Fanconi's anemia treated by allogeneic marrow transplantation

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.     

碱性成纤维细胞生长因子对大鼠脑血肿周围组织和海马bax及bcl-2基因表达的调节

目的:观察碱性成纤维细胞生长因子对大鼠脑出血后出血灶周围脑组织和出血侧海马bax、bcl-2基因表达的影响,探讨神经营养因子对神经细胞调亡的调控。方法:实验于2006-01/10在广西医科大学医学科学实验中心完成。①取成年清洁级Wistar大鼠72只,雌雄各半,体质量250g左右。②采用脑内囊注射胶原酶建立大鼠脑出血模型,动物于苏醒后按Bederson法进行神经病学评分,评分>3分后入选本实验,入选72只大鼠随机抽签法分为3组,每组24只。碱性成纤维细胞生长因子组按8μg/kg剂量肌肉注射,1次/d;生理盐水组肌肉注射等剂量的生理盐水,1次/d;模型组不作任何干预。③每组分别于干预后1,3,7d随机抽取8只大鼠,麻醉状态下取出血灶周围脑组织和出血侧海马,采用半定量反转录-聚合酶链反应检测调亡调控基因bax mRNA,bcl-2mRNA的表达。结果:在建立脑出血模型中共5只大鼠死亡,随后对死亡动物进行解剖,发现脑内血肿量过大,致脑疝形成而导致死亡,后随机补充动物。72只大鼠进入结果分析。①血肿周围脑组织bax mRNA表达:干预后3d,7d,碱性成纤维细胞生长因子组血肿周围脑组织bax mRNA表达比生理盐水组明显减少(3d:0.54±0.19,0.76±0.23,P<0.05;7d:0.45±0.19,0.71±0.16,P<0.01)。②血肿周围脑组织bcl-2mRNA表达:干预后3d,7d,碱性成纤维细胞生长因子组的血肿周围脑组织bcl-2mRNA表达比生理盐水组明显增高(3d:0.68±0.25,0.39±0.19,P<0.05;7d:0.80±0.21,0.48±0.18,P<0.01)。③出血侧海马bax mRNA表达:干预后3d和7d,碱性成纤维细胞生长因子组的出血侧海马bax mRNA表达比生理盐水组均明显减少(3d:0.54±0.18,0.70±0.11;7d:0.43±0.24,0.69±0.18,P均<0.05)。④出血侧海马bcl-2mRNA表达:干预后3d和7d,碱性成纤维细胞生长因子组的出血侧海马bcl-2mRNA表达比生理盐水组均明显增多(3d:0.66±0.11,0.50±0.15;7d:0.72±0.12,0.52±0.22,P均<0.05)。结论:碱性成纤维细胞生长因子能调节凋亡相关基因,提高大鼠脑出血后大脑脑组织和海马bcl-2mRNA的表达,降低bax mRNA的表达。     

Effective removal of copper by plasma exchange in fulminant Wilson's disease

BACKGROUND: Patients who present with fulminant hepatic failure due to Wilson's disease may develop hemolytic anemia and renal insufficiency. In this entity, acute hepatocellular necrosis triggers the release of copper ions into the circulation, which leads to toxic effects on red cell metabolic pathways and hemolysis. STUDY DESIGN AND METHODS: The utility of therapeutic plasma exchange to rapidly remove copper and reduce toxic serum copper levels was studied in two patients with fulminant Wilson's disease. RESULTS: Intensive plasma exchange using fresh-frozen plasma replacement removed substantial amounts of copper from the hypercupremic patients, resulting in a rapid reduction in serum copper levels and decreased hemolysis. The net copper removal was proportional to the serum level, ranging from 7,000 to 11,800 micrograms per procedure in one patient and from 3,700 to 6,800 micrograms in the other. CONCLUSION: Plasma exchange allows a rapid reduction in elevated serum copper levels in patients with fulminant Wilson's disease. This leads to an amelioration of hemolytic anemia and provides clinical stabilization until liver transplantation can be performed.     

Murine Hertwig's anemia: premature death after normal bone marrow transplantation is radiation dose-dependent

Marrow transplantation therapy in mice with heritable blood disorders usually leads to rapid blood cell normalization, but is sometimes followed by pancytopenia and premature death. This is especially true in mice with Hertwig's anemia (an/an). Unlike the +/+ recipients, 100% of whom survive for over a year, 66% of the mutant mice die by 6 months posttransplantation, and the rest die soon thereafter. It is not clear whether premature death is due to the radiation dose (10 Gy) or to the fact that the F1 mutant mice receive parental-type cells known to induce hybrid resistance. In the present report, experiments were designed to determine whether the F1-an/an host is more sensitive to radiation and/or resistant to continued expansion of the parental-type +/+ cells. The mutant mice are, indeed, more sensitive to irradiation, with an LD100/30 of 7 Gy as compared with an LD100/30 of 10 Gy for the +/+ mice. The times of anemia onset and death for mutant mice implanted with +/+ cells postirradiation is also radiation dose-dependent. Further evidence that death is due to host radiation damage rather than F1 hybrid resistance was provided by transplanting cells from three morbid 10 Gy-irradiation recipients into unirradiated, anemic, stem cell-deficient, F1-W/Wv secondary hosts. All recipients were repopulated by the original parental cells, were cured of their anemia, and survived for 52 weeks posttransplantation. The an/an mouse's heightened susceptibility to radiation damage appears to be the major factor in early death after transplantation therapy.     

Evaluation design of a reactivation care program to prevent functional loss in hospitalised elderly: A cohort study including a randomised controlled trial

Background

Elderly persons admitted to the hospital are at risk for hospital related functional loss. This evaluation aims to compare the effects of different levels of (integrated) health intervention care programs on preventing hospital related functional loss among elderly patients by comparing a new intervention program to two usual care programs.

Methods/Design

This study will include an effect, process and cost evaluation using a mixed methods design of quantitative and qualitative methods. Three hospitals in the Netherlands with different levels of integrated geriatric health care will be evaluated using a quasi-experimental study design. Data collection on outcomes will take place through a prospective cohort study, which will incorporate a nested randomised controlled trial to evaluate the effects of a stay at the centre for prevention and reactivation for patients with complex problems. The study population will consist of elderly persons (65 years or older) at risk for functional loss who are admitted to one of the three hospitals. Data is prospectively collected at time of hospital admission (T0), three months (T1), and twelve months (T2) after hospital admission. Patient and informal caregiver outcomes (e.g. health related quality of life, activities of daily living, burden of care, (re-) admission in hospital or nursing homes, mortality) as well as process measures (e.g. the cooperation and collaboration of multidisciplinary teams, patient and informal caregiver satisfaction with care) will be measured. A qualitative analysis will determine the fidelity of intervention implementation as well as provide further context and explanation for quantitative outcomes. Finally, costs will be determined from a societal viewpoint to allow for cost effectiveness calculations.

Discussion

It is anticipated that higher levels of integrated hospital health care for at risk elderly will result in prevention of loss of functioning and loss of quality of life after hospital discharge as well as in lower burden of care and higher quality of life for informal caregivers. Ultimately, the results of this study may contribute to the implementation of a national integrated health care program to prevent hospital related functional loss among elderly patients.

Trial registration

The Netherlands National Trial Register: NTR2317     

Open-access transvaginal sonography in women of reproductive age with abnormal vaginal bleeding: a descriptive study in general practice

Background

Diagnostic ultrasonography is used by GPs in approximately 10% of patients of reproductive age with abnormal vaginal bleeding. Transvaginal sonography is recommended as a first-line diagnostic instrument for assessing uterine pathology.

Aim

To assess if findings resulting from openaccess sonography were in agreement with the GPs’ working hypotheses and if these findings contributed to GPs’ management.

Design and setting

Prospective observational cohort study of GPs working in the health district of the Academic Medical Center, Amsterdam and their patients consulting with abnormal vaginal bleeding.

Method

Data on patients’ history, GPs’ primary working hypotheses, and intended management were recorded. After sonography, GPs recorded their actual management.

Results

A total of 122 patients were included by 18 GPs from June 2003 to December 2004. Data from 89 patients were available for analysis. The GPs’ working hypotheses implied ‘no structural pathology’ in 65/89 patients, and ‘fibroids’ in 24/89 patients. Sonographic findings were confirmed in 50/65 patients where ‘no structural pathology’, and in 14/24 of those where ‘fibroids’ were expected. Initially, GPs had intended to refer nine patients to a gynaecologist. Actual management after sonographic assessment was watchful waiting or drug therapy in 57/89 patients. Eighty-nine per cent of these patients had normal sonographic findings. The actual referral rate rose to 27/89 patients. In 17 referred patients, sonographic findings were suggestive of intracavitary abnormalities.

Conclusion

Open-access sonography contributed to more accurate diagnoses and improved GPs’ management of women with abnormal vaginal bleeding.     

阿德福韦双酯治疗拉米夫定耐药的慢性乙肝患者时出现的耐药问题

背景:阿德福韦双酯(ADV) 是一种有效治疗野生型和耐拉米夫定乙肝病毒(HBV)的核苷酸类药物。在使用核苷酸类药物治疗慢性乙肝时,当治疗时间为 48、96、144周时,耐ADV变异体出现的累积发生率分别为0、 0．8-3％和0-5．9％。目的:研究67例对拉米夫定耐药且接受ADV治疗的慢性乙肝患者耐ADV病毒变异体的表型和基因型特点。方法:HBV DNA含量采用实时定量PCR技术。ADV变异体检测采用基质辅助激光解吸电离／飞行时间质谱为基础的基因分型