Morphological effects of imatinib mesylate (STI571) on the bone marrow and blood of patients with Philadelphia chromosome (Ph) positive chronic myeloid leukaemia

There have been few reports on the morphological findings in patients with chronic myeloid leukaemia (CML) undergoing treatment with imatinib mesylate. We examined morphological changes in the marrow and peripheral blood of 27 patients with chronic phase (CP), accelerated phase (AP) and blastic phase (BP) CML, 3 and 6 months after treatment with imatinib. At 3 months there was a significant clearance of leukaemic cells as evidenced by a complete haematological response (CHR) in the peripheral blood in 25 patients, together with reduced marrow cellularity in 25 (median reduction CP 42%; AP/BP 68%) and a reduction in the number of megakaryocytes (13 of 18 CP: five of six AP/BP; three patients did not have an assessable marrow) with an increase in the amount of normal megakaryopoiesis. After 6 months, there was continued morphological improvement in eight of 17 CP patients (one patient died after 3 months) with continued cytogenetic response (7 out of 15 patients with assessable metaphases had no abnormal Ph+ cells and three had <35% Ph+ cells) and maintenance of haematologic response in all patients. After an initial response to treatment at 3 months in the AP/BP group, with CHR and a reduction in cellularity in all patients, we found morphological evidence of a loss of response to treatment, with an increase in leukaemic cells, as evidenced by loss of CHR in three of nine and an increase in median cellularity in five patients. No patient in this group achieved a complete cytogenetic response. In summary, in CML-CP patients treated with 6 months of imatinib, there was a significant reduction in leukaemic cells as evidenced by a haematolological response in the peripheral blood, together with reduced marrow cellularity, restoration of morphologically normal haemopoiesis and a meaningful cytogenetic response. Maintaining a response to treatment appeared less likely to occur in the AP/BP group patients, especially those who did not achieve any cytogenetic response to treatment.     

高血压理想治疗研究(HOT)

标　　题:1高血压理想治疗研究2高血压理想治疗随机研究的主要结果:强化降压治疗及小剂量阿司匹林对高血压患者的作用作　　者　1ＨａｎｓｓｏｎＬ.2ＨａｎｓｓｏｎＬ.ＺａｎｃｈｅｔｔｉＡ,ＣａｒｒｕｔｈｅｒｓＤＧ,ｅｔａｌ.　　参考文献　1ＢｌｏｏｄＰｒｅｓｓｕｒｅ,1993,2:62～682Ｌａｎｃｅｔ,1998,351:1755～1762研究的疾病　高血压病。目　　的　①评估主要心血管事件(非致死性、急性和无症状性心肌梗死、非致死性脑卒中以及各种原因的心血管死亡)和3种ＤＢＰ靶水平(≤90ｍｍＨｇ,≤85ｍｍＨｇ,≤80ｍｍＨｇ)的关系,以及与积极抗…     

An outbreak of cyclosporiasis in 1996 associated with consumption of fresh berries- Ontario

BACKGROUND:

A large foodborne outbreak of cyclosporiasis occurred in North America in 1996. An index cluster of cases associated with a catered event on May 11, 1996, in Ontario sparked the recognition of this outbreak in Canada.

OBJECTIVES:

To describe the Ontario experience with the North American outbreak of cyclosporiasis in 1996.

PATIENTS AND METHODS:

Public health units investigated the index and subsequent event-associated clusters. Investigations included retrospective cohort studies of clusters, traceback of suspect foods and a case-control study of sporadic cases. These activities, coordinated with those in the United States, were part of an international investigation.

RESULTS:

In Ontario, 232 cases of cyclosporiasis (20 laboratory-confirmed and 72 clinically defined cases associated with seven events plus 140 additional laboratory-confirmed sporadic cases) were identified between May 1 and July 30, 1996. For the index cluster, a strawberry flan with raspberries and blueberries was the only significant exposure (relative risk 2.16, P=0.02). Fresh berries were served at all seven events associated with clusters of cases. Raspberries were definitely served at three events, possibly served at three events, and not served at one event. Only imported berries were available in Ontario in May 1996, when initial clusters and sporadic cases were identified. The raspberries served at the two events with well documented traceback data came from Guatemala. Univariate analyses of the matched case-control study demonstrated that illness was associated with consumption of raspberries (matched odds ratio 21.0, 95% CI 3.48 to 448) and strawberries (matched odds ratio 28.5, 95% CI 4.02 to 478). Further evidence amassed by the international investigation compellingly implicated Guatemalan raspberries as the vehicle of the outbreak.

CONCLUSION:

Cyclosporiasis may be acquired domestically from the consumption of contaminated produce. The scope and vehicle of this international foodborne outbreak were recognized through a coordinated public health response.Key Words: Canada, Cyclosporiasis, Cyclospora cayetanensis, Foodborne outbreakCyclosporiasis is caused by ingestion of oocysts of Cyclospora cayetanensis, a parasite which was first recognized in the late 1970s (1). The clinical picture of cyclosporiasis can be indistinguishable from that of giardiasis, cryptosporidiosis and isosporiasis. The main symptom is watery diarrhea that occurs in a relapsing, cyclical pattern, lasting for several days to weeks; it is often associated with weight loss and fatigue. In immunocompromised hosts, especially those with AIDS, the duration and severity of illness may be increased (2). The recommended treatment for cyclosporiasis is a seven-day course of trimethoprim/sulphamethoxazole, but patients with AIDS may require both longer courses of therapy and maintenance therapy (2,3).Cyclospora oocysts, measuring 8 to 10 μm in diameter, are recognized as nonrefractile spheres (containing refractile globules) on light microscopic examination of wet preparations of stool. With modified acid-fast staining, some oocysts may stain deep red, others may stain pink and still others may remain unstained as glassy, membranous oocysts (4).Foodborne and waterborne transmission are now well established (5-7). Before 1995, outbreaks were infrequent and usually associated with waterborne transmission (5,6). In Canada before 1996, case reports were associated with travellers returning from developing countries (8). In Ontario, Brennan et al (9) reported an estimated prevalence of 0.5 cases/1000 stool examinations based on a survey examining 80,000 stool samples submitted to three parasitology laboratories from June 1993 through June 1995 (9).In May 1996, the North York Public Health Department in Ontario was notified by a local primary care physician of several cases of cyclosporiasis among guests who had attended a wedding reception on May 11, 1996. Simultaneously, another cluster of cases was being investigated in Houston, Texas; and several state health departments in the United States reported an increased number of cases of cyclosporiasis to the Centers for Disease Control and Prevention, Atlanta, Georgia (CDC). These clusters and sporadic cases were ultimately recognized as part of a North American outbreak of cyclosporiasis for which preliminary investigations implicated both strawberries and raspberries. This paper describes the Ontario experience with the North American outbreak of cyclosporiasis in 1996.     

Percutaneous treatment of torrential tricuspid regurgitation with prior dehisced tricuspid annuloplasty ring

The International Journal of Cardiovascular Imaging -     

Donor methylenetetrahydrofolate reductase genotype is associated with graft-versus-host disease in hematopoietic stem cell transplant patients treated with methotrexate

Methotrexate (MTX), used as a graft-versus-host disease (GvHD) prophylactic agent in hematopoietic stem cell transplantation (HSCT), exerts its effect via folate cycle inhibition. A critical enzyme involved in folate metabolism is 5,10-methylenetetrahydrofolate reductase (MTHFR). We examined the association of a single nucleotide polymorphism (SNP) at position 677 in the MTHFR gene on GvHD outcomes in allogeneic HSCT patients administered MTX. MTHFR genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 193 HSCT patients and donors. A total of 140 patients were transplanted with an HLA-matched related donor and 53 with an unrelated donor. GvHD outcomes were compared between genotypes by univariate and multivariate analysis. The combined donor 677CT and TT genotypes were associated with a decreased incidence of GvHD (acute and chronic combined) in HSCT recipients with an HLA-matched related donor (75% at 1 year in the CT and TT group compared with 91% in the wild type CC group, P=0.01), increased time to onset of first GvHD (P=0.001) and time to first GvHD treated with systemic therapy (P=0.022). Unrelated donor MTHFR genotype was not associated with outcome parameters and no associations of recipient genotype in either related or unrelated donor cohorts were observed.     

An Animal Model Allowing Controlled Receptor Expression for Molecular Ultrasound Imaging

Reported in this study is an animal model system for evaluating targeted ultrasound (US) contrast agents binding using adenoviral (Ad) vectors to modulate cellular receptor expression. An Ad vector encoding an extracellular hemagglutinin (HA) epitope tag and a green fluorescent protein (GFP) reporter was used to regulate receptor expression. A low and high receptor density (in breast cancer tumor bearing mice) was achieved by varying the Ad dose with a low plaque forming unit (PFU) on day 1 and high PFU on day 2 of experimentation. Targeted US contrast agents, or microbubbles (MB), were created by conjugating either biotinylated anti-HA or IgG isotype control antibodies to the MB surface with biotin-streptavidin linkage. Targeted and control MBs were administered on both days of experimentation and contrast-enhanced US (CEUS) was performed on each mouse using MB flash destruction technique. Signal intensities from MBs retained within tumor vasculature were analyzed through a custom Matlab program. Results showed intratumoral enhancement attributable to targeted MB accumulation was significantly increased from the low Ad vector dosing and the high Ad vector dosing (p = 0.001). Control MBs showed no significant differences between day 1 and day 2 imaging (p = 0.96). Additionally, targeted MBs showed a 10.5-fold increase in intratumoral image intensity on day 1 and an 18.8-fold increase in image intensity on day 2 compared with their control MB counterparts.     

中枢神经系统中胰岛素的信号传导

胰岛素及其信号传导系统对机体的中枢和外周组织产生广泛的作用，调控着营养物质的吸收、分布、代谢和储存。外界有关营养物质的来源和类型的信息与有关体内脂肪储存的激素信息（如胰岛素）实现整合。对这些传人信息的反应是神经通路激活，影响能量流动和物质代谢，从而保证生育繁衍后代。有越来越多的证据支持以下假说：由胰岛素分泌缺乏或作用缺陷引起的巾枢神经系统胰岛索信号传导障碍，是糖尿病和肥胖等代谢性疾病的病理机制之一。这个假说有助于解释糖尿病与肥胖之间的密切关联。脑部曾经被认为是不依赖胰岛素的，但是上述假说认为胰岛素在大脑中的作用是葡萄糖和能量代谢的决定因素。     

Reduced-intensity allogeneic haemopoietic stem cell transplantation induces durable responses in patients with chronic B-lymphoproliferative disorders

Thirty-six patients with chronic B-lymphoproliferative disorders (B-LPD) underwent reduced-intensity allogeneic transplantation (RIT) from HLA-identical related donors. Diagnoses included follicular (n=17), mantle cell (n=9) and small lymphocytic lymphoma (n=2), and chronic lymphocytic leukaemia (n=8). Median age at transplant was 51 years (range, 30-66) and time from diagnosis was 3.4 years (range, 0.3-9.5). At transplant, 28% were in CR, 36% were in PR and 36% were chemorefractory. Conditioning therapy included fludarabine and either cyclophosphamide (n=27) or melphalan (n=9). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin (CsA)/methotrexate (n=21), CsA/mycophenolate mofetil (n=13) or CsA alone (n=2). Eight patients died owing to acute GVHD (n=3), infection in association with chronic GVHD (n=4) and intra-abdominal bleeding (n=1). Treatment-related mortality was 8% at day 100, and 17 and 20% at one and two years, respectively. The cumulative incidence of grade II-IV acute GVHD was 58%, whereas limited and extensive chronic GVHD occurred in 25 and 56%, respectively. No patient has relapsed or progressed. At a median follow-up of 48 months, overall survival probability is 80% (95% CI, 67-93%). We confirm that RIT in chronic B-LPD can result in high and durable CR rates but with significant incidences of acute and chronic GVHD.