Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.      

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.      

Acute changes in urine protein excretion may predict chronic ifosfamide nephrotoxicity: a preliminary observation

Purpose: To evaluate proteinuria occurring early after ifosfamide therapy and to assess the use of changes in proteinuria in the prediction of severe chronic nephrotoxicity. Methods: One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to characterize urine protein excretion in 12 children with solid tumours before and after the first course of ifosfamide treatment, and in 24 healthy children. Chronic nephrotoxicity was evaluated at 6 months after ifosfamide treatment and graded as none, mild, moderate or severe. Results: Urine from healthy children and from 10 of 12 patients before ifosfamide therapy showed a protein band with a molecular weight (95.4 kDa) corresponding to that of Tamm-Horsfall protein but no lower molecular weight proteins. After the first course of ifosfamide this 95.4-kDa protein was lost in six of ten patients with a concomitant appearance of a low molecular weight proteinuria (<70 kDa) in eight. Tamm-Horsfall protein was lost in two of five patients who subsequently developed no or mild nephrotoxicity and in four of five patients who subsequently developed moderate or severe nephrotoxicity. Conclusions: Early subclinical changes in urine protein excretion after ifosfamide, manifested by a loss of Tamm-Horsfall protein excretion, may be predictive of subsequent chronic nephrotoxicity. Received: 27 August 1996 / Accepted: 25 July 1997     

博莱霉素与IL-2治疗癌性胸水的临床研究

目的观察既能控制胸水而又可以减少治疗次数的药物的疗效.方法常用胸穿套管针建立闭式引流,在胸水基本流净、肺复张基础上予以博莱霉素(BLM)30～50 mg;IL-2 40万U做胸腔内一次性灌注.结果总有效率86.7%.毒副作用:发热、寒战者占28.3%(38℃以下者),轻度胸痛占33.3%,皮肤色素沉着者占40.0%,脱发占30.0%,食欲不振占28.9%.结论 BLM治疗癌性胸水疗效好,毒副作用轻,易为患者接受.     

Mortality: What Are the Roles of Risk Factor Prevalence,Screening, and Use of Recommended Treatment?

CONTEXT: Despite advances in early detection and prevention of cervical cancer, women living in rural areas, and particularly in Appalachia, the rural South, the Texas/Mexico border, and the central valley of California, have had consistently higher rates of cervical cancer mortality than their counterparts in other areas during the past several decades. METHODS: This paper reviews the published literature from 1966 to July 2002 to assess three potential pathways underlying this excess mortality--high human papilloma virus (HPV) prevalence, lack of or infrequent screening and advanced disease at diagnosis, and under-use of recommended treatment and shorter survival. FINDINGS: Living in rural areas may impose barriers to cervical cancer control, including lack of transportation and medical care infrastructures. Population characteristics that place women at greater risk for developing and dying from cervical cancer, such as low income, lack of health insurance, and physician availability, are concentrated in rural areas. Published data, however, are insufficient to identify the key reasons for the observed mortality patterns. CONCLUSIONS: At this time, given the lack of definitive evidence in the published literature, decisions about priorities in areas with high rates of cervical cancer mortality will depend on knowledge of current levels of screening, incidence, and stage distribution; and service delivery infrastructures, resources, and acceptability of interventions to the target population.     

Exploring the decision-making preferences of people with colorectal cancer

OBJECTIVES: To explore patient views on participation in treatment, physical care and psychological care decisions and factors that facilitate and hinder patients from making decisions. DESIGN: Qualitative study using semi-structured interviews with patients. SETTING AND PARTICIPANTS: Three NHS Trusts in the north-west of England. Theoretical sampling including 41 patients who had been treated for colorectal cancer. RESULTS: For patients, participation in the decision-making process was about being informed and feeling involved in the consultation process, whether patients actually made decisions or not. The perceived availability of treatment choices (surgery, radiotherapy, chemotherapy) was related to type of treatment. Factors that impacted on whether patients wanted to make decisions included a lack of information, a lack of medical knowledge and trust in medical expertise. Patients perceived that they could have a more participatory role in decisions related to physical and psychological care. CONCLUSION: This study has implications for health professionals aiming to implement policy guidelines that promote patient participation and shared partnerships. Patients in this study wanted to be well informed and involved in the consultation process but did not necessarily want to use the information they received to make decisions. The presentation of choices and preferences for participation may be context specific and it cannot be assumed that patients who do not want to make decisions about one aspect of their care and treatment do not want to make decisions about other aspects of their care and treatment.     

What does it mean to involve consumers successfully in NHS research? A consensus study

OBJECTIVE: To obtain consensus on the principles and indicators of successful consumer involvement in NHS research. DESIGN: Consensus methods were used. An expert workshop, employing the nominal group technique was used to generate potential principles and indicators. A two-round postal Delphi process was used to obtain consensus on the principles and indicators. SETTING AND PARTICIPANTS: Participants were drawn from health, social care, universities and consumer organizations. A purposive sampling strategy was used to identify people who had experience and/or knowledge of consumer involvement in NHS research. Six researchers and seven consumers participated in an expert workshop. Ninety-six people completed both rounds of the Delphi process. MAIN OUTCOME MEASURES: Consensus on principles and indicators of successful consumer involvement in NHS research. RESULTS: Eight principles were developed through an expert workshop and Delphi process, and rated as both clear and valid. Consensus was reached on at least one clear and valid indicator by which to measure each principle. CONCLUSIONS: Consensus has been obtained on eight principles of successful consumer involvement in NHS research. They may help commissioners, researchers and consumers to deepen their understanding of this issue, and can be used to guide good practice.     

角膜塑型术矫正近视二年后的临床观察

目的 :探讨角膜塑型术 (Orthokeratology ,简称Or tho K镜 )矫正近视的远期疗效 ,了解其对近视的矫正及控制近视进展的效果。并观察其安全程度。方法 :配戴Ortho K镜二年以上的青少年近视眼患者 ,共 86例 16 6眼 ,平均年龄(15 .5± 2 .6 )岁 ( 10～ 2 5岁 ) ,平均屈光度 ( - 4 .0 2± 1.78)D( -1.5～ - 7.0D)。对配戴前、后的角膜曲率、角膜地形图、角膜厚度、眼轴、眼压进行检测 ,平均观察期为 ( 2 8.2 5± 3.74 )个月。结果 :配戴前后平均裸眼视力分别为 0 .2 1± 0 .10和0 .99± 0 .2 3,差异有非常显著性 (P <0 .0 1) ;配戴前后角膜水平曲率均值分别为 ( 4 3.0 5± 1.10 )D和 ( 4 0 .84± 1.38)D ;配戴前后眼轴 (眼球前后径 )均值分别为 ( 2 4 .93± 0 .82 )mm和( 2 5 .16± 0 .82 )mm ,每年眼轴增长均值为 ( 0 .12± 0 .4 1)mm ;配戴前后角膜厚度均值分别为 ( 0 .5 6 5± 0 .0 30 )mm和 ( 0 .5 5 7±0 .0 34)mm ,配戴后角膜厚度平均变薄 0 .0 0 9mm ,差异有显著性 (P <0 .0 1) ;配戴前后眼压均值分别为 ( 15 .95± 2 .92 )mmHg和 ( 15 .35± 2 .6 0 )mmHg ,配戴后眼压平均下降 0 .6 0mmHg,差异有显著性 (P <0 .0 1)。配戴Ortho K镜期间有 79眼发生过角膜点状浸润 ,占配戴眼数的 4 7.31%。结论 :Or t