Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence

AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer.METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT, n = 90), long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with immunohistochemistry for CD44v6. The extent and intensity of membranous and cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern, were analyzed.RESULTS: Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous CD44v6 expression, the staining pattern in the invasive front was determined as “front-positive” and in 41% as “front-negative”. The latter pattern was associated with narrower circumferential margin (P = 0.01), infiltrative growth pattern (P < 0.001), and shorter disease-free survival in univariate survival analysis (P = 0.022) when compared to the “front-positive” tumors.CONCLUSION: The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease.     

Ruling Out Myocardial Infarction with Troponin T and Creatine Kinase MB Mass: Diagnostic and Prognostic Aspects

Objective - To investigate the time window for ruling out myocardial infarction (MI) with troponin T (TnT) and creatine kinase isoenzyme MB mass (CK-MBm) and the prognosis of patients with ruled-out MI diagnosis. Design - The study was based on 397 patients admitted with a suspected acute coronary syndrome but with relief of symptoms within 24 h. Results - MI diagnosis was confirmed with elevated TnT (> 0.10 µg/l) in 108 patients, in 91% within 12-24 h from the onset of symptoms, and in 99% within 12 h from admission. In 94 of these patients CK-MBm became elevated (> 5.0 µg/l), in 95% within 10-12 h from the onset of symptoms, and in 99% within 6 h from admission. Among patients with ruled-out MI diagnosis, the 1-year incidence of recurrent coronary events was 29% in those with positive history of coronary heart disease (CHD) but only 7% in those without prior CHD ( p < 0.001). Conclusion - Using TnT or CK-MBm, MI can be ruled out within 12 h from admission in the majority of patients. Among patients with ruled-out MI diagnosis, positive history of CHD is an important determinant of prognosis.     

Estrogen receptor-1 genotype is related to coronary intima thickness in young to middle-aged women

OBJECTIVE: The incidence of coronary disease in premenopausal women is about one-half that in men of similar age. The estrogen receptor-1 (ESR1, c.454-397T>C) CC variant genotype is associated with the severity of coronary artery disease (CAD) and an increased risk of myocardial infarction in men. The purpose of the present study was to investigate whether this ESR1 CC variant also disposes to atherosclerosis in women in terms of increased total coronary artery intima thickness. MATERIAL AND METHODS: A total of 125 forensic autopsy cases of women aged 15 to 49 years were investigated. The thickness of the coronary intima, which reflects the severity of atherosclerosis, was measured by computerized image analysis. The ESR1 c.454-397T>C genotype was determined by polymerase chain reaction (PCR). RESULTS: The mean intima thicknesses in the three genotype groups were 428+/-298 microm (TT), 494+/-371 microm (CT) and 636+/-436 microm (CC). We found that, on average, women with the CC genotype had a thicker coronary intima compared with that of women with the TT genotype, even after adjusting for age and body mass index (BMI) (p = 0.030). The intermediate group (TC) did not significantly differ from either the CC or the TT genotype group in this respect. CONCLUSION: Our results point to the importance of ESR1 genotype in relation to cardiovascular disease susceptibility.     

Brown adipose tissue function is accompanied by cerebral activation in lean but not in obese humans

Brown adipose tissue (BAT) is able to generate heat and dissipate energy in response to cold exposure in mammals. It has recently been acknowledged that adult humans also have functional BAT, whose metabolic activity is reduced in obesity. In healthy humans, the cerebral mechanisms that putatively control BAT function are unclear. By using positron emission tomography (PET), we showed that cold-induced BAT activation is associated with glucose metabolism in the cerebellum, thalamus, and cingulate, temporoparietal, lateral frontal, and occipital cortices in lean participants, whereas no such associations were found under warm control conditions. The cold-induced increase in cerebral glucose metabolism was more robust in lean than obese participants. Cerebral glucose metabolism was not associated with skeletal muscle or white adipose tissue glucose uptake under warm or cold conditions. In conclusion, BAT metabolism was accompanied by the activation of specific cerebral regions, and this shows an uncharacterized role that the brain plays in the regulation of BAT function. In obese participants, the cold-induced response in cerebral activity was attenuated that provides a clue for obesity-induced impairment in BAT metabolism.     

Low biological aggressiveness of screen-detected lung cancers may indicate over-diagnosis

All cases of lung cancer diagnosed in the Tampere University Hospital catchment area in 1983–1987 were identified, analyzed for DNA flow cytometry and followed up to 1992. The patients were classified into 3 groups: screen-detected, symptom-detected, and detected by chance. The biological aggressiveness as indicated by DNA flow cytometry was not related to the survival of the symptom-detected patients. Also the screen-detected patients with an aggressive tumour (aneuploid or high S-phase fraction, SPF) had the same survival as the symptom-detected patients. The survival of screen-detected patients with a diploid or low SPF tumour was significantly better than that in the other groups. It is concluded that some of the previously known discrepancy of no effect on mortality and effect on survival of lung-cancer screening may be due to over-diagnosis, i.e., detection of morphologically malignant but biologically indolent lesions by screening. © 1996 Wiley-Liss, Inc.     

Knee osteoarthritis in former runners,soccer players,weight lifters,and shooters

Objective. To determine the relationship between different physical loading conditions and findings of knee osteoarthritis (OA). Methods. We selected 117 male former top-level athletes (age range 45–68 years) who had participated in sports activities with distinctly different loading conditions: 28 had been long-distance runners, 31 soccer players, 29 weight lifters, and 29 shooters. Histories of lifetime occupational and athletic knee loading, knee injuries, and knee symptoms were obtained, and subjects were examined clinically and radiographically for knee findings of OA. Results. The prevalence of tibiofemoral or patellofemoral OA based on radiographic examination was 3% in shooters, 29% in soccer players, 31% in weight lifters, and 14% in runners (P = 0.016 between groups). Soccer players had the highest prevalence of tibiofemoral OA (26%), and weight lifters had the highest prevalence of patellofemoral OA (28%). Subjects with radiographically documented knee OA had more symptoms, clinical findings, and functional limitations than did subjects without knee OA. By stepwise logistic regression analysis, the risk for having knee OA was increased in subjects with previous knee injuries (odds ratio [OR] 4.73), high body mass index at the age of 20 (OR 1.76/unit of increasing body mass index), previous participation in heavy work (OR 1.08/work-year), kneeling or squatting work (OR 1.10/work-year), and in subjects participating in soccer (OR 5.21). Conclusion. Soccer players and weight lifters are at increased risk of developing premature knee OA. The increased risk is explained in part by knee injuries in soccer players and by high body mass in weight lifters.     

Maternal origin of transferrin receptor positive cells in venous blood of pregnant women

We studied the origin of transferrin receptor (CD71) positive cells in blood from seven women pregnant with a male fetus in order to explore if fetal cells could be detected among them. We used a technique that allows direct chromosomal analysis by in situ hybridization on immunologically and morphologically classified cells. Enrichment was performed by magnetic activated cell sorting (miniMACS)® using an anti-CD71 monoclonal antibody. The cells were immunophenotyped by alkaline phosphatase anti-alkaline phosphatase immunostaining with the same antibody. The origin of the immunophenotyped cells was studied by in situ hybridization using an X cosmid Y repeat chromosome specific probe cocktail. CD71 positive cells were found in six of the seven women at the range of 4 to 43 in respective samples. Over 90% of the CD71 positive cells were nucleated erythrocytes. None of the detected positive cells were shown to be fetal. Thus, the use of transferrin receptor antigen alone in combination with the miniMACS® may not be sufficient for enrichment of fetal cells.