Electrocardiographic ST-segment changes during acute, severe isovolemic hemodilution in humans

BACKGROUND: Controversy exists regarding the lowest blood hemoglobin concentration that can be safely tolerated. The authors studied healthy resting humans to test the hypothesis that acute isovolemic reduction of blood hemoglobin concentration to 5 g/dl would produce an imbalance in myocardial oxygen supply and demand, resulting in myocardial ischemia. METHODS: Fifty-five conscious healthy human volunteers were studied. Isovolemic removal of aliquots of blood reduced blood hemoglobin concentration from 12.8 +/- 1.2 to 5.2 +/- 0.5 g/dl (mean +/- SD). Removed blood was replaced simultaneously with intravenous fluids to maintain constant isovolemia. Hemodynamics and arterial oxygen content (Cao2) were measured before and after removal of each aliquot of blood. Electrocardiographic (ECG) changes were monitored continuously using a Holter ECG recorder for detection of myocardial ischemia. RESULTS: During hemodilution, transient, reversible ST-segment depression developed in three subjects as seen on the electrocardiogram during hemodilution. These changes occurred at hemoglobin concentrations of 5-7 g/dl while the subjects were asymptomatic. Two of three subjects with ECG changes had significantly higher heart rates than those without ECG changes at the same hemoglobin concentrations. When evaluating the entire study period, the subjects who had ECG ST-segment changes had significantly higher maximum heart rates than those without ECG changes, despite having similar baseline values. CONCLUSION: With acute reduction of hemoglobin concentration to 5 g/dl, ECG ST-segment changes developed in 3 of 55 healthy conscious adults and were suggestive of, but not conclusive for, myocardial ischemia. The higher heart rates that developed during hemodilution may have contributed to the development of an imbalance between myocardial supply and demand resulting in ECG evidence of myocardial ischemia. However, these ECG changes appear to be benign because they were reversible and not accompanied by symptoms.     

Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study.

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicities, and clinical effect of tipifarnib, a farnesyltransferase (FTase) inhibitor, in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs (EIAEDs). This study compares the pharmacokinetics and pharmacodynamics of tipifarnib at MTD in patients on and off EIAEDs. PATIENTS AND METHODS: Recurrent malignant glioma patients were treated with tipifarnib using an interpatient dose-escalation scheme. Pharmacokinetics and pharmacodynamics were assessed. RESULTS: Twenty-three assessable patients taking EIAEDs received tipifarnib in escalating doses from 300 to 700 mg bid for 21 of 28 days. The dose-limiting toxicity was rash, and the MTD was 600 mg bid. There were significant differences in pharmacokinetic parameters at 300 mg bid between patients on and not on EIAEDs. When patients on EIAEDs and not on EIAEDs were treated at MTD (600 and 300 mg bid, respectively), the area under the plasma concentration-time curve (AUC)(0-12 hours) was approximately two-fold lower in patients on EIAEDs. Farnesyltransferase inhibition was noted at all tipifarnib dose levels, as measured in peripheral-blood mononuclear cells (PBMC). CONCLUSION: Toxicities and pharmacokinetics differ significantly when comparing patients on or off EIAEDs. EIAEDs significantly decreased the maximum concentration, AUC(0-12 hours), and predose trough concentrations of tipifarnib. Even in the presence of EIAEDs, the levels of tipifarnib were still sufficient to potently inhibit FTase activity in patient PBMCs. The relevance of these important findings to clinical activity will be determined in ongoing studies with larger numbers of patients.     

The Impact of Comprehensive Care for Joint Replacement Bundled Payment Program on Care Delivery

Background

Comprehensive Care for Joint Replacement (CJR) is a Medicare initiative to test the impact of holding a hospital accountable for services provided during an episode of care for a lower extremity joint arthroplasty on costs and quality. This study examines whether hospital participation in CJR is associated with having programs focused on improving posthospitalization care or reducing costs using a survey of orthopedic surgeons.

Local Tobacco Control: Application of the Essential Public Health Services Model in a County Health Department’s Efforts to Put It Out Rockland

In 2000, Rockland County, a small suburban county north of New York City, dedicated $1 million of its Master Settlement Agreement funds to a comprehensive tobacco control program, Put It Out Rockland. Developed and implemented by the county health department, this program used an essential public health services model and an ongoing financial investment, within the context of strong statewide tobacco control efforts, to lower adult smoking rates to 9.7% and to reduce both smoking among youths and exposure to secondhand smoke over the ensuing decade. By combining state funds and local dollars for a total of $6.75 cost per capita, this comprehensive effort yielded 11 000 fewer smokers and translated to a potential savings of more than $24 million for the county.     

BrainSpace: Relating Neuroscience to Knowledge About Everyday Life

Knowledge about the brain and the human nervous system ultimately relates to human thought, perception, and behavior. People use natural languages like English to talk about “common sense” concepts, but the brain processes that produce them are described in a highly technical vocabulary. BrainSpace tries to relate technical concepts in anatomy and chemistry to a general body of common sense knowledge, Open Mind Common Sense. It uses the novel inference technique of Blending, to perform joint inference between technical neuroscience knowledge and common sense knowledge, and vice versa. The current paper reports preliminary results showing that BrainSpace’s inference organizes concepts such as the “visual brain,” “dynamic brain,” and deep brain stimulation in an intuitively plausible manner, indicating that it can serve as a foundation for interpreting more specific experimental and medical data.     

Brachial vessel injuries: high morbidity and low mortality injuries

Introduction  

Reports of arterial injuries from both the civilian and military arenas report the brachial artery as the most frequently injured vessel, accounting for approximately 25–33% of all peripheral arterial injuries. The brachial artery is surrounded by important peripheral nerves —the median, ulnar and radial, and also parallels the humerus and associated veins. Due to its close proximity to these structures, associated nerve and osseous injuries are frequent with residual neuropathy from such nerve injuries, often the main sources of permanent disability.     

Serum angiotensin converting enzyme levels in patients with alpha 1-antitrypsin variants

Serum angiotensin converting enzyme levels were measured in 184 subjects having either MM, MZ, ZZ, or MS Pi-types of alpha 1-antitrypsin. Elevated angiotensin converting enzyme levels were detected in 31 percent of the patients with the MZ Pi-type, 20 percent of the patients with the ZZ Pi-type, and 20 percent of the patients with the MS Pi-type compared with 1.33 percent of those with normal MM Pi-type. The mean serum angiotensin converting enzyme levels were also significantly higher in those with the MZ, ZZ, and MS Pi-types. Multiple family members of two families were found to have both the Z variant and angiotensin converting enzyme elevations, suggesting the possibility of a genetic linkage. Alpha 1-antitrypsin deficiency must be added to the list of disease states potentially associated with elevated serum angiotensin converting enzyme levels.