Biomedical subjects
Publications and source records attributed to M Irving.
We report three cardiological complications of total parenteral nutrition in four patients, all of the complications were detected by two-dimensional echocardiography. We discuss these complications and make suggestions as to the role of echocardiography in patients on total parenteral nutrition.
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One thousand consecutive deaths from injury in 11 coroner's districts in England and Wales were reviewed by four independent assessors, who studied necropsy reports to identify deaths in hospital that might have been preventable. Of 514 patients admitted to hospital alive, 102 deaths (20%) were judged by all four assessors to have been potentially preventable. When those cases in which three out of four assessors considered that the death was preventable were added the total rose to 170 (33%). Nearly two thirds of all non-central nervous system deaths were judged to have been preventable. The median age of the 170 patients whose deaths were preventable was 41, and the mean Injury Severity Score was 29. Further analysis suggested that the preventable deaths were principally the result of failure to stop bleeding and prevent hypoxia and the absence of, or delay in, surgical treatment. The results closely parallel those from similar studies from the United States and suggest that there are serious deficiencies in the services for managing severe injury in England and Wales. Debate is needed now on how to correct these deficiencies. In particular, the place of trauma centres must be considered.
Birefringence measurements were used to investigate crossbridge orientation in demembranated muscle fibres of frog and rabbit. Birefringence depends on the interfilament spacing as well as on crossbridge orientation, so conditions were chosen such that changes in interfilament spacing were either eliminated or known from previous studies. At sarcomere length 2.3 micron there was a large birefringence decrease on putting relaxed fibres into rigor; at 3.7 micron this gave no change in birefringence. A simple model for crossbridge structure was used to interpret the birefringence data; it seems likely that reorientation of subfragment-1 (S-1) is responsible for the observed change. Decoration of rigor fibres with exogenous S-1 gave a birefringence increase corresponding to S-1 binding with its long axis at about 50 degrees to the fibre axis. The corresponding mean S-1 angle in relaxed muscle was estimated as about 35 degrees. When relaxation of rigor fibres was initiated by photolysis of caged-ATP in the absence of Ca2+ the birefringence increase showed two components, one 20 times faster than the other. The fast component was accompanied by a decrease of rapid stiffness, suggesting that it is caused by some crossbridges detaching to take up an orientation more parallel with the fibre axis. However the mechanical measurements indicated the presence of some active force generating crossbridges at this time, even in the absence of Ca2+, and these may also make a contribution to the fast birefringence component. Birefringence transients following ATP release in the presence of Ca2+ suggest that crossbridges are on average more perpendicular to the fibre axis during active force generation than in the rigor state.
Four of the techniques proposed for in vivo volume-selected NMR spectroscopy have been compared using a simple phantom with a large background water signal which was outside the region of interest. The methods VSE, SPACE, SPARS, and DIGGER all use pulsed field gradients for spatial encoding and were tested with a symmetric and an asymmetric phantom. SPACE was used to obtain volume-selected 1H NMR spectra of a human leg, demonstrating excellent discrimination between bone marrow and muscle.
This article describes a new apparatus for making simultaneous optical measurements on single muscle fibers at three different wavelengths and two planes of linear polarization. There are two modes of operation: mode 1 measures the individual absorbances of light linearly polarized along and perpendicular to the fiber axis, and mode 2 measures retardation (or birefringence) and the average of the two absorbance components. Although some intact frog twitch fibers were studied, most experiments used cut fibers (Hille, B., and D. T. Campbell. 1976. Journal of General Physiology. 67:265-293) mounted in a double-Vaseline-gap chamber (Kovacs, L., E. Rios, and M. F. Schneider. 1983. Journal of Physiology. 343:161-196). The end-pool segments were usually exposed for 2 min to 0.01% saponin. This procedure, used in subsequent experiments to make the external membranes in the end pools permeable to Ca indicators (Maylie, J., M. Irving, N. L. Sizto, G. Boyarsky, and W. K. Chandler. 1987. Journal of General Physiology. 89:145-176; Maylie, J., M. Irving, N. L. Sizto, and W. K. Chandler. 1987. Journal of General Physiology. 89:41-143), was routinely employed so that all our cut fiber results would be comparable. A simple method, which does not require microelectrodes, allowed continual estimation of a fiber's membrane (rm) and internal longitudinal (ri) resistances as well as the external resistance (re) under the Vaseline seals. The values of rm and ri obtained from cut fibers with this method agree reasonably well with values obtained from intact fibers using microelectrode techniques. Optical measurements were made on resting and action potential-stimulated fibers. The intrinsic fiber absorbance, defined operationally as log10 of the ratio of incident light to transmitted light intensity, was similar in intact and cut preparations, as were the changes that accompanied stimulation. On the other hand, the resting birefringence and the peak of the active change in cut fibers were, respectively, only 0.8 and 0.7 times the corresponding values in intact fibers. Both the amplitude and the half-width of the active retardation signal increased considerably during the time course of cut fiber experiments; a twofold increase in 2 h was not unusual. Such changes are probably due to a progressive alteration in the internal state of the cut fibers.
The Ca indicator tetramethylmurexide was introduced into cut fibers, mounted in a double-Vaseline-gap chamber, by diffusion from the end-pool solutions. The indicator diffused rapidly to the central region of a fiber where optical recording was done and, if removed, diffused away equally fast. The time course of concentration suggests that, on average, a fraction 0.27 of indicator was reversibly bound to myoplasmic constituents and the free diffusion constant was 1.75 x 10(-6) cm2/s at 18 degrees C. The shape of the resting absorbance spectrum suggests that a fraction 0.11-0.15 of tetramethylmurexide inside a fiber was complexed with Ca. After action potential stimulation, there was a rapid transient change in indicator absorbance followed by a maintained change of opposite sign. The wavelength dependence of both changes matched a cuvette Ca-difference spectrum. The amplitude of the early peak varied linearly with indicator concentration and corresponded to an average rise in free [Ca] of 17 microM. These rather diverse findings can be explained if the sarcoplasmic reticulum membranes are permeable to Ca-free indicator. Both Ca-free and Ca-complexed indicator inside the sarcoplasmic reticulum would appear to be bound by diffusion analysis and the Ca-complexed form would be detected by the resting absorbance spectrum. The transient change in indicator absorbance would be produced by myoplasmic Ca reacting with indicator molecules that freely diffuse in myoplasmic solution. The maintained signal, which reports Ca dissociating from indicator complexed at rest, would come from changes within the sarcoplasmic reticulum. A method, based on these ideas, is described for separating the two components of the tetramethylmurexide signal. The estimated myoplasmic free [Ca] transient has an average peak value of 26 microM at 18 degrees C. Its time course is similar to, but possibly faster than, that recorded with antipyrylazo III (Maylie, J., M. Irving, N. L. Sizto, and W. K. Chandler. 1987. Journal of General Physiology. 89:83-143).
The Ca indicator arsenazo III was introduced into cut frog twitch fibers by diffusion from end-pool segments rendered permeable by saponin. After 2-3 h, the arsenazo III concentration at the optical recording site in the center of a fiber reached two to three times that in the end-pool solutions. Thus, arsenazo III was bound to or taken up by intracellular constituents. The time course of indicator appearance was fitted by equations for diffusion plus linear reversible binding; on average, 0.73 of the indicator was bound and the free diffusion constant was 0.86 x 10(-6) cm2/s at 18 degrees C. When the indicator was removed from the end pools, it failed to diffuse away from the optical site as rapidly as it had diffused in. The wavelength dependence of resting arsenazo III absorbance was the same in cut fibers and injected intact fibers. After action potential stimulation, the active Ca and dichroic signals were similar in the two preparations, which indicates that arsenazo III undergoes the same changes in absorbance and orientation in both cut and intact fibers. Ca transients in freshly prepared cut fibers appeared to be similar to those in intact fibers. As a cut fiber experiment progressed, however, the Ca signal changed. With action potential stimulation, the half-width of the signal gradually increased, regardless of whether the indicator concentration was increasing or decreasing. This increase was usually not accompanied by any change in the amplitude of the Ca signal at a given indicator concentration or by any obvious deterioration in the electrical condition of the fiber. In voltage-clamp experiments near threshold, the relation between peak [Ca] and voltage usually became less steep with time and shifted to more negative potentials. All these changes were also observed in cut fibers containing antipyrylazo III (Maylie, J., M. Irving, N. L. Sizto, and W. K. Chandler. 1987. Journal of General Physiology. 89:83-143). They are considered to represent a progressive change in the physiological state of a cut fiber during the time course of an experiment.
The Ca indicator antipyrylazo III was introduced into cut frog twitch fibers by diffusion (Maylie, J., M. Irving, N. L. Sizto, and W. K. Chandler. 1987. Journal of General Physiology. 89:41-81). Like arsenazo III, antipyrylazo III was largely bound to or sequestered by intracellular constituents; on average, a fraction 0.68 was so immobilized. After action potential stimulation, there was an early change in absorbance, with a wavelength dependence that nearly matched a cuvette Ca-difference spectrum. As with arsenazo III, this signal became prolonged as experiments progressed. In a freshly prepared cut fiber containing 0.3 mM indicator, the absorbance change had an average half-width of 10 ms at 18 degrees C. The peak amplitude of this Ca signal depended on the indicator concentration in a roughly parabolic manner, which is consistent with a 1:2 stoichiometry for Ca:indicator complexation and, for indicator concentrations less than or equal to 0.4 mM, constant peak free [Ca]. If all the antipyrylazo III inside a fiber can react normally with Ca, peak free [Ca] is 3 microM at 18 degrees C. If only freely diffusible indicator can react, the estimate is 42 microM. The true amplitude probably lies somewhere in between. The time course of Ca binding to intracellular buffers and of Ca release from the sarcoplasmic reticulum is estimated from the 3- and 42-microM myoplasmic [Ca] transients. After action potential stimulation, the release waveform is rapid and brief; its latency after the surface action potential is 2-3 ms and its half-width is 2-4 ms. This requires rapid coupling between the action potential in the transverse tubular system and Ca release from the sarcoplasmic reticulum. The peak fractional occupancy calculated for Ca-regulatory sites on troponin is 0.46 for the 3-microM transient and 0.93 for the 42-microM transient. During a 100-ms tetanus at 100 Hz, the corresponding fractional occupancies are 0.56 and 0.94. The low value of occupancy associated with the low-amplitude [Ca] calibration seems inconsistent with a brief tetanus being able to produce near-maximal activation (Blinks, J. R., R. Rudel, and S. R. Taylor. 1978. Journal of Physiology. 277:291-323; Lopez J. R., L. A. Wanck, and S. R. Taylor. 1981. Science. 214:47-82).
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The use of magnetic resonance imaging, in the demonstration of internal human anatomy and in the diagnosis of disease, has the major advantages that the technique is noninvasive, does not require the use of ionizing radiation and that it can demonstrate neurological and cardiovascular lesions that cannot be diagnosed easily by other imaging methods. Magnetic resonance imaging is derived from the principle that certain atomic nuclei in a strong magnetic field will absorb pulses of radiofrequency energy; when the pulse is finished the nuclei will emit radiowaves at the same frequency. These radiowaves are received by specially designed aerials or coils and the information is collected by a computer which reconstructs an image of internal anatomy in a similar way to that of x-ray computed tomography (CT). By changing the strength of the magnetic fields and the frequency of the radiowave pulses, it is possible to examine different sections within the body. The first magnetic resonance images of humans were obtained in Australia in October 1985 on the research instrument of the Queensland Medical Magnetic Resonance Research Centre, which is based at the Mater Hospital in Brisbane, and is part of the University of Queensland's Department of Radiology.
Between January, 1977, and March, 1986, 200 patients were registered as receiving home parenteral nutrition (HPN) in the UK and the Republic of Ireland. Although 28 centres contributed case-reports, 75% of the cases were registered by 7 centres. Most patients started treatment between the ages of 10 and 40 years, a reflection of the high incidence of Crohn's disease during these decades. The three main indications for HPN were Crohn's disease (90 patients), mesenteric vascular disease (27), and extensive small-bowel resection for volvulus or other benign enteric disease (14). 85 patients required treatment for less than 1 year and 17 have been on treatment for more than 2 years. Patients whose indication for HPN was a primary intestinal disease had a better quality of life than did those in whom the intestinal failure was secondary to a systemic disorder. Of the 108 patients who have completed treatment 56 have been able to resume enteral nutrition through adaptation of the remaining bowel, or closure of a fistula. 34 have died, 19 as a consequence of the underlying disease and 10 of complications of treatment. The incidence of catheter-related sepsis varied between 0.2 and 0.9 episodes per year of treatment (overall 0.35) depending on the length of experience of the supervising centre.
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A consecutive series of 282 patients undergoing splenectomy on one surgical unit has been studied to ascertain the incidence of postoperative subphrenic abscess. Only two atypical subphrenic abscesses occurred (0.17 per cent), a rate of abscess formation much lower than that reported in other series. We believe that the use of low-pressure closed suction drainage to the splenic bed accounts for this low rate.