Intestinal and extra-intestinal tumor multiplicities in the Apc1638N mouse model after exposure to X-rays

Seven-week-old Apc1638N mice were exposed to a single dose of 5 Gy total-body X-irradiation resulting in a 8-fold increase in the number of intestinal tumors and a reduction of the lifespan to an average of 6 months. The distribution of tumors along the intestinal tract as well as the adenoma/carcinoma ratio, were similar between non-irradiated and irradiated animals. Semi-quantitative PCR analysis of intestinal-tumor DNA revealed that 10 out of 14 tumors had lost the wild-type Apc allele. However, in contrast to spontaneous Apc1638N intestinal tumors in which the LOH event at the Apc locus involves the entire chromosome 18 (1), in 6 out of 10 tumors derived from X-irradiated animals the Apc loss is associated with only a partial intrachromosomal deletion. The remaining tumors have lost all chromosome 18 markers tested. In addition to the intestinal tumors, female Apc1638N mice are susceptible to the development of mammary tumors. Upon X-irradiation, Apc1638N mice show a striking 15-fold increase in mammary tumors. Moreover, Apc1638N mice spontaneously develop other extra-intestinal neoplasia, such as desmoid-like lesions similar to those associated with familial adenomatous polyposis (FAP), the human syndrome caused by germline mutations in the APC gene. Spontaneous desmoid growth is sex-dependent, as male Apc1638N mice develop 3-fold more desmoids than female mice. Interestingly, X-irradiation seemed to increase the number of desmoids per animal nearly twofold only in female Apc1638N mice. Five out of 9 desmoids found in Apc1638N mice exposed to X-ray displayed loss of the wild-type Apc allele.      

A long-term prospective study of varicella vaccine in healthy children

BACKGROUND: Studies in Japan and the United States have shown that varicella vaccine is both safe and efficacious. In 1984, we undertook a 10-year prospective study using a research lot of Oka/Merck varicella vaccine to assess antibody persistence and breakthrough chickenpox rates. In 1987, we began a similar prospective study with lots made in production facilities that ended after 6 years because many children were given a second dose. The purpose of this study is to report humoral antibody persistence and breakthrough chickenpox rates after 6 to 10 years of prospective follow-up. METHODS: One hundred forty-three seronegative children received a research lot (950 plaque-forming units/dose) with 97.9% seroconversion by an assay for fluorescent antibody to membrane antigen (FAMA). One hundred thirty-eight children received production lots (1145 to 3265 plaque-forming units/dose) with 93.5% seroconversion. Yearly chickenpox exposure surveys were completed by phone, and children were seen by a study nurse whenever chickenpox was suspected. A subset in each group had serum collected every 2 years and tested for FAMA antibody. RESULTS: In the research group there have been 25 cases of chickenpox in 137 seroconverters in a period of more than 10 years (yearly rate of 1.7%). In the production lot group there have been 22 cases of chickenpox in 129 seroconverters in a 6-year period (yearly rate of 2.8%). In the research group the median titer rose from 1:16 to 1:64 between 1 and 10 years. In the production group, the median titer did not change between 1, 2, and 4 years. Median antibody titers were compared between the research and production groups at 1, 2, and 4 years and did not differ. The rate of development of modified chickenpox has not increased with time since vaccination, and neither has the case severity. Children with FAMA titers /=64. CONCLUSIONS: 1) Modified chickenpox has occurred in approximately 2% to 3% of vaccinees per year, regardless of the vaccine lot given. 2) FAMA titers have risen between 1 and 10 years in research lot recipients and remained the same in production lot recipients. 3) The likelihood of modified chickenpox developing is inversely related to the 6-week postvaccination FAMA titer.     

The Atherosclerosis Risk in Young Adults (ARYA) study: rationale and design

Introduction: Despite recent advances in treatment, cardiovascular disease (CVD) is still health problem number one in western societies. Aiming at specific prevention strategies for high-risk individuals and shifting the available prevention programs towards younger age groups might increase the success of primary prevention. However, before addressing age-specific prevention programs, more insight in the determinants of early vascular damage and increased cardiovascular risk is warranted as well as insight in determinants increased cardiovascular risk, including vascular damage, at an early age. The Atherosclerosis Risk in Young Adults (ARYA) study was specifically designed to address this issue. Objectives: The ARYA study started off with studies evaluating (1) whether it is possible to predict cardiovascular risk at young adulthood by routinely measured adolescent data, and (2) evaluating the role of birth characteristics and adolescent characteristics to the development of vascular damage at young adulthood. Methods: The ARYA study comprises of two cohorts of young adults. The Utrecht cohort includes 750 young adults, aged 27–30 years. The Hague-cohort includes 261 young adults born between 1963 and 1968. Data on birth characteristics, growth in early infancy as well as adolescent anthropometry, blood pressure, lipids, body mass index were obtained from the original medical records of the Municipal Health Service. In 1999/2001, the extent of subclinical vascular damage was measured using carotid wall thickness and aortic stiffness. Also, data on adult cardiovascular risk profile, bone density and central blood pressure were assessed, fasting blood was drawn and timed overnight urine samples were collected. Conclusion: The ARYA study is aimed to provide data on early determinants of cardiovascular risk, including vascular damage, at an early age. This knowledge enhances the understanding of atherosclerosis development and CVD risk and is needed to improve the available primary prevention programs.     

Cardiovascular risk factors. II. Signs of vascular damage: practical implications

In recent years, an increasing amount of information has become available on new indicators of cardiovascular damage, their determinants and the value of these indicators in the prediction of the development of cardiovascular disease. These indicators include carotid intima-media thickness, ECG characteristics, endothelial function and the measurement of coronary calcium. These indicators are currently used predominantly in cardiovascular disease research. At present, only limited information is available as to whether these indicators are useful in clinical practice for estimating the absolute risk of cardiovascular disease in an individual. The relative value of these newer indicators compared to the routinely collected risk factor information such as medical history, lifestyle, anthropometric variables, blood pressure and lipids is also not yet well established. The recent Dutch guidelines for the initiation of treatment with blood pressure lowering and lipid lowering drugs as a function of the absolute risk of cardiovascular disease within 10 years for the individual patient point toward the urgent necessity for research in the area of new risk indicators of vascular damage.     

The EUROSTROKE cohorts: a short description and data analytical approach

This paper describes the design and methodology of the participating cohorts in the EUROSTROKE project. Information is given about the cohort sampling, its size, the follow up procedures and event classification. Information is also given about the measurement of the cardiovascular and cerebrovascular risk factors in each of the cohorts separately. The cohorts described are the Caerphilly study in Cardiff, United Kingdom; the Kuopio Ischaemic Heart disease study in Kuopio, Finland; the Portugal study in Coimbra, Portugal; the EPIC cohort in Athens, Greece; the Ilsa study from Firenze, Italy; the Rotterdam Study in Rotterdam, the Netherlands, and the Novosibirsk cohort in Novosibirsk, Russia.     

烧伤患者早期血清及创面渗出液中舒普深的药代动力学

0　引言　烧伤感染是烧伤常见并发症及主要死亡原因之一 [1 ] .作好防治 ,成为必须解决的课题 .本研究从烧伤患者血清及创面渗出液中舒普深的药代动力学变化规律 ,提出烧伤早期合理应用抗生素的给药方案 .1　材料和方法1.1　材料　本组患者共 16例 ,平均烧伤面积 (6 1.7± 16 ) % .一次给予舒普深成人 2 .0 g,儿童 5 0 mg· kg- 1 ,在 (2 2± 2 .8)min内静脉滴注完毕后 1,2 0 ,6 0 ,12 0 ,30 0和 6 0 0 m in抽取血标本 ,创面渗出液标本抽取则按 5 ,2 0 ,6 0 ,12 0 ,2 40 ,36 0 ,480和 6 0 0 min进行 .1.2　方法1.2 .1　微生物平皿扩散法 (M…     

Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease.

Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related beta-protein. Silver stain-positive, "senile plaque-like" structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approximately equal to 4000 and its partial amino acid sequence to position 21 showed homology to the beta-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of beta-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.     

Validation of a malnutrition screening tool for patients receiving radiotherapy

Nutrition screening identifies individuals who are malnourished or at risk of becoming malnourished and who may benefit from nutrition support. The aim of this study was to validate a new malnutrition screening tool (MST) in cancer patients undergoing radiotherapy. The MST was compared with the subjective global assessment (SGA) of nutritional status. One hundred and six patients attending two cancer care centres in Australia were independently rated as well nourished or malnourished using SGA and at risk or not at risk of malnutrition using the MST. Convergent validity of the MST was established by determining the ability of the MST to predict SGA. According to SGA, 89% of the patients were well nourished and 11% were moderately malnourished. According to the MST, 28% of patients were at risk of malnutrition. The MST had a sensitivity of 100% and a specificity of 81%. The positive predictive value was 0.4 and the negative predictive value was 1.0. The MST is easy to use and is a strong predictor of nutritional status. The malnutrition screening tool is a simple, quick, valid tool that can be used to identify radiation oncology outpatients who are at risk of malnutrition.