Inhibition of ADP-induced P-selectin expression and platelet-leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin

Platelet-leukocyte interactions are recognised to have pro-inflammatory effects, which may be important in the pathophysiology of ischaemic heart disease. Clopidogrel and the novel intravenous antithrombotic agent AR-C69931MX act at the level of the platelet P2Y12 receptor, which is known to amplify platelet activation, aggregation and other responses induced by numerous platelet agonists. We studied the effects of clopidogrel and aspirin on ADP-induced platelet-leukocyte conjugate formation and P-selectin expression in healthy volunteers. The effects of clopidogrel and AR-C69931MX administered to patients with ischaemic heart disease were also assessed. AR-C69931MX and aspirin were also studied in vitro. Clopidogrel and AR-C69931MX suppressed ADP-induced platelet aggregation, P-selectin expression and platelet-leukocyte conjugate formation whereas aspirin had no inhibitory effect. These effects of clopidogrel and AR-C69931MX may confer therapeutic benefits in the management of acute coronary syndromes.     

反应停治疗难治性多发性骨髓瘤25例

1临床资料我院2001-02/2004-01接受2个疗程卡氮芥 环磷酰胺 马法兰 泼尼松 长春新碱或2个疗程长春新碱 阿霉素 地塞米松方案化疗无效或复发的难治性多发性骨髓瘤患者25(男16,女9)例,年龄42～80(中位年龄57.2)岁.单用反应停口服治疗,起始剂量200 mg/d,如无不良反应,每周增加100 mg,根据患者耐受情况,最高剂量为600 mg/d,3 mo为1疗程.服药期间禁止使用糖皮质激素类药物及细胞毒药物.     

Effects of protein kinase C activators on phorbol ester-sensitive and - resistant EL4 thymoma cells

Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12- myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester- resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase C's (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK activation, but differed in their abilities to induce JNK activation and interleukin-2 synthesis. PD 098059, an inhibitor of the mitogen activated protein (MAP)/ERK kinase kinase MEK, partially inhibited ERK activation and completely blocked phorbol ester-induced cell death in sensitive cells. Thus MEK and/or ERK activation, but not JNK activation or interleukin-2 synthesis, appears to be required for phorbol ester-induced toxicity. Alterations in phorbol ester response pathways, rather than altered expression of PKC isoforms, appear to confer phorbol ester resistance to EL4 cells.      

Retrobulbar hydatid cyst: Assessment of two cases

A 54-year-old man with a unilocular hydatid cyst within the infero-posterior angle of the orbit and a 6-year-old male child with a unilocular hydatid cyst within the supero-medial angle of the orbit are presented. The retrobulbar cysts were diagnosed with computed tomography and ultrasonography and were treated after serologic confirmation.     

Mycobacterial infection in an inner city children's hospital

Childhood tuberculosis is perceived by many as a disease of the past. Experience in a children's hospital serving a deprived population suggested that tuberculosis and other mycobacterial infections were not declining in clinical practice. Fifty three tuberculous and 11 atypical mycobacterial infections were identified between 1978 and 1992. There was no decline in tuberculosis and nine of the 11 atypical infections occurred in the last five years. Altogether 40% of cases of tuberculosis were in non-Asian children; 32% had arrived in the UK or visited family overseas in the previous year; and 38% had a history of tuberculosis contact, usually a close adult relative. Nationally, the previous decline in tuberculosis in all ages has reversed. In the local health districts in London's east end, childhood tuberculosis has also stopped declining and seems to be increasing. It is regrettable that BCG vaccination has been abolished by some districts in the UK, against current recommendations. Childhood tuberculosis is still common in the practice described here, including among children who do not fall into conventionally recognised high risk groups. Inner city dwellers and junior doctors are both highly mobile populations, adding to the risk that paediatricians, particularly those in training, may encounter tuberculosis with little or no previous experience of the condition.     

Protein nutrition, faecal flora and iron metabolism: the role of milk-based formulae

This paper explores the role of milk-based formulae in achieving four aspects of nutritional health in infants and toddlers: in the suckling, to mimic the amino acid metabolism and the faecal flora of a breast-fed baby; in the weanling, to achieve adequate protein intakes in later infancy and beyond and to achieve satisfactory haemoglobin concentrations in the early toddler years. Milk-based formulae have two roles in infant nutrition: as so-called breast milk substitutes and as a safety net during the weaning period; the latter role may be the more important.     

Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis

One hundred and twenty eight Brazilian children with lymphoblastic leukaemia were intensively treated with a Berlin-Frankfurt-Munich based protocol. More children had a white cell count above 50 x 10(9)/l (31%) then observed in developed countries. After a median follow up of 31 months (11-58 months), the estimated probability of relapse free survival was 41% (7%) for the whole group. After adjustment in the Cox's multivariate model, malnutrition was the most significant adverse factor affecting duration of complete remission. Age above 8 years and high peripheral white cell count were also significant adverse factors. Among the nutritional indices, the height for age and weight for age z scores were both significant, whether the cut off points of z-2 or z = -1.28 were chosen to define malnutrition. A strong statistical association between the two indices was found; the contribution of height for age z score to the prediction of relapse free survival was more significant. Children with height for age z score < -2 had a relapse risk of 8.2 (95% confidence interval 3.1 to 21.9) relative to children with z score > -2. The results of this study suggest that socioeconomic and nutritional factors should be considered in the prognostic evaluation of children with leukaemia in developing countries.     

Patterns of tumor initiation in choroidal melanoma

This study attempts to document the occurrence of tumors with respect to clock hour location and distance from the macula and to evaluate tumor location in relation to retinal topography and light dose distribution on the retinal sphere. Analysis of patterns of tumor initiation may provide new evidence to clarify the controversy regarding the possible light-related etiology of choroidal melanoma. Incident cases of choroidal and ciliary body melanoma in Massachusetts residents diagnosed between 1984 and 1993 were the basis for analysis. Conventional fundus drawings and photos were used to assess the initiation site of each tumor. The initiation site was defined as the intersect between the largest tumor diameter and the largest perpendicular diameter of the tumor. Initiation sites were recorded using spherical coordinates. The retinal sphere was divided into 61 mutually exclusive sectors defined according to clock hour and anteroposterior distance from the macula. Rates of initiation were computed for each sector, overall, and according to gender and other clinical factors. Results were similar in left and right eyes; therefore, these were combined in analysis. Tumor initiation had a predilection for the macula (P < 0.0001). Overall, no significant clock hour preference was observed (P = 0.63). However, the parafoveal zone showed a strong circular trend (P < 0.01), with highest rates occurring in the temporal region, and the lowest rates occurring in the nasal region. Rates of occurrence in six progressively more anterior concentric zones (designated as the foveal, parafoveal, posterior, peripheral, anterior, and ciliary body zones) were 21.4, 14.2, 12.1, 8.9, 4.5, and 4.3 counts per spherical unit per 1000 eyes, respectively. Concentric zone location did not vary by gender (P = 0.93) or laterality (P = 0.78). However, posterior location was associated with light iris color (P = 0.01). Tumor diameters were largest in the peripheral region of the fundus and smallest in the macular and ciliary body zone (P < 0.001). Clock hour location was not influenced by gender (P = 0.74), laterality (P = 0.53), iris color (P = 0.84), or tumor diameter (P = 0.73). Results suggest that tumor initiation is not uniformly distributed, with rates of occurrence concentrated in the macular area and decreasing monotonically with distance from the macula to the ciliary body. This pattern is consistent with the retinal topography and correlates positively with the dose distribution of solar light on the retinal sphere.