Prognostic value of CD40 in adult soft tissue sarcomas.

PURPOSE: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value. EXPERIMENTAL DESIGN: CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases. RESULTS: Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively. CONCLUSIONS: These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas.     

A comparison in cosmetic outcome between per-operative interstitial breast implants and delayed interstitial breast implants after external beam radiotherapy.

BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in cosmetic outcome were investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per-operative implant were compared to 123 patients having a delayed interstitial implant in a matched case-control study. Cosmesis was scored on a four-point-scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63 months, three observers found no difference in cosmetic outcome between the two groups after adjustment for variables found to be related with cosmesis (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34 cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing per-operative implants has not led to smaller implants. The method of performing brachytherapy does not result in marked differences in cosmetic outcome.     

Frequent loss of expression of the cyclin-dependent kinase inhibitor p27(Kip1) in estrogen-related Endometrial adenocarcinomas.

PURPOSE: p27(Kip1) is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of gynecological tumors, including breast, ovarian, and cervical carcinomas. The role of p27 in endometrial cancer remains controversial. EXPERIMENTAL DESIGN: In the present study, p27 protein expression was investigated by immunohistochemistry in a series of 217 endometrial adenocarcinomas and, where present, in synchronous normal endometrium, simple and complex hyperplasia (with or without atypia), and cystic atrophy. The relationship between p27 expression and clinical outcome was also evaluated. RESULTS: Immunohistochemical analysis revealed a significant loss of p27 expression from normal (33%) through hyperplastic endometrium (50%) to endometrial adenocarcinomas (71%; P 相似文献   

Doxorubicin pharmacokinetics: the effect of abnormal liver biochemistry tests

We studied variability in doxorubicin pharmacokinetics in 24 patients with abnormal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography. The relationship between doxorubicin clearance (dose/AUC) and liver biochemistry tests (AST, bilirubin, albumin, alkaline phosphatase and indocyanine green clearance) was investigated. Patients with a raised bilirubin level had reduced doxorubicin clearance, but there was no clear relationship between the extent of this elevation and the reduction in doxorubicin clearance. Doxorubicin clearance was lower in patients with an isolated increase in AST than in those with normal liver biochemistry, but this difference was not statistically significant. Nevertheless, there was a significant correlation between reduced doxorubicin clearance and both raised serum AST levels and low indocyanine green clearance. These pharmacokinetic data suggest that current dose reductions based solely on the extent to which bilirubin is elevated may not be optimal. Received: 20 October 1997 / Accepted: 20 January 1998     

Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing

Type I collagen is the main collagen in tendons; type III collagen is present in small amounts. Ruptured Achilles tendons contain a significantly greater proportion of type Ill collagen, which predisposes them to rupture. We used an in vitro model to determine whether tenocytes from Achilles tendons that were ruptured (N = 22), nonruptured (N = 7), tendinopathic (N = 12), and fetal (N = 8) show different behavior. Samples of Achilles tendon were digested with collagenase and the released tenocytes were collected. Primary tenocyte cultures were established and subsequently cultured onto glass coverslips. Once a confluent monolayer was obtained, the cell populations were "wounded" by scraping a pipette tip along the surface. The cultures were further incubated for either 1, 4, 8, 12, 16, or 24 hours, and production of types I and II collagen was assessed by immunostaining. In cultures from ruptured and tendinopathic tendons, there was increased production of type Ill collagen. Athletic participation places excess stress on the Achilles tendon, which could potentially lead to areas of microtrauma within the tendon. These areas may heal by the production of type III collagen, which is an abnormal healing response. Accumulation of such episodes of microtrauma could resuit in a critical point where the resistance of the tissue to tensile forces is compromised and tendon rupture occurs.     

Seasonal variation of hip fracture at three latitudes

We studied the seasonal variation of hip fracture admissions at three different latitudes: Scotland (56 degrees North; 54,399 admissions); Shatin, Hong Kong (22 degrees North; 4180 admissions); and Auckland, New Zealand (36 degrees South; 2257 admissions). We calculated the extent of seasonal variation (amplitude) and the time of year of the peak value (acrophase) by fitting a sine curve to monthly data using cosinor analysis. A significant seasonal variation was found in all three countries, at a high level in Scotland (p < 0.01) and Hong Kong (p < 0.001), but just significant in New Zealand (p < 0.05). The extent of the seasonal change was very similar in Scotland and New Zealand, but, as expected, the peak in New Zealand (early September) was approximately six months ahead of Scotland (mid February). In Hong Kong, the amplitude was three times greater than in Scotland and the peak occurred a month earlier. There is neither snow nor ice in Hong Kong, and this provides powerful evidence against a major influence of conditions underfoot causing extra falls in winter. In Scotland there was a significant increase in the proportion of deaths in winter as compared to summer. The Scotland/Hong Kong amplitude difference is striking, but it is unknown whether this has a genetic or environmental explanation. The cause of seasonal death difference to a given injury is also unknown. Possible mechanisms are discussed, but the purpose is to report two new epidemiological features, without wild speculative hypotheses. The findings should be viewed as leads to further epidemiological, clinical and more basic research.     

Social difficulties and victimization in children with SLI at 11 years of age.

Specific language impairment is sometimes thought to be associated with concurrent difficulties in the area of social and behavioral development (N. Botting and G. Conti-Ramsden, 2000; D. P. Cantwell and L. Baker, 1987; M. Fujiki, B. Brinton, and C. Todd, 1996; S. Redmond and M. Rice, 1998). The present study follows a group of 242 children, initially studied at age 7 years when they attended language units in England, and assesses their social and behavioral status at age 11 years. In total, 64% of the children were found to have scores on the Rutter behavioral questionnaire (M. Rutter, 1967) of 9 or above (clinical threshold); 34% scored over the threshold for the Strengths and Difficulties questionnaire (R. Goodman, 1997); and 39% scored below average on the Peer Competence subscale of the Harter Perceived Competence Scale (S. Harter and R. Pike, 1984). On further analysis, these generalized difficulties were characterized mainly by poor social competence. In addition, 36% of the cohort were at risk of being regular targets for victimization compared to 12% of a comparison sample of typically developing peers. Few associations were found between social outcome and other measures, including nonverbal intelligence, overall linguistic skill, gender, and longitudinal measures taken previously. Importantly, however, pragmatic language difficulties measured on the Children's Communication Checklist (D. V. M. Bishop, 1998) were most strongly related to poor social outcome and to expressive language related to victimization.     

School vision screening, ages 5–16 years: the evidence-base for content, provision and efficacy

The optometric profession in the UK has a major role in the detection, assessment and management of ocular anomalies in children between 5 and 16 years of age. The role complements a variety of associated screening services provided across several health care sectors. The review examines the evidence-base for the content, provision and efficacy of these screening services in terms of the prevalence of anomalies such as refractive error, amblyopia, binocular vision and colour vision and considers the consequences of their curtailment. Vision screening must focus on pre-school children if the aim of the screening is to detect and treat conditions that may lead to amblyopia, whereas if the aim is to detect and correct significant refractive errors (not likely to lead to amblyopia) then it would be expedient for the optometric profession to act as the major provider of refractive (and colour vision) screening at 5-6 years of age. Myopia is the refractive error most likely to develop during primary school presenting typically between 8 and 12 years of age, thus screening at entry to secondary school is warranted. Given the inevitable restriction on resources for health care, establishing screening at 5 and 11 years of age, with exclusion of any subsequent screening, is the preferred option.