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Recent years have seen a steady increase in the application of physical techniques to medical and biological research. This was bound to happen in view of the widespread use of instrumentation generally, in other fields of research. However, the medical and biological professions are peculiar in that here professional workers will have had little or no training in physics or electronic engineering.

Within the discipline of ophthalmology, fluorescence angiography has achieved popularity in the past decade as a method of investigation, demonstrating abnormalities in the retinal and choroidal circulations. Alterations in Bruch's membrane and the overlying pigment epithelium are seen as modifications in the pattern of underlying choroidal fluorescence. A large volume of literature has accumulated around the technique and its interpretation in various aspects of ocular disease. In this issue of the J7urnal of Medical Genetics dedicated to Professor Arnold Sorsby, it is appropriate to present a brief essay on the application of this technique to a subject of interest to him, genetically determined degenerations of the fundus oculi.

SummaryA morphological alteration of yeast-like cells of C. albicans and C. stella-toidea has been shown to occur within 1 hour after injection into the subcutaneous tissues of mice. Yeast-like cells of other members of the genus Candida failed to exhibit these alterations under the same conditions. The yeast-like cells of C. albicans had formed elongated pseudomycelia within 1 hour after injection. At later times considerable growth of these filaments with the appearance of septa was observed. Other species of the genus Candida retained their typical yeast-like morphology. It has been postulated that filamentation of C. albicans in vivo serves as a hindrance to ingestion by mouse phagocytes. The results suggest a significant role for these morphologically altered organisms in the pathogenesis of experimental moniliasis in the mouse.

In this article, the author reviews methods such as infrared gas analysis, mass spectrometry and gas chromatography in a qualitative manner.

A method is proposed for reducing the time required to determine spin-lattice relaxation times of individual lines in a high resolution NMR spectrum. The steady-state response of the spins to a repetitive sequence of 90° pulses is measured at two different pulse repetition rates, and the relaxation times derived from the ratio of the intensities of a given line in the two Fourier transformed spectra. The technique has been made the basis of an automatic program which adapts the pulse rate parameter in order to optimize the determination of the relaxation times. Applied to the carbon-13 spectrum of cortisone acetate the proposed method gives results in good agreement with those obtained by the widely used inversion-recovery technique. The spin-lattice relaxation times found for the methyl, methylene, methine and quaternary carbon atoms of cortisone acetate are found to fall into four quite distinct ranges.

The textile industry can be divided into three main sections - for the spinning of yarns, the production of fabric and the final conversion to finished cloth. The first two are predominantly mechanical processes and the last predominantly, though not wholly, chemical. The technological advances in each section in the last few years have been tremendous. Speeds of processing, quality standards of both machines and products, and number and variety of products have all increased at an exciting pace. Virtually all the advances have depended in some form or other upon improved instrumentation, and the further advances that are now contemplated will necessitate even more instruments for both testing and control. The paper will illustrate the steps already taken and suggest some of the foreseeable needs in the field of instrumentation.

The orientation of a satellite can be calculated if the aspect of two or more known reference vectors can be measured with respect to a body-fixed coordinate frame. On the Telstar satellites one such line may be determined by solar aspect cells, but the other is determined by ground observation of flashes of sunlight reflected from three mirrors mounted on the spinning satellite. The simple geometric considerations are discussed, as are the optimum placement of the mirrors, the amount of data to be used, and an error analysis. Spin-axis orientation data are used as the basis for steering the spin axis by ground command of the current in a coil of wire around the equator of the satellite.

Observations were made during both spontaneous and artificial respiration on 12 fit patients anesthetized for routine surgical procedures. Above a tidal volume of 350 ml (BTPS), the anatomical dead space was close to the predicted normal value for the subject. Below 350 ml, it was reduced in proportion to the tidal volume. The physiological dead space (below the carina) approximated to 0.3 times the tidal volume for tidal volumes between 163 and 652 ml (BTPS). Throughout the range the physiological dead space was considerably in excess of the anatomical dead space measured simultaneously. The difference (alveolar dead space) varied from 15 to 231 ml, being roughly proportional to the tidal volume. The mean arterial to end-tidal CO2 tension difference was 4.6 (S.D. ±2.5) mm Hg and not related to tidal volume or arterial CO2 tension. None of the findings appeared to depend on whether the respiration was spontaneous or artificial. Submitted on September 25, 1959

Summary1) Adult garter snakes (Thamnophis spp.) inoculated intraperitoneally, overwintered WEE virus for at least 139 days. There was a steady decline in virus, with only 1 of 14 showing a viremia after 92 days hibernation. With warm spring weather, (139 days after virus inoculation) 9 of 14 animals exhibited a viremia with blood titers varying from 10-1 to 10-3.5. 2) Two of 4 garter snakes inoculated with WEE virus and kept at 4°C, for 17 days harbored the virus in the blood, but not the brain. One snake harbored the virus in the brain but not in the blood. No virus was detected in either blood or brain after 17 days at 4°C in one of the snakes.

The action of a micro-argon gas chromatographic detector, as described by Lovelock in 1960, is investigated in quantitative terms. It is found that the field strength within the detector lies in the range 0.2-15 v cm-1 torr-1 for a polarizing voltage of 1 kv. There is, accordingly, very little ionization by electron collision, although each primary electron is found to create about 55 metastable argon atoms before reaching the anode. A comparison is made between the theoretical response of the detector, without space charge limitation, for propane concentrations, and that obtained by experiment. The cross section for destruction of an argon metastable atom to ionize propane is calculated to be 2 × 10-15 cm2. An expression is also derived for the effect of the positive ion space charge within the detector. It is found that the electrostatic field distribution begins to be distorted for propane concentrations greater than 10-5, which is reasonably in accordance with the response curve.

The spin–spin relaxation of individual lines in a high‐resolution NMR spectrum has been studied by a technique which extracts an essentially “monochromatic” component from the Carr–Purcell spin‐echo response by means of a narrow‐band filter. The resulting selectivity significantly reduces the complexity of the modulation of the spin‐echo amplitude due to homonuclear spin–spin coupling, and further simplification may be achieved by double irradiation experiments. Echo modulation has been used as a precise measure of the 0.051‐Hz long‐range coupling in 3‐bromothiophene‐2‐aldehyde, normally hidden by magnet inhomogeneity. It is proposed that modulation and spin–spin relaxation effects are best analyzed in the general case by calculating the Fourier transformation of the envelope of the spin‐echo peaks. The general term suggested for this new mode of presentation is the “spin‐echo spectrum.” It consists of a set of resonance responses with widths determined by the relevant spin–spin relaxation times, at freueqncies determined by the various modulation components of the spin‐echo decay. The present study concentrates on operating conditions (low pulse repetition rate and “first‐order” spin coupling) where the resonance frequencies correspond to one‐half the sums and differences of the spin coupling constants. This special case of a spin‐echo spectrum is called a “J spectrum.” When the spin‐echo response appropriate to a single group of chemically shifted nuclei is observed selectively, the transformation gives a “partial J spectrum” which can be used as an aid to the assignment of the full spectrum. J spectra are illustrated for a typical first‐order three‐spin system—the ring protons of methyl furoate.

A versatile nuclear magnetic resonance spectrometer using a superconducting magnet is described. Details of the magnet are given and the important features of the spectrometer are described. A novel probe design is discussed and examples of the spectrometer performance are shown.

To evaluate technique for producing hypoxia in patients during radiotherapy, anesthetized dogs were hyperventilated with N2 for 3 min. End-tidal Po2 fell rapidly to near zero, but arterial Po2 fell to 10 mm Hg with mixed venous Po2 fractionally higher. Mean tissue Po2 of cortical gray matter fell to 0.7 mm Hg, white matter to 1.7, and subcutaneous tissue to 1.8, but muscle fell only to 7.8 mm Hg. Reasons for failure of oxygen washout are discussed. N2 inhalation; radiosensitivity; muscle Po2; brain Po2; tissue Po2; polarography; cerebral cortical cell inhibition; arterio-venous Po2 Submitted on October 25, 1962

The use of a disposable paper laminate waistcoat is described to provide a multi-way connection to electrodes and transducers during monitoring from a patient. The waistcoat removes the strain of the multi-way cable of the monitor unit from the individual electrodes. It also conceals the electrodes and protects them from vomit.

Partial hepatectomy by means of a carbon-dioxide laser has been performed in 13 dogs. The operative technique is described, and its advantages and the absence of morbidity and mortality during the 10 weeks after operation are discussed.

The frequency response characteristics for interrupted infra-red radiation are described for four condenser-microphone type detectors as used in nondispersive infra-red gas analysers. Three of the detectors are of conventional dimensions. The fourth is a subminiature type, and its use is described with a field-effect transistor amplifier. It is shown that markedly increased optical modulation frequencies can be used with infra-red pneumatic detectors, without radical reductions in output signal, if the dimensions of the device are drastically reduced. This has been accounted for on theoretical grounds. The frequency responses obtained are examined and shown to correlate adequately with mathematically predicted profiles. Low frequency attenuation is explained on the grounds of thermal conductivity effects and leakage paths across the transducer diaphragm, whereas a high frequency maximum for one detector is shown to arise from Helmholtz resonation due to the chamber configuration.

The liquid-vapour equilibria for the systems nitrous oxide-oxygen and carbon dioxide-oxygen are presented in the form of isotherms on a pressure-composition graph, and isobars on a temperature graph, up to 200 atmospheres (207×106 N m−2). In the case of premixed cylinders of a 50/50 nitrous oxide-oxygen mixture used as an analgesic any liquid phase formed as a result of cooling the cylinder to not lower than −40°C can be dispersed by storing the cylinder horizontally for 24 hours at a temperature not less than 5°C.

When a nuclear spin system is subjected to a repetitive sequence of strong radiofrequency pulses, a steady state is established where there is a dynamic balance between the effect of the pulses and spin relaxation. Under certain readily satisfied pulse conditions, the deviation of the intensity of the free induction signal from its thermal equilibrium value is an exponential function of the pulse interval with time constant equal to the spin–lattice relaxation time. The determination is unaffected by spin–spin relaxation provided that the interval between pulses is long enough to permit all transverse components of magnetization to be eliminated, and provided precautions are taken to inhibit spin‐echo formation. Through Fourier transformation of the transient response, high resolution spectra with many component resonances may be studied, and the spin–lattice relaxation times of the individual lines determined. The technique lends itself particularly well to repeated accumulation of the transient signal for the purpose of improving sensitivity. It has been applied to the problem of determining the spin–lattice relaxation rates of the eight different carbon‐13 resonances in 3,5‐dimethylcyclohex‐2‐ene‐1‐one. The results span a range from 2.6 to 39 sec, and are in good agreement with those obtained by applying 180°–t–90° sequences to the same sample.

The various factors which affect the signal-to-noise ratio with which a magnetic resonance can be detected are discussed. The analysis is in terms of nuclear resonance but the differences for electron resonance are pointed out. The methods of optimizing the parameters involved are described and typical values are given. In favourable cases significant changes in the resonance intensity may be achieved by double resonance methods: some of these methods are described briefly.

A double-beam-in-time infra-red analyser is described which uses transistor circuitry and an indium antimonide detector. Waveband selection is performed by optical interference filters working in conjunction with magnetic pick-ups. The instrument can be powered from a 6 v d.c. supply, and the optical portion pressurized with nitrogen for use in potentially explosive atmospheres. The techniques used render the instrument insensitive to shock and vibration.

Suitably processed, corona, stabilizer tubes filled with pure hydrogen are shown to have a running voltage stability over 24 hours of better than 0.02% and over 1000 hours of better than 1%. The variation of slope resistance with pressure and current has been investigated and the results compared with theoretical prediction. The variation of running voltage with temperature shows small positive coefficients (approximately 0.005% per °C). Some investigations into maximum current drawn show the possibility of this being raised by suitable glow discharging.

Values of stroke volume calculated from five different formulas utilising parameters derived from the aortic-pressure pulse waveform were compared with stroke-volume values calculated from the thoracic electrical-impedance waveform, which was recorded simultaneously with the aortic-pressure waveform. A total of 195 beats from three closed-chest anaesthetised dogs were compared. During the recording of the impedance and blood-pressure waveforms, the cardiac output was measured by dye and saline dilution. The mean of stroke-volume values from the impedance method was 39% greater than the mean ‘stroke volume’ calculated by dividing the dye cardiac-output value by the mean heartrate measured during the recording of the dye-dilution curve. The correlation between impedance and dye cardiac-output values was 0·879. The correlation of dye ‘stroke volume’ with values calculated by all four formulas was about 0·89. Individual stroke volumes could be markedly affected by variations in the beat-by-beat values of the total systemic resistance.

A combination of non-selective, single-selective, double-selective, and triple-selective pulse experiments has been used to determine the magnitude of specific dipole–dipole, interproton spin–lattice relaxation contributions for 1,2,3,4,7,7-hexachloro-6-exo-benzoyloxybicyclo[2.2.1]hept-2-ene and provides a direct measure for the interproton distances, in excellent agreement with estimates based on Dreiding molecular models and computer simulation; the quality control experiments necessary for quantitative conformational studies are illustrated.

A system for the study of cellular bioeffects in the frequency range of 38 to 48 GHz and 65 to 75 GHz is described. High coupling efficiency (greater than 99 percent) provides a method for determining the energy absorption by the samples. An aqueous test medium was pumped through tapered waveguide sample holders. Temperature differences as low as +- 0.01°C were measured using pairs of thermocouples. Compensatory electrical heating of the control sample holders was employed for reduction of temperature differences.

A double beam infrared vapour analyser employing a 2 mW He-Ne laser as the source of 3.39 mu m radiation is described. Its performance in the analysis of ethyl alcohol vapour-air mixtures is given with regard to sensitivity and baseline drift and some results obtained from breath alcohol measurements with human subjects are reported.

A compact cathode-ray tube display gas chromatograph has been constructed for the routine analysis of anaesthetic vapours or similar volatile materials. The analysis is performed by a stainless-steel capillary column feeding into a micro-argon detector. The chromatogram is displayed on a six inch square long persistence cathode-ray tube. A pneumatic gain control and a separate timing channel are provided. The instrument would be of use, with suitable modifications, in industrial and research applications for the rapid analysis of vapour mixtures. The instrument is compact and portable and permanent recording can be made if desired.

An apparatus for the generation of typical respiratory patterns is described. Two pistons are driven by a half horse-power servomotor operated by a Velodyne speed control system. The desired waveform is produced by means of a cam or photoelectric function generator.

Regular trains of short strong radiofrequency pulses allow frequency selective excitation in Fourier transform NUR experiments. Applications include the measurement of proton coupled spectra from individual carbon sites, spin locking, solvent peak suppression and the study of chemical exchange by saturation transfer.

The retinal vessel calibre responses to controlled stimulation of the autonomic nervous system were studied in 10 healthy subjects, using sustained isometric muscle contraction as stimulus. Each subject was studied twice using different mydriatic agents, (1) g.tropicamide 1% a parasympatholytic agent and (2) g. phenylephrine 10% a sympathetic agonist. In the tropicamide study, there was a mean arteriolar constriction of 8.1% (SEM 1.67, p less than 0.001) and venule constriction of 3.7% (SEM 0.85, p less than 0.001) with a mean rise in diastolic blood pressure of 27.4 mmHg (SEM 2.95, range: 13-45 mmHg). When g. phenylephrine 10% was used, there was a mean arteriolar constriction of 8.6% (SEM 1.68, p less than 0.001) and venule constriction of 4.8% (SEM 1.22, p less than 0.001) with a mean rise in diastolic blood pressure of 29.2 mmHg (SEM 2.56, range: 17-44 mmHg). There was no significant difference in retinal vessel calibre in the recovery phase compared to baseline phase (p greater than 0.05) or between the two mydriatic agents on vessel responses (p greater than 0.05). There was no correlation between the rise in diastolic blood pressure and the degree of retinal vessel constriction, during handgrip contraction in either study. This study has demonstrated a significant association between retinal vessel calibre and systemic autonomic nerve stimulation. The possible mechanisms for the retinal vessel constriction observed in this study are discussed.

Disseminated candidiasis usually occurs in profoundly immunocompromised hosts. We described a case of disseminated macronodular cutaneous candidiasis in a man with no known risk for immunosuppression other than alcoholic liver disease and a second case of multiple macronodular cutaneous abscesses in an alcoholic man who had no evidence of systemic dissemination. One patient had testicular candidiasis, a previously unreported site of infection in disseminated candidiasis. Tests showed neutrophil and lymphocyte function to be normal; however, a marked defect in serum opsonization was demonstrated in one patient. It is postulated that chronic alcoholism with alcoholic liver disease resulted in impaired serum opsonization, which, in turn, predisposed these patients to candidal infection.

An investigation has been made into the form of the EMG signals from the human bladder and urethral and anal sphincters. A buildup of the low frequency detrusor EMG before micturition occurs in some patients and this is more marked in patients with urgency. A good correlation occurs between the amount of EMG activity and bladder activity as assessed by the cystometrogram. Marked spike activity has been seen in the detrusor EMGs of patients with irritable bladders. The comparison of anal and urethral sphincter EMGs is of interest from the viewpoint of the anatomy of the urethral sphincter and the mechanism of micturition.

A recently-introduced laminated material which accepts light only over a small angle on either side of the normal was compared to standard Polaroid sunglasses. A preliminary trial failed to show any superiority of the new material in reducing glare for patients with moderate cataract.

An estimate of the proportion of the patients admitted to an acute hospital who will need intensive therapy at some time is between 1% and 2% [9]. Units of less than six beds are uneconomical in terms of staffing, accommodation, essential services and equipment, while one with more than ten beds becomes unwieldy. In a general hospital it is usually possible for the ICU to accept all types of emergency, but the coronary care unit (CCU) should be adjacent to the ICU if this is feasible.

The suitability of the peak value of the first derivative of the thoracic electrical impedance dZ/dtmax has been investigated in dogs as a non-invasive index of changes in myocardial contracility by comparing if with the peak left ventricular dP/dt and the peak values of aortic blood velocity and acceleration. An increase in the inspired halothane concentration was used to produce changes in contracility. In 5 dogs the combined values for the correlation coefficient between dZ/dtmax peak velocity and acceleration were respectively 0.937, 0.954 and 0.950. In 14 out 15 comparisons p less than 0.001 and in one, p less than 0.01. On these grounds, dZ/dt max is proposed as a variable worthy of sconsideration in patient monitoring.