SUMMARY In 35 open chest anesthetized dogs coronary and aortic blood flow were measured with electromagnetic flowmeters while aortic and distal coronary blood pressure and an epicardial ECG were recorded. A fixed amount of stenosis (60-80%) was produced in the coronary artery by an externally applied plastic cylinder. In 24 of the 35 dogs the coronary blood flow showed cyclical reductions to near zero, with a sudden spontaneous return to near control levels. During reduced flow the epicardial ECG showed ST-segment depression suggestive of ischemia, and ventricular premature beats were often noted. Six animals died acutely during episodes of reduced flow.MANY STUDIES OF MYOCARDIAL INFARCTION AND SUDDEN DEATH from coronary heart disease have been reported. The significance of acute occlusive thrombi as a precipitating cause is widely debated.' 2 Acute coronary occlusion by thrombi were found in 21%' to 88%4 of those infarcted hearts examined at autopsy. These data vary with the investigative technique and material examined. In many patients with coronary artery disease and sudden death no acute thrombus or other mechanism for producing acute coronary insufficiency is demonstrated at post mortem examination and an episode of transient ischemia precipitating arrhythmia is often postulated.Platelet aggregation is involved in the formation of arterial thrombi and is not prevented by coumarin or heparin anticoagulant therapy.5 Mechanical damage of platelets can induce platelet aggregation in vitro6 and thrombosis occurs in areas of turbulent flow.7 It has been postulated that the turbulent flow produced at the sites of atherosclerotic plaques may play a role in thrombus formation by inducing platelet aggregation.' It has also been postulated that sudden coronary death may result from platelet aggregates in the epicardial arteries of man.8'9We present experimental evidence here that a fixed stenosis in a narrowed coronary artery promotes periodic in vivo platelet aggregation which transiently increases obstruction and decreases coronary blood flow. The possible significance of these observations to coronary disease in man is discussed.Material and Methods Thirty-five healthy adult mongrel dogs of both sexes were anesthetized with morphine sulfate (3 mg/kg) followed one hour later by sodium pentobarbital (30 mg/kg). Respiration was maintained using a positive pressure respirator, and the heart was exposed through a left thoracotomy at the fifth intercostal space in the usual fashion. After 35 mg/kg of aspirin were given intravenously the cyclical reductions in coronary blood flow were abolished and the in vitro platelet aggregations were reduced from a control of 62.1 ± 15 units (Born technique) to an average of 23.7 ± 12 units. Histologic sections of the narrowed coronary artery obtained when coronary flow was reduced show an amorphous mass in the lumen which was thought to be a platelet aggregate. Perhaps a similar process of platelet aggregation occurs in the stenosed coronary arteries in man, producing acute coronary...

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Copper deficiency is rarely reported as a cause of neutropenia and anemia through mechanisms not clearly understood. Most cases have been found in malnourished infants or persons receiving total parenteral nutrition without adequate copper. We report on two otherwise healthy young adults with severe neutropenia and anemia secondary to copper deficiency of unclear etiology, which quickly resolved after supplementation with copper gluconate. Both women consumed excessive quantities of soft drinks, which may have contributed to the development of their copper deficiency. Two cases of an unexplained copper deficiency anemia and neutropenia in otherwise healthy young adults found at a single institution over a short period of time suggests that this problem may be more widespread than is currently realized. Am. J. Hematol. 81:546-549, 2006. V V C 2006 Wiley-Liss, Inc.

P reliminary data have indicated that overexpression of HER-2/neu is correlated with more aggressive disease, an increased metastatic potential, and a poorer prognosis in patients with breast carcinoma. 1-3 Trastuzumab, a humanized anti-HER-2 antibody, reportedly is unable to penetrate the blood-brain-barrier and to our knowledge its efficacy in patients with brain metastases remains unclear. 4 -6 We conducted a retrospective study to evaluate whether patients with HER-2/neu-positive breast carcinoma have an increased risk of developing brain metastases.After approval from the institutional review board of West Virginia University, the pathology reports of 703 breast carcinoma patients who were diagnosed between April 1998 and January 2003 were reviewed. Based on immunohistochemistry or fluorescence in situ hybridization positivity, all patients who were positive for HER-2/neu were identified and their medical charts reviewed with regard to their course of disease and sites of metastases.Of the 703 patients studied, 164 (23%) were found to be positive for HER-2/neu; a sufficient oncologic history was available for 102 patients. Thirty-one patients (30%) developed distant metastases (95% confidence interval [95% CI], 0.223-0.399) during follow-up lasting a median of 57 months. Brain metastases were reported to have developed in 15 of these 31 patients (48%)(95% CI, 0.320 -0.652). A proportional hazards model was fit to the data to explore the association between patient age and time to the development of metastases. A significantly positive association (P ϭ 0.01) was found to exist between the two variables. Other models for censored data (Weibul, log-normal, and exponential models) were fitted and were found to produce nearly identical P values (Fig. 1).The results of this small retrospective study demonstrate that younger women with HER-2/neu-positive breast carcinoma may have a higher risk of developing brain metastases than previously reported for the general metastatic breast carcinoma patient population. This 442