Ki-67 expression in primary breast carcinomas and their axillary lymph node metastases: clinical implications

Proliferative activity of tumour cells assessed by immunohistochemical Ki-67 expression is one of several prognostic indicators in breast cancer. The major objective of this study was to investigate the prognostic impact of Ki-67 proliferative activity in the axillary lymph node metastases and in the matched primary breast carcinoma from 194 patients. There was a statistically significant up-regulation of Ki-67 protein in the metastatic deposit compared to where the primary tumour was found (p = 0.001). A low Ki-67 index in both the primary and the metastatic tumours was a favorable prognostic factor. A high index in both primary and metastatic lesion and an up-regulation from a low index in the primary tumour to a high index in the metastatic deposit represented an unfavorable prognostic factor. Multivariate analysis showed that Ki-67 expression in the metastases was a superior independent prognostic factor of clinical outcomes compared to that in the primary tumours. Ki-67 expression in ≥10% of carcinoma cells in the primary tumours and ≥15% in the nodal metastases seems to be optimal cut-off levels. Ki-67 is of value as an independent prognostic factor in breast cancer.     

Reduced lipid peroxidation in dilated hearts of cardiomyopathic turkeys

Adverse pulmonary reactions to some nitrofuran antibiotics are thought, in part, to involve production of reactive oxygen radicals. Furazolidone, a nitrofuran antibiotic, causes a dilated cardiomyopathy in domestic turkeys. The mechanism of this drug induced cardiomyopathy is unknown. We investigated the possible role of free radical injury in this heart failure model. Left ventricular lipid peroxidation capacity, assessed by two methods (the thiobarbituric acid reactive substances and lipid hydroperoxides assays respectively), was investigated in five 5-8 week old cardiomyopathic turkeys with severe cardiac dilatation, left ventricular dysfunction and systemic hypotension, and in five control birds. Superoxide dismutase activity, total and manganese, was also measured in the crude left ventricular homogenates. Both lipid peroxidation products were reduced in the myopathic hearts: thiobarbituric acid reactive substances (malondialdehyde) 70(SEM 4) v 86(3) nmol.100 mg protein-1 in controls, p less than 0.02; and lipid hydroperoxides 29(7) v 74(14) nmol.100 mg protein-1, p less than 0.02. Total superoxide dismutase activity was similar in cardiomyopathic and control hearts: 670(26) v 657(105) nitrite units.100 mg protein-1. Although total superoxide dismutase activity was unchanged, we found decreased manganese superoxide dismutase in the dilated hearts compared with controls (54% v 84% of total activity, p less than 0.02). In separate in vitro experiments furazolidone (2-10 mg.g wet weight-1) did not increase malondialdehyde production in turkey (or rat) left ventricular homogenates. These results indicate that cardiomyopathy induced by furazolidone is associated with decreased myocardial lipid peroxidation. Although as yet unexplained, the decrease may be due to a diminished amount of heart lipid susceptible to peroxidation accompanying the process of cardiac hypertrophy and dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced heart lipid peroxidation precedes cardiac dilatation in turkeys with naturally occurring cardiomyopathy

STUDY OBJECTIVE--The aim of the study was to determine if reduced heart lipid peroxidation in 1-2 month old turkeys with furazolidone induced dilated cardiomyopathy is drug related and model dependent, a non-specific characteristic of the dilated turkey heart, or if alterations of heart lipid peroxidation can occur prior to onset of cardiac dilatation, and therefore may be involved in its pathogenesis. DESIGN--Ventricular lipid peroxidation capacity and superoxide dismutase activity were measured in controls and in turkeys with spontaneous cardiomyopathy at various ages (newly hatched, 7-10 d, and 1-2 months) and stages of the disease. SUBJECTS--46 turkeys with naturally occurring dilated cardiomyopathy and 29 age matched controls were used at hatch, 7-10 d, and 1-2 months of age. MEASUREMENTS AND MAIN RESULTS--Heart lipid peroxidation, measured by thiobarbituric acid reactive substances (malondialdehyde), was found to be reduced not only in the dilated hearts of 1-2 months old cardiomyopathic turkeys [114(SEM 10) v 176(21) nmol.100 mg-1 protein, p = 0.023] but also in the non-dilated hearts of 9-10 day old cardiomyopathic turkeys [135(17) v 274(35) nmol.100 mg-1 protein, p = 0.004]. Ventricular superoxide dismutase activity was similar in control and cardiomyopathic turkeys at all stages and there was the expected increase with age. In control turkeys ventricular superoxide dismutase activity in 1-2 month old birds, at 718(52) nitrite units.100 mg-1 protein, was significantly higher than values in 7-10 day old turkeys [398(31) nitrite units.100 mg-1 protein, p = 0.001]. CONCLUSIONS--Decreased lipid peroxidation capacity is present in the dilated hearts of spontaneously cardiomyopathic turkeys. However, it is also decreased in cardiomyopathic turkeys at 9-10 d (the time of highest mortality) prior to the onset of cardiac dilatation. Therefore, alterations in heart lipid composition may be involved in the pathogenesis of this cardiomyopathy and not simply a result of the cardiac dilatation/hypertrophy process.     

Myocardial high-energy phosphate levels in cardiomyopathic turkeys

A congestive cardiomyopathy (CCM) model occurs in inbred broad-breasted turkeys and is manifested by reduced hatchability and a high mortality within a week of hatching. In the survivors, cardiac dilation begins by 3-4 weeks of age and further mortality occurs from chronic congestive heart failure. The mechanisms behind these changes is unknown, and, therefore, we investigated what role, if any, myocardial energy metabolism might play in these events. Ventricular myocardial samples were obtained for analysis of adenine nucleotides (ATP, ADP, AMP) and creatine phosphate (CP) in control and CCM turkeys, 1-31 days old. The adenine nucleotide energy charge (EC) was calculated using the formula EC = ATP + 1/2ADP/(ATP + ADP + AMP). We found the myocardial ATP levels and EC in CCM hearts at 1-2 days were reduced. In control turkeys, no significant age-related differences were found in myocardial high-energy phosphate compounds or in the EC. This depression in the energy metabolism of CCM turkeys may also be reflected in their poor hatchability. By 6-10 days, however, ATP levels had recovered and remained normal despite the onset of cardiac dilation and failure at 3-4 weeks of age in CCM turkeys. Because CP levels in control and CCM turkey hearts were similar in all age groups, significant ischemia did not appear to be present after hatching in CCM turkeys. Our results suggest, therefore, that an insult probably prior to hatching produced depressed myocardial energy levels in CCM turkeys and led to reduced hatchability. This early insult appears to be significant, in that late cardiac dysfunction resulted despite the recovery of myocardial ATP levels.     

Effects of orthodontic force on enamel formation in normal and hypocalcemic rats

Maxillary incisors of young rats fed a diet deficient in calcium and vitamin D for 4 weeks developed hypoplastic enamel surfaces. In the enamel of maxillary incisors of deficiently fed rats as well as in normal rats, an orthodontic force (50 gin) acting on their incisors for 3–7 days induced foldings in the enamel, globular projections from the surface and marked hypoplastic defects. However, the orthodontic force produced clusters of free-lying enamel matrix only in the nutritionally deficient rats. In view of these observations, it might be concluded that disturbances in enamel formation which cause hypoplasias can he caused both by mechanical trauma and hypocalcemia. Furthermore, it seems that hypocalcemia increases the susceptibility to mechanical trauma of ameloblasts in their secretory stage. Whether the changes in enamel formation noted in the hypocalcemic rats is a direct effect of lowered serum calcium or due to the increase in parathyroid hormone is not known at present.     

Swedish dentists' perceptions of their patients.

Swedish dentists' perceptions of patient behavior problems, levels of stress experienced by the dentists in relation to such behavior, and general problem areas in their occupational situation were investigated by means of a self-administered questionnaire mailed to a sample of 485 Swedish dentists. The questionnaire assessed 16 different patient behavior problems and an additional number of other occupationally related problem areas. A total of 342 replies (71.4%) were analyzed. The relationship between the occurrence of behavior problems and the resulting level of stress was inversely proportional. This implies that Swedish dentists feel confident in dealing with behavior problems in their patients. Furthermore, this study shows that most dentists (93%) feel positive about their work and believe that their work is highly appreciated by their patients (96%) and colleagues (84%).     

Association of varicella,myocarditis, and congestive cardiomyopathy

Summary A retrospective study of children dying with active varicella revealed 11 of 17 cases who had unsuspected interstitial myocarditis at the time of their death.In addition, a prospective study of 6 children, consecutively admitted to the hospital with active varicella, were evaluated for evidence of cardiac dysfunction by echocardiography, ECG, and serum enzyme levels. All 6 children had Reye's syndrome in association with active varicella. Evidence of myocardial involvement, consistent with acute congestive cardiomyopathy, was documented in 4 of the 6 children.This study suggests that the heart is commonly involved in varicella infections and that cardiac involvement should be considered in children with this disease.This work was supported in part by the Dwan Family Fund and by Grant HL18204 from the National Institutes of Health, and was part of the Ray C. Anderson Symposium.     

ANALYSIS OF POLYBROMINATED DIPHENYL ETHERS IN SWEDISH HUMAN MILK. A TIME-RELATED TREND STUDY, 1972-1997

A previously described method for analysis of organochlorine compounds in human milk was adopted for analysis of brominated diphenyl ethers ( BDEs) substituted with three to six bromine atom s. Analytes were extracted from hum an milk with the lipophilic gel Lipidex 5000. Further purifications were performed on partly deactivated aluminum oxide and silica gel columns, followed by gel permeation chromatography. The concentrations of BDEs were determined by gas chromatography/mass spectrometry (GC/MS). The average recoveries of 2,2',4-triBDE (BDE-17), 2,4,4'-triBDE (BDE28) , 2,2',4,4'-tetraBDE (BDE-47), 2,3',4,4'-tetraBDE (BDE-66), 2,2',3,4,4'-pentaBDE (BDE-8 5) , 2,2',4,4',5-p entaBDE (BDE-99), 2,2',4,4',6-pentaBDE (BDE-100) , 2,2',4,4',5,5'-hexaBDE (BDE-153), and 2,2',4,4',5,6'-hexaBDE (BDE-154) added to the samples before extraction ranged from 86% to 102% . Pooled samples of breast milk, collected at eight time periods between 1972 and 1997, were analyzed for PBDEs. BDE-47 was the most abundant PBDE congener in all samples. In total, eight PBDE congeners were identified in the milk. The sum of the concentrations of BDE congeners in human milk increased from 0.07 to 4.02 ng/g lipids during the 25-yr period studied.