Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial

BACKGROUND: The concentration of osteopontin (SPP1) in plasma is associated with tumour hypoxia. The DAHANCA 5 trial found that the hypoxia radiosensitiser nimorazole significantly improved the outcome of radiotherapy for patients with head and neck cancer compared with placebo. However, whether all patients benefit from such modification of hypoxia is unclear. We aimed to assess whether the concentration of plasma osteopontin could predict response to the hypoxia radiosensitiser. METHODS: Plasma concentrations of osteopontin were measured by use of ELISA from stored samples of 320 patients randomised in the DAHANCA 5 trial. Samples were grouped into tertiles according to high (167-1382 microg/L), intermediate (69-166 microg/L), or low (0-68 microg/L) concentrations of plasma osteopontin, and analysed for locoregional tumour control and disease-specific survival at 5 years. FINDINGS: Overall, locoregional tumour failure and disease-specific mortality were more frequent in patients assigned placebo than in those assigned nimorazole (relative risk [RR] 0.51 [95% CI 0.32-0.79] and 0.54 [0.35-0.85], respectively). Locoregional tumour failure was more frequent in patients with high concentrations of osteopontin assigned placebo than in those with high concentrations assigned nimorazole (0.19 [0.08-0.44]), as was disease-specific mortality (0.25 [0.11-0.59]). However, neither locoregional tumour failure nor disease-specific mortality differed between groups for patients with low concentrations of plasma osteopontin (0.79 [0.26-1.70]) and (0.69 [0.31-1.51]) or for those with intermediate concentrations (0.90 [0.41-1.98] and 0.89 [0.41-1.96], respectively). INTERPRETATION: High plasma concentrations of osteopontin are associated with a poor outlook after radiotherapy for patients with head and neck cancer, but can be improved by use of nimorazole. High concentrations of osteopontin can predict clinically relevant hypoxia, and might identify patients who will benefit from modification of hypoxia during radiotherapy.     

Capsular flap for correction of contour deformities of the breast

We describe a technique in which the breast implant capsule is used to fill localized depressions in the breast, including those under the nipple-areola complex. Capsules have been reported to persist long-term and their high vascularity renders them suitable for use as flaps.     

Early nasal continuous positive airway pressure in a cohort of the smallest infants in Denmark: neurodevelopmental outcome at five years of age

AIM: To evaluate neurodevelopmental outcome at age 5 y of age in a cohort of preterm children treated mainly with nasal continuous positive airway pressure (CPAP) in the neonatal period. METHODS: A national prospective observational study was conducted in Denmark which included all 269 surviving children with a birthweight below 1000 g or a gestational age below 28 wk born in Denmark in between 1994 and 1995. A total of 164 children (61%) had been treated with nasal CPAP only in the neonatal period. A reference group (n = 76) of term children was studied in parallel. RESULTS: Of the 269 surviving children, 252 (94%) were examined. Twenty-four children (10%) had cerebral palsy, and three children were blind. No case of hearing impairment was detected. Nineteen percent of the index children had an IQ score <-- 2 SD and 42% had an IQ score <-- 1 SD of the mean score of the reference group. CONCLUSIONS: The intellectual development of children in this cohort treated with early nasal CPAP did not suggest a higher proportion of adverse effects on the brain compared to the published follow-up studies of preterm children treated with mechanical ventilation. In our population-based cohort, however, the survival rate for infants below 25 wk of gestation was relatively low and this may indicate a limit for the use of early nasal CPAP.     

双链断裂修复蛋白hKu70缺陷细胞株的建立及其生物学特性

目的 建立并鉴定DNA双链断裂(DSB)修复蛋白hKu70缺陷细胞株,并观察该缺陷细胞的某些生物学效应,用于AKu70基因功能及职业有害因素对DNA双链断裂修复影响的研究。方法 用构建的AKu70基因反义RNA绿色荧光蛋白真核表达载体(pEGFP—CI—K)转染人胚肺成纤维细胞(HLF),用蛋白兔疫印迹法鉴定转染细胞中AKu70基因的表达水平。同时观察转染细胞生长形态,绘制生长曲线,软琼脂培养法鉴定恶性程度。结果 pEGFP—CI—K载体在转染细胞内可较稳定表达,hKu70蛋白缺陷细胞株AKu70基因的蛋白表达水平下降了42％,转染后hKu70蛋白缺陷细胞生长形态、生长速度无明显变化,软琼脂培养未见细胞集落。结论 成功建立和鉴定了hKu70蛋白缺陷细胞株,该缺陷不足以单独引起可观察的某些生物学效应。     

Gender differences in severity, symptomatology and distribution of melancholia in major depression

BACKGROUND: Studies of gender differences in the clinical presentation of depression have provided divergent results. This study aimed at analyzing gender differences in severity, symptomatology and distribution of melancholia in major depression. SAMPLING AND METHODS: The study comprised 930 in- and out-patients (652 women, 278 men) from 6 randomized controlled trials. All patients fulfilled DSM-III or DSM-III-R criteria for major depression. The 17-item Hamilton Depression Scale (HDS) was applied to all patients. A multi-axial evaluation was completed using the Newcastle 1 Depression Rating Scale from 1965 for melancholia (N1) in a subsample of patients (n = 439). A factor analysis on the HDS was performed. Non-parametric statistical tests were used and only gender differences greater than 20% were considered clinically relevant. RESULTS: The median on the HDS total score was 22 and the median number of symptoms was 13 for both men and women. Presentation of specific symptoms was similar for men and women. The factor analysis revealed no gender differences, and neither did analyses on symptoms of Axes II and IV. According to the N1, 80% of the men and 66% of the women suffered from melancholic depression (p = 0.004). CONCLUSIONS: In a large and broad sample of in- and out-patients with major depression, the severity and symptomatology of depression were similar for men and women. Melancholic depression was significantly more frequent among male than female patients. Inclusion and exclusion criteria in the randomized controlled trials provided a selected group of patients, which limited the generalisability of the results to an exclusive subgroup of patients treated for depression in routine clinical practice.     

头孢克肟胶囊人体药动学研究及生物等效性评价

目的：研究头孢克肟胶囊在健康人体内的药动学及生物等效性。方法：以18名健康志愿者为试验对象，采用同体交叉试验方法，分别单剂量口服受试制剂或参比制剂各400mg，采用HPLC法测定血浆中药物浓度。结果：参比制剂和受试制剂的tmax分别为（3．39±0．50）和（3．39±0．50）h，cmax分别为（2．33±0．33）和（2．27±0．25）μg／mL，t1／2分别为（3．92±0．85）和（4．41±0．68）h，AUC0～16分别为（14．61±2．67）和（14．82±2．02）μg·h·mL^-1，AUC0～∞分别为（16．00±3．13）和（16．81±2．62）μg·h·mL^-1。结论：受试制剂与参比制剂生物等效，受试制剂的相对生物利用度为（98．69±13．13）％。     

Gain beyond cosmesis: Demonstration of psychosocial and functional gains following successful strabismus surgery using the adult strabismus questionnaire adult strabismus 20

Background:

Strabismus adversely affects psychosocial and functional aspects; while its correction impacts positively.

Aim:

The aim was to evaluate the gains in scores: Overall scores (OASs), psychosocial subscale scores (PSSs) and functional subscale scores (FSSs) following successful surgical alignment.

Settings and Design:

We evaluated changed scores in the adult strabismus 20 (AS-20) questionnaire, administered before and after successful surgery.

Materials and Methods:

Thirty adults horizontal strabismics, were administered the AS-20, at baseline, and at 6-week and 3-month. Group-wise analysis was carried out based on gender, strabismus type (esotropia [ET] or exotropia [XT]), back-ground and amblyopia.

Statistical Analysis:

We used Wilcoxon, and Mann-Whitney U-tests. Significance was set at P ≤ 0.05.

Results:

At baseline, there were no significant differences within the groups, except that those with amblyopia significantly scored less than nonamblyopes in OAS (median scores: 53.8 vs. 71.3; P = 0.009) and FSS (56.3 vs. 85.3; P = 0.009). OAS, PSS and FSS showed significant gains at 6-week and 3-month (all Wilcoxon P < 0.001). Compared with males, females showed significantly more gain at 3-month (OAS: 37.9 vs. 28.7; P = 0.02), on account of PSS gain (49.6 vs. 37.5; P = 0.01). The ET performed better than XT only on the FSS at 6-week (28.7 vs. 15.0; P = 0.02). Vis-à-vis the nonamblyopes, the amblyopes showed significantly more benefit at 6-week alone (OAS: 18.7 vs. 28.7; P = 0.04), largely due to gains in PSS.

Conclusions:

Successful strabismus surgery has demonstrated significant gains in psychosocial, functional and overall functions. There is some evidence that gains may be more in females; with a trend to better outcomes in ET and amblyopes up to 6-week.