Diagnosis of inherited enzymatic deficiencies with tears: Fabry disease.
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Biomedical subjects
Publications and source records attributed to D L Johnson.
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The effects were examined of various patterns of interruption--of continuous noise by periods of quiet--on the growth and recovery of temporary threshold shift of hearing over an exposure period of 24 h. Monaural thresholds of hearing were measured prior to, during, and following exposure to a pink noise at a level of 85 dBA and to four conditions in which the pink noise was interrupted with various on-off ratios. The interrupted exposure patterns and levels were adjusted to make their average levels equivalent to 85 dBA. Among the results: 1) the growth of TTS clear.ly reached an asymptote for all interrupted exposure conditions, even when the TTS was as small as 5 dB, 2) the interrupted exposures produced lower asymptotic levels than the continuous exposure with the same amount of energy, and 3) the TTS recovery patterns were essentially the same at 1 h and beyond, for all conditions. These data support the concept that, following a long exposure, one should be provided at least as much time for recovery as the duration of the exposure.
The enzymatic diagnosis of hemizygotes with Fabry disease and heterozygous carriers was accomplished by the fluorometric determination of alpha-galactosidase activities in tears. Two components of total alpha-galactosidase activity were differentiated by their relative thermostabilities and by chromatography on DEAE-cellulose. The major component, alpha-galactosidase A, was thermolabile and represented approximately 90% of total activity; the remaining activity was thermostable, eluted at a slightly higher salt concentration and was designated alpha-galactosidase B. A single, symmetric pH optimum was observed for total alpha-galactosidase activities from heterozygotes and normal individuals, whereas the total activity from hemizgotes, which was about 10% of that in normal controls, had a broad pH profile, identical to those for alpha-galactosidase B activities from all individuals studied. The apparent Km values for total activities were 3.2, 4.0, and greater than 13 mM for normal individuals, heterozygotes, and hemizygotes, respectively. In contrast, apparent Km values for alpha-galactosidase B activities were greater than 13 mM for all individuals, further suggesteng that the residual activity in hemizygotes with Fabry disease represented the alpha-galactosidase B component. of the potential inhibitors studied, alpha-D-melibiose was found to competitively inhibit total alpha-galactosidase activity (Ki approximately 10 mM). These studies demonstrate that tears provide an easily obtainable source of freshly secreted enzyme for the diagnosis of hemizygotes and heterozygotes with Fabry disease and suggest that tears may be useful for the diagnosis of other inborn errors of metabolism.
Five cases of nosocomial infection caused by Serratia marcescens were traced to backflow of blood from nonsterile evacuated blood-collection tubes. The mechanism of backflow was investigated theoretically and the conditions were determined under which backflow can occur. The theory was confirmed by experiments conducted on a simulated venous system and by measurements of the venous pressure in the brachial vein of a patient during application and removal of a tourniquet. Various possible solutions to the backflow hazard include strict adherence to correct venipuncture technique, sterilization of all blood-collection tubes, improvement of the vacuum in the tubes and incorporation of a check valve into the system.
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The oxidation rate of arsenite in seawater is very slow. Of the parameters investigated which might affect this rate the most important were temperature, initial arsenite concentration, salinity and pH. An empirical rate expression was developed from experimental data which led to a prediction that the natural rate of oxidation in the ocean is about 0.023 micromoles of As(III) per liter each year. This value is about twice the natural concentration of arsenite; the only mechanism which seems able to account for the continued presence of arsenite is biological reduction of arsenate.
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Four male subjects were exposed to infrasound ranging from 1 through 20 Hz for a period of 8 min up to levels of 144 dB re 20 micropascal. There was no objective evidence (including audiograms) of any detrimental effect due to infrasound; however all subjects experienced painless "pressure build-up" in the middle ear that was relieved by valsalva maneuver or by cessation of infrasound, and voice modulation and body vibration consistently occurred. It is concluded that infrasound exposures as high as 144 dB are safe for healthy subjects, at least for periods of 8 min, and it is predicted that longer exposures will also be safe.
An investigation was carried out using a variety of pacemakers and all the types of weapons detectors in common use in Canada, to determine whether or not such detectors present a hazard to pacemaker bearers. The results indicate that only left-side implants of unipolar sensing pacemakers are likely to be affected, that ventricular fibrillation initiated by interference-induced competitive pacing is the only conceivable hazard, but that the probability of 10(-9) for the occurrence of this event is so low that it may be completely disregarded. Physicians may therefore reassure pacemaker bearers of their safety in and around airport weapons detectors.
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