Optical sectioning microscopes with no moving parts using a micro-stripe array light emitting diode.

We describe an optical sectioning microscopy system with no moving parts based on a micro-structured stripe-array light emitting diode (LED). By projecting arbitrary line or grid patterns onto the object, we are able to implement a variety of optical sectioning microscopy techniques such as grid-projection structured illumination and line scanning confocal microscopy, switching from one imaging technique to another without modifying the microscope setup. The micro-structured LED and driver are detailed and depth discrimination capabilities are measured and calculated.

High speed optically sectioned fluorescence lifetime imaging permits study of live cell signaling events.

We present a time domain optically sectioned fluorescence lifetime imaging (FLIM) microscope developed for high-speed live cell imaging. This single photon excited system combines wide field parallel pixel detection with confocal sectioning utilizing spinning Nipkow disc microscopy. It can acquire fluorescence lifetime images of live cells at up to 10 frames per second (fps), permitting high-speed FLIM of cell dynamics and protein interactions with potential for high throughput cell imaging and screening applications. We demonstrate the application of this FLIM microscope to real-time monitoring of changes in lipid order in cell membranes following cholesterol depletion using cyclodextrin and to the activation of the small GTP-ase Ras in live cells using FRET.

Near- to mid-infrared picosecond optical parametric oscillator based on periodically poled RbTiOAsO(4).

We describe a Ti:sapphire-pumped picosecond optical parametric oscillator based on periodically poled RbTiOAsO(4) that is broadly tunable in the near to mid infrared. A 4.5-mm single-grating crystal at room temperature in combination with pump wavelength tuning provided access to a continuous-tuning range from 3.35 to 5microm , and a pump power threshold of 90 mW was measured. Average mid-infrared output powers in excess of 100 mW and total output powers of 400 mW in ~1-ps pulses were obtained at 33% extraction efficiency.

Quantum-well intermixing for the control of second-order nonlinear effects in AlGaAs multiple-quantum-well waveguides.

We present experimental evidence to demonstrate the feasibility of a promising new quasi-phase-matching technique in AlGaAs multiple-quantum-well waveguides. Non-phase-matched second-harmonic-generation measurements indicate that, for sub-half-bandgap excitation near 1.5 microm , quantum-well intermixing by impurity-free vacancy disordering results in a reduction of the nonlinear susceptibility chi((2))(zxy) (~340 pm/V) by 17%. Relatively low intermixed waveguide losses, and the high spatial resolution of the impurity-free vacancy disordering process, suggest that periodic intermixing along the direction of propagation should lead to useful frequency-conversion efficiencies.

Ultralow-pump-threshold, femtosecond Cr(3+):LiSrAlF(6)laser pumped by a single narrow-stripe AlGaInP laser diode.

We report what we believe to be the first demonstration of a Kerr-lens mode-locked Cr(3+):LiSrAlF(6)laser that is pumped by a single narrow-stripe AlGaInP laser diode with a diffraction-limited output beam. A novel low-loss three-mirror laser cavity design is described in which strong, localized Kerr lensing was exploited such that 75-fs-duration pulses were obtained for only 36mW of incident pump power. This pump power was maintained for 18h by just three AA batteries as the electrical power source. We have shown that mode locking can be sustained for pump powers as low as 22mW.

Bright solitary pulses in AlGaAs waveguides at half the band gap.

We show that bright temporal solitonlike pulses can propagate in AlGaAs waveguides excited in the half-bandgap spectral regime. The use of an antiresonant reflecting optical waveguide permits the dispersion of the waveguide to be controlled so that a mode with anomalous dispersion can propagate.

Detection of bacteraemia by the continuously monitoring BacT/Alert system.

AIMS: To analyse a continuously monitoring blood culture system with respect to the time to detection of various groups of organisms, their clinical importance, and the relative efficacy of the aerobic and anaerobic bottles. METHODS: Four thousand blood cultures were monitored and the information relating to the positive cultures was noted and analysed. RESULTS: Four hundred and seventy seven blood cultures were detected as positive, 81% (387/477) of which were detected within 48 hours. The most pathogenic organisms were detected in the shortest period, less pathogenic later and those generally regarded as contaminants last. Clinically important isolates were also detected earlier. Many positive blood cultures were detected in only one bottle of the set, even those regarded as clinically important. CONCLUSIONS: The management of continuously monitoring blood culture systems could be improved by considering time to detection trends. Clinicians should be aware of the relatively rapid detection of clinically important, positive blood cultures in relation to patient treatment.

Self-mode-locked NaCl:OH(-) color-center laser.

We have demonstrated self-mode locking of an NaCl:OH,(-) color-center laser by exploiting the Kerr effect in a rod of high-nonlinearity glass placed within the laser cavity. The mode-locking process was initiated by a regenerative acousto-optic modulation, and sub-100-fs pulses were produced at wavelengths of ~1575 nm.

Spotlight article: thrombolysis in unstable angina: randomized double-blind trial of t-PA and placebo. Circulation 1992;85: 150-7. (Freeman MR, Langer A, Wilson RF, Morgan CD, Armstrong PW.).

This is a well-written and executed study that indicates that infusion of t-PA in patients with unstable angina does not decrease in-hospital cardiac events and, in fact, may worsen myocardial perfusion. The small sample size requires further study replication.

Acute congestive heart failure: pharmacologic intervention.

Acute CHF is a highly unstable condition that requires immediate pharmacologic intervention. Mechanisms that are normally used to control the release of neurohormones are impaired in CHF. Therapeutic interventions produce hemodynamic and clinical benefits in part by restoring a balance of the neurohormonal system. This balance is achieved by interfering with actions of vasoconstriction and potentiating the effects of vasodilation and contractility. To maintain an optimal healing atmosphere, the patient's individualized needs for social support and spiritual beliefs must be considered. How the patient perceives his or her illness may also impact patient hemodynamics and outcomes.

Altered beta adrenergic receptor function in subjects with symptomatic mitral valve prolapse.

Individuals with mitral valve prolapse (MVP) frequently show symptoms of a hyperadrenergic state. beta adrenergic receptor characteristics were compared in the lymphocytes of subjects with symptomatic MVP and control subjects during rest and exercise. At rest, the proportion of receptors binding agonist with high affinity, as determined from isoproterenol competition for (-)[125I]-iodopindolol binding sites, was greater in MVP subjects than in controls. With exercise, the proportion of high-affinity receptors in MVP subjects decreased to control levels. Isoproterenol stimulation of lymphocyte 3',5'-cyclic adenosine monophosphate (cyclic AMP) also was greater in MVP subjects than in controls at rest, but not during exercise. Plasma catecholamine concentrations in MVP subjects were normal during both rest and exercise. Unlike exercise, isoproterenol infusion elicited clinical manifestations of increased adrenergic responsiveness in MVP subjects. The beta receptor in exercised MVP subjects exhibited unusually high affinity agonist binding (i.e. a lower dissociation constant KH than in either the same subjects at rest or exercised controls) and also abnormal coupling to the stimulatory guanine nucleotide-binding regulatory protein (GS) of adenylate cyclase, as reflected by the inability of guanine nucleotide to convert the receptor to a low-affinity state. These findings suggest that functional alteration of the beta adrenergic receptor, in the absence of abnormal plasma catecholamine levels, might contribute to the hyperadrenergic state of MVP subjects at rest. However, desensitization of high affinity beta receptors or altered receptor-GS coupling might preserve normal adrenergic responsiveness during exercise.

Captopril in the treatment of chronic CHF.

Captopril is an effective oral drug that helps break the cycle of CHF. Improvements in symptomatology, functional capacity and exercise tolerance are seen with long-term therapy. Captopril is an important addition to the present drug therapy of CHF.

Absolute bioavailability and dose proportionality of betaxolol in normal healthy subjects.

The absolute bioavailability and dose proportionality of betaxolol [(+/-)-1-(p-[2-cyclopropylmethoxy)ethyl]phenoxy]-3- (isopropylamino)-2-propanol hydrochloride], a cardioselective beta-adrenergic antagonist effective in the treatment of angina and hypertension, was studied in 12 healthy male subjects using a four-way crossover Latin Square design. Each subject received a 10-mg iv dose administered by constant-rate infusion over a period of 30 min and three oral doses (10, 20, and 40 mg). Blood and urine were collected over a 48-h period and analyzed for betaxolol using gas-liquid chromatography with electron capture detection. Maximum concentrations occurred 3-4 h after the dose. The maximum mean (+/- SD) blood concentrations normalized to the 10-mg oral dose were 21.6 +/- 3.7, 21.1 +/- 3.7, and 22.5 +/- 4.0 micrograms/L following the 10-, 20-, and 40-mg doses, respectively. A significant lag time of 10-80 min was observed after oral doses but was not related to dose size. The terminal slope (ts), absolute bioavailability (F), and renal clearance (CLr) were likewise not affected to an important degree by dose (ts: 0.043 +/- 0.006, 0.044 +/- 0.005, 0.046 +/- 0.006 h-1; F: 0.88 +/- 0.08, 0.82 +/- 0.06, 0.84 +/- 0.07; CLr: 0.68 +/- 0.22, 0.69 +/- 0.19, 0.65 +/- 0.22 mL/min kg). Unlike many beta-adrenergic antagonists, betaxolol has a long half-life (13-20 h) and high and consistent bioavailability (70-90%), and its disposition is independent of the size of the administered dose.

Hemodynamic effects of a constant intravenous infusion of piroximone in patients with severe congestive heart failure.

The hemodynamic effects and serum levels of piroximone (MDL 19,205), a new inotropic agent with vasodilating properties, were measured in 10 patients with chronic severe congestive failure during a constant 48-h infusion. The initial five patients (group A) received piroximone at 10 micrograms/kg/min; however, because a sustained increase in heart rate greater than or equal to 25% from baseline developed in two patients and an episode of paroxysmal supraventricular tachycardia developed in another, the last 5 patients (group B) received an 8 micrograms/kg/min infusion. Because the steady-state hemodynamic alterations of group A prior to the onset of tachyarrhythmias were similar to those of group B, these results were combined. A significant increase in cardiac output from 3.65 +/- 0.31 (SE) to 5.20 +/- 0.49 L/min and decrease in pulmonary capillary wedge pressure (27 +/- 2 to 20 +/- 2 mm Hg), right atrial pressure (18 +/- 2 to 11 +/- 2 mm Hg), and systemic vascular resistance (1811 +/- 172 to 1293 +/- 80 dynes.s.cm-5) occurred (all p less than 0.05) without a significant change in mean arterial pressure. The peak plasma piroximone level was lower in the eight patients who did not develop a sustained increase in heart rate greater than or equal to 25% above baseline (2.1 +/- 0.5 micrograms/ml; range 1.6-2.9 micrograms/ml) than in the two who did (5.0 and 5.8 micrograms/ml). The latter two patients had the highest serum creatinine levels in the study population.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of prolonged intravenous therapy with enoximone in patients with severe congestive heart failure.

The hemodynamic differences between bolus administration and constant intravenous infusion over a 48-h period with enoximone, a new positive inotropic/vasodilator agent, were evaluated. Twenty-four patients were studied, 15 patients in the bolus group (Group A) and nine patients in the constant infusion group (Group B). The overall hemodynamic results were similar in both groups. Cardiac output increased in Group A from 3.1 +/- 0.71 to 5.5 +/- 1.3 L/min and in Group B from 3.6 +/- 1.0 to 5.9 +/- 1.2 L/min. Significant decreases occurred in pulmonary capillary wedge pressure (30 +/- 7 to 20 +/- 8 mm Hg and 37 +/- 5 to 21 +/- 11 mm Hg) and systemic vascular resistance (2184 +/- 456 to 1300 +/- 305 dyn.s.cm-5 and 1752 +/- 415 to 1035 +/- 130 dyn.s.cm-5). Group A required repeat drug boluses every 3-5 h to maintain these hemodynamic effects. The terminal blood half-life of enoximone derived following the continuous infusion in Group B was 10.6 +/- 7.0 h. In conclusion, intravenous enoximone produces acute salutary hemodynamic effects in patients with severe congestive heart failure that can be sustained for at least 48 h by intermittent boluses or a continuous infusion.

Prognostic value of exercise-induced ventricular ectopic activity for mortality after acute myocardial infarction.

To evaluate the importance of ventricular ectopic activity on the predischarge treadmill exercise test for predicting mortality in patients after acute myocardial infarction (AMI), 163 patients with uncomplicated AMI were studied using symptom limited low-level treadmill exercise testing and 24-hour ambulatory electrocardiographic monitoring before hospital discharge. All patients were followed for at least 2 years or until recurrent AMI, coronary artery bypass grafting or death. Seventeen patients (10%) died during the follow-up period, 15 patients (9%) had recurrent AMI and 45 patients (28%) underwent bypass surgery. Ventricular ectopic activity was the only single treadmill abnormality that predicted subsequent cardiac death; angina pectoris, electrocardiographic ST-segment depression and a hypotensive blood pressure response did not. The mortality rate in the 20 patients with exercise-induced ventricular ectopic activity was 25%, compared with 8% in those without (p less than 0.004). Furthermore, in this patient population, exercise-induced ventricular ectopic activity was a much better predictor of cardiac death than that detected by ambulatory monitoring. Thus, ventricular ectopic activity on the predischarge treadmill exercise test is an important risk factor for death after AMI.