SARS preparedness checklist for state and local health officials

A planning checklist for widespread severe acute respiratory syndrome, modeled on an Association of State and Territorial Health Officials (ASTHO) pandemic influenza planning checklist, was developed jointly by ASTHO, the National Association of County and City Health Officials, and the Centers for Disease Control and Prevention. This checklist, distributed May 2003, has been widely used.     

The multi-targeted kinase inhibitor SU5416 inhibits small cell lung cancer growth and angiogenesis, in part by blocking Kit-mediated VEGF expression

SU5416 is a multi-targeted kinase inhibitor that potentially has the ability to directly block tumor growth by inhibiting Kit signaling, as well as blocking angiogenesis by inhibiting vascular endothelial growth factor receptor (VEGFR) signaling. Previous work has demonstrated that SU5416 efficiently blocks Kit-mediated growth of small cell lung cancer (SCLC) in vitro. To determine the drug's effect on in vivo growth of SCLC, we studied its activity, alone and in combination with carboplatin, in chemotherapy-resistant H526, and chemotherapy-sensitive H209 murine xenograft models. SU5416 efficiently inhibited Kit activity in vivo when administered on a twice-weekly schedule. When administered over a 3-week period to animals bearing established tumors, it inhibited growth by at least 70%. It was at least as effective as carboplatin in suppressing growth of H526 xenografts. However, the combination with carboplatin was not superior to the most active single agent in either xenograft model at the doses and schedule utilized. SU5416 clearly inhibited growth in part by inhibiting angiogenesis, with microvessel density dropping by approximately 50% in treated xenografts. In addition to the recognized mechanism of inhibition of VEGFR, we uncovered a novel mechanism of angiogenesis suppression by demonstrating reduced VEGF expression in SU5416-treated xenografts. In vitro, stem cell factor treatment of the H526 cell line enhanced expression of VEGF, which was efficiently blocked with SU5416. Thus, we have demonstrated that SU5416 can inhibit SCLC growth by directly inhibiting tumor cell proliferation and by inhibiting angiogenesis, in part by inhibiting Kit-mediated VEGF expression. These data suggest that kinase inhibitors that target both Kit and VEGFR could play an important role in the treatment of SCLC, as well as other malignancies that express Kit.     

Measurements of regional alveolar oxygen pressure using hyperpolarized 3He MRI

RATIONALE AND OBJECTIVES: The aim of this work is to review hyperpolarized (HP) helium-3 (3He) magnetic resonance imaging (MRI) methods to measure regional alveolar oxygen partial pressure (P(A)O2) and oxygen depletion rate (R) in the lung. We point out limitations of the methods and suggest improvements to increase their accuracy. MATERIALS AND METHODS: P(A)O2 and R can be extracted from series of HP gas images acquired during breath hold by making use of the depolarizing effect of oxygen on HP gas. To separate oxygen-induced depolarization from other depolarizing effects, several techniques can be used. We review currently used techniques and point out their advantages and limitations. RESULTS: We show that the precision of oxygen measurements depends on a variety of parameters and can vary within the measurement volume. Accuracy of the measurement also can be influenced by diffusion of oxygen and polarized 3He and generally is different for single-slice and multislice measurements. We present numerical simulations, phantom data, and in vivo data for illustration. CONCLUSION: HP 3He MRI is a noninvasive, nonionizing, and repeatable imaging method that allows for quantitative analysis of lung function. The current techniques for measuring P(A)O2 have the potential to deliver clinically relevant functional images.     

Inhibition of alpha(v)beta3 integrin survival signaling enhances antiangiogenic and antitumor effects of radiotherapy.

The involvement of alpha(v)beta3 and alpha(v)beta5 integrins in angiogenesis and the use of integrin antagonists as effective antiangiogenic agents are documented. Radiotherapy is an important therapy option for cancer. It has been shown that ionizing radiation exerts primarily antiangiogenic effects in tumors but has also proangiogenic effects as the reaction of the tumor to protect its own vasculature from radiation damage. Here, we show that combined treatment with S247, an Arg-Gly-Glu peptidomimetic antagonist of alpha(v)beta3 integrin, and external beam radiotherapy are beneficial in local tumor therapy. We found that radiation up-regulates alpha(v)beta3 expression in endothelial cells and consecutively phosphorylates Akt, which may provide a tumor escape mechanism from radiation injury mediated by integrin survival signaling. In the presence of S247, the radiation-induced Akt phosphorylation is strongly inhibited. Our studies on endothelial cell proliferation, migration, tube formation, apoptosis, and clonogenic survival show that the radiosensitivity of endothelial cells is enhanced by the concurrent administration of the integrin antagonist. The in vitro data are successfully translated into human glioma (U87), epidermoid (A431), and prostate cancer (PC3) xenograft models growing s.c. on BALB/c-nu/nu mice. In vivo, the combination of S247 treatment and fractionated radiotherapy (5 x 2.5 Gy) leads to enhanced antiangiogenic and antitumor effects compared with either monotherapies. These results underline the importance of alpha(v)beta3 integrin when tumors protect their microvasculature from radiation-induced damage. The data also indicate that the combination of integrin antagonists and radiotherapy represents a rational approach in local cancer therapy.     

妊娠诱发先天异常输尿管结石梗阻1例

1病例报告女,26岁.因孕5 mo余,右腰腹部间断性疼痛3 d伴高烧,于2004-05-27急诊入本院泌尿外科.患者疼痛难忍,向右下腹放射,间歇性,无恶心呕吐,无尿急、尿频、尿痛,伴发热,体温最高可达40℃,既往无泌尿系患病史.查体: T 40℃,P 110次/min,BP 16/10 kPa,R 21次/min.痛苦面容,心肺正常,右肾区及右输尿管走行区扣击痛.     

阿司匹林与埃索美拉唑合用较氯吡格雷减少高危患者再次溃疡出血的发生

问题：在有阿司匹林诱发溃疡出血史的患者中，用氯毗格雷预防溃疡出血复发，是否不次于小剂量阿司匹林加埃索美拉唑？[编者按]     

Medical decisions for troubled breathing in nursing home residents

This paper aims to gain insight into the medical decision-making processes undergone in a nursing home in response to troubled breathing. Participants were 20 residents of a large, nonprofit nursing home, six of whom died by the time of data collection. The mean age was 88 yr, and 70% were female. Diagnostic tests and medication were the most frequently used treatments. The most important considerations reported were the resident's quality of life, family wishes, and the relative effectiveness of alternative treatment options. In 45% of the cases, the physicians reported family involvement. In 30% of cases, the physicians would have wanted less treatment if they were in the resident's condition. Troubled breathing emerges as an end-of-life symptom for many residents. An analysis of the decision-making process and its evaluation could foster improved care of these symptoms.     

Epilepsy in The Alienist and Neurologist, 1880-1920

PURPOSE: To study the history of epilepsy from 1880 to 1920. METHODS: We reviewed all 40 volumes of The Alienist and Neurologist and identified articles concerning primarily epilepsy. We analyzed three of these articles in greater detail. RESULTS: The Alienist and Neurologist published "Original Contributions,"Selections," (abstracts from other journals written by the editorial board), "Editorials," and (book) "Reviews." Of 258 epilepsy articles, there were 40 Original Contributions, 164 Selections, 39 Editorials, and 15 Reviews. These articles included 71 on therapy (41 medication, 13 surgery, and 17 other therapies); 66 general discussions; 46 on etiology or symptoms; 34 case studies; 28 social/legal articles; and 13 autopsy or pathology articles. CONCLUSIONS: Analysis of The Alienist and Neurologist provides a unique and valuable perspective on the clinical practice and academic world of epileptology during the decades around the turn of the twentieth century.     

Viral studies on amniotic fluid from fetuses with and without abnormalities detected by prenatal sonography

OBJECTIVE: To study the prevalence of viruses (cytomegalovirus [CMV] adenoviruses and enteroviruses) in amniotic fluid samples from fetuses with and without anomalies detected by prenatal sonography. STUDY DESIGN: Fluid samples obtained aseptically from 474 women undergoing genetic amniocentesis at our institutions from 1995 to 1996 were stored at -20 degrees C. Fetal anomalies (renal, central nervous system, gastrointestinal and cardiac) were detected by ultrasound in 162 of the fetuses. At a later date, the samples were retrieved, blinded, and tested by virus isolation techniques for CMV, adenoviruses and enteroviruses. Fisher's exact test was used for statistical analysis. RESULTS: The prevalence of viral isolation in amniotic fluid samples in fetuses with anomalies was 2.5% for CMV, 1.3% for adenovirus and 1.2% for enterovirus. Structurally normal fetuses had prevalences of 0.3%, 0% and 0%, respectively. CONCLUSION: The prevalence of viruses, especially CMV, appears to be higher in amniotic fluid from fetuses with sonographically detected anomalies.     

Improved effect of an antiangiogenic tyrosine kinase inhibitor (SU5416) by combinations with fractionated radiotherapy or low molecular weight heparin

The effect of combining SU5416 with fractionated radiotherapy or with low molecular weight (LMW) heparin (dalteparin) was studied in U87 human glioblastoma xenografts in nude mice. SU5416 is antiangiogenic by a specific inhibition of the vascular endothelial growth factor receptor 2 (VEGFR-2), and heparins are assumed to bind VEGF. Both SU5416 (100 mg/kg every second day in 5 days) and 3 Gyx5 produced moderate, yet significant, growth inhibition. Tumors treated with concomitant irradiation and short-term SU5416 maintained a lower growth rate during regrowth than the other treatment groups (P=.007). Dalteparin (1000 IE/kg subcutaneously once a day) had no growth-inhibitory effect on its own, but when this LMW heparin was added to the SU5416 schedule, a significantly enhanced growth inhibition was obtained. VEGF protein content in tumors was not significantly altered by SU5416, but a significant decrease in VEGF levels was found in tumors treated with concomitant dalteparin and SU5416 compared with controls (P=.03). We conclude that: 1) an additive growth-inhibitory effect is obtained by combining SU5416 and fractionated radiotherapy; and 2) LMW heparin (dalteparin), in combination with SU5416, decreases the level of VEGF in tumors and increases the growth-inhibitory effect of SU5416.