Three-dimensional optical disk data storage via the localized alteration of a format hologram.

Three-dimensional optical data storage is demonstrated in an initially homogenous volume by first recording a reflection grating in a holographic photopolymer. This causes the entire volume to be weakly reflecting to a confocal read/write head. Superposition of two or three such gratings with slightly different k-vectors creates a track and layer structure that specialized servo detection optics can use to lock the focus to these deeply-buried tracks. Writing is accomplished by locally modifying the reflectivity of the preexisting hologram. This modification can take the form of ablation, inelastic deformation via heating at the focus, or erasure via linear or two-photon continued polymerization in the previously unexposed fringes of the hologram. Storage by each method is demonstrated with up to eight data layers separated by as little as 12 microns.

Solid-state qubits with current-controlled coupling.

The ability to switch the coupling between quantum bits (qubits) on and off is essential for implementing many quantum-computing algorithms. We demonstrated such control with two flux qubits coupled together through their mutual inductances and through the dc superconducting quantum interference device (SQUID) that reads out their magnetic flux states. A bias current applied to the SQUID in the zero-voltage state induced a change in the dynamic inductance, reducing the coupling energy controllably to zero and reversing its sign.

Initial experience with factor-Xa inhibition in percutaneous coronary intervention: the XaNADU-PCI Pilot.

BACKGROUND: Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). OBJECTIVES: To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX-9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. PATIENTS AND METHODS: Patients undergoing elective, native-vessel PCI (n = 175) were randomized 4 : 1 to open-label DX-9065a or heparin in one of four sequential stages. DX-9065a regimens in stages I-III were designed to achieve concentrations of > 100 ng mL-1, > 75 ng mL-1, and > 150 ng mL-1. Stage IV used the stage III regimen but included patients recently given heparin. RESULTS: At 15 min median (minimum) DX-9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL-1 in stages I-IV, respectively. Median whole-blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti-FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL-1, respectively. Stage II enrollment was stopped (n = 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX-9065a dose. CONCLUSIONS: Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double-bolus and infusion DX-9065a dosing. Monitoring of DX-9065a may be possible using whole-blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study.

Ten-year follow-up of survival and myocardial infarction in the randomized Coronary Artery Surgery Study.

The Coronary Artery Surgery Study (CASS) randomized 780 patients to an initial strategy of coronary surgery or medical therapy. Of medically randomized patients, 6% had surgery within 6 months and a total of 40% had surgery by 10 years. At 10 years, there was no difference in cumulative survival (medical, 79% vs. surgical, 82%; NS) and no difference in percentage free of death and nonfatal myocardial infarction (medical, 69% vs. surgical, 66%; NS). Patients with an ejection fraction of less than 0.50 exhibited a better survival with initial surgery treatment (medical, 61% vs. surgical, 79%; p = 0.01). Conversely, patients with an ejection fraction greater than or equal to 0.50 exhibited a higher proportion free of death and myocardial infarction with initial medical therapy (medical, 75% vs. surgical, 68%; p = 0.04) although long-term survival remained unaffected (medical, 84% vs. surgical, 83%; p = 0.75). There were no significant differences either in survival and freedom from nonfatal myocardial infarction, whether stratified on presence of heart failure, age, hypertension, or number of vessels diseased. Thus, 10-year follow-up results confirm earlier reports from CASS that patients with left ventricular dysfunction exhibit long-term benefit from an initial strategy of surgical treatment. Patients with mild stable angina and normal left ventricular function randomized to initial medical treatment (with an option for later surgery if symptoms progress) have survival equivalent to those patients randomized to initial surgery.

The Thrombolysis in Myocardial Infarction (TIMI) Trial phase II: additional information and perspectives.

Given the many thrombolytic agents and the number of ways in which they can be combined with mechanical revascularization, the treatment of acute myocardial infarction has been the subject of active study and lively debate, which are likely to continue for some time. Several studies, including TIMI IIA (2,3,10,22), have suggested that immediate catheterization and angioplasty offer no clinical benefit and have a greater complication rate than a more delayed invasive strategy, but TIMI II (1) and SWIFT (16) trials have suggested that an even more conservative strategy of reserving catheterization and coronary angioplasty after thrombolytic therapy for patients with recurrent spontaneous or exercise-induced ischemia may be the most desirable approach for the majority of patients similar to those entered into these trials.

Variables predictive of good functional outcome following thrombolytic therapy in the Thrombolysis in Myocardial Infarction phase II (TIMI II) pilot study.

Before commencing the randomized Thrombolysis in Myocardial Infarction phase II (TIMI II) study, 370 patients were administered intravenous recombinant tissue plasminogen activator (rt-PA) within 4 hours of onset of acute myocardial infarction (AMI) and assigned to 2-hour (immediate) percutaneous transluminal angioplasty (n = 33), 18- to 48-hour (delayed) angioplasty (n = 288) or no angioplasty (n = 49) in a nonrandomized, observational pilot study. Left ventricular ejection fraction at rest and during exercise was assessed by gated equilibrium radionuclide ventriculography at hospital discharge and again at 6 weeks. At hospital discharge, ejection fraction averaged 50% at rest and 56% at peak exercise. At 6-week follow-up, ejection fraction averaged 50% at rest and 53% at peak exercise. At 6-week follow-up, resting ejection fraction average 49% in the 2-hour angioplasty group, 49% in the 18- to 48-hour angioplasty group and 55% in the no-angioplasty group. Variables independently predicting "good functional outcome" at 6-week follow-up (survival with resting ejection fraction greater than equal to 50% and no decrease with exercise) in the 18- to 48-hour angioplasty group were fewer leads with ST-segment elevation greater than or equal to 0.1 mV, younger age, rapid normalization during rt-PA infusion of ST segments or dramatic relief of chest pain, absence of arrhythmias within the first 24 hours of treatment initiation, no prior infarction and not a cigarette smoker at entry. Thus, the TIMI II pilot study demonstrates that most patients with AMI of less than or equal to 4-hour duration treated with rt-PA have good ventricular function after AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolysis in Myocardial Infarction (TIMI) Trial--phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase.

Two hundred ninety patients with acute myocardial infarction were treated according to random assignment with an intravenous infusion of either 80 mg of recombinant tissue plasminogen activator (rt-PA) over 3 h or 1.5 million units of streptokinase over 1 h. Patients received an intravenous bolus of heparin (5,000 U [USP]) before pretreatment coronary angiography and a continuous infusion (1,000 U/h) starting 3 h later. The frequency of major and minor hemorrhagic events (33% rt-PA, 31% streptokinase) and associated transfusions (22% rt-PA, 20% streptokinase) were comparable in both groups. More than 70% of bleeding episodes in each group occurred at catheterization or vascular puncture sites. Precipitable fibrinogen levels, measured in plasma samples collected in the presence of a protease inhibitor (aprotinin), declined in rt-PA and streptokinase groups by averages of 26 and 57% at 3 h and by 33 and 58% at 5 h, respectively (rt-PA versus streptokinase, p less than 0.001). At 5 h the plasma plasminogen declined by 57% (rt-PA) and 82% (streptokinase) (p less than 0.001); plasma fibrin(ogen) degradation products were higher in streptokinase-treated patients (244 +/- 12 micrograms/ml, mean +/- SE) than in rt-PA-treated patients (97 +/- 9 micrograms/ml, p less than 0.001). At 27 h, plasma fibrinogen and plasminogen levels were lower and fibrin(ogen) degradation products higher than pretreatment levels in both groups. The frequency of hemorrhagic events was higher in patients with greater changes in plasma factors at 5 h; within treatment groups the levels of fibrin(ogen) degradation products correlated with bleeding complications (p less than 0.005). Thus, in the doses administered, rt-PA induces systemic fibrinogenolysis that is substantially less intense than that induced by streptokinase. The high frequency of bleeding encountered is related to the protocol used, including vigorous anticoagulation, arterial punctures and thrombolytic therapy. These findings emphasize the need for avoidance of invasive procedures and for meticulous care in the selection and management of patients subjected to thrombolytic therapy.

Implications for acute intervention related to time of hospital arrival in acute myocardial infarction.

The time from onset of symptoms to arrival in the hospital emergency room (ER) was studied in 778 patients randomized into a study of acute myocardial infarction (AMI) size limitation. Patients at relatively high risk of death after AMI (including those with preexisting diabetes mellitus, systemic hypertension or congestive heart failure), women and older patients arrived significantly later in the ER than did patients without these characteristics. A significantly higher mortality rate was observed in patients who arrived late, i.e., those who arrived more than 2 hours after the onset of chest pain, even though patients with hemodynamic compromise (bradycardia, hypotension) tended to arrive earlier. The difference in long-term mortality between those who arrived early (within 2 hours of onset of chest pain) and those who arrived late was accounted for by the baseline differences between these 2 groups. These baseline differences may influence the effects of early interventions in AMI. In addition, these findings have implications for education of high-risk patients who could benefit the most from aggressive early intervention.

Cerebrovascular diseases in a fixed population of Hiroshima and Nagasaki, with special reference to relationship between type and risk factors.

A study was made of the incidence of cerebrovascular disease, the chronological trends, and the relationship between the disease types and risk factors in 16,491 citizens of Hiroshima and Nagasaki. The subjects underwent medical examination at least once between 1958-74, and were free of cerebrovascular disease at the initial examination. During the 16-year period, 1.162 cases of cerebrovascular disease developed in the study population, with diagnosis definite in 621. By type, there were 108 cases of cerebral hemorrhage, 469 cases of cerebral infarction, 33 cases of subarachnoid hemorrhage, and 11 cases of other unclassifiable types. As a risk factor of cerebral hemorrhage, elevation of systolic and diastolic blood pressure was the most closely related to onset, and left ventricular hypertrophy on electrocardiogram (ECG), and proteinuria were also related. However, a tendency was seen for the risk to be higher when the levels of serum cholesterol were lower. In cerebral infarction, aging like systolic blood pressure, was a most important risk factor. Left ventricular hypertrophy on ECG, proteinuria, and diabetes could also be risk factors. However, the relation to blood pressure, especially diastolic blood pressure, was not so great as in the case of cerebral hemorrhage.

Morphologic changes produced by amdinocillin alone and in combination with beta-lactam antibiotics: in vitro and in vivo.

Scanning electron microscopy was used to study the morphologic effects of amdinocillin (mecillinam) when combined with several beta-lactam antibiotics in vitro (Escherichia coli, three isolates; Klebsiella pneumoniae, one isolate) and also in vivo (E. coli, one isolate). Ovoid forms were found in the cultures of E. coli and K. pneumoniae following in vitro exposure to amdinocillin. This characteristic in vitro effect was also produced in the amdinocillin-treated E. coli-infected mouse. Varying degrees of filament formation were seen both in vitro and in vivo with the other beta-lactam antibiotics tested. The in vitro combination of amdinocillin with the beta-lactam antibiotics produced morphologic effects on E. coli and K. pneumoniae (enhanced cell distortion and lysis) not seen with the individual agents at the doses tested. Amdinocillin was synergistic with ampicillin, carbenicillin, and cephalothin in mice challenged with E. coli 736; scanning electron microscopy of bacteria from peritoneal lavages of mice treated with these synergistic combinations indicated that the organisms were more enlarged and distorted than those from animals receiving the individual agents. The enhanced morphologic effect observed in vivo was in agreement with the in vitro effect. Viable counts of bacteria recovered from mice treated with ampicillin plus amdinocillin were appreciably less than those from mice treated with each agent alone. The morphologic results from the scanning electron microscopy study point to a synergistic or enhanced effect of amdinocillin in combination with beta-lactam antibiotics and are in accord with prior reports of the synergistic effects of amdinocillin.

Clinical engineering services at the VA Medical Center, Los Angeles.

A large, modern Medical Center requires clinical engineering services to account for all medical equipment utilized in the treatment of the short-visit clinic patient, as well as the critically ill, who require extensive hospital, surgical or medical health care. The clinics act as multiphasic screening systems, providing simple treatment and referral for more extensive medical treatment. The hospital provides the necessary medical systems to accommodate the extensive daily patient flow. Few of the clinics can provide the facilities or machines to handle the expense of newer diagnostic and therapy requirements. Manpower and funding for maintenance today is concentrated in the fast-growing Radiology, Radiation Therapy/Nuclear Medicine, and Laboratory areas of the Medical Center. These departments require service specialists, and large amounts of dedicated funding to balance and insure reasonable maintenance of the newer, high-technology equipment. Growth of such technology in the hospital must be matched by the growth of service professionals in biomedical engineering departments.

Small cardiac lesions. Fibrosis of papillary muscles and focal cardiac myocytolysis.

Three types of small cardiac lesions were described and illustrated: (1) focal type of papillary muscle fibrosis, evidently a healed infarct of the papillary muscle present in 13% of autopsies, is a histologically characteristic lesion associated with coronary artery disease and healed myocardial infarction, (2) diffuse type of papillary muscle fibrosis, probably an aging change present in almost half of the autopsies, is associated with sclerosis of the arteries in the papillary muscle, is identifiable histologically, and apparently is not associated with any cardiac abnormality, and (3) focal cardiac myocytolysis, a unique histologic lesion, usually multifocal without predilection for any area of the heart, is associated with ischemic heard disease, death due to cancer complicated by nonbacterial thrombotic endocarditis and microthrombi in small cardiac arteries as well as with other diseases. Differentiation of the 2 types of papillary muscle fibrosis is important in the study of papillary muscle and mitral valve dysfunction. Focal cardiac myocytolysis may contribute to the fatal extension of myocardial infarcts.

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Coronary heart disease risk factors in Japan and Hawaii.

Various risk factors were evaluated to explain a significantly greater incidence of coronary heart disease in men of Japanese ancestry resident in Hawaii compared with men resident in Japan. The independent predictors of incidence of coronary heart disease in both Japan and Hawaii were systolic blood pressure, serum cholesterol, relative weight and age. These factors appeared to influence incidence similarly in both areas because in each case the correlation coefficients for Japan and Hawaii did not differ significantly. The hypothesis that the greater incidence in Hawaii could be attributed to differences in levels of these risk factors was tested with the Walker-Duncan method. The four variable multiple logistic function describing the probability of coronary heart disease in Japan was applied to the cohort characteristics observed in Hawaii. The estimated incidence thus obtained was not significantly different from that actually observed in the men resident in Hawaii. Therefore the increased coronary risk profile in Hawaii compared with Japan can account for the greater incidence of coronary heart disease in the former. Current cigarette smoking was significantly related to the risk of coronary heart disease in Hawaii but not in Japan. This difference requires further investigation.

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Incidence of myocardial infarction and death from coronary heart disease.

The incidence of myocardial infarction and death from coronary heart disease was studied in defined samples of 45 to 68 year old Japanese men in Japan, Hawaii and California. The incidence rate was lowest in Japan where it was half that observed in Hawaii (P less than 0.01). The youngest men in the sample in Japan were at particularly low risk. The incidence among Japanese men in California was nearly 50 percent greater than that of Japanese in Hawaii (P less than 0.05). A striking increase in the incidence of myocardial infarction appears to have occurred in the Japanese who migrated to the United States; this increase is more pronounced in California than in Hawaii.

Earlier onset of QRS in anterior precordial ECG leads: precision of time interval measurements.

Onset of QRS was compared between simultaneously recorded conventional ECG leads in 84 subjects with clinically normal hearts from a defined population sample. Mean onset of QRS was 6.4 msec earlier in lead V1 and 7.4 msec earlier in V2 than in lead II. These differences were statistically significant. The measuring system was adapted from drafting techniques and took into account variations in paper speed which occurred during recording. Interobserver differences equivalent to greater than 1 msec occurred in 3.9% of timeline measurements, but in in 38% of QRS onset measurements. The lower precision in measuring QRS onset may be attributed to baseline oscillations and to the relatively slow rate of voltage change at the onset of ventricular depolarization.