Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast,and its prognostic implications

Summary One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977–1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfiet al. and Fisheret al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfiet al. need to be sharpened and simplified in order to reduce inter-and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.     

在药物洗脱支架时代，社会抑制可调节消极情绪对经皮冠状动脉介入后心脏预后的影响

目的:消极情绪对心脏预后具有不利影响。探讨社会抑制(在社会相互接触中抑制自我表现)是否可调节消极情绪对经皮冠状动脉介入(PCI)治疗后临床预后的作用。方法和结果:来自RESEARCH登记(鹿特丹的Erasm us医疗中心)的875例患者在PCI后6个月完成了抑郁、焦虑、消极(一般为消极情绪)以及社会抑制量表的评估。终点为评估后9个月发生的主要不良心脏事件犤M ACE;死亡、心肌梗死、冠状动脉搭桥术(CABG)或PCI犦。共发生100例次M ACE;与消极评分高而抑制评分低的患者(13/136,10%)相比,消极情绪及抑制评分均较高的患者(38/254,15%;P=0.018…     

Human brain atlas: For high-resolution functional and anatomical mapping

We present the new computerized Human Brain Atlas (HBA) for anatomical and functional mapping studies of the human brain. The HBA is based on many high-resolution magnetic resonance images of normal subjects and provides continuous updating of the mean shape and position of anatomical structures of the human brain. The structures are transformable by linear and nonlinear global and local transformations applied anywhere in 3-D pictures to fit the anatomical structures of individual brains, which, by reformatting, are transformed into a high-resolution standard anatomical format. The power of the HBA to reduce anatomical variations was evaluated on a randomized selection of anatomical landmarks in brains of 27 young normal male volunteers who were different from those on whom the standard brain was selected. The HBA, even when based only on standard brain surface and central structures, reduced interindividual anatomical variance to the level of the variance in structure position between the right and left hemisphere in individual brains. © 1994 Wiley-Liss, Inc.     

A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.     

Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease.

BACKGROUND: The occurrence of small vessel arteriosclerosis in the myocardium, kidney, and lung in dogs with naturally occurring myxomatous mitral valve disease has not been previously investigated systematically. METHODS: Twenty-one dogs with naturally occurring congestive heart failure and 21 age-matched, sex-matched, and weight-matched control dogs underwent extensive pathological and histopathological examination. Morphometry and scoring of tissue sections were used to measure arterial narrowing and fibrosis in the myocardium, kidney, and lung; and intimal thickness and plaque formation in the aorta and pulmonary artery. RESULTS: Dogs with congestive heart failure had significantly more arterial narrowing in the left ventricle (P < .003), lung (P < .0001), and kidney (P < .02); intimal-medial thickening in the pulmonary artery (P = .04); and fibrosis in the left ventricle (P < .0001) than control dogs. However, they did not have more plaque formation or intimal-medial thickening in the aorta than controls. There was significantly more arterial narrowing in papillary muscles than in all other locations in dogs with congestive heart failure (P < .002). In control dogs, arterial changes were less pronounced and did not differ in different locations. CONCLUSIONS: Dogs with naturally occurring myxomatous mitral valve disease have significantly more arterial changes in the myocardium, lung, and kidney, and significantly more fibrosis in the myocardium than control dogs. This could have important implications in the management of myxomatous mitral valve disease and raises interesting questions about the occurrence and importance of intramural small vessel disease in humans with primary mitral valve prolapse.     

Delayed-onset primary cytomegalovirus disease after liver transplantation.

Clinical practice guidelines recommend antiviral prophylaxis to cytomegalovirus (CMV) donor-positive/recipient-negative (D+/R-) liver transplant recipients. We assessed the outcome of this strategy by determining the incidence, clinical features, and risk factors of CMV disease among CMV D+/R- liver transplant recipients who received antiviral prophylaxis. Sixty-seven CMV D+/R- liver transplant recipients (mean age+/-standard deviation: 49.5+/-11.4 years; 75% male) received oral ganciclovir [n=9 (13%)] or valganciclovir [n=58 (87%)] prophylaxis for a median duration of 92 days (interquartile range: 91-100). No breakthrough CMV disease was observed during antiviral prophylaxis. However, primary CMV disease was observed in 2%, 25%, 27%, 27%, and 29% of patients at 1, 3, 6, 12, and 24 months, respectively, after antiviral prophylaxis was stopped. The incidence of delayed-onset primary CMV disease was similar between those who received oral ganciclovir and valganciclovir. Nine (47%) patients had CMV syndrome, 8 (42%) had gastrointestinal CMV disease, and 2 (11%) had CMV hepatitis. Female patients (P=0.01) and younger age at transplant (P=0.03) were associated with an increased risk, whereas diabetes mellitus (P<0.001) was significantly associated with a lower risk of delayed-onset primary CMV disease. Allograft loss or mortality occurred in 8 (12%) patients during the median follow-up period of 3.31 (range: 0.8-5.9) years. No significant association was observed between CMV disease and patient and allograft survival. In conclusion, CMV disease remains a common complication in CMV D+/R- liver transplant patients during the contemporary era of antiviral prophylaxis. Female patients and younger patients are at increased risk of delayed-onset primary CMV disease.     

Neural classifier construction using regularization, pruning and test error estimation

In this paper we propose a method for construction of feed-forward neural classifiers based on regularization and adaptive architectures. Using a penalized maximum likelihood scheme, we derive a modified form of the entropic error measure and an algebraic estimate of the test error. In conjunction with optimal brain damage pruning, a test error estimate is used to select the network architecture. The scheme is evaluated on four classification problems.     

Electromyography of the internal anal sphincter performed under endosonographic guidance description of a new method

PURPOSE: The aim of our study was to investigate internal anal sphincter electromyographic signals. METHODS: Electromyography of the internal anal sphincter was performed with platinum wire electrodes in six healthy volunteers (three males and three females), inserted under endosonographic guidance. Platinum wire electrodes were also inserted into the external anal sphincter. Activity of both the internal and external anal sphincter in a 40-second period was measured. RESULTS: Internal anal sphincter median activity was 22.1 (range, 5.5–67.6) μ V. Slow-wave activity was 47 cycles/minute (range, 34–55 cycles/minute). After inflation of a rectal balloon with air until a constant relaxation of the anal canal was obtained, a decrease in internal anal sphincter activity to 15.9 (1.2–31.3) μV as well as a decrease in slow-wave activity to 34 cycles/minute (range, 27–40 cycles/minute) was found. The original internal anal sphincter EMG was resumed after deflation of the rectal balloon. External anal sphincter median activity was 31 (range, 0.77–18.6)μV. During inflation of the rectal balloon, a reflex increase in external sphincter EMG activity was found. With the rectal balloon fully inflated a part of this increase was still present, 11.0 (1.9–24.6)μV. In some of the subjects, this increased activity was superimposed on the internal anal sphincter recordings as well. During a voluntary squeeze it was not possible to identify internal anal sphincter activity due to activity of the external anal sphincter totally overriding the internal anal sphincter signal. CONCLUSION: Precise EMG recordings from the internal anal sphincter is possible with endosonographic guidance of the electrodes, except during voluntary squeezing of the external anal sphincter.     

Influence of physical activity on plasma digoxin in hospitalised patients

The influence of physical activity on the plasma digoxin concentration was investigated in 13 digitalised patients suffering from a variety of cardiac diseases. Plasma digoxin concentration was determined four times during two consecutive days. In the morning, the standing position and one hour of physical activity caused a consistent and significant decrease in the plasma digoxin concentration, the mean reduction being 26.7 percent. In the afternoon, no consistent changes of plasma digoxin concentration were observed during one hour's rest. Consequently, we suggest standardisation of the blood sampling procedure so that no blood collection takes place in the morning until the patient has been performing normal physical activity for at least one hour.