癌症化学预防的分子靶标

乙肝病毒和人乳头状瘤病毒分别是肝细胞癌和子宫颈癌的风险因素,针对这2种病毒感染的疫苗已在临床上成功用于癌症化学预防。分子靶向药物能够预防乳腺癌（雷洛昔芬与他莫昔芬）、大肠腺瘤（塞来昔布）和前列腺癌（非那雄胺）。然而,化学预防广泛应用于临床还不现实。分子靶标的深入研究将扩展化学预防的范围并使其个性化。     

Effects of atomoxetine and methylphenidate on attention and impulsivity in the 5-choice serial reaction time test

Deficits in attention and response inhibition are apparent across several neurodegenerative and neuropsychiatric disorders for which current pharmacotherapy is inadequate. The 5-choice serial reaction time test (5-CSRTT), which originated from the continuous performance test (CPT) in humans, may serve as a useful translational assay for efficacy in these key behavioral domains. The selective norepinepherine reuptake inhibitor, atomoxetine, represents the first non-stimulant based drug approved for Attention Deficit Hyperactivity Disorder (ADHD) and has replaced methylphenidate (Ritalin) as the first line in pharmacotherapy for the treatment of ADHD. Methylphenidate and atomoxetine have different cortical and sub-cortical neurochemical signatures that could predict differences in cognitive and non-cognitive functions. The present experiments investigated the effects of acute methylphenidate and atomoxetine in male long Evans rats in the 5-choice serial reaction time (5CSRT) test that is hypothesized to serve as a model of vigilance and impulsivity behaviors associated with ADHD. Long Evans rats were trained to perform at 75% correct responses with fewer than 20% missed trials in the 5CSRT test (500 ms stimulus duration, 5 s inter-trial interval (ITI)). By varying the ITI (10, 7, 5, and 4 s) on drug test days, impulsivity (as defined by premature responses) was dramatically increased with a concomitant decrease in attention (percent correct). Subsequently, animals were treated with methylphenidate (2.5 and 5 mg/kg, i.p.) or atomoxetine (0.1, 0.5 and 1 mg/kg, i.p.) using this design. In Experiment 1, treatment with methylphenidate modestly improved overall attention but the highest dose of methylphenidate (5.0 mg/kg) significantly increased impulsivity. In contrast, treatment with atomoxetine induced a marked decrease in impulsivity whilst modestly improving overall attention. Interestingly, no effect was observed on measures of performance (e.g. motivation/sedation) with atomoxetine, whilst moderate hyperactivity (faster overall response latencies; magazine, correct, incorrect) was observed in the methylphenidate group. Those data suggest that the 5CSRT test can be used to differentiate stimulant and non-stimulant pharmacotherapies on measures of impulsivity.     

Teardrop-shaped red cells in autoimmune hemolytic anemia

The presence of teardrop-shaped red cells in peripheral blood has traditionally been felt to reflect altered marrow architecture, namely myelofibrosis. We evaluated two patients with splenomegaly, moderately severe hemolytic anemia due to warm-reactive IgG anti-red cell autoantibody, and bone marrow erythroid hyperplasia without myelofibrosis. A striking predominance of teardrop-shaped red cells was noted upon examination of their blood films. Removal of a spleen containing extramedullary hematopoiesis in one and resolution of splenomegaly in the other were accompanied by disappearance of these cells. Our observations support a role for the spleen and for extramedullary hematopoiesis in the pathogenesis of this distinctive red cell morphologic abnormality.     

Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis

We studied the effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.     

Primary malignant lymphoma of the thyroid: a clinicopathological analysis.

A retrospective analysis of 70 patients with primary malignant lymphoma of the thyroid treated at this institute between 1965-1983 has been conducted. The clinicopathological features and prognostic factors have been studied. The mean age was 67.5 years and there was a marked female:male ratio of 8:1. A total of 32 (45.7%) Stage IE and 38 (54.3%) Stage IIE patients were identified. In 64 cases histological material was reviewed and classified employing the Kiel classification. All the tumors were of B cell lineage and the majority were follicle center cell type. A biopsy only was performed in 27 patients, lobectomy in 11 patients, subtotal thyroidectomy in 27 and macroscopic thyroidectomy in 5 patients. All patients were treated with radiotherapy. The overall 5-year survival was 42%, with 63% for Stage IE and 27% for Stage IIE. The corrected overall 5-year survival was 49% with 68% for Stage IE and 36% for Stage IIE. The corresponding overall relapse free survival was 42% with 60% for Stage IE, and 31% for Stage IIE. Factors of prognostic significance for relapse and survival were stage, radiotherapy dose, stridor, retrosternal extension and fixation.     

神经外科中高渗盐注射液应用研究进展

控制脑水肿和颅内压(ICP)升高是神经外科围手术期治疗的重要组成部分.颅脑创伤、动脉梗塞、静脉高压/梗塞、大脑内出血、蛛网膜下腔出血、肿瘤和术后脑组织水肿的治疗过程中ICP的控制都是决定患者预后的关键因素.虽然利用渗透压脱水药物是控制ICP的最基础的工具,但却缺乏前瞻性研究以指导其运用,高渗盐被认为是甘露醇的替代物,早期的数据表明每种药的用药指征最终取决于ICP的病因.在这篇综述中,我们总结了有关高渗盐(HS)治疗颅内高压的相关数据,以及这些数据和我们有关HS的经验是如何指导目前的ICP治疗的.     

A scanning and transmission electron microscopic study of human nodular goitre

This paper is a concurrent scanning and transmission electron microscopic study of 13 cases of nodular goitre.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.