A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor control

OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the control of early stage nasopharyngeal carcinoma (NPC) treated with a combination of external radiotherapy and brachytherapy, MATERIALS & METHODS: We reviewed the records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who received definitive radiotherapy in Chang Gung Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with a minimum of 2 years. All patients were treated with megavoltage external radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4 Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to examine the effect of several variables on prognosis. RESULTS: The 5-year rates were 86.4% for local control, 84.7% for disease free survival, 88.5% for actuarial survival and 84.2% for overall survival. The treatment group (combination of time and dose of irradiation) was the most important prognostic factor according to Cox's proportional hazard model. Patients receiving radiation at a total dose of < or = 75 Gy completed in < 12 weeks showed the best prognosis. CONCLUSION: Treatment time and total treatment dose are both important factors in treating early stage NPC. Decreasing the total radiation time to < 12 weeks and not exceeding a radiation dose of 75 Gy gave the best results.      

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

1-取代吡唑烷酮类抗惊构效关系的研究

1-正癸基吡唑烷-3-酮(Ⅱ结构式见表1)是欧洲专利报道的一种新型减肥剂。White等报道该化合物可通过血脑屏障,并对γ-氨基丁酸氨基转移酶(GABA-T)有强烈的抑制活性,但对谷氨酸脱羧酶的抑制作用较弱,因此可引起脑内γ-氨基丁酸(GABA)水平的升高,故我们相信应有抗惊活性。经我们合成后,发现Ⅱ确有良好的抗癲痫活性,抗小鼠最大电     

Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data

Background: We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients.

Methods: We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model.

Results: A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% – 9.4) and 16.4% (95% CI 16.19% – 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 – 75), 71 (66 – 80+), 74.5 (65 – 89), 75 (66 – 81+) and 79.5 (60 – 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 – 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 – 1.87, p < 0.00001).

Conclusion: Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.     

Feasibility of Shelter-Based Mental Health Screening for Homeless Children

Homeless children are known to be at risk for mental health and behavioral disorders due to housing instability and family and environmental risk factors, such as domestic violence. However, homeless children seldom receive screening for mental health and behavioral disorders with validated instruments. Moreover, few examples exist of programs that integrate outreach, screening, referral to appropriate diagnostic and therapeutic services, and care coordination. We describe early results of the Medical Home for Homeless Children Project, whose nurse care coordinators work with homeless families to conduct standardized nursing assessments that include evidence-based screening for child mental health and behavioral disorders with referral and case management for mental and behavioral health services. Screening identified a group of children with mental health issues that warranted referral, and many of those referrals were successfully completed.Family homelessness is a problem in the United States. Sheltered homeless families represented about one-third (535,447) of the 1.5 million homeless people in the U.S. in 2009, and children comprised nearly 60% (321,268) of these individuals.¹ In the last decade, the percentage of adults and children who were homeless in Duval County, Florida, increased by 19.9%.² In Florida, children comprise 16.1% of all sheltered homeless individuals.³ Homeless children have higher rates of mental and behavioral health problems than housed children, and homeless children are especially at risk for conditions such as anxiety and depression.^4,5 Indeed, one study indicated that the majority (78%) of school-age homeless children had a behavior problem, academic delay, or depression.⁵ These higher rates of mental health problems among homeless children may be the result of adverse childhood experiences associated with homelessness.⁶ Access to mental health services is often limited due to the families'' unstable living arrangements and system barriers,⁷ and this situation commonly leads to a failure to address mental health needs in homeless children.⁸The high-risk status of homeless children creates a critical need for screening, referral, and coordination of mental health services; however, there is little reported research on whether these programs are feasible and practical.⁹ Strategies such as mental health outreach and screening among homeless children may represent one way to identify child mental health problems early in the life course and represent an opportunity for preventing mental health symptoms from worsening in childhood and persisting into adulthood.¹⁰ When screening is combined with referral and care coordination within a medical home model, the overall strategies may address the system- and family-level barriers and facilitate appropriate treatment in this difficult-to-reach group. However, research on this type of coordinated approach to mental health services for homeless children is scant. To provide more insight into this issue, this study focused on the research question, “What mental health screening and referral rates might be achieved by a nurse-led medical home for homeless children?”     

G6PD San Francisco: a new variant of glucose-6-phosphate dehydrogenase associated with congenital nonspherocytic hemolytic anemia

Congenital nonspherocytic hemolytic anemia in an adult male of Scandinavian ancestry was associated with virtual absence of G6PD activity in red cells. Characterization of G6PD purified from leukocytes using standard WHO techniques revealed diminished electrophoretic mobility, marked lability on heating at 46 degrees C, normal pH optimum and utilization of alternate substrates (2-deoxy G6P, D-amino NADP), elevated Km NADP, and striking susceptibility to NADPH inhibition. The variant G6PD, which appears to be unique, has been designated G6PD San Francisco. An unusual feature of the variant enzyme, susceptibility to inactivation by brief periods of dialysis, could be prevented by addition of 200 microM NADP to the dialysis solution. In red cells, where G6PD activity was essentially absent, regeneration of reduced glutathione was totally curtailed in vitro, while in leukocytes, where residual G6PD activity was approximately 60% of normal, hexose monophosphate shunt activity, oxygen consumption during phagocytosis, and bacterial killing were unimpaired. Thus, instability of the variant enzyme rather than its unfavorable kinetics appeared to be an important determinant of abnormal cell function.