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A solenoid magnet using high-temperature superconductor tape was designed, fabricated, and tested for its suitability as beam scanner. After successful cooling tests, the magnet performance was studied using DC and AC currents. With DC current the magnet was successfully operated as mirror coils for a 2.45 GHz ECR ion source. The coils could be operated at 100 A and frequencies above 1 Hz. The installation of iron pole pieces and return yokes, enabled us to generate fields in excess of 2 T at 197 A DC. In AC mode this magnet can be operated in the ranges of 0.14–1.73 and 1.22–1.67 T at frequencies of 0.05 and 0.25 Hz, respectively.

In addition to heavy ion collisions (RHIC Design Manual, Brookhaven National Laboratory), RHIC will also collide intense beams of polarized protons (I. Alekseev, et al., Design Manual Polarized Proton Collider at RHIC, Brookhaven National Laboratory, 1998 [2]), reaching transverse energies where the protons scatter as beams of polarized quarks and gluons. The study of high energy polarized protons beams has been a long term part of the program at BNL with the development of polarized beams in the Booster and AGS rings for fixed target experiments. We have extended this capability to the RHIC machine. In this paper we describe the design and methods for achieving collisions of both longitudinal and transverse polarized protons in RHIC at energies up to s =500 GeV .

For the Relativistic Heavy Ion Collider (RHIC) Spin Project, super-conducting helical dipole magnets are being constructed. These magnets will be used in `Siberian Snakes’ and `Spin Rotators', which manipulate spin direction of proton beams in RHIC. The dipole field in these magnets rotates 360° and is required to reach a magnetic field strength of more than 4.0 T. The bore radius of the coils and the magnetic length of the magnets are 50 and 2400 mm, respectively. To ascertain the performance of these magnets, which are built using a new “coil in a slot” technique, a half-length model has been fabricated and tested. The quench performance, field uniformity and rotation angle have been investigated. The measured values in the model magnet agreed well with field calculations. These results demonstrate the adequacy of the fabrication method adopted in the model magnet.

A sixty-five-year old female, with a past history of variant angina and asthma, collapsed after complaining of chest pain and regained spontaneous circulation by resuscitation. An electrocardiograph showed a QS pattern on the precordial leads and sonography revealed a takotsubo cardiomyopathy-like movement. During induced hypothermic therapy for protection of her brain and heart using a drug which dilated the coronary artery, she collapsed again with ventricular flatter for 40 min; however, she re-obtained return of spontaneous circulation and eventually regained consciousness. After correction of eosinophilia by steroids, the variant angina with life-threatening arrhythmia and asthma attack subsided. She was discharged and ambulatory 14 days after admission with normal motion of the cardiac wall. This is the first case of Kounis syndrome associated with takotsubo cardiomyopathy. The mechanism of the concurrent condition of this case is herein discussed.

The effects of four kinds of 2'-deoxy-L-nucleoside 5'-triphosphates and L-ATP, which are enantiomers of natural D-dNTPs and D-ATP, on deoxycytidine kinase (dCK) partially purified from mouse leukemic P388 cells were investigated. Only L-dCTP did not act as a phosphate donor while other L-dNTPs and L-ATP showed 15-30% of the activity of the corresponding D-dNTP or D-ATP. L-dCTP inhibited dCK non-competitively with 2'-deoxycytidine (D-dCyd) and competitively with phosphate donor D-ATP. These inhibitory effects of L-dCTP on dCK were similar to the results of earlier studies using D-dCTP. Thus, L-dCTP was shown to be capable of serving as a feedback inhibitor for dCK instead of D-dCTP. Mouse dCK was also able to phosphorylate L-dCyd, as demonstrated in the case of human dCK. The present results suggest that the chirality of not only dCyd as the substrate but also nucleotides as the substrate or effector is not strictly discriminated by dCK.

The metabolism of testosterone (TS) and its 17-O-acyl derivatives (acyl = acetyl, benzoyl and hemi-succinoyl) was studied using radioactive compounds in organotypic coculture of human dermal fibroblasts (living skin equivalent, LSE). When TS was applied to the epidermal-side of LSE in a small volume of acetone solution, both 5α-reduced and 17-dehydrogenated metabolites were observed in the dermal-side culture solution, though the formation of the 5α-reduced metabolites, dihydrotestosterone (DHT) and dihydroandrosterone (DHA), depended greatly on the culture conditions. The metabolic activity of LSE for testosterone was higher than that of excised hairless-rat skin. The metabolism of ester prodrugs of TS in LSE was dependent on their physicochemical properties and susceptibility to enzymatic hydrolysis. Application of acetyl-TS and benzoyl-TS resulted in a high formation of the 17-dehydrogenated metabolite, androstenedione (ADO), though a very small amount of the prodrug was observed in the dermal side. Succinoyl-TS, a hydrophilic ester with very low susceptibility to hydrolysis, was quite resistant to both 5α-reduction and 17-dehydrogenation, and more than 90% of the radioactivity appearing on the dermal side was from the prodrug itself and from TS. The hydrophilic and enzymatically stable TS derivative may be a good candidate compound with which to administer TS transdermally.

To evaluate the response of patients with chronic atrial fibrillation (AF) to exercise, 79 male patients (mean age 64 +/- 1 years) with AF underwent resting two-dimensional and M-mode echocardiography and symptom-limited treadmill testing with ventilatory gas exchange analysis. Patients were classified by underlying disease into five subgroups: no underlying disease (LONE: n = 17), hypertension (HT: n = 11), ischemic heart disease (n = 13), cardiomyopathy or history of congestive heart failure (CHF: n = 26), and valvular disease (n = 12). A higher maximal heart rate than expected for age was observed (175 vs 157 beats/min), which was most notable in the LONE and HT subgroups. Maximal oxygen uptake (VO2 max) was lower than expected for age in all groups. Patients with CHF had a lower resting ejection fraction than all other patients (p < 0.001), a lower VO2 max, and a lower maximal heart rate than LONE and HT patients (p < 0.001). Stepwise regression analysis demonstrated that echocardiographic measurements at rest were poor predictors of VO2 max and VO2 at the ventilatory threshold. Among clinical, morphologic, and exercise variables, maximal systolic blood pressure accounted for the greatest variance in exercise capacity, but it explained only 35%. In patients with AF the higher than predicted maximal heart rates may be a compensatory mechanism for maintaining exercise capacity after the loss of normal atrial function. However, even in the absence of underlying disease, it does not appear to compensate fully for a compromised exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

While there is still much debate in the literature regarding the specific MET levels at which there are differences in survival, the following points have become clear with the growing body of reports in the literature. Exercise capacity seems to be an independent predictor of mortality, and when it is combined with other clinical, exercise, or angiographic data, it becomes very powerful in this regard. This relates to both overall mortality and to that from cardiovascular disease. There is still a need for the establishment of mortality data related to MET levels adjusted for age and activity status. A low exercise capacity of less than 6 METs indicates a higher mortality group, probably regardless of the underlying extent of coronary disease or left ventricular function. Analysis of the CASS data has indicated that these patients benefit from coronary artery bypass surgery with respect to survival. An exercise capacity of greater than 10 METs designates an excellent survival group, again despite the extent of coronary artery disease or left ventricular function. If 10 METs truly exerts a “protective effect” that obviates any survival benefit from coronary artery bypass surgery, this has enormous implications for cost containment and medical care. It is nonetheless important to remember that this level of exercise capacity does not imply the absence of either coronary disease or triple-vessel coronary disease. Exercise capacity is related to more than just cardiovascular fitness and integrity. It is dependent upon a combination of other physiologic components as well, including pulmonary function, health status of other organ systems, nitrogen balance, nutritional status, medications, orthopedic limitations, and others. Nonetheless, exercise capacity has been established as a powerful predictor of survival and deserves equal emphasis with that of ST segment interpretation in the evaluation of exercise test responses.

Rectal absorption of Zidovudine (3′-azido-3′-deoxythymidine, AZT) was investigated in order to determine the feasibility of developing AZT suppositories. Although the small intestine shows a higher absorption rate than the stomach and large intestine in rats, considerable absorption of AZT was observed from the lower large intestine (8 cm above the anus). A sustained-release suppository was prepared by direct compression of hydroxypropyl cellulose (HPC) with AZT. During in vivo experiments in rats, this suppository (10 mg or 37.5 μmol AZT/kg) maintained constant plasma levels above 1 μM for more than 6 h. The results suggest that suppositories can prove useful as an alternative dosage form of AZT administration.

In vitro permeation of zidovudine (azidothymidine, AZT), a potent antiviral agent acting on acquired immunodeficiency syndrome, through a rat skin from isopropyi myristate (IPM) solution was significantly enhanced by the addition of N -methyl-2-pyrrolidone (MP) as a penetration enhancer. When 50 μl of the IPM solution containing 12 mg/ml of AZT and 20% of MP was applied on rat abdominal skin, about 1 μM of the plasma concentration of AZT was observed at 1–2 h after the application, though the concentration decreased rapidly and was undetectable at 6 h. Though 34% of the applied AZT remained in the IPM solution on the rat skin at 10 h, MP was not detected. In order to maintain a constant level of MP in the solution, ethylene-vinyl acetate copolymer membrane was used for its controlled release in the transdermal delivery system of AZT. A considerable plasma concentration of AZT could be maintained for 10 h after application of this MP release-controlled transdermal system.

The relative rates of enzymatically catalyzed hydrolysis of various esters of p -acetylaminobenzoic acid (APAB) and variously acylated acetaminophen (APAP) derivatives were measured. Neutral, anionic, and cationic esters were examined. The enzyme sources adopted were rat intestinal homogenate, rat liver homogenate, rat plasma, and a partly purified commercial enzyme. In both APAB and APAP esters, neutral esters were the most sensitive of the enzyme sources examined, and the sensitivity was due to the carbon chain length. The APAB esters were enzymatically more stable than the APAP esters. The relative rates of hydrolysis of these esters varied depending on the enzyme source. The ability of structure recognition was good in rat intestinal homogenate, but weak in rat plasma. These results suggest that ester prodrugs can be designed to cleave preferentially at selected sites along the pathway between absorption and disposition in the body.

The existence of O 2 − or HOO − has been observed by epr at g = 2.008 and 2.03 on samples of manganese dioxide pretreated between 100 and 400 °C. The relative value of the epr absorption decreased with an increase in the pretreatment temperature. The concentration of surface traps determined by the DPPH method was nearly proportional to the relative value of the epr absorption on manganese dioxide. Furthermore, O 2 − or HOO − on the surface of manganese dioxide acts as an active site during the dehydrogenation reaction of isopropanol.

Fifteen pyrimidine-related compounds were evaluated for their ability to inhibit enzymatic degradation of 5-fluoro-2′-deoxyuridine (FUdR). Acyclothymidine [5-methyl-1-(2′-hydroxyethoxymethyl)uracil] showed the highest inhibitory effect on the phosphorolytic degradation of FUdR in various tissue homogenates derived from mouse, rat, and beagle organs. Both the drug (FUdR) and the inhibitor (acyclothymidine) were esterified with appropriate aliphatic acids in order to synchronize their behavior after simultaneous oral administration. The antitumor activity of orally administered FUdR esters was potentiated by the simultaneous oral administration of the acyclothymidine esters, but not by acyclothymidine.

Percutaneous absorption of azidothymidine (AZT) was examined in rats. When AZT was applied as a solution in 10% oleic acid/water on the abdominal skin which had been treated with 10% oleic acid/water for 24 h, considerable plasma concentrations of AZT were observed.