The effect of variability of unattended information on global and local processing: evidence for lateralization at early stages of processing

Visual objects can often be analyzed as hierarchical in structure, composed of local elements that are spatially arranged to form a global shape. The brain mechanisms involved in the analysis of hierarchical figures have been under considerable scrutiny in recent years, and one of the many interesting features that have emerged is that there is an asymmetry across the two hemispheres for global (right hemisphere) vs local (left hemisphere) processing. Event-related potentials (ERP) were used to examine selective attention to global or local levels of hierarchical figures to determine the stage of processing at which the asymmetry first emerges. Two conditions were tested, one in which unattended information was variable from trial to trial, and one in which it was not. The variability of unattended information influenced the lateralization of processing. Presentation of invariable, neutral distractors resulted in global/local processing asymmetries at early stages (P1). In contrast, presentation of variable, task-relevant distractors resulted in processing asymmetries that occurred at much later stages (N2). Our hypothesis is that lateralized enhancement of neural populations in extrastriate cortex results from both selective attention to locations in the visual field, as well as selective attention to global or local information. We suggest that unattended information that varies from trial to trial is processed in parallel with attended information, masking hemisphere biases for local vs global information at early stages of processing.     

Holoprosencephaly: recent advances and new insights

Holoprosencephaly is a relatively common brain malformation occurring in 5-12/100,000 live births. The astonishing growth in molecular genetic medicine has provided the field of developmental nervous system malformations with new perspectives and tools for unraveling its mysteries and offering better information for clinicians and families. This is particularly evident in the group of complex midline malformations known as holoprosencephaly. Although new molecular findings have shed light on some of the causes and manifestations of this malformation, there remains a need to build on the existing clinical knowledge so that we may develop more effective treatments and improve the quality of life of these patients.     

Hepatitis and cholestasis in infancy: clinical and nutritional aspects

A major complication of cholestasis is fat malabsorption related to decreased intestinal bile acids, which leads to malnutrition and fat-soluble vitamin deficiency. The impaired excretion of bile acids leads to a low intraluminal micellar concentration that causes long-chain triglyceride lipolysis and absorption to be ineffective. Medium-chain triglycerides (MCTs) are more readily absorbed when there are low concentrations of bile acids and therefore are a good source of fat calories; MCTs can be administered as MCT-containing formulas. In those children who are unable to take sufficient calories by mouth, it is important to start nocturnal enteral feeding to improve nutritional status. In infants with cholestasis, the absorption of fat-soluble vitamins (A, D, E and K) that require bile acids is also impaired, and supplementation is mandatory. Vitamin K deficiency may be responsible for hypoprothrombinaemia, which may lead to bleeding diathesis, Vitamin K (phytomenadione) should therefore be promptly administered intravenously, at a dose of 1 mg. Chronic vitamin E (α-tocopherol) deficiency is associated with a progressive neuromuscular syndrome that can cause cerebellar ataxia, areflexia and peripheral neuropathy. Supplements are given orally in doses of 3–5 times the normal requirement if cholestasis is incomplete. In complete cholestasis, supplements must be given intramuscularly at monthly intervals. In infants who fail to thrive, dietary supplements of carbohydrate polymers and MCTs are required.     

中国健康志愿者单剂静滴甲磺酸加替沙星注射液的药代动力学

目的:研究中国健康成年男性志愿者单剂静滴甲磺酸加替沙星注射液的药代动力学。方法:按药物临床试验管理规范(GCP)指导原则设计试验方案。选择9名受试者分别依次单刘静滴100,200和400mg的甲磺酸加替沙星注射液后,应用HPLC测定血药浓度,采用3P97软件进行数据处理,求出药代动力学参数。结果:受试者分别给药后,药-时曲线符合二房室模型,主要药代动力学参数C_(max)分别为1.10±0.19,2.17±0.33和3.16±0.47mg·L~(-1);t_(1/2)β分别为7.42±1.99,8.41±2.72和8.46±2.83h;AUC_(0-∞)分别为4.45 ±0.71,11.10±1.81和23.03±3.83mg h·L~(-1)。原形药主要经肾排泄,48h尿药累积排泄率分别为(43.08±15.79)％,(51.33±23.69)%和(45.67±18.22)％。结论:9名静滴甲磺酸加替沙星注射液后,药-时曲线符合二房室模型。提示甲磺酸加替沙星在100～400mg剂量内药物体内过程基本呈线性动力学特征而无饱和性,主要排泄途径为肾脏。     

Osteoblast Gene Expression in Rat Long Bones: Effects of Ovariectomy and Dihydrotestosterone on mRNA Levels

The steroid sex hormones exert major effects on bone formation although the molecular events associated with their activity remain unclear. We have investigated the effects of ovariectomy and dihydrotestosterone (DHT) administration to both sham-operated and ovariectomized (ovx) rats on the bone mRNA levels of osteoblast genes. Rats were randomly allocated to either sham or ovariectomy operations and were administered either vehicle or 40 mg/kg body weight DHT by silastic tube implants at the time of operation for 8 weeks, at which time they were killed and total RNA was extracted from the long bones. Northern blot analysis indicated that the mRNA levels of the bone cell genes α1(I) collagen, alkaline phosphatase, osteocalcin, and osteopontin were markedly increased in ovx rats between 6- and 30-fold. DHT administration to ovary-intact, estrogen-sufficient rats increased the mRNA levels of α1(I) collagen, alkaline phosphatase, osteopontin, and osteocalcin between 3- and 9-fold. In contrast, DHT did not alter levels of these mRNA species in ovx rats. The data demonstrate that estrogen deficiency increased mRNA levels of genes expressed during osteoblast development and suggest an interplay between estrogen and androgen action in regulating the expression of a number of bone cell genes. Received: 20 May 1999 / Accepted: 21 January 2000     

Comparison between isotropic and nonisotropic dosimetry systems during intraperitoneal photodynamic therapy

BACKGROUND AND OBJECTIVE: On-line monitoring of light fluence during intraperitoneal photodynamic therapy (IP PDT) is crucial for safe light delivery. A flat photodiode-based dosimetry system is compared with an isotropic detector-based system in patients undergoing IP PDT. STUDY DESIGN/MATERIALS AND METHODS: Flat photodiodes and spherical detectors were placed side by side in the abdomen, for simultaneous light dosimetry in 19 patients. Tissue phantom experiments were performed to provide a preliminary estimate of the tissue optical properties of the peritoneum. RESULTS: The conversion factor between systems for 630-nm light was found to be 1.7 +/- 0.12. The mu(eff) of the tissues in the abdomen is estimated to vary between 0.5 cm(-1) to 1.4 cm(-1) assuming a mu(s)' = 7 cm(-1). CONCLUSIONS: The measured conversion factor should allow for comparison of light fluences with future clinical protocols that use an isotropic-based detector system. Differences in the optical properties of the underlying tissues may contribute to the variability in light measurements.     

Recognition of islet-directed peripheral blood lymphocytes in vitro before rejection of allogeneic grafted islets

A co-culture of splenic lymphocytes with allogeneic pancreatic islets [i.e., mixed lymphocyte islet co-culture (MLIC)] for 96 hr leads to reduction of beta-cells and to an allospecific induction of major histocompatibility complex (MHC) class II antigens on beta-cells. The intent of our investigation was to determine whether peripheral blood lymphocytes (PBL) obtained from allogeneic islet-grafted BB/OK rats (=sensitization in vivo) cause similar alterations to donor-specific islet cells. PBL prepared before transplantation, before (at day 7) and after islet rejection were co-cultured for 24 hr with donor-specific islets. PBL obtained at any time before and after transplantation caused reduction of beta-cells and enhancement of intercellular adhesion molecule-1(+)/beta-cells. Induction of MHC class II+ beta-cells was most pronounced with PBL obtained before rejection. Down-regulation of major histocompatibility complex class I+ beta-cells was caused by PBL that had been obtained from grafted animals only; it was most pronounced before islet rejection and has never been observed with lymphocytes from nongrafted normoglycemic rats. The 24-hr MLIC is capable of recognizing functionally active, donor-specific lymphocytes and is able to distinguish between the effects of sensitized and nonsensitized lymphocytes.     

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.     

原发性乳腺恶性淋巴瘤六例临床分析

目的 分析原发性乳腺恶性淋巴瘤的临床特点,探讨其诊断、分期和治疗方法。方法回顾分析我院自1995～2002年收治的6例原发性乳腺恶性淋巴瘤和1980～2002年国内主要文献报道的279例原发性乳腺恶性淋巴瘤的临床特征、诊断情况和治疗方法,进行对比分析。结果 285例病例均为非霍奇金淋巴瘤(NHL),免疫学检查证实有282例为B细胞源性(98.9％);女性268例,占94.0％;病灶位于右侧163例,占57.2％;Ⅰ期和Ⅱ期的原发性乳腺恶性淋巴瘤占89.8％。经手术、化疗、放疗等综合治疗后,生存期2～206个月,中位生存期最短23个月,最长56个月。结论 原发性乳腺恶性淋巴瘤绝大部分为B细胞源性非霍奇金淋巴瘤(NHL),Ⅰ期、Ⅱ期多见。对于原发性乳腺恶性淋巴瘤,诊断是关键,确诊后经手术、化疗、放疗等综合治疗,可以获得较长的生存期,疗效十分满意。