192Ir low dose rate brachytherapy for boosting locally advanced prostate cancers after external beam radiotherapy: a phase II trial.

BACKGROUND AND PURPOSE: To evaluate on 201 locally advanced prostatic cancers prospectively treated in a phase II trial, the efficacy of a combination of external beam radiotherapy (39.6 Gy) and (192)Ir low dose rate brachytherapy (Bt) (40-45 Gy). PATIENTS AND METHODS: Sixty-four patients were included in the intermediate prognosis group with only one of the following adverse factors (PSA > 10 ng/ml, Gleason score > or = 7 or clinical stage > or =T2b) and 137 in the unfavourable group when at least two of these factors were present. RESULTS: The actuarial 4 years biochemical no evidence of disease is 82.8% for the entire population. It is, respectively, 97 and 76% in the intermediate and unfavourable prognosis groups (P < 0.0001). Grade > or =3 late urinary complications occurred in 13 patients (6.5%). Eight patients (4%) presented late grade 2 rectal complications but no grades 3-5 was observed. CONCLUSIONS: Even if an alpha/beta of 1.5-3 Gy theoretically favours the use of a high dose rate mode of irradiation, the early results presented here are as good as those reported for similar groups of patients with high dose rate treatments. Late toxicity is identical but our urinary toxicity is within the less favourable and rectal toxicity within the most favourable results. We can postulate that while inducing very high hyperdosage regions (V150) mainly focused on the peripheral zone, most of the Bt techniques consist of a more ablative treatment. Many of the radiobiological studies on Bt did not in fact take into account the heterogeneity of irradiation inside the CTV. This study highlights the need to explore pulsed dose rate therapies, permanent implant and new available radioisotopes such as (169)Ytterbium that will offer the safety of low and lower dose rates. The actual late toxicity of the different Bt techniques is not yet inexistent indeed.     

细胞间黏附分子-1在实验性自身免疫性脑脊髓炎大鼠中表达的动态变化及作用

目的探讨细胞间黏附分子-1(ICAM-1)在实验性自身免疫性脑脊髓炎(EAE)大鼠中表达的动态变化及其作用。方法分别取免疫后第4、6、8、10、12、14、16、18、20天EAE大鼠脑和脊髓制成石蜡切片,行HE染色和ICAM-1半定量免疫组化分析。结果免疫后第8天ICAM-1表达即出现明显上调,早于临床症状的发生;随免疫后时间的延长,ICAM-1表达呈逐渐增高后缓慢下降的变化趋势,并且与EAE大鼠病情评分呈显著正相关(r=0.57,P=0.003)。结论ICAM-1的表达上调可能在EAE发病中具重要作用。     

Anxiety in medically III patients

Anxiety disorders and anxiety symptoms are highly prevalent in the general population and more so in the medically ill. They have a number of negative consequences for these patients and may worsen the outcome of the medical illness and increase health care utilization. In the evaluation of these patients, it is of paramount importance to identify the etiology of the anxiety and, in particular, to differentiate primary from secondary anxiety. Management includes medications (especially benzodiazepines and selective serotonin reuptake inhibitors) and psychotherapy (particularly cognitive-behavioral therapy).     

Sources of Variability in the Detection of Cerebral Emboli with Transcranial Doppler During Cardiac Surgery

OBJECTIVE: The application of intensity thresholds for embolus detection with transcranial Doppler (TCD) can exclude from analysis an unrecognized proportion of high-intensity transient signals (HITS))whose intensities are below the threshold. The lack of consistent threshold criteria between clinical trials may explain part of the discrepancy in the reported HITS counts. We investigated the effect of choosing different thresholds on the sensitivity and specificity of detecting HITS during cardiopulmonary bypass (CPB). METHODS: Two observers independently analyzed TCD recordings from 8 patients under CPB. Doppler signals were classified as true HITS, equivocal HITS, artifacts, and Doppler speckles according to preestablished criteria. The relative intensity of Doppler signals was measured by two different methods (TCD software vs manual). Receiver Operating Characteristic curves determined the optimal threshold for each of the two intensity methods. RESULTS: Reviewers achieved agreement in 96% of 2190 Doppler signals (kappa = 0.90). Relative intensities calculated with the TCD-software method were 3 dB (95% CI: 3.0-3.4) higher than the manual method. The optimal threshold was found at 10 dB (sensitivity: 99%; specificity: 90.8%) with the software method and at 7 dB with the manual method (sensitivity: 96%; specificity: 83%). The use of an intensity threshold 2 dB higher than the optimal increased the rejection of true HITS by 8% and 14%, respectively. CONCLUSIONS: Using intensity thresholds higher than the optimal for embolus detection decreases HITS counts. Choosing a threshold depends on the type of method used for measuring the signal intensity. Uniform threshold criteria and comparative studies between different Doppler devices are necessary for making clinical trials more comparable.     

Gamma-hydroxybutyric Acid Tolerance and Withdrawal in a Rat Model

Long-term daily use of gamma-hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors' knowledge, there are currently no animal models of GHB withdrawal. OBJECTIVES: The authors studied and described the effect of chronic dosing of GHB (3-6 days) on tolerance and withdrawal in a rat model. METHODS: Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1-8, 0.75 g/kg for doses 9-12, 1 g/kg for doses 13-16, 1.25 g/kg for doses 17-24, 1.5 g/kg for doses 25-32, 1.75 g/kg for doses 33-40, and 2 g/kg for doses 41-48. Following the last dose of GHB, the rats were scored using a 16-point ethanol intoxication-withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. RESULTS: Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. WITHDRAWAL: The scores for all rats dosed with GHB increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p < 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No rats developed seizures. CONCLUSIONS: Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3-6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal.     

丹参对持续癫痫幼鼠脑损伤保护作用的实验研究

目的 探讨丹参对持续癫痫发作诱发幼鼠脑神经元损伤是否具有保护作用。方法 皮下及腹腔注射贝美格针诱发健康幼龄鼠癫痫持续状态发作。光镜下观察神经元病变情况；电镜观察海马神经元超微结构的改变。结果 持续癫痴组幼鼠脑组织光镜下可见明显的神经元病变。电镜下可见海马区神经元的超微结构病变。丹参治疗组神经元病变均轻于持续癫痴组；而正常对照组未见类似病变。结论 丹参在组织、细胞和亚细胞水平对持续癫病幼鼠脑神经元损伤具有一定的保护作用，为临床有效防治小儿惊厥性脑损伤提供了可靠的实验依据。     

MR T2加权成像显示胆囊壁增厚点状高信号的意义

目的研究病理组织学证实的胆囊腺肌瘤病、慢性胆囊炎和管壁增厚型胆囊腺癌在MRL加权成像（T2WI）显示病变胆囊壁点状高信号的特征。方法38例患者（胆囊腺肌瘤病16例，慢性胆囊炎13例，管壁增厚型胆囊腺癌9例），每例均进行了MR常规T1WI、常规T2WI和3mm薄层T2WI及MR胰胆管成像（MRCP）。所有患者均接受了胆囊切除手术。2名高年资放射科医生共同分析不同序列MRI，观察胆囊壁增厚及T2WI显示病变胆囊壁点状高信号的不同表现，将观察结果与病理组织学检查所见对照。结果所有患者的胆囊壁均明显增厚，厚度范围5～15mm，平均9mm。T2WI显示病变胆囊壁存在各种各样的点状高信号，在胆囊腺肌瘤病，点状高信号分布于整个增厚的胆囊壁，且数量较多（5～15个／cm^2），较大（直径2～7mm），边界清楚，呈现中等至明显高信号；在慢性胆囊炎，点状高信号主要位于增厚胆囊壁的黏膜侧，数量较少（3～5个／cm^2），较小（直径2～4mm），边界清楚，呈中等至明显高信号；在管壁增厚型胆囊腺癌，点状高信号边界欠清，呈现稍高信号，其数量和大小差异较大，分布范围取决于癌组织浸润胆囊壁的深度。结论胆囊腺肌瘤病、慢性胆囊炎和管壁增厚型胆囊腺癌在T2WI呈现的点状高信号有一定差别，正确识别这些点状高信号的特征有助于鉴别诊断良恶性胆囊壁增厚。     

The molecular and clinical impact of hepatocyte growth factor, its receptor, activators, and inhibitors in wound healing

Wound healing involves a number of cellular and molecular events, many of which are controlled by soluble growth factors. In the process of healing, hepatocyte growth factor, a cytokine known to act as mitogen, motogen, and morphogen, has been postulated to play multiple roles during several stages of this complex biological process. Produced primarily by stromal fibroblasts, hepatocyte growth factor regulates angiogenesis, vascular permeability, cell migration, matrix deposition and degradation, and other biological processes. The current article discusses recent progress in understanding the multiple roles played by this growth factor in tissue repair.     

Use of an in vitro model of tissue-engineered human skin to study keratinocyte attachment and migration in the process of reepithelialization

To produce a stable epidermis, keratinocytes need to be firmly attached to the basement membrane. However, following wounding, keratinocytes are required to develop a migratory phenotype in order to reepithelialize the wound. To investigate some of the issues underlying reepithelialization, we have developed a three-dimensional in vitro model of tissue-engineered skin, comprising sterilized human dermis seeded with human keratinocytes and dermal fibroblasts. Using this model, we have shown that the inclusion of fibroblasts within the model increases the stability of keratinocyte attachment. We have also demonstrated that keratinocyte migration occurs most effectively in the absence of a basement membrane and following the inclusion of fibroblasts in the model. In addition, subjecting the keratinocyte layer to mechanical trauma induces a migratory phenotype. We conclude that this three-dimensional in vitro wound model can be used to increase our understanding of the factors that enhance keratinocyte migration and hence wound healing in vivo.