bw. Rats fed alcohol only had the highest catalase activity, treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity. Increased AST, ALP and ALT activities were observed in rats fed alcohol only respectively, treatment with pineapple peel extract drastically reduced their activities.

Conclusions

The positive modulation of lipid peroxidation, catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcohol-induced oxidative stress is an indication of its protective ability in the management of alcohol-induced toxicity.     

Impairment of both nitric oxide-mediated and EDHF-type relaxation in small mesenteric arteries from rats with streptozotocin-induced diabetes

BACKGROUND AND PURPOSE

To investigate whether diabetes affects either or both nitric oxide (NO)-mediated and endothelium-derived hyperpolarizing factor (EDHF)-type relaxation in endothelium-dependent relaxation of mesenteric arteries from streptozotocin-induced diabetic rats.

EXPERIMENTAL APPROACH

Wire myography was employed to examine endothelial function of mesenteric arteries. Superoxide levels were measured by L-012 and lucigenin-enhanced chemiluminescence. Western blotting was used to quantify protein expression levels.

KEY RESULTS

Superoxide levels were significantly increased in diabetic mesenteric arteries compared with normal arteries. Diabetes significantly reduced the sensitivity to the endothelium-dependent relaxant, acetylcholine (ACh) in mesenteric arteries. When the contribution of NO to relaxation was abolished by N-nitro-L-arginine (L-NNA) + a soluble guanylate cyclase inhibitor (ODQ), the sensitivity to ACh was significantly decreased in the diabetic arteries compared with normal arteries, indicating an impaired EDHF-type relaxation despite increased expression of intermediate- and small-conductance calcium-activated potassium channels. Conversely, when the contribution of EDHF was inhibited with TRAM-34 + apamin + iberiotoxin, maximum relaxations to ACh were significantly decreased in diabetic compared with normal arteries, suggesting that the contribution of NO was also impaired by diabetes. Basal levels of NO release, indicated by contraction to L-NNA, were also significantly decreased in diabetic arteries. Western blot analysis demonstrated that diabetic arteries had an increased expression of Nox2, decreased pSer⁴⁷³Akt and a reduced proportion of endothelial NO synthase (eNOS) expressed as a dimer, indicating uncoupling.

CONCLUSION AND IMPLICATIONS

The contribution of both NO and EDHF-type relaxations was impaired in diabetes and was caused by increased oxidative stress, decreased pSer⁴⁷³Akt and/or eNOS uncoupling.     

Prospective randomised controlled trial of transobturator tapes in management of urodynamic stress incontinence in women: 3-year outcomes from the evaluation of transobturator tapes study

Background

There is a lack of information on the long-term outcomes of transobturator tension-free vaginal tape (TO-TVT) in the surgical treatment of female stress urinary incontinence (SUI).

Objectives

To assess the 3-yr outcomes following TO-TVT and to compare the effectiveness of inside-out versus outside-in approaches.

Design, setting, and participants

A 3-yr follow-up study of the Evaluation of Transobturator Tapes (E-TOT) trial, a randomised controlled trial (RCT) conducted with women undergoing TO-TVT as a sole procedure between April 2005 and April 2007 in a tertiary urogynaecology centre in the United Kingdom.

Intervention

Patients (n = 341) were randomised to undergo either TVT-O (Ethicon Inc., Somerville, NJ, USA) for the inside-out approach or TOT-Aris (Coloplast Corp., Minneapolis, MN, USA) for the outside-in approach.

Outcome measurements and statistical analysis

The primary outcome was patient-reported success rate. Secondary outcomes included further treatment for SUI, improvement in quality of life, late complications, and risk factors for late failures. Categorical variables were compared using the chi-square or Fisher exact test. Within-group comparison was undertaken using Wilcoxon and Mann-Whitney tests. Risk factors for late failures were assessed in a multivariate regression model. All statistical analysis was performed using SPSS v.18.0 (IBM Corp., Armonk, NY, USA).

Results and limitations

The 3-yr follow-up was completed by 238 of the 341 women (70%). The overall success rate, based on Patient's Global Impression of Improvement response, was 73.1%, with no significant difference between the inside-out and the outside-in TO-TVT (73.18% vs 72.3%; odds ratio: 0.927; 95% confidence interval, 0.552–1.645; p = 0.796). Compared with the 1-yr follow-up, there was a significant reduction in the patient-reported success rate (p = 0.005); however, no independent risk factors were identified. A clinically significant improvement (≥10 points) was seen in 80% (n = 191) of women, with no significant difference between both groups (p = 0.113). Twenty-two women (6%) underwent further surgical treatment within 3 yr. The lack of an objective outcome assessment is a potential limitation of this RCT.

Conclusions

The E-TOT RCT showed a 73% patient-reported success rate for TO-TVT at 3-yr follow-up, with no significant differences between inside-out and outside-in approaches. There was a significant drop in patient-reported success rates between 1 and 3 yr.     

Preoperative determinants for failure of transobturator tapes in the management of female urodynamic stress incontinence

Objectives

To determine significant preoperative risk factors for failure of transobturator tapes.

Methods

Secondary analysis of data from the E-TOT (Evaluation of Transobturator Tapes) study. Patient-reported outcomes (n = 310) and objective outcomes (n = 297) were analyzed using univariate and multivariate analyses.

Results

On univariate analysis, body mass index (BMI) ≥  35, maximum urethral closure pressure (MUCP) ≤ 30 cm H₂O, preoperative mixed incontinence on urodynamics, history of at least one previous incontinence procedure, and preoperative symptoms of urgency, nocturia, or urgency incontinence were associated with failure. On multivariate regression, BMI ≥ 35 (OR 6.37; 95% CI, 1.73-23.44; P = 0.005), nocturia (OR 2.18; 95% CI, 1.04-4.58; P = 0.039), urgency incontinence (OR 3.35; 95% CI, 1.07-10.51; P = 0.039), and previous incontinence surgery (OR 2.33; 95%CI, 1.1-5.48; P = 0.048) were independently associated with patient-reported failure. MUCP ≤ 30 cm H₂O (OR 7.06; 95% CI, 2.85-17.48; P < 0.001) and previous incontinence procedure (OR 6.22; 95%CI, 2.34-16.52; P < 0.001) were independently associated with objective failure.

Conclusion

History of previous incontinence surgery was the only independent risk factor for failure of transobturator tapes based on both the patient-reported and objective outcome.     

A community-based long-term follow up of women undergoing obstetric fistula repair in rural Ethiopia

Objectives  To assess urinary and reproductive health and quality of life following surgical repair of obstetric fistula.
Design  Follow-up study.
Setting  A newly established fistula clinic (2004) at Gimbie Adventist Hospital, a 71-bedded district general hospital in West Wollega Zone, in rural Western Ethiopia.
Population  Thirty-eight women (86%) of 44 who had undergone fistula repair were identified in their community.
Methods  Community-based structured interviews 14–28 months following fistula repair, using a customised questionnaire addressing urinary health, reproductive health and quality of life.
Main outcome measures  Urinary health at follow up was assessed as completely dry, stress or urge incontinence, or fistula. King's Health Questionnaire was modified and used for the quality-of-life assessment.
Results  At follow up, 21 women (57%) were completely dry, 13 (35%) suffered from stress or urge incontinence and three (8%) had a persistent fistula. Surgery improved quality of life and facilitated social reintegration to a level comparable to that experienced before fistula development for both women who were dry and those with residual incontinence ( P  =   0.001). For women still suffering from fistula no change was seen ( P  =   0.1). Four women became pregnant following their surgery, among which there was one maternal death, three stillbirths and one re-occurrence of fistula.
Conclusion  Community-based, long-term follow up after fistula repair succeeded in Western rural Ethiopia. Despite one-third still suffering stress or urge incontinence, the women reported improved quality of life and social reintegration after fistula closure.     

Combined hepatocellular-cholangiocarcinoma: A clinicopathological study

Combined hepatocellular-cholangiocarcinoma (HCC-CC) is an uncommon form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. We reviewed 21 cases of this tumour diagnosed between 1972 and 1996 (patient age range 16–79 years; mean patient age 49.7 years; 18 male and three female patients). Histologically, the majority (n= 18) of tumours were ‘mixed’ tumours, in which areas of hepatocellular and biliary epithelial differentiation were intimately mixed within the same tumours. Two patients had separate tumours in which discrete nodules of HCC and CC occurred in the same livers. One patient had a ‘fibrolamellar’ tumour that histologically simulated the fibrolamellar variant of HCC, but some of the tumour cells were mucin-producing cells. Of the 21 cases, mucin was demonstrable in 16 and, in the few mucin-negative tumours, electron microscopic studies confirmed the presence of the dual differentiation. The tumours frequently exhibited an invasive character with frequent venous permeation, direct invasion into adjacent liver parenchyma and tumour microsatellite formation, similar to that of ordinary HCC. Histological evidence of cirrhosis or chronic hepatitis was present in 77.8% of patients and 75% of patients were hepatitis B surface antigen positive. Raised serum α-fetoprotein (AFP) levels (above 300 ng/mL) were present in 61.5% of patients and AFP was detected immunohistochemically in 55% of tumours. The overall survival times of patients with HCC-CC were short. In conclusion, HCC-CC showed clinical and pathological features more akin to those of ordinary HCC than to CC.