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The localization of effects from magnetic coil stimulation is not immediately obvious. We measured the magnetic fields produced by several different coils and compared the results with theoretical calculations. Magnetic stimuli were delivered from a Cadwell MES-10 magnetic stimulator using 3 circular coils (one 9 cm in diameter; two with an angulated extension, 5 and 9 cm in diameter) and twin oval coils arranged in a butterfly shape (each coil approximately 4 cm in diameter) and from a Novametrix Magstim 200 using two circular flat-spiral coils (6.7 and 14 cm in diameter). Peak-induced strength of the magnetic field was recorded with a measuring loop (1 cm in diameter) at different distances from the center of the coil. When the measuring loop was moved in the same plane laterally from the center of the coil, for all coils except the butterfly-shaped coil, the field was highest in the center and fell off near the circumference of the coil. The field dropped progressively when measurements were made more distant from the plane of the coils. The electric field induced from the magnetic coil could be calculated from the coil geometry. For all coils except the butterfly-shaped coil, the largest electric field was at the circumference of the coils. The 6.7 cm flat-spiral coil induced currents similar to those induced by the larger coils but more focally. The butterfly-shaped coil induced the largest currents under its center, where the circumferences of the two component coils come together. The component of the electric field parallel to the wire in the center of this coil was the largest and most localized.

An optical multichannel analyzer capable of recording spectra at sampling rates up to 100 kHz is described. The instrument, designed to gather data on the kinetic reaction mechanisms of biological preparations such as cytochrome oxidase and bacteriorhodopsin, features a massively parallel approach in which each photosensing element of the detector array has a dedicated amplifier, integrator, analog to digital converter, and sample buffer. The design has 92 such elements divided in two separate arrays, each of which sits at the focal plane of a 1/4 m Ebert spectrometer. The spectrometers may be tuned to cover independent, 130 nm wide, regions of the spectrum from 350 nm to 900 nm with a dispersion of 2.8 nm per element. Each detection channel has 12-bit resolution with an electronic dark count of 1 count and may be sampled 1024 times during a single experiment with dynamically variable sampling intervals from 10 microseconds to several seconds. Time averaging of up to thousands of consecutive laser-initiated kinetic cycles allows analyses of spectral changes < 0.001 optical density units. A personal computer with custom software provides a number of features: entry of experiment parameters; transfer of data from temporary buffers to permanent files; real time display; multiple spectrum averaging; and control and synchronization of associated system hardware. Optical fibers or lenses provide coupling from a parabolic reflector Xenon arc monitoring light source, through the sample chamber, to the entry slit of the monochromator. The instrument has been used for extensive studies on the rapid kinetics and definition of reaction sequences of the energy-transducing enzymes cytochrome oxidase and bacteriorhodopsin. Some results from these studies are discussed.

The kinetics of Na movement across the tight junctions of MDCK cells, grown on coverslips and perfused with HEPES or bicarbonate Ringer at 37 degrees C, were investigated after filling the lateral intercellular spaces (LIS) of the epithelium with SBFO, an Na-sensitive fluorescent dye. Dilution and bi-ionic potential measurements showed that MDCK cell tight junctions, although cation-selective, were poorly permeable to N-methyl-D-glucamine Cl (NMDG) but freely permeable to Li. In previous experiments in which Na was replaced by NMDG, a very slow decrease in LIS Na concentration (time constant = 4.8 min) resulted. In the present study, reduction of perfusate Na from 142 to 14 or 24 mM with Na replaced by Li caused LIS Na concentration to decrease with a time constant of 0.43 min. The time constant for Na increase of the LIS was 0.28 min, significantly shorter than that for Na decrease because of the additional component of transcellular Na influx. Ouabain eliminated the transcellular component and equalized the time constants for Na influx and efflux. These results were incorporated into a mathematical model which enabled calculation of the transcellular and paracellular Na fluxes during fluid reabsorption. Regulation of the Na permeability of individual tight junctions by protein kinase A (PKA) was evaluated by treating the monolayers with the Sp-cAMPS, a cAMP substitute, or Rp-cAMPS, a specific inhibitor of PKA. Stimulation of PKA strikingly increased tight junctional permeability while PKA inhibition diminished junctional Na permeability.

Purpose: Phase I study designed to determine the maximum tolerated dose of intraoperative photodynamic therapy (PDT) at laparotomy/debulking surgery in patients with refractory or recurrent, disseminated intraperitoneal tumors. Methods and Materials: Patients received dihematoporphyrin ethers (DHE) 1.5–2.5 mg/kg by i.v. injection prior to surgery. Patients resected to ≤5 mm of residual disease underwent laser light delivery to all peritoneal surfaces. Results: Fifty-four patients entered the study. Thirty-nine underwent laser light delivery/PDT. PDT dose was escalated by increasing DHE from 1.5 to 2.5 mg/kg, shortening the interval between DHE injection and surgery from 72 to 48 hr, and increasing the light dose. Initially, 630 nm red light alone was used. In this group, PDT of 2.8–3.0 J/cm 2 induced small bowel edema and resulted in 3 small bowel perforations after bowel resection or enterotomy. Further light dose escalation, however, was achieved by switching to less penetrating 514 nm green light to the bowel/mesentery. In later patients, whole peritoneal PDT was supplemented with boost doses of 10–15 J/cm 2 red light or 5–7.5 J/cm 2 green light to high risk areas. Small bowel complications were not seen after switching to less penetrating green light. Dose limiting toxicities occurred in 2 of 3 patients at the highest light dose of 5.0 J/cm 2 green light with boost. These patients had pleural effusions that required thoracentesis and postoperative respiratory support for 7–9 days, while one had a gastric perforation. At potential follow-up times of 3.8–43.1 months (median 22.1 months), 3039 patients are alive and 939 are free of disease. Conclusion: The maximum tolerated dose of intraoperative PDT following debulking surgery performed 48 hr after intravenous administration 2.5 mg/kg DHE is 3.75 J/cm 2 of 514 nm green light to the entire peritoneal surface with boosts to 5.0–7.5 J/cm 2 of 514 nm green light or 10–15 J/cm 2 of 630 nm red light to sites of gross disease encountered at surgery.

Photodynamic therapy involves the use of light of appropriate wavelength to excite a photosensitizer resulting in tissue destruction. The photosensitizer dihematoporphyrin ether is selectively retained in tumors allowing for tumor destruction while sparing normal structures. Accessibility of skin tumors makes them well suited for photodynamic therapy. Tissue and tumor dihematoporphyrin ether content is estimated based on the amount of dihematoporphyrin ether administered. In our study, skin dihematoporphyrin ether content was measured in guinea pigs transcutaneously by a hand-held fluorometer and compared with dihematoporphyrin ether determinations done on skin biopsy specimens. Fluorometry was performed on guinea pigs receiving 0, 2.5, 5, 10, and 25 mg/kg of dihematoporphyrin ether. Transcutaneous measurements of skin fluorescence increased with increasing dihematoporphyrin ether dose and correlated well with skin dihematoporphyrin ether content as determined by extracting dihematoporphyrin ether from skin samples. Transcutaneous fluorescent measurements of guinea pigs given 0 and 2.5, 2.5 and 5, 5 and 10, and 10 and 25 mg/kg of dihematoporphyrin ether differed in a statistically significant manner. Transcutaneous fluorometric determination of dihematoporphyrin ether content and extraction of dihematoporphyrin ether from skin samples were able to reflect differences in dihematoporphyrin ether dosing and presumably skin dihematoporphyrin ether content. However, transcutaneous fluorometry provides an instantaneous estimate of tissue dihematoporphyrin ether without the need for a tissue sample. This may provide a clinical tool to predict more accurately the optimal light dose necessary to maximize photodynamic therapy.

• Patients with disseminated intraperitoneal malignant neoplasms were given intra-abdominal photodynamic therapy. Patients received dihematoporphyrin ethers intravenously 48 to 72 hours before laparotomy at doses of 1.5 to 3.0 mg/kg. At operation, as much tumor as possible was resected. Red light (630 nm) was delivered to all peritoneal surfaces from an argon-pumped dye laser at doses ranging from 0.2 to 3.0 J/cm 2 in an escalating fashion. Viscera and peritoneal surfaces were anatomically isolated and exposed to light for intervals calculated to deliver the prescribed energy. Light was delivered to mesentery and bowel by a flat-cut optical fiber, while other areas, including diaphragm, viscera, omental bursa, gutters, and pelvis, were delivered light through a diffusing wand. Twenty-three patients (13 with ovarian cancer, eight with sarcoma, and two with pseudomyxoma peritoneii) underwent photodynamic therapy. Five of eight patients cleared positive peritoneal cytologies after treatment. Six patients remained clinically free of disease for up to 18 months, and five patients had treatment-related complications. Intraperitoneal phototherapy is technically feasible and deserving of clinical evaluation. ( Arch Surg . 1991;126:318-324)

• Photodynamic therapy involves the use of light of appropriate wavelength to excite a photosensitizer resulting in tissue destruction. The photosensitizer dihematoporphyrin ether is selectively retained in tumors allowing for tumor destruction while sparing normal structures. Accessibility of skin tumors makes them well suited for photodynamic therapy. Tissue and tumor dihematoporphyrin ether content is estimated based on the amount of dihematoporphyrin ether administered. In our study, skin dihematoporphyrin ether content was measured in guinea pigs transcutaneously by a hand-held fluorometer and compared with dihematoporphyrin ether determinations done on skin biopsy specimens. Fluorometry was performed on guinea pigs receiving 0,2.5,5, 10, and 25 mg/kg of dihematoporphyrin ether. Transcutaneous measurements of skin fluorescence increased with increasing dihematoporphyrin ether dose and correlated well with skin dihematoporphyrin ether content as determined by extracting dihematoporphyrin ether from skin samples. Transcutaneous fluorescent measurements of guinea pigs given 0 and 2.5, 2.5 and 5, 5 and 10, and 10 and 25 mg/kg of dihematoporphyrin ether differed in a statistically significant manner. Transcutaneous fluorometric determination of dihematoporphyrin ether content and extraction of dihematoporphyrin ether from skin samples were able to reflect differences in dihematoporphyrin ether dosing and presumably skin dihematoporphyrin ether content. However, transcutaneous fluorometry provides an instantaneous estimate of tissue dihematoporphyrin ether without the need for a tissue sample. This may provide a clinical tool to predict more accurately the optimal light dose necessary to maximize photodynamic therapy.

Fluorometric biochemical analyses based on the enzyme coupled NAD-NADH reaction are limited in sensitivity by sample background fluorescence. An order of magnitude improvement in sensitivity has been achieved with a fluorometer designed to automatically measure sample fluorescence with high precision, before and after the enzymatic reaction, to give a precise value for a small change in the fluorescence level. The design of this instrument has been optimized for precision of photometric measurement and includes automatic processing of 20 samples, automatic reagent addition, and digital signal processing. Performance tests show a capability for measuring changes in sample fluorescence of 1% with a precision of about 5%.

A precision thermistor bridge and thermistor is described for use in a thermal titration calorimeter or a high-speed stopped- or continuous-flow calorimeter of the Roughton type. These are compared and evaluated with regard to several other types of detectors, including the platinum resistance thermometer, thermocouple, transistor thermometer, and capacitance thermometers. At this time the best detection for our purpose seems to be a specially constructed 20-100 kΩ thermistor used in conjunction with a new ac lock-in amplifier bridge. The sensitivity of the system is equivalent to a peak-to-peak noise of 25 x 10-6 °C, with a 100-ms time constant and 1 µW power dissipation in the thermistor. Long-term drift of the bridge, without an oven, was 1 x 10-6 °C/min.

A subdural electrode was designed and constructed with 3 pairs of contacts to make 3 dipoles. The dipoles well approximate the expected magnetic behavior for a current dipole and can be used clinically to test localization capabilities of magnetoencephalography.

A method of using a field effect transistor to record single cell discharges through a closed system from the cerebral cortex of human patients is described. There have been no complications encountered in six patients under investigation.

Heat conduction calorimeters are widely used in the biological sciences, but baseline instability, low resolution, electrical noise and motion artifacts have limited their utility. Two main sources of noise, baseline fluctuation or drift and a motion artifact, were traced to amplifier drift, a small (0.015 degrees C) gradient within the constant temperature cylinder, and the method of installing the thermopiles. The addition of heaters to the top and bottom of the cylinder reduced the gradient to approximately 0.003 degrees C and greatly reduced the slow component of the motion artifact. The drift error was reduced by proper mounting of the amplifier and its external components and the enclosure of the calorimeter in a temperature-controlled box. An R-C model of the heat flow in the calorimeter was developed which was employed to discover several means of increasing sensitivity without increasing the rise-time of the calorimeter. Analysis, also based on the model, showed that variations in the air gap between the cell and cell holder can be a major source of error when the calorimeter is used to investigate the kinetics of a chemical reaction. This analysis also showed that the time for the heat to flow through the solution in the cell can be the dominant factor in determining the rise-time of the instrument. The heat conduction calorimeter described here has improved characteristics: a baseline stability of 200 nJ x s-1 (peak-to-peak) over a 48 h period; a resolution of 200 nJ x s-1; a sensitivity of 6.504 +/- 0.045 J x V-1 x s-1 referred to the sensor output; and a rise-time of 122 s for the 10-90% response.

Three young adults with intractable complex partial seizures were studied by electroencephalography, magnetoencephalography, and electrocorticography. Interictal electroencephalographic (EEG) spikes for each patient were grouped according to their morphological characteristics and distribution across channels. Mapping of simultaneously recorded magnetoencephalographic signals produced dipolar patterns from which the three-dimensional locations of equivalent current dipoles were calculated, whereas the mapping of EEG spikes showed single regions of electronegativity. The magnetic spikes were localized to the anterotemporal lobe, and the EEG spikes were localized somewhat anterior or posterior to the magnetic spikes. The magnetoencephalographic findings corresponded well with intraoperative electrocorticographic and depth-electrode findings of discharging areas located over the lateral temporal lobe and on the basal and mesial surfaces of the temporal cortex.

The construction and use of two polyvinyl chloride, solid‐state membrane ion‐selective electrodes, one selective to tetraphenylphosphonium (TPP+) [to measure membrane potential (ΔΨ)] and the other selective to salicylate ion [to measure the pH gradient (ΔpH)], are described. A reaction vessel is fitted with these two electrodes plus a pH and an oxygen electrode. The signals from all four electrodes pass through an electronic interface to a microcomputer which filters out noise, corrects for relaxation time delay of electrodes as needed, converts the raw readings to real time kinetic values for rate of oxygen uptake, rate of proton extrusion, ratio of protons extruded per atom of oxygen consumed, membrane potential, the pH gradient across the membrane and the proton motive force. These values are continuously updated every 90 ms and passed to a multipen recorder for observation.

The surge of interest in medical research with positron-emitting nuclides has been accompanied by improvements in the design of positron emission tomographs (scanners). Bismuth germanate has emerged as the scintillation material of choice for high resolution scanners, as its detection efficiency with small crystals is higher than that of NaI. Other detector materials, such as CsF, may be useful when timing accuracy is of great importance, as in high count rate studies or time-of-flight measurements. Circular detector arrays are now generally preferred because they provide the best sensitivity and uniformity of coverage. Multiple rings are used to increase the axial coverage. Other design parameters, such as detector and collimator dimensions, are surveyed and their effect on scanner performance is discussed.

Two improved systems for the determination of the difference in pH between two solutions at the same temperature are described, both of which have a long-term stability of ±1 × 10 −4 pH unit and a peak-to-peak noise level of 5 × 10 −5 pH unit when operated in the differential mode. The cells are constructed of Delrin which has been found to be inert in biological fluids. These cells, with a volume of 1 ml, can be electrically connected to each other via a dialysis membrane and are thermostated during the duration of the pH measurements to ±0.01°C. In a second configuration, combination microelectrodes are inserted into each cell; thus the dialysis membrane is not necessary. To demonstrate the application of these systems to reactions of biological interest where pH changes occur, we investigated the hexokinase-catalyzed reaction between ATP and glucose in a phosphate buffer. The concentrations of glucose determined from the observed changes in pH by a numerical solution to the equilibrium equations are in excellent agreement with the analytical values.

Functional, electrical and structural details of an aversive stimulator for autistic children are presented. Design considerations and compromises needed to obtain satisfactory size, cost, convenience, safety, reliability and effectiveness are discussed. Limited clinical trials are reported.

A simple electronic device for superimposing a dot grid of known spacing on a TV monitor used for the display of computed tomography images is described. The device connects directly to the cable leading to the TV monitor and requires no other system interconnection.