Procoagulant activity of platelets.

A simplified, semiautomated, quantitative method to evaluate platelet procoagulant activity was evaluated on plasma that contained widely divergent concentrations of platelets. When fewer than 100,000 platelets/cu mm were present, excellent correlation between platelet concentration and clotting time was noted, with correlation best in the range 30,000 to 100,000 platelets/cu mm. When platelets were present in concentrations greater than 100,000/cu mm, no alteration in clotting time as a function of platelet count was noted. These observations were consistent with clinical observations that patients with greater than 100,000 platelets rarely bleed and that those with fewer than 30,000 platelets bleed in an unpredictable fashion. The procedure appears to be of potential value in evaluation of patients for defects in platelet factor 3 release.


Frequency discrimination for bands of noise.

Recoding of speech in order to improve discrimination for profoundly deaf people has been tried in various ways. One of these is frequency transposition of voiceless consonants. Some authors report positive and very promising results. Others, however, have not found any significant difference when using control groups with normal amplification. One reason might be a poor frequency discrimination. Is it possible to establish what minimum hearing capacity the listener must show for a successful use of frequency transposition? Using noise bands with different Q factors and varying the levels, the thresholds as minimum midfrequency shift have been measured. Great individual variations have been shown. There is a significant difference between (1) threshold values at different Q factors, (2) threshold values at different frequencies, and (3) threshold values for increasing and decreasing frequency, position of deltaf. There is a significant interaction between (1) frequency and position of deltaf, (2) Q factor and position of deltaf, and (3) between Q factor and frequency. There is also a significant triple interaction between Q factor, frequency, and position of deltaf.


Identification and discrimination of speech sounds in monosyllabic meaningful words and nonsense words by children.

297 children aged 9-14 with normal hearing and intelligence level were examined by speech audiometry. Ten lists with monosyllabic meaningful and nonsense words were used. All the lists were phonemically and structurally balanced in the same way and were applied with an intensity level varying between 26 dB and 61 dB. The identification and discrimination scores for Polish speech sounds were calculated from written-response sheets. The identification scores were generally significantly lower for nonsense words, and up to a certain extent, increased with age. An examination of the discrimination scores showed that confusions were related to the distinctive features of the phonemes. The results represent the first stage of a project on speech sound identification in children and may have practical implications for the rehabilitation of children with hearing loss.


Clinical psychophysics. Illustrated by the problem of auditory overload.

In some patients with sensorineural hearing loss, masking extends over an abnormally wide range toward the higher frequencies. Most likely the main determinant is excessive harmonic distortion. Under this assumption, the masking measured with a probe tone at 2 kHz, due to a masker tone of 1 kHz, should be dependent upon the phase of the probe tone. This has been confirmed experimentally; it proved possible to derive the strength and phase of the equivalent second harmonic from the data. For normal ears, the strength was found to depend upon the SPL of the masker in the expected, quadratic manner. The phase was found to exhibit a startlingly rapid transition over nearly 360 degrees within one octave (500-1 000 Hz fundamental). Results of clinical measurements with the same method will be discussed.


Verbal tests of central audition.

The use of sensitized verbal tests in the diagnosis of central deafness is critically reviewed. The concept of intrinsic (neural) redundancy is the main point in the operational model; different modalities of coupling between intrinsic and extrinsic redundancy bring forth different patterns of intelligibility. The age of the subject thus becomes critical; on the contrary, the influence of the IQ can be minimized by carefully selecting the tests. These can be divided into monaural and dichotic; among the latter, only the tests involving competing information are of value, whilst the so-called summation tests should now be disregarded. The clinical results are only briefly quoted, since they are well-known. The contribution to the advances in neurophysiology seems to be more interesting. The influence of reticular formation on auditory stimulation, the crossing of the auditory pathways, the existence of a secondary auditory area have been psychoacoustically confirmed by the use of the monaural tests. In their turn, the dichotic competing message tests have enabled a beautiful model of language perception to be drawn, and have definitely demonstrated the so-called hemispheric specialization (or dominance) for verbal and nonverbal messages.


Effect of contralateral noise on speech detection and speech reception thresholds.

Speech detection thresholds (SDT) and speech reception thresholds (SRT) for spondee words were obtained on 20 normal hearing listeners while white or speech noise making was presented to the contralateral ear. Each masker was presented continously or pulsed simultaneously with the onset of each spondee word. Several masker sensation levels (SL) of 30, 40, 50, 60, 70, and 80 dB were employed, and the amount of masking (threshold shift) was determined for each condition. Small but consistent SDT and SRT shifts were apparent at low masker SLs (30 dB). FOR 60-80 DB masker SLs, the shifts were about 3.5 dB for each 10-dB increase in the masker. The greater threshold shifts at the higher masker SLs may have resulted from transcranial conduction and/or activation of the acoustic reflex. The pulsed masker condition had more of an effected on the SDT than on the SRT; SDT shifts were consistently larger for each masker SL when the masker was pulsed compared to continuous presentation. Overall, the average threshold shifts ranged from about 1 to 11 dB as the masker SL was increased from 30 to 80 dB. These data suggest that central masking is operating for masker SLs below 60 dB; for higher masker SLs, the increased threshold shifts probably result from a combination of central masking, transcranial conduction, and acoustic stapedius reflex action. The clinical implications of central masking are also discussed.


Most comfortable listening for the loudness and intelligibility of speech.

The effect of instructional set upon most comfortable listening (MCL) was investigated among normal listeners. MCL level and range were determined (method of limits) in relation to listening for comfortable speech loudness versus comfortable speech intelligibility. The results indicate that instructional set does influence listener performance. the mean MCL level for comfortable speech intelligibility was significantly higher (4.96 dB) than the mean level for comfortable speech loudness; the mean MCL range for comfortable speech intelligibility was higher by 7.33 dB and wider by 7.10 dB than the mean range for speech loudness. Ascending stimulus presentation obtained comparable MCL levels for both listening conditions, whereas descending presentation obtained a mean MCL level almost 10 dB higher for comfortable speech intelligibility than for comfortable speech loudness. Males achieved slightly higher MCL levels than did females for both loudness (4.32 dB) and intelligibility (4.96 dB) criteria. It was concluded that the nature of the instructional set be taken into account when interpreting comfortable listening measures.


[The auditory intensity discrimination and its audiological and clinical applications (author's transl)].

Studies on this type of discrimination are very interesting, as they can be made at suprathreshold levels. The nature of auditory intensity discriminations and the most useful methods for measuring the auditory intensity difference limens are briefly described. The most important results obtained with normal subjects are then presented; the monaural intensity difference limens, the intensity difference limens measured on one ear while stimulating the other ear by an unvarying tone or a noise, are treated successively. The most important clinical applications of the intensity auditory difference limens are presented (especially, the monaural intensity difference limens, and the difference lemens on one ear in presence of an unvarying tone on the other ear). New explanations of the results obtained in the monaural intensity difference limen tests used are proposed, based on the localization areas in the cochlea, along the auditory nervous system and in the higher auditory centers. New suggestions for the use of the difference limens in audiometry are made.


Threshold-duration function of the acoustic reflex in man.

The threshold-duration function of the acoustic reflex was investigated in 5 male and 5 female adult, normal-hearing humans and in 3 adult male subjects with hearing loss of cochlear etiology. Reflex threshold was obtained at stimulus durations of 10, 20, 50, 100, 200, and 500 msec and at frequencies of 500, 1 000, 2 000, 3 000, and 4 000 Hz. Three commercially available acoustic bridges were employed, the Madsen ZO-70 and Grason-Stadler 1720 electroacoustic bridges, and the Grason-Stadler-Zwislocki model 3 mechanical-acoustic bridge. A probe-tone frequency of 220 Hz was used in all measures. The reflex threshold-duration function for normal-hearing subjects was found to encompass a much greater range of intensity than the psychophysically assessed auditory threshold temporal integration function. A sex difference was found which may be explained by subclinical noise-induced cochlear pathology in the male subjects with subsequent truncation of the reflex threshold-duration function. The function was also found to be truncated in the 3 subjects with hearing loss diagnosed to be of cochlear etiology. The implications of these findings for control of stimulus duration in clinical reflex measurement was discussed.


Stapedius reflex abnormalities in multiple sclerosis.

Thirteen patients suffering from multiple sclerosis were analyzed by a Madsen ZO 70 electroacoustic bridge connected to an electronystagmograph through an impedance adaptor. Threshold, amplitude, decay and difference limen of intensity (DLI) of the stapedius reflex were examined for the frequencies 500, 1 000, 2 000 and 4 000 Hz. The difference between standard audiometric results and stapedius reflex data stresses the value of reflex measurements in assessing brain stem pathology.


The generation of large pyroninophilic cells in the lymphoid tissues of rats infused with cell-free lymph.

The thoracic duct of Wistar strain rats was cannulated during 5 days for studying the effect of selective lymphocyte depletion on the lymphoid tissue. A technique for the continuous infusion of cell-free lymph, whole lymph of Eagle's medium to the rat with the thoracic duct fistula is described in detail. The prolonged drainage of lymph from rats was followed by lymphopenia, sever atrophy of lymphoid tissues and the depletion of small lymphocytes in the thymus-dependent areas of spleen and lymph nodes. The infusion of cell-free lymph into the drained rat resulted in the recovery of the weight of lymphoid tissues and in the massive proliferation and accumulation of large cells with prominent nucleoli and intensely pyroninophilic cytoplasm in the lymphocyte depleted areas of the peripheral lymphoid tissues and thymic cortex. There was histological evidence that the large pyroninophilic cells developed well in the spleen and tended to localize preferentially around the periarteriolar region through the marginal zone bridging channels to the red pulp. The infusion of Eagle's medium was found ineffective in restoring the weight of the lymphoid tissues and in bringing about the proliferation of lymphoid cells. The rats infused with whole lymph showed almost similar findings biologically and histologically to those of sham-operated rats.


Age-related changes in the incorporation of [14-C] leucine into myofibrillar and sarcoplasmic proteins of red and white muscles of chicks.

Studies on the incorporation of DL-[1- 14-C] leucine into myosin, total myofibrillar protein and total sarcoplasmic protein have shown age-dependent alterations in the rate of synthesis of these protiens in red and white skeletal muscles of chicks. During the early phase of ex ovo development white muscle synthesizes significantly higher amounts of myofibrillar proteins, especially myosin, in comparison with red muscle. The rate of sarcoplasmic protein synthesis in red and white muscles one day after hatching is almost identical. The red muscle shows a markedly higher rate of sarcoplasmic protein synthesis from 10 days after hatching. The incorporation of amino acid into various protein fractions of both the muscle types decreases with advancing age. In adult chicks red muscle displays a higher ability to synthesize sarcoplasmic and myofibrillar proteins.


Central auditory fatigue.

The results of this study, based on evoked responses and single-neuronal responses, reveal that there is a central involvement in auditory fatigue. In these experiments, cochlear potentials (microphonic and whole-nerve action potential) and inferior colliculus electrical responses were simultaneously obtained before and after excessive sound exposure. In general, sound exposure produced a greater reduction of the collicular evoked responses than of the cochlear microphonics and action potentials. Recordings from single neurons support the evoked-response findings.


Some physical considerations in the choice of techniques for ossiculoplasty.

A comparative study between the monobloc tympano-ossicular implant and the classical columellar technique is made. Although both give satisfactory audiometric results, the follow-up of the columellar restoration showed some post-operative disadvantages, namely: invagination and perforation of the tympanic membrane, slipping of the columella, and fixation of the columella to the tympanic ring (bony annulus) or to the promontory. In view of the normal tympano-malleal fixation, the normal static pressure accomodation in the incudo-malleal joint and the normal topological situation, monobloc implant obviates the disadvantages inherent in the columellar technique. Two aspects of the monobloc implant need further examination; these are the restoration of the correct rotation axes and the incudo-stapedial connection.


Lung liquid production and composition in the "in utero" foetal lamb.

Experiments were carried out on foetal lambs in utero from 103 to 133 days' gestation, to measure the daily flow and solute composition of liquid from the foetal lung. The mean daily flow from foetuses with a tracheal fistula was 231 ml/day (9.6 ml/h), while the mean hourly flow in foetuses with a tracheal loop was 5.1 ml/h. The pattern of flow of lung liquid was intermittent and irregular, with short periods of rapid flow interspersed with longer periods of slow and no flow. The Na+, Ca2+, Mg2+, Cl- and urea concentrations showed no significant change with increasing gestational age, but the K+ concentration showed a significant rise. It is concluded that the lung of the foetal lamb behaves as an exocrine gland, secreting a substantial volume of liquid of a relatively constant composition.


Depression of jejunal dipeptide transport by pyridoxine deficiency in the rat.

Three dipeptides (L-alanyl-L-alanine, beta-alanyl-L-histidine and L-prolylglycine), representative of distinctly different transport groups, and a dicarboxylic acid dipeptide (L-glutamyl-L-glutamic acid) showed a quantitatively equivalent decrease of absorption (mean difference, 12% disappearance 15 min-1 5 cm-1) from jejunal loops in vivo in pyridoxine deficient rats, compared with pyridoxine-repleted controls. Analysis of results for seven dipeptides, including three studied previously, indicated that pyridoxine deficiency caused a general or non-specific reduction in dipeptide transport, similar for all dipeptides. Decrease in dipeptide transport in vitamin deficiency ran parallel to, but was significantly less than, the decrease in amino acid transport, suggesting in theory involvement of pyridoxine in a common cellular efflux mechanism or, less likely, in the energetics of active transport.


Effects of D-amphetamine and of secobarbital on optokinetic and rotation-induced nystagmus.

Although vestibular nystagmus is known to be affected by variations in mental states, little information is available about the effects of drugs on vestibular responses when a) subjects are either alert or relaxed, and b) visual stimuli are available or denied. In this study, 30 men were assigned to d-amphetamine sulphage (10 mg), secobarbital sodium (100 mg), or placebo (no drug) groups. With subjects alert in darkness, the drugs had no differential effect on rotation-induced vestibular nystagmus; when subjects were relaxed there was significantly less nystagmus than in the alert condition, particularly for the seco-barbital group. With vision permitted, d-amphetamine had no statistically different effect on nystagmus from the placebo. However, subjects given secobarbital were unable to use visual fixation effectively to suppress vestibular eye movements and their visual-following ability as measured by optokinetic nystagmus was also suppressed. Control over the mental activity of subjects and assessment of oculomotor-related functions both with and without opportunities for visual fixation are both important in evaluating drug effects.


Effects of a glucose meal on human pulmonary function at 1600-m and 4300-m altitudes.

The effects of a high-glucose meal on pulmonary function were observed in seven healthy males at medium (1,600 m) and high (4,300 m) altitude. Thirty minutes after the ingestion of 410 kcal (109.9 g cerelose) of glucose, peak serum glucose values were noted with a subsequent decrease over 3 h to below fasting levels at both elevations. At the same time, triglyceride levels continued to decline from 104.2 to 83.3 mg at 1,600 m and 103.7 to 80.5 mg/100 ml at 4,300 m, with differences being significant after 2 h. Both V-E and V-T increased in response to translocation to altitude; however, only V-T increased by 10.9% and 13.3% at 0.5 h for 1,600 m and 4,300 m, respectively. The V-o-2 increased during glucose elevation at 4300 m, while P-A-O2 remained essentially unchanged except for differences associated with translocation to altitude. A 13.9% increase was noted in D-L-CO followign glucose ingestion at 4,300 m along with a decreased triglyceride levels. The elevated D-L-CO values suggest an increase in gas exchange at the alveolar-capillary (A-c) level following the ingestion of a glucose meal for individuals transported to high altitude.


Reactions to sonic booms: a report of two studies and a general evaluation of startle effects.

Two separate studies are reported. The first attempted to determine a sonic boom level below which startle would not occurr. Subjects were exposed indoors to six simulated sonic booms having outside overpressures of 50, 30, and 16 N/m-2 (inside levels of 74, 71, and 65 dBA). Approximately 20% of the subjects gave small arm-hand responses to the two higher exposure levels, while none responded to the lowest level. In the second study, subjects were exposed indoors to a series of 12 simulated booms in order to assess habituation effects. Outside overpressures were 130 and 50 N/m-2 (indoor levels of 81 and 72 dBA). Significant, but not complete, habituation occurred to booms of both levels. Autonomic and eyeblink responses, as well as ratings of annoyance, were obtained in both studies. The final section summarizes the expected behavioral, autonomic, and subjective effects of exposure to various levels of sonic booms.


Arm-reach capability of USAF pilots as affected by personal protective equipment.

Thirty-two USAF pilots participated in a study to determine the effects of personal protective equipment upon arm-reach capability. The reach envelope of each pilot was measured under two experimental conditions: 1) shirt-sleeved with the inertial reel unlocked; and 2) wearing complete winter flying assembly with the inertial reel locked. Selected descriptive statistics are presented for each of five angular positions. Arm-reach envelopes for various percentile values obtained for the two experimental conditions at 10 knob distances from the deck are shown. The results indicate that there are singificant practical differences in arm-reach capability between the shirt-sleeved and the complete winter flying assembly conditions.


Disorientation phenomena in naval helicopter pilots.

The incidence of pilot disorientation in fixed- and rotary-wing aircraft has been previously investigated, but special orientation problems of naval helicopter pilots engaged in operations at sea and landing on moving platforms have not been previously investigated. A questionnaire concerning disorientations was answered anonymously and individually by 104 active naval helicopter pilots. Fifty-six percent indicated one or more espisodes of severe disorientation, and 8.6% indicated having experienced severe disorientation five or more times while piloting helicopters. A number of factors conducive to disorientation were identified. Some precipitating factors appear to be specific to operations over water or over a moving deck, although some of these may well have their counterparts in special operations over land. Other factors are common to fixed-wing as well as rotary-wing aircraft. A number of potential countermeasures for various precipitating factors are discussed.


Instrumented personal exercise during long-duration space flights.

This paper reports the results of instrumented personal exercise performed in flight by the Skylab 3 and Skylab 4 crewmen. These data include physiological responses to maximum aerobic exercise on a cycle ergometer at the conclusion of an 84-d exposure to zero-G (Sklyab 4). The bioinstrumentation provided continuous vectorcardiograph heart rate and cycle ergometer work level; minute updates of systolic and diastolic blood pressure, VO-2, V-CO-2, and VE. All Skylab 4 crewmen had higher V-O-2-max (cc/kg/min) at completion of the 84-d earth orbital mission than they had 4 d before launch. Two of these Skylab 4 crewmen, the scientist pilot and pilot, showed high levels of aerobic fitness with V-O-2-max of 54 and 51 cc/kg/min respectively at a heart rate of 185 beats/min and a workload of 286 w.


Electrolyte changes at 3500 m in males with and without high-altitude pulmonary edema.

Ten normal healthy male subjects between 20-30 years of age were initially examined at Delhi (200 m) and thereafter air-lifted to an altitude of 3,500 m. Excretion of sodium, potassium and chloride in urine and their plasma level were determined at sea level (SL) and daily at high altitude (HA) for 4 d. At HA, four subjects developed high-altitude pulmonary edema (HAPE), four remained normal, and two suffered from acute mountain sickness. The results on normals and HAPE are presented. There was increased excretion of potassium at HA in both groups resulting in reduction of plasma level. The sodium and chloride excretion was also increased in normals at HA irrespective of urine volume. In HAPE cases, the sodium and chloride excretion was related to urine output. With the retention of fluid, the excretion of these ions in urine was diminished without a parallel change in plasma levels.


Coronary hemodynamics during positive (+G-z) acceleration.

Left circumflex (LC) and left anterior descending (LAD) coronary flows, coronary perfusion pressure (P-ca), and arterial O-2 content (Cao-2) were determined in five dogs, lightly anesthetized with chloralose, during exposures to +2.0 and +3.0 G-Z stress; and for three of these dogs at +3.5-G-Z. At +2.0 G-Z, except for one dog with the most marked decrease in P-ca, KC and LAD flows increased above control by 15 s and thereafter gradually returned toward control; coronary resistances were significantly below control at 15 and 30 s (p smaller then 0.05). At +3.0 G-Z, LC and LAD flows were significantly greater than control (p smaller 0.05) from 30 to 60 s, while resistances were below control (p smaller than 0.05). At +3.5 G-Z, LC flow was maintained above control by a much reduced resistance, with P-ca below control; LAD flow increased in one dog, remained unchanged in one, and decreased slightly in one, although resistance always decreased. Cao-2 did not change significantly at any +G-Z level, and myocardial O-2 transport paralleled the changes in coronary flow.


Federal Aviation Administration's behavioral research program for defense against hijackings.

Behavioral research has been significant contributions to the government's successful program for defense against hijackers. Today's boarding gate defenses have a leading role in that program, but they were rejected until creation of the behavioral profile made selective search feasible. Metal detectors now make search of all travelers practical but with increasing involvement of boarding gate employees, so a behavioral program is used to monitor their performance. Experience shows that some persons have penetrated boarding gate defenses, so another requirement was in-flight defenses. Flightpersonnel had defeated some past hijackers, so a behavioral analysis of past hijackings was used to identify tactics for in-flight defense. These were incorporated into training programs and distributed to all U.S. airlines, many government organizations, and foreign carriers. Research continues for updating these and developing new courses for special needs, such as defense against gangs.


Human whole-body exposure to infrasound.

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.


Development of aerospace nursing.

In the initial development, the primary purpose of the USAF aerospace nursing program was to prepare the nurse to function as an integral member of the aerospace medical team in support of bioastronautics, occupational health and aerospace medical research programs. The absence of an expanded manned space program has required the aerospace nurse to redirect her energies toward the immediate needs of the aerospace medicine program. Many of the aerospace nurse's more specific functions are dependent upon the mission objectives of the command and military base to which she is assigned. Aerospace nursing reflects a concern for the total health needs of the Air Force community and the application of a holistic approach. It includes all aspects of health and all environmental hazards which alter health. The development of aerospace nursing paves the way for this expanded view of nursing practice.


Intraspecific red cell enzyme variation in the pigtailed macaque (Macaca nemestrina).

The erythrocytes of 350 pigtailed macaques (Macaca nemestrina) were examined for electrophoretic variation of hemoglobin and 26 enzymes. Seven enzymes showed variation in more than 1% of individuals: phosphoglucose isomerase, phosphoglucomutase-1, soluble NADP-dependent isocitric dehydrogenase, peptidase A, peptidase C, 2,3-diphosphoglycerate mutase, and acid phosphatase. Variation with lesser frequency was found in soluble glutamic-oxalacetic transaminase, phosphoglycerate kinase, lactic dehydrogenase, and hemoglobin. Only eight samples were tested for esterase D, and one of these had a variant phenotype. Enzymes with no clear variation were adenylate kinase, adenosine deaminase, phosphofructokinase, hexokinase, pyruvate kinase, glyceraldehyde 3-phosphate dehydrogenase, aldolase, phosphoglycerate mutase, phosphopyruvate hydratase (enolase), phosphoglucomutase-3, and superoxide dismutase. There was father-to-son transmission of PGI, PGM-1, peptidase C, 6PGD, 2,3-DPGAM, NADP-ICD, and acid phosphatase variants, suggesting that these loci are autosomal as in man.


Purine mutants of mammalian cell lines. II. Identification of a phosphoribosylpyrophosphate amidotransferase-deficient mutant of Chinese hamster lung cells.

A class of purine auxotrophs blocked early in the purine biosynthetic pathway was examined. The inability of these mutants to accumulate formylglycinamide ribotide (FGAR) in the presence of azaserine suggested that one or more of the first three enzymes of the pathway were either missing or defective. By direct enzyme assay, phosphoribosylpyrophosphate (PRPP) amidotransferase (E.C. 2.4.2.14) was found to be absent in extracts of mutant cells. Thus these cells were unable to convert PRPP to phosphoribosylamine (PRA). By reacting ribose 5-phosphate with ammonium ions, PRA was generated nonenzymatically in the incubation mixture, thus enabling us to test for the presence of the two enzymes required to convert PRA to FGAR. It was demonstrated that sufficient amounts of these enzymes, phosphoribosylglycineamide synthetase (E.C. 6.3.1.3) and phosphoribosylglycineamide formyltransferase (E.C. 2.1.2.2), were present in mutant extracts to allow synthesis of FGAR to occur once PRA was so provided.


Inheritance of erythrocyte glucose 6-phosphate dehydrogenase in the red-necked wallaby, Macropus rufogriseus (Desmarest), consistent with paternal X inactivation.

Data are presented on a polymorphism for erythrocyte glucose 6-phosphate dehydrogenase (G6PD) in a kangaroo species. Only one of the two alleles is expressed in any individual regardless of its sex. Population and breeding data are consistent with the hypothesis of X linkage of the locus, with the paternally derived X chromosome being inactive in erythroblasts of females.


Isolation of four components from purified human erythrocyte hypoxanthine-guanine phosphoribosyltransferase by isoelectric focusing.

Erythrocyte HGPRT from a male donor was partially purified by DEAE-cellulose chromatography and by fractionation between 35 and 65% ethanol. Isoelectric focusing of the ethanol fraction resolved HGPRT activity into four components which were numbered I-IV beginning with the one nearest the cathode. A second isoelectric focusing of component II (the most active) resulted in 94% of the activity as a single component. When mixed, however, the four components could be separated again by isoelectric focusing. The appearance of these different molecular forms of the enzyme could be due to post-transcriptional alterations or to formation of enzyme complexes.


The effect of phenobarbitone on protein synthesis by liver polyribosomes in fed and starved rats.

1. The effect of phenobarbitone on the rate of protein synthesis and on the sedimentation patterns of various liver subcellular fractions containing ribosomes was studied in rats. 2. Phenobarbitone treatment increased the incorporation of [114C]leucine into protein by all preparations, provided they had not been subjected to preliminary treatment with Sephadex G-25. The phenobarbitone-induced effect on incorporation was associated with a gain in liver weight and a higher degree of polyribosomal aggregation. 3. Preparations that were treated with Sephadex G-25 incorporated more radioactivity into protein, but did not show the response to phenobarbitone treatment. 4. When the influence of starvation and phenobarbitone was studied separately on membrane-bound and membrane-free polyribosomes, it was shown that whereas both classes of polyribosomes were affected by starvation, apparently only the former class was susceptible to phenobarbitone stimulation of protein synthesis. 5. The decreased capacity for protein synthesis of polyribosomes from starved rats was independent of their association with the membranes of the endoplasmic reticulum, but resulted from polyribosomal disaggregation, from an intrinsic defect of the polyribosomes themselves and from changes in composition of the cell cap. 6. The results are discussed in relation to the problem of the control of protein biosynthesis and of the functional separation of membrane-bound and membrane-free polyribosomes.


Lack of influence of the membranes of the endoplasmic reticulum on the capacity for protein synthesis of the rat liver polyribosomes.

The influence of the membranes of the endoplasmic reticulum on the functional properties of liver polyribosomes was studied in rats. The evidence seems to exclude the idea that the activity of the polyribosomes is under the control of the membranes.


Albumin, fibrinogen and transferrin synthesis in isolated rat hepatocyte suspensions. A model for the study of plasma protein synthesis.

A system using hepatocyte suspensions in vitro was developed for studying the synthesis of albumin, fibrinogen and transferrin. Conditions for optimum survival of the hepatocyte and for synthesis of these plasma proteins were defined for this system. These conditions included the use of horse serum (17.5 percent, v/v, heat-inactivated), an enriched medium (Waymouth's MB 752/1), an O2 tension of between 18.7 times 10(3) and 26.7 times 10(3) Pa and constant stirring. Albumin, fibrinogen and transferrin synthesis rates were obtained of 0.32 p 0.094(10), 0.12 p 0.030(11) and 0.097 p 0.017(10) [mean p S.D. (n)]mg/h per g of hepatocytes respectively. These rates were maintained for the first 12h of study and synthesis continued at a diminished rate up to 48h. The synthesis of albumin was decreased in a medium containing less amino acids and glucose, but that of fibrinogen was substantially unaffected. ATP concentrations up to 12h and RNA/DNA ratios up to 24h were comparable with values in vivo. The ability to study cells up to 48h permitted us to find that the addition of a mixture of hormones consisting of glucagon, cortisol, tri-iodothyronine and growth hormone enhanced fibrinogen synthesis. Addition of insulin to the above mixture resulted in increased synthesis for albumin and transferrin but not for fibrinogen.


Microbial metabolism of the pyridine ring. Metabolic pathways of pyridine biodegradation by soil bacteria.

1. Two bacteria, a Bacillus sp. and a Nocardia sp. (strain Z1) were isolated from soil by enrichment with 0.1 percent (v/v) pyridine and grew rapidly on this compound as sole C, N and energy source. The monohydroxypyridines, tetrahydropyridine, piperidine and some other analogues were not utilized for growth or oxidized by washed suspensions of either bacterium. 2. Cell-free extracts were unable to metabolize pyridine even after supplementation with a variety of cofactors or protecting agents. Treatment of cells with toluene led to rapid loss of the ability to oxidize pyridine. 3. In the presence of 10mM-semicarbazide at pH 6.0, Nocardia Z1 accumulated a semialdehyde idenditied as its 2,4-dinitrophenylhydrazone by chromatography, mixed melting point, mass spectrometry and isotope trapping from [2,6(-14)C]pyridine as glutarate semialdehyde. 4. Extracts of this bacterium prepared from cells grown with pyridine or exposed to the gratuitous inducer 2-picoline, contained high activities of a specific glutarate semialdehyde dehydrogenase. 5. Cells grown with pyridine or glutarate also contained a glutaric dialdehyde dehydrogenase, an acyl-CoA synthetase and elevated amounts of isocitrate lyase but no glutaryl-CoA dehydrogenase. 6. Bacillus 4 accumulated in the presence of 10mM-semicarbazide several acidic carbonyl compounds from pyridine among which was succinate semialdehyde. Extracts of this bacillus after growth of the cells with pyridine contained an inducible succinate semialdehyde dehydrogenase in amounts at least 50-fold over those found in succinate-grown cells. 7. Two mutants of this bacillus, selected for their inability to grow on pyridine were deficient in succinate semialdehyde dehydrogenase. 8. In the presence of 0.2mM-KCN, washed suspensions of Bacillus 4 accumulated formate and possibly formamide from pyridine. The use of [14C]pyridine showed that formate was derived from C-2 of the pyridine ring. 9. The organism had a specific formamide amidohydrolase cleaving formamide quantitatively to formate and NH3. 10. Formate was further oxidized by the particle fraction. There was no soluble formate dehydrogenase in extracts.


Some observations on chlorophyll(ide) synthesis by isolated etioplasts.

1. A modified procedure for the isolation of etioplasts from dark-grown barley is described and the regeneration of phototransformable protchlorophyll(ide) was demonstrated in the isolated plastids. 2. On exposure of the etioplasts to a long-term flash illumination, chlorophyll(ide) synthesis from a precursor pool, which includes all the protochlorophyllide, was demonstrated. 3. Added delta-aminolaevulinic acid failed to be significantly incorporated into chlorophyll(ide) in the etioplasts despite its extensive incorporation into porphyrin precursors of chlorophyll and haem compounds. The findings are discussed in terms of the inability of etioplasts to carry out the metal-insertion step in chlorophyll synthesis. 4. An elevated chlorophyll(ide) concentration was attained in the etioplasts by increasing the size of the utilizable precursor pool by pre-feeding whole plants with delta-aminolaevulinic acid, isolating the etioplasts and subjecting them to the flash illumination.


Sterol biosynthesis in the echinoderm Asterias rubens.

1. [2(-14)C]Mevalonic acid injected into the echinoderm Asterias rubens (Class Asteroidea) was effectively incorporated into the non-saponifiable lipid. 2. The most extensively labelled compounds were squalene and the 4,4-dimethyl sterols with much lower incorporations into the 4alpha-monomethyl and 4-demethyl sterol fractions. 3. Labelled compounds identified were squalene, lanosterol, 4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol and 4alpha-methyl-5alpha-cholest-7-en-3beta-ol; these are all intermediates in sterol biosynthesis. 4. The major sterol in A. rubens, 5alpha-cholest-7-en-3beta-ol, was also labelled showing that this echinoderm is capable of sterol biosynthesis de novo. 5. No evidence was obtained for the incorporation of [2(-14)C]mevalonic acid into the C28 and C29 components of the 4-demethyl sterols or 9beta,19-cyclopropane sterols found in A. rubens and it is assumed that these sterols are of dietary origin. 6. Another starfish Henricia sanguinolenta also incorporated [2(-14)C]mevalonic acid into squalene and lanosterol. 7. Various isolated tissues of A. rubens were all capable of incorporation of [2(-14)C]mevalonic acid into the nonsaponifiable lipid. With the body-wall and stomach tissues radioactivity accumulated in squalene and the 4,4-dimethyl sterols, but with the gonads and pyloric caecae there was a more efficient incorporation of radioactivity into the 4-demethyl sterols, principally 5alpha-cholest-7-en-3beta-ol.


Peptidoglycan synthesis in Bacillus licheniformis. The inhibition of cross-linking by benzylpenicillin and cephaloridine in vivo accompanied by the formation of soluble peptidoglycan.

The synthesis of peptidoglycan by an autolysin-deficient beta-lactamase-negative mutant of Bacillus licheniformis was studied in vivo in the absence of protein synthesis. Benzylpenicillin and cephaloridine inhibited the formation of cross-bridges between newly synthesized peptidoglycan and the pre-existing cell wall. This inhibition, detected by measurement of the incorporation of N-acetyl[14C]glucosamine into the glycan fraction of the cell wall, was reversed by treatment with beta-lactamase and washing. Inhibition of D-alanine carboxypeptidase by benzylpenicillin was not reversed under similar conditions. Cells in which the initial penicillin inhibition of transpeptidation had been reversed showed an increased sensitivity to a subsequent addition of the antibiotic. Chemical analysis of peptidoglycan synthesized after reversal of penicillin inhibition revealed the presence of excess of alanine resulting from the continued inhibition of D-alanine carboxypeptidase. When the cell walls were digested to yield muropeptides so that the degree of cross-linking could be measured, the product after reversal of penicillin inhibition contained fewer cross-links than did the control preparation. Cultures treated with benzylpenicillin and cephaloridine continued to synthesize uncross-linked soluble peptidoglycan, which accumulated in the medium. This soluble material was all newly synthesized peptidoglycan and did not result from autolysis of the bacteria. The average chain lengths of the glycan synthesized in vivo and released as soluble peptidoglycan in the presence of both benzylpenicillin and cephaloridine were similar to those found previously in this organism.


Short communications. Subunit A from cholera toxin is an activator of adenylate cyclase in pigeon erythrocytes.

Intact cholera toxin and its purified subunit A both activate the adenylate cyclase of pigeon erythrocyte membranes, but subunit B does not. The activation by subunit A is unaffected by treatments that inhibit whole toxin by interfering with the binding of subunit B to cell membranes.


Aerobic lactate production by mammary tissue.

Glucose uptake and L-lactate production were measured in cell, slice and intact tissue preparations of mammary glands from late-pregnant and lactating rats. The tissues showed extensive conversion of glucose into lactate in vitro, but not in vivo. Therefore aerobic lactate formation is not a normal feature of mammary tissue, but occurs in vitro as the result of some metabolic derangement.


Hydroxypyruvate as a gluconeogenic substrate in rat hepatocytes.

At concentrations of 2mM and above hydroxypyruvate produced no glucose with isolated rat liver cells, although it was rapidly utilized. At a lower concentration of hydroxypyruvate or in the presence of substrates which generate reducing equivalents (ethanol or butyrate), appreciable amounts of glucose were formed from hydroxypyruvate. A possible explanation for this phenomenon is discussed.


Stimulation of the pathway of porphyrin synthesis in the liver of rats and mice by griseofulvin, 3,5-Diethoxycarbonyl-1,4-dihydrocollidine and related drugs: evidence for two basically different mechanisms.

Griseofulvin and isogriseofulvin cause, like 3,5-diethoxycarbonyl-1,4-dihydrocollidine, a fall in the activity of the hepatic enzyme porphyrin-metal chelatase and accumulation of protoporphyrin in the liver. Analogues of either griseofulvin or 3,5-diethoxycarbonyl-1,4-dihydrocollidine which do not decrease the chelatase activity are not porphyrogenic on their own, but can potentiate the porphyria caused by 3,5-diethoxycarbonyl-1,4-dihydrocollidine. This suggests the existence of two basically different mechanisms by which drugs stimulate the pathway of porphyrin synthesis in the liver.


The conversion of cholest-5-en-3beta-ol into cholest-7-en-3beta-ol by the echinoderms Asterias rubens and Solaster papposus.

1. The echinoderms Asterias rubens and Solaster papposus (Class Asteroidea) metabolize injected [4(-14)C]cholest-5-en-3beta-ol to produce labelled 5alpha-cholestan-3beta-ol and 5alpha-cholest-7-en-3beta-ol. 2. Conversion of 5alpha-[4(-14)C]cholestan-3beta-ol into 5alpha-cholest-7-en-3beta-ol was demonstrated in A. Rubens. 3. Incubations of A. rubens with [4(-14)C]cholest-4-en-3-one resulted in the production of labelled 5alpha-cholestan-3-one, 5alpha-cholestan-3beta-ol and 5alpha-cholest-7-en-3beta-ol. 4. [4(-14)C]Sitosterol was metabolized by A. rubens to give 5alpha-stigmastan-3beta-ol and 5alpha-stigmast-7-en-3beta-ol. 5. The significance of these results in relation to the presence of alpha7 sterols in starfish is discussed.


Effects of gamma-irradiation on biosynthesis of different types of ribonucleic acids in normal and regenerating rat liver.

1. The effect of gamma-irradiation (4000rd) on the synthesis of ribosomal (pre-rRNA) and heterogeneous nuclear RNA (pre-mRNA) in normal and in regenerating rat liver was studied by using 40 min labelling with [6(-14)C]orotic acid. 2. Partial hepatectomy caused a sharp transient increase in the specific radioactivity of the endogenous low-molecular-weight RNA precursors in the livers of both normal and irradiated rats. Irradiation of intact animals did not affect the pool. 3. Irradiation enhanced the synthesis of pre-rRNA for at least 12h. The synthesis of pre-mRNA was also enhanced, but only in the first 3h after irradiation. 4. Partial hepatectomy strongly stimulated the synthesis of both pre-rRNA and pre-mRNA. 5. The synthesis of pre-rRNA was enhanced also in regenerating liver of animals irradiated before or after the operation. The conclusion can be drawn that the early increase in the synthesis of ribosomal RNA is a non-specific cellular response to different injuring factors. 6. The only case where irradiation caused an early inhibition of RNA synthesis was that of pre-mRNA in regenerating liver. This supports the hypothesis that ionizing radiation does not suppress the transcription per se but affects the mechanisms of activation of new genes (cellular programming).


Optical measurement of the catalase-hydrogen peroxide intermediate (Compound I) in the liver of anaesthetized rats and its implication to hydrogen peroxide production in situ.

The spectrophotometric determination of the catalase-H2O2 intermediate (Compound I) was extended to the liver in situ in anaesthetized rats. The rate of H2O2 production was determined for the liver in situ with endogenous substrates, and in the presence of excess of glycollate. Glycollate infusion doubled H2O2 production rate in the liver of air-breathing rats, and caused a fourfold increase when rats breathed O2 at 1 times 10(5) Pa. Hyperbaric O2 up to 6 times 10(5) Pa did not increase H2O2 generation supported by endogenous substrates, nor did it increase H2O2 production above that produced by 1 times 10(5) Pa O2 in glycollate-supplemented rats. The rates of ethanol oxidation via hepatic catalase and via alcohol dehydrogenase in the whole body were separately measured. The contribution of hepatic catalase to ethanol oxidation was found to be approx. 10 percent in endogenous conditions and increased to 30 percent or more of the total ethanol oxidation in rats supplemented with glycolate.


Metabolism of xanthine and hypoxanthine in the tea plant (Thea sinensis L.).

1. The metabolism of xanthine and hypoxanthine in excised shoot tips of tea was studied with micromolar amounts of [2(-14)C]xanthine or [8(-14)C]hypoxanthine. Almost all of the radioactive compounds supplied were utilized by tea shoot tips by 30 h after their uptake. 2. The main products of [2(-14)C]xanthine and [8(-14)C]hypoxanthine metabolism in tea shoots were urea, allantoin and allantoic acid. There was also incorporation of the label into theobromine, caffeine and RNA purine nucleotides. 3. The results indicate that tea plants can catabolize purine bases by the same pathways as animals. It is also suggested that tea plants have the ability to snythesize purine nucleotides from glycine by the pathways of purine biosynthesis de novo and from hypoxanthine and xanthine by the pathway of purine salvage. 4. The results of incorporation of more radioactivity from [8(-14)C]hypoxanthine than from [2(-14)C]xanthine into RNA purine nucleotides and caffeine suggest that hypoxanthine is a more effective precursor of caffeine biosynthesis than xanthine. The formation of caffeine from hypoxanthine is a result of nucleotide synthesis via the pathway of purine salvage.


A mannosyl-carrier lipid of bovine adrenal meddulla and rat parotid.

1. The transfer of mannose from GDP-(U-14-C)mannose into endogenous acceptors of bovine adrenal medullla and rat parotid was studied. The rapidly labelled product, a glycolipid, was partially purified and characterized. 2. It was stable to mild alkaline hydrolysis but yielded (14-C)mannose on mild acid hydrolysis. It co-chromatographed with mannosyl phosphoryl dolichol in four t.l.c. systems and on DEAE-cellulose acetate. Addition of dolichol phosphate or a dolichol phosphate-enriched fraction prepared from pig liver stimulated mannolipid synthesis. 3. The formation of mammolipid appeared reversible, since addition of GDP to a system synthesizing the mannolipid caused a rapid loss of label from the mannolipid. UDP-N-acetylglucosamine did not inhibit mannolipid synthesis except at high concentrations (2 mM), even though in the absence of GDP-mannose, N-acetylglucosamine was incorporated into a lipid having the properties of a glycosylated polyprenyl phosphate. 4. Mannose from GDP-mannose was also incorporated into two other acceptors, (2y being insoluble in chloroform-methanol (2:1, v/v) but soluble in choloroform-methanol-water (10:10:3, by vol.) and (ii) protein. These are formed much more slowly than the mannolipid. 5. Exogenous mannolipid served as a mannose donor for acceptors (i) and (ii), and it is suggested that transfer of mannose from GDP-mannose to mannosylated protein occurs via two intermediates, the mannolipid and acceptor (i).


The control of tricarboxylate-cycle oxidations in blowfly flight muscle. The steady-state concentrations of citrate, isocitrate 2-oxoglutarate and malate in flight muscle and isolated mitochondria.

1. Blowfly (Phormia regina) flight-muscle mitochondria were allowed to oxidize pyruvate under a variety of experimental conditions, and determinations of the citrate, isocitrate, 2-oxoglutarate and malate contents of both the mitochondria and the incubation medium were made. For each intermediate a substantial portion of the total was present within the mitochondria. 2. Activation of respiration by either ADP or uncoupling agent resulted in a decreased content of citrate and isocitrate and an increased content of 2-oxoglutarate and malate when the substrate was pyruvate, APT and HCO3 minus. Such a decrease in citrate content was obscured when the substrate was pyruvate and proline owing to a large rise in the total content of tricarboxylate-cycle intermediates in the presence of proline and ADP. 3. An experiment involving oligomycin and uncoupling agent demonstrated that the ATP/ADP ratio is the main determinant of flux through the tricarboxylate cycle, with the redox state of nicotinamide nucleotide being of lesser importance. 4. Addition of ADP and Ca-2+ to activate the oxidation of both glycerol 3-phosphate and pyruvate, simulating conditions on initiation of flight, gave a decrease in citrate and isocitrate and an increase in 2-oxoglutarate and malate content. 5. There was a good correlation between these results with isolated flight-muscle mitochondria and the changes found in fly thoraces after 30s and 2 mihorax. 6. It is concluded that NAD-isocitrate dehydrogenase (EC 1.1.1.41) controls the rate of pyruvate oxidation in both resting fly flight muscle in vivo and isolated mitochondria in state 4 (nomenclature of Change & Williams, 1955).


The binding of L-tryptophan to serum albumins in the presence of non-esterified fatty acids.

Bovine, human and rat serum albumins were defatted and palmitic acid, oleic acid and lauric acid added in various molar ratios. The binding of L-tryptophan to these albumins was measured at 20 degrees C in a 0.138 M salt solution at pH 7.4, by using an ultrafiltration technique, and analysed in terms of n, the number of available tryptophan-binding sites per albumin molecule, with apparent association constant, k. 2. n and k were 0.90 and 2.3x10(-4)M(minus-1) respectively for defatted bovine serum albumin and 0.87 and 9.7x10(-3)M(-minus-1) for human albumin. Addition of palmitic acid did not decrease n until the molar ratio, fatty acid/bovine albumin, approached and exceeded 2. The decrease in k was small and progressive. In contrast, lauric caused a marked decrease in n and k at ratios as low as 0.5. A similar distinction between the effects on n of palmitic acid and oleic acid and those of lauric acid was seen for human albumin. k for human albumin was not significantly affected by fatty acids under the conditions studied. 3. It is concluded that primary long-chain fatty acid sites interact only weakly with the tryptophan site on albumin and that inhibition of tryptophan binding occurs when secondary long-chain sites are occupied. Primary medium-chain fatty acid sites are distinct from primary long-chain sites but may be grouped with secondary long-chain sites. 4. The relationship between free and bound tryptophan in samples of rat plasma (Stoner et al., 1975) is discussed in terms of a similar but limited study of rat albumin.


A kinetic study of sulphate transport in rat liver mitochondria.

The kinetics of sulphate uptake catalysed by the dicarboxylate carrier were measured. The Km value for sulphate is about 0.3 mM. A completely competitive relation exists between the influxes of sulphate and malonate, whereas the relation between sulphate and phosphate is of the mixed type. The inhibition of sulphate influx by mersalyl and bathophenanthroline is similar to that of malonate influx and different from the inhibition of phosphate influx. It is considered that sulphate and malonate probably bind to the same locus on the carrier, whereas phosphate occupies a different site. The possible implications of this conclusion are discussed.


Protein synthesis in chloroplasts. Characteristics and products of protein synthesis in vitro in etioplasts and developing chloroplasts from pea leaves.

The function of plastid ribosomes in pea (Pisum sativum L.) was investigated by characterizing the products of protein synthesis in vitro in plastids isolated at different stages during the transition from etioplast to chloroplast. Etioplasts and plastids isolated after 24, 48 and 96h of greening in continuous white light, use added ATP to incorporate labelled amino acids into protein. Plastids isolated from greening leaves can also use light as the source of energy for protein synthesis. The labelled polypeptides synthesized in isolated plastids were analysed by electrophoresis in sodium dodecyl sulphate-ureapolyacrylamide gels. Six polypeptides are synthesized in etioplasts with ATP as energy source. Only one of these polypeptides is present in a 150 000g supernatant fraction. This polypeptide has been identified as the large subunit of Fraction I protein (3-phospho-D-glycerate carboxylyase EC 4.1.1.39) by comparing the tryptic 'map' of its L-(35S)methionine-labelled peptides with the tryptic 'map' of large subunit peptides from Fraction I labelled with L-(35S)methionine in vivo. The same gel pattern of six polypeptides is seen when plastids isolated from greening leaves are incubated with either added ATP or light as the energy source. However, the rates of synthesis of particular polypeptides are different in plastids isolated at different stages of the etioplast to chloroplast transition. The results support the idea that plastid ribosomes synthesize only a small number of proteins, and that the number and molecular weight of these proteins does not alter during the formation of chloroplasts from etioplasts.


Modification of the template capacity of liver chromatin for form-B ribonucleic acid polymerase by food intake in rats under controlled feeding schedules.

Nuclei from liver of rats accustomed to eating during the first 8h of a daily 12h dark period demonstrate an increased capacity to synthesize RNA 6H after the beginning of the feeding period. 2. This increase is accompanied by a higher yield of extractable form-B DNA-dependent RNA polymerase activity. 3. The endogenous RNA polymerase activity associated with nuclear chromatin is also stimulated by food intake. Both purified and chromatin-associated form-B enzyme activities exhibit different ionic strength requirements after food intake. 4. The sensitivity of exogenous (added) form-B-enzyme to changes in ionic strength changes after feeding when chromatin is used as template. 5. Chromatin extracted from the liver of fed rats is a better template for form-B-enzyme than chromatin extracted from starved rats.


Metabolic changes in rats during developing thiamin deficiency.

Determinations of rectal temperature, blood glucose, plasma free fatty acids, liver acetyl-CoA and carcass fat of thiamin-deficient rats indicated that during the ensuing anorexia they metabolized their fat reserves more rapidly than did pair-fed normal controls. Their lower metabolic rate indicates that the reserves mobilized are utilized inefficiently.


A micro method for simultaneous determination of galactosyltransferase and 5'-nucleotidase activities in cell fractions.

Galactosyltransferase and 5'-nucleotidase were assayed in the same reaction mixture, with ovalbumin as exogenous acceptor of (14-C)galactose and with (3-H)AMP as the substrate for the 5'-nucleotidase assay. The substrates and reaction products of either assay had no significant effect on the activity of the other enzyme.


The management of radioactive wastes resulting from emergency situations on land and sea.

The term 'emergency' applies to unplanned events that have generated, or had the potential to generate, radioactive wastes that could not be handled locally. Reports of past emergencies form the basis for discussion of future trends in emergency situations, the factors that influence waste management, the technology of waste management and personnel requirements. The number of past emergencies has been small and these have not increased the volume of radioactive wastes significantly. The majority of future emergencies are likely to be associated with reactors as they have been in the past. Little change in the nature of the waste is expected, although the greater use of separated plutonium may create some new problems. The factors that influence emergency waste management fall into two categories, those that are concerned with the location of the emergency event, and those concerned with the characteristics of the wastes. As in the past, it can be expected that in most emergencies proven waste management techniques will be adapted to suit the local circumstances but there is a need for simpler and more economic methods. Trained personnel and comprehensive planning are cited as key factors in successful waste management operations.


Changes in LH and prolactin in arteriosclerotic femal breeder rats.

Serum levels of LH and prolactin were measured in repeatedly-bred, arteriosclerotic female rats. Serum LH was abnormally decreased on the afternoon of proestrus and estrus. The extent of the depression of circulating LH levels parallels the severity of the arteriosclerosis. Serum prolactin was significantly increased above normal at proestrus, and the degree of prolactin increase was also correlated with the degree of severity of arteriosclerosis. It is suggested that frequent and repeated pregnancies affect the hypothalamic-pituitary-adrenal-gonadal axis leading to hormonal and metabolic imbalance, which may play a causal role in the pathogenesis of the spontaneous arteriosclerosis which appears in repeatedly-bred rats.


Effect of hyperlipidemic rat serum on the synthesis of collagen by chick embryo fibroblasts.

The effect of hyperlipidemic rat serum and its fractions on the synthetic functions of embryonic fibroblasts was studied. Moderately hypercholesterolemic sera (100-140 mg/100 ml) stimulated the synthesis of collagen, but not the synthesis of non-collagenous proteins nor the incorporation of glucosamine or cytidine. The stimulating principle was nondialyzable. It was not associated with the isolated total lipoproteins but was found in the infranatant fraction of sera centrifuged at a density of 1.220.


Lysolecithin-dependent release of cholesterol from rat plasma.

We studied the effect of lysolecithin on the clearing of plasma cholesterol. The immediate and maximal conversion of plasma lecithin to lysolecithin was produced in rats by intravenous injection of phospholipase A. The changes which took place in the converted lysolecithin and of cholesterol were followed in rats which had previously received [32-P]phosphate and [14-C]cholesterol. We followed simultaneously the in vitro changes in blood removed immediately after the in vivo administration of phospholipase A. The experiments showed that a substantial part of the plasma lecithin was converted to lysolecithin within the first minute after intravenous administration of phospholipase A. In the course of 60 min of blood incubation, the ratio of plasmatic lysolecithin in the closed system continued to increase. At the same time the content of cholesterol also increased. In vivo, the converted lysolecithin was quickly released from the plasma, so that within 10 min the original lecithin content dropped to 15-5% depending on the dose of phospholipase A that had been administered. The content of sphingomyelin and lysolecithin, which increased only temporarily shortly after injection, did not alter during the experiment. The level of plasma cholesterol esters, however, dropped significantly, whereas the free cholesterol content increased. The molar ratio of the drop in lipid phosphorus and cholesterol esters in plasma after the administration of phospholipase A was similar. A significantly higher cholesterol content was found in the liver of animals treated with phospholipase A.


In vivo thrombolysis. An experimental model in rhesus monkeys.

An experimental model of diffuse thromboembolism in the intrarenal circulation of the rhesus monkey was produced by intra-arterial injection of homogenised, homologous [125-I]fibrin. A sequential study of thromolysis was carried out using the conventional method of determining the thromboembolic index in the arteries of both kidneys together with radioautography and counting of radioactivity in the renal homogenate. Quantitative estimation of radioactivity in the renal homogenate, as well as radioautography of kidney sections provided more accurate and sensititve indices of the thrombolytic process than the conventional thrombembolic index. Studies on blood coagulation and fibrinolysis revealed only mild changes corresponding to the dynamics of thrombolysis in vivo. It was further noted that the thrombolytic mechanism in rhesus monkeys is very active and can clear thromboemboli from the intrarenal arteries within 8 days of their induction


Comparison of the effects of halofenate (MK-185) and clofibrate on plasma lipid and uric acid concentration in hyperlipoproteinemic patients.

The plasma lipid and serum uric acid lowering effect of halofenate (MK-185, 1 g/day) was compared with the action of clofibrate (2 g/day) in a double-blind 1-yr study in 23 patients with Type 2, 3, 4, and 5 hyperlipoproteinemia. It could be demonstrated that clofibrate decreased the plasma cholesterol concentration significantly to 75% and the triglyceride concentration to 49% of the placebo period level. Halofenate produced no consistent effect on plasma cholesterol but ther was an average reduction of the plasma triglyceride concentration to 84%, which was, however, not significant. If only the Type 4 patients were taken into account, a mean significant decrease to 47% of the triglyceride concentration was observed during the second 24-week period of treatment. In contrast, halofenate lowered the serum uric acid concentration significatnly to 77% of the placebo period level, whereas the decreasing action of clofibrate was weaker (88%) and of lesser significance.


Effect of iron deficiency anemia on the development of atherosclerosis in chicks.

The effect of iron deficiency anemia on the development of atherosclerosis was investigated in chicks. The control group of birds were fed a basal diet, the atherosclerosis group received 1% cholesterol. The lipid content of the aortas of the chicks in atherosclerosis and atherosclerosis-anemia group also developed anemia of appreciable severity in 12 weeks. Hemoglobin and PCV were taken as the index of anemia, while the lipid constituents were determined in plasma and aortic tissue for atherosclerosis. Hypercholesterolemia of almost equal severity occurred in both atherosclerosis and atherosclerosis-anemia groups. The abnormal rise of cholesterol and other lipid material in the aortas of the atherosclerosis and atherosclerosis-anemia groups of birds indicates that iron deficiency anemia did not markedly affect the development of atheroslcerosis; it did not offer any protection in chickens and, in fact, a slight potentiating effect was observed.


Quantitative and qualitative serum lipoprotein analysis. Part 2. Studies in male survivors of myocardial infarction.

The fasting concentration of cholesterol and triglycerides in serum and in very low (VLDL), low (LDL) and high (HDL) density lipoproteins (LP) was determined 3 months after a myocardial infarction (MI) in 54 men, and the values obtained were compared to those in 61 healthy male control subjects. The mean triglyceride concentration in MI patients was significantly increased in serum, VLDL, LDL and HDL by 74%, 110%, 30% and 12% respectively, compared to controls. The mean cholesterol concentration was significantly raised by 16%, 120% and 14% in serum, VLDL and LDL but decreased by 22% in HDL. Hypertriglyceridaemia occurred in 58% of MI patients. Of these patients, two-fifths had hypertriglyceridaemia only and three-fifths had combined hyperlipidaemia. The hypertriglyceridaemia was caused by elevation of only VLDL triglycerides in 26%, only LDL triglycerides in 19%, VLDL and LDL triglycerides in 23% and by various other combinations of raised LP triglyceride levels in 25% of cases. Hypercholesterolaemia was found in 41% of MI subjects. Of these, one-sixth had elevation of cholesterol levels, while five-sixths had combined hyperlipidaemia. The LP abnormalities underlying hypercholesterolaemia were increased of only VLDL cholesterol levels in 36%, only LDL cholesterol in 14% and both VLDL and LDL cholesterol in 50% of cases. The low HDL cholesterol values in comparison to controls were related to higher VLDL triglyceride values in MI patients, since HDL cholesterol fell significantly with increasing VLDL triglyceride levels. When HDL cholesterol was related to similar VLDL triglyceride levels, there were no major differences between controls and MI.


Quantitative and qualitative serum lipoprotein analysis. Part 1. Studies in healthy men and women.

Preparative ultracentrifugal and electrophoretic analysis of serum lipoproteins was performed in 30-70-year-old healthy, fasting males (N = 80) and females (N = 77), randomly selected from the Uppsala region, Sweden. The concentrations of cholesterol and triglycerides in total serum and in VLDL,LDL and HDL lipoprotein classes are reported. Total serum, VLDL and LDL triglycerides and cholesterol concentrations increased with age, while HDL cholesterol and triglyceride concentrations did not vary with age. Overweight persons had higher total serum triglyceride, higher VLDL cholesterol and triglyceride and lower HDL cholesterol levels. The upper 90% population limit values for non-overweight males/females were: total triglycerides (mmol/l) 2.5/2.0, total cholesterol (mg/100 ml) 298/300, VLDL triglyceride 1.80/1.05, VLDL-cholesterol 32/33, LDL triglyceride 0.69/0.69, LDL cholesterol 210/218, HDL triglyceride 0.32/0.34 and HDL-cholesterol 69/93. The 2 major differences between males and females were that females had lower VLDL but higher HDL concentrations. For VLDL there was a very strong and for LDL a moderately strong positive correlation between cholesterol and triglyceride contents. In HDL however, the mearsured amounts of cholesterol and triglycerides did not correlate at all. Sinking pre-beta lipoproteins was found in about 25% of cases and a second pre-beta band floating at d 1.006, late pre-beta, was found in 35% of male and 25% of female subjects. Subjects with sinking pre-beta lipoprotein did not differ from other subjects with regard to the concentration of cholesterol and triglycerides in the 3 lipoprotein classes. Males, but not females, with the late pre-beta (LPB), had an increased amount of cholesterol in VLDL and a raised cholesterol-triglyceride ratio in this lipoprotein class. Also the LDL triglyceride level was increased in males with the late pre-beta lipoprotein.


Partial identification of the fibrinolytic activators in onion.

A steam-distilled and an ether extract of onion have both been found to enhance blood fibrinolysis without depressing fibrinogen content in groups of human volunteers. Chemical analysis has shown which sulphur-containing compounds were in highest concentration and common to both and thus likely to carry this property, but their very intense and prolonged flavour precludes their clinical use. One sulphur containing but nearly odourless compound has been identified as having indirect fibrinolytic potential. A species difference in respect of fibrinolysis has been found between English and Spanish onion but is of little importance.


ABO blood groups, age and work in ischaemic heart disease.

In a series of male survivors of ischaemic heart disease there were fewer patients belonging to the risk-factor blood group (group A) before than after age 55 who were either non-infarction patients in light work or infarction patients in active or heavy work. Conversely, there were more A's before than after age 55 who were either non-infarction patients in active or heavy work or infarction patients in light work.


Scanning electron microscopy: arterial endothelial integrity after fixation at physiological pressure.

The luminal surface of normal rabbit aorta was examined by scanning electron microscopy (SEM) after outlining endothelial cells by staining intercellular junctions with silver. When aortas were fixed in situ at physiological pressure before processing for SEM, a reliable assessment of the morphological integrity of the endothelium was possible. In contrast, when aortas were excised and placed in fixative, contraction of the sub-endothelial structures made interpretation of endothelial integrity difficult.


Electron microscopical study of myocardial biopsy material in congenital heart block.

Myocardial tissue from the left ventricle of two children with congenital atrioventricular block and recurrent Admas-Stokes attacks was obtained during the procedure of epicardial pacemaker implantation and studied with the electron microscope. One patient had a familial cardiomyopathy, the other had no clinical abnormality apart from the conduction defect. Proliferation of mitochondria was common in both cases. Focal interstitial fibrosis and pronounced proliferation of transverse tubules were found in the myocardial cells of the patient with familial cardiomyopathy. Deep invaginations of the sarcolemmma with formation of intracytoplasmic channels were present in the second case. The possibility that the numerous transverse tubules could serve as additional pathways for impulse conduction is discussed.


His bundle recordings in bradycardia-dependent AV block induced by premature beats.

Symptomatic bradycardia-independent atrioventricular block occurred in a patient with right bundle-branch block, left anterior hemiblock, and prolonged HV interval. The arrhythmia, triggered by a spontaneous or induced premature beats, appeared when the post-extrasystolic PP and HH intervals increased to a critical value. Reinitiation of atrioventricular conduction required the presence of ventricular escapes. Bradycardia-dependent atrioventricular block was related to either an enhanced or slightly rising slope of diastolic depolarization, or to a decrease in membrane responsiveness. The patient also, most probably, had tachycardia-dependent atrioventricular block. Both types of conduction disturbance occurred in the same part of the intraventricular conducting system, either in the low His bundle or left bundle-branch or its posteroinferior division. It is suggested that the electrophysiological study of cases with prolonged HV intervals should include procedures which can expose bradycardia-dependent atrioventricular block.


Effects of atrial pacing site on atrial and atrioventricular nodal function.

The effects of the site used for atrial pacing on atrial and atrioventricular nodal conduction were assesed in 16 patients. In 13 patients, three atrial pacing sites were used: high right atrium, low lateral right atrium, and midcoronary sinus. Two recording sites were used: low septal right atrium, including His electrogram, and high right atrium. Stimulus (S) to high right atrium interval was longest with coronary sinus pacing (76 plus or minus 7 ms) (P less than 0.001), and shortes with high right atrial pacing (41 plus or minus 3 ms) (P less than 0.05). There was no significant difference in stimulus to low septal right atrium from all three pacing sites. Atrial functional and effective refractory periods were not significantly different. Mean low septal right atrium to His was significantly shorter from the coronary sinus (93 plus or minus 8 ms) (P less than 0.001), as compared to high right atrium (139 plus or minus 16 ms), and low lateral right atrium (129 plus or minus 13 ms) pacing. AV nodal functional and effective refractory periods, and the paced rate producing AV nodal Wenckebach were not significantly different when comparing the three sites. Left atrial appendage and high right atrium were similarly compared in three additional patients, and no significant differences were found in conduction times and refractory periods.


Atrioventricular conduction in patients with clinical indications for transvenous cardiac pacing.

Eighty patients with clinical indications for cardiac pacing had atrioventricular conduction analysed by His bundle study. The indications for cardiac pacing included high grade atrioventricular block, sick sinus node syndrome without tachycardia, bradycardia-tachycardia syndrome, unstable bilateral bundle-branch block, and uncontrolled ventricular irritability. Complete heart block, Wenckeback block (Mobitz I), and 2:1 block were noted proximal and distal to the His bundle. Mobitz II block only occurred distal to the His bundle. Of special interest were the high incidence of distal conduction abnormalities by His bundle analysis (40/80, 50%), the re-establishment of normal atrioventricular conduction in acutely ill patients with recent evidence of heart block, and the high incidence of intraventricular conduction disturbances on standard electrocardiogram (48/80, 60%).


Assessment of 3-year prognosis in survivors of acute myocardial infarction.

A 3-year follow-up with regard to survival was made of 475 initial survivors of an acute myocardial infarction originally treated in a coronary care unit. Previous diseases, complications during the hospital stay, as well as findings recorded on discharge from hospital, were used to construct a prognostic stratification. By multivariate analyses maximum respiratory rate during the coronary care unit stay, left bundle-branch block, and age proved prognostically most important. Using only these factors, patient groups with a 3-year monthly mortality up to 74 per cent were characterized.


Variations in right and left coronary blood flow in man with and without occlusive coronary disease.

The relation of angiographically recognized coronary occlusion to regional myocardial blood flow has not been studied adequately in spite of its clinical significance. This is particularly important, as revascularization procedures, based on angiographic studies, are being performed with increasing frequency. To compare the severity of reduction in flow to the severity of coronary occlusion, regional myocardial blood flow (85-Kr washout) was measured in 34 patients. Selective coronary anteriograms were obtained using the Sones technique, and occlusions were graded as a percentage of luminal diameter. Of 26 right coronary arteries for which satisfactory arteriograms and coronary blood flow measurements were obtained, 16 were normal and 10 had significant stenosis (greater than 50%). Dominant right coronary arteries appeared to have high flows (67 plus or minus 6 ml min-minus1 per 100 g muscle) and a greater incidence of occlusion (10 of 20) than nondominant arteries, which had less flow (41 plus or minus 2 ml min-minus1 per 100 g muscle) and a lower incidence of occlusion (1 of 8). Coronary blood flow in 16 normal left coronary arteries was 84 plus or minus 5 ml min-minus1 per 100 g muscle and in 15 with 50 per cent or greater occlusion, 68 plus or minus 3 ml min-minus1 per 100 g muscle. Though coronary blood flow appeared reduced when lesions of both the right and left coronary arteries were present, a critical reduction was seen only when occlusion was greater than 90 per cent.


Radioimmunoassay of serum digoxin in relation to digoxin intoxication.

Serum digoxin estimations were done in 98 patients receiving digoxin for heart failure of varied aetiology. Digoxin toxicity or the lack of it was determined on the basin of established electrocardiographic criteria. Fifty-two patients were classified as 'toxic' and 46 as 'non-toxic'. The difference is the mean digoxin levels between the two groups was highly significant (P less than 0.001). The mean serum digoxin level in 'non-toxic' patients was slightly higher than that found by other investigators. Fairly good correlations have been noted between different dosage schedules and various rhythm disturbances. Death was attributed to digoxin toxicity in only 2 patients who showed electrocardiographic evidence of intoxication at the time of death.


Evaluation of haemodynamic effects of intravenous propranolol at low dosage (1 and 2 mg) in acute myocardial infarction.

The haemodynamic effects of intravenous propranolol at low dosage (1 and 2 mg) have been evaluated on 14 patients in the acute stage of myocardial infarction. The first 1 mg propranolol was not followed by any significant variation in the variables measured. After the second 1 mg propranolol, the heart rate, cardiac index, and stroke index decreased significantly but moderately. Changes in pulmonary wedge pressure were not significant. It is concluded that intravenous propranolol in the small dosage of 1 or 2 mg, at which antiarrhythmic effect is still produced, has only a negligible depressant myocardial effect.


Haemodynamic effects of a new inotropic agent (dobutamine) in chronic cardiac failure.

The haemodynamic effects of dobutamine were studied in 14 patients with chronic congestive cardiac failure. Heart rate, central venous, pulmonary arterial, pulmonary wedge, and aortic pressures, aortic dp/dt, cardiac output, cardiac index, stroke volume, and pulmonary and systemic vascular resistances were measured or derived. Dose-response curves were obtained by recording all measurements before and after intravenous infusion of dobutamine at rates of 2.5, 5, and 10 mug/kg per min for periods of 30 minutes each. Significant increases in mean values were observed for cardiac output from 3.7 to 6.4 l/min (82%), for stroke volume from 44 to 64 ml (39%), and aortic dp/dt from 692 to 1414 mmHg/s (92.0 to 188.1 kPa/s (76%). Heart rate increased only moderately from 86 to 101 per minute (31%). Significant reduction occurred in pulmonary wedge and central venous pressures. Mean aortic and pulmonary pressures did not change significantly, as a measure of decreased vascular resistances. The drug was uniformly well tolerated. The predominant inotropic effects of dobutamine without tachycardia or arrhythmias may be valuable in severe heart failure.


Non-invasive recording of His bundle potential in man. Simplified method.

In 6 cases with sinus rhythm and one with atrial fibrillation, the bipolar surface electrocardiograms were taken through band pass filters simultaneously with the intracavitary His bundle electrogram, and averaged using a signal processer. By these relatively simplified procedures 'blips' considered to be derived from His bundle potentials between PR segments could be recorded. It was found that 'blips' originating from the His bundle were recorded most distinctly when a cathode was applied to the posterior mid-line and an anode to the sternum, both at the level of the fourth intercostal space. In some instances it was possible to record 'blips' probably derived from the bundle-branches. To identify the onset of ventricular potentials it was necessary to refer to the surface electrocardiograms taken with a usual time constant. The interval from the onset of 'blip' to the onset of ventricular activity (BV) agreed perfectly with the directly recorded His bundle to ventricle conduction time (HV) in 6 out of 7 cases investigated, and in the remaining case this interval was found to be only 1 ms longer than the HV.


Phentolamine for vasodilator therapy in left ventricular failure complicating acute myocardial infarction. Haemodynamic study.

In 15 patients with acute myocardial infarction associated with signs of left ventricular dysfunction, phentolamine was infused intravenously in a dose of 10 mg per hour. This therapy induced a substantial reduction in mean right atrial pressure from 10 to 7 mmHg (1.3 to 0.9 kPa) (P) less than 0.001), and in pulmonary capillary wedge pressure from 20 to 13 mmHg (2.7 to 1.7 kPa) (P less than 0.001). The cardiac index increased from 2.5 to 3.0 1/min per m-minus 2 (P less than 0.001) accompanied by a fall in both the systemic and pulmonary vascular resistances (P less than 0.001). On the other hand, the mean stroke work index did not change significantly after phentolamine, because of tar resistance. With the dose used the mean arterial pressure decreased from 112 to 99 mmHg (14.9 to 13.2 kPa) (P less than 0.001). No adverse effects attributable to the drug treatment were noted. Benefits of this treatment are probably related to reduction in the impedance of left ventricular ejection and possibly to its relaxant effect on the venous tone. The drug may also improve subendocardial perfusion by decreasing left diastolic ventricular pressure. This could possibly limit extension of necrosis. Thus vasodilator therapy appears to be of particular interest in left ventricular failure complicating acute myocardial infarction, where inotropic agents may be contraindicated.


Effects of phentolamine on coronary blood flow in patients with recent myocardial infarction.

The myocardial clearance of rubidium may be obtained by praecordial counting after intravenous injection of Rb-minus 86 Cl. Eight patients with recent myocardial infarction had this determination performed before and after the infusion of 10 mg phentolamine at a rate of 0.3 mg/minute. The average predrug myocardial clearance of Rb was 89.3 plus or minus 29.9 ml/min per 100 g myocardium. After phentolamine, the average myocardial clearance rose to 117.3 plus or minus 33.3 ml/min per 100 g myocardium (P LESS THAN 0.01). An explanation for this findings is presented as well as its possible clinical applications.


Right atrial laceration. Complication of external cardiac massage.

Right atrial laceration is described as a complication of external cardiac massage in two patients. In each there was a pre-existent cause of weakness of the atrial wall. There was pronounced right atrial dilation with attenuation of the wall in one case, and in the other there was a granulomatous myocarditis involving the atrial wall. The significance of atrial laceration as a complication of traumatic injuries to the heart is discussed.


Aortic stenosis, angina, and coronary artery disease. Interrelations.

Sixty-nine patients over age 35 with severe valvular aortic stenosis were investigated for concomitant coronary artery disease. Forty (57.9%) had clinical angina pectoris. Sixteen (23.2%) had significant coronary occlusive disease by arteriography. Of those with angina, 13 patients (32.5) had significant coronary arterial obstruction, while in the pain-free group only (10.3%) had occlusive coronary disease. It is concluded that patients with severe aortic stenosis who are free of angina have only a small, but definite, chance of having significant coronary disease.


Supravalvular aortic stenosis. Echocardiographic features.

The echocardiographic manifestations of segmental supravalvular aortic stenosis are described in 2 patients. The diagnosis was confirmed by cardiac catheterization in both and at operation in 1. A systematic echocardiographic approach to such patients is described. The characteristic finding in these patients was the narrowing of the diameter of the aortic lumen at the stenotic area just distal to the aortic valve. As the transducer sweeps further cephalad the aortic lumen widens to a normal diameter. In one patient treated surgically, postoperative echogram demonstrated the narrowing to be reduced.


Advanced heart block aggravated by carbamazepine.

This report presents a serious adverse reaction to the anticonvulsant compound carbamazepine. A woman was admitted to hospital for recurrent attacks of syncope. She suffered from atrioventricular block of the Mobitz type II. Carbamazepine suppressed the conduction in her already defective Purkinje fibres and induced ventricular stand-still with subsequent Adams-Stokes attacks.


Clinical presentation of a myocardial rhabdomyosarcoma.

A case initially diagnosed as tricuspid insufficiency in which critical review of the clinical findings pointed to a diagnosis of pulmonary outflow obstruction is described. At necropsy a myocardial rhabdomyosarcoma was found with associated thromboembolism. The cardinal features were the rapid development of a loud systolic murmur, clinical evidence of right ventricular enlargement and failure with large jugular presystolic 'a' waves, and a reduction in the intensity of the pulmonary component of the second sound, a shift in the QRS axis to the right, and an increase in the cardiothoracic ratio.


An evaluation of procaine in the treatment of malignant hyperpyrexia.

Procaine has been advocated in the treatment of malignant hyperpyrexia, whereas lignocaine has been shown to worsen the condition. Using muscle from patients susceptible to malignant hyperpyrexia in vitro, it has been demonstrated that muscle contracture can occur with procaine on its own, and in one patient the halothane-induced contracture was potentiated by procaine. In other patients the concentration of procaine required to abolish the halothane-induced contracture was markedly above the clinical dose range. In a study of lignociane and procaine on a caffeinated rat muscle (a suggested model for malignant hyperpyrexia) no significant difference was found in the ability of these local anaesthetics to alter resting tension of halothane-treated muscle; with both drugs the resting tension rose in a dose-related manner. The use of procaine as the drug of first choice in patients with malignant hyperpyrexia is challenged.


Effects of changes of frequency and tidal volume of controlled ventilation: measurements at constant arterial Pco2 in dogs.

Seven Alsatian dogs were anaesthetized with thiopentone, paralysed with pancuronium, and ventilated with 1% halothane in a mixture of air and oxygen in such a way as to maintain Paco2 at 40 mm Hg and Pao2 at 150 mm Hg. From various respiratory and circulatory measurementts the following variables were determined: physiologicaldeadspace, cardiac output, venous admixture, respiratory compliance and resistance, and oxygen and carbondioxide exchcnage. After a controlseries of measurements at a ventilator frequency of was doubled to 50/min and adjustments to tidal volume and inspired oxygen concentration made to maintain constancy of blood gas tensions. The same procedure was followed again at 25/min, l/min and finally at 25/min. At each frequency the I:E ratio was kept at 1/2, the shape of the inspiratory flow waveform was kept constant (a rapid increase followed by a steady decline to zero) and expiration was passive to atmosphere. Mean results showed that physiological deadspace changed relatively little with frequency so that the deadspace:tidal volume ratio increased significantly on changing to 50/min (by 24%) and decreased significantly on changing to 6/min (by 46%). Changes of cardiac output and venous admixture were either not significant or on the borderline of significance and the 95% confidence limits of these changes were within +14%, --12% for cardiac outpur and within plus or minus1.4% of cardiac output for venous admixture. Tt is concluded that, provided Paco2 and Pa02 and mean air way pressure are kept constant, the frequency of ventilation is not important, even over a wide range of values.


The estimation of carbon dioxide concentration in the presence of nitrous oxide, using a Lloyd-Haldane apparatus.

A method of gas analysis is described for estimating carbon dioxide in the presence of nitrous oxide, using a modified Lloyd-Haldane apparatus. Some of the sample, after scrubbing with soda-lime, bubbles through the potash and this eliminates the solubility effect of nitrous oxide by equilibrating the standard potash solution with nitrous oxide at the tension of the sample analysed and eliminating absorption of nitrous oxide from the burette. The results show close agreement with another apparatus and method based on different principles. The method is absolute, requiring neither empirical nor theoretical correction.


Deaths associated with anaesthesia.

The incidence of deaths associated with anaesthesia at Royal Prince Alfred Hospital for the period 1963-72 inclusive was 1:502. An analysis of the 408 deaths showed that more than half of them occurred in association with major cardiovascular and neurosurgical procedures. The number of deaths attributable to anaesthesia alone was 15 (3.7%). This was a marked reduction by comparison with the number in the previous decade (20.9%).


Quality of spinal extradural anaesthesia: the influence of spinal nerve root diameter.

Profiles on the progress of spinal extradural anaesthesia were made in 246 patients using various concentrations of lignocaine, bupivacaine and etidocaine. The advance of analgesia through the different dermatomes showed a consistent and orderly spread on the upper lumbar and thoracic segments. This spread was irregular through the lower lumbar and upper sacral segments. The first sacral segment was especially difficult to block with an overall failure rate of 17.53% with presently available concentrations of various local anaesthetics. This failure was abolished with the use of etidocaine 1.5%. The presence of a delay or failure at the level of L5-S2 is probably related to the larger diameter of these nerve roots as ascertained from measurements in 11 cadavers.


Postoperative extradural analgesia following thoracic surgery: a feasibility study.

The feasibility of providing postoperative analgesia using thoracic extradural blockade following thoracotomy has been assessed. Extradural block was produced by intermittent injections of 0.5% bupivacaine with adrenaline 1:200,000 or a continuous infusion of 0.25% or 0.125% bupivacaine. The only toxic symptom was drowsiness which was most frequent after a continuous infusion of 0.25% bupivacaine and with arterial plasma bupivacaine concentrations above 1.5 mug/ml. Arterial hypotension was a troublesome complication with all techniques although stability of arterial pressure was more easily achieved with a continuous infusion technique. However, this produced a high incidence of urinary retention. Practical aspects and effectiveness of providing extradural analgesia in patients following thoracotomy are discussed.


Control of the malignant hyperpyrexic syndrome in MHS swine by dantrolene sodium.

Experiments are described which demonstrate that dantrolene sodium effectively terminates the syndrome of malignant hyperpyrexia induced in susceptible swine by exposure to halothane. Dantrolene is also shown to block initiation of the syndrome of malignant hyperpyrexia by halothane in MHS swine. Therapeutic use of this drug in patients with anaesthetic-induced malignant hyperpyrexia appears to be indicated.


Pancuronium and the neonate.

Pancuronium bromide was used safely as the muscle relaxant for neonatal anaesthesia. No untoward effects were seen and the neuromuscular block was successfully reversed in all patients. The potency ratio of pancuronium as compared with tubocurarine ranged from 9:1 at birth to 6:1 at one month of age.


Anaesthetic management of reconstruction of the lower portion of the trachea. Case report.

A case of tracheal stenosis following chest injuries is reported. The anaesthetic technique used for partial resection of the intrathoracic portion of the trachea is described. Problems of ventilation during this type of operation are discussed.


Total calcium content of skeletal muscle isolated from humans and pigs susceptible to malignant hyperthermia.

Total calcium content of both human and porcine MHS skeletal muscle is significantly less than normal. This data is consistent with the concept that some organelle (probably the sarcoplasmic reticulum, the mitochondrion or even the sarcolemma) within the MHS muscle stores less than normal amounts of calcium. The large variability between muscle specimens rules out measurement of total calcium content of skeletal muscle as a routine diagnostic test for malignant hyperthermia susceptibility.


Thrombin-induced disseminated intravascular coagulation in the dog. I: Demonstration of microthrombi in lung.

Disseminated intravascular coagulation was induced in dogs by the infusion of a fibrinolytic inhibitor followed by thrombin. The deposition of microthrombi in the lung was demonstrated by radioactive labelling of platelets and fibrinogen.


Thrombin-induced disseminated intravascular coagulation in the dog. II. Cardiorespiratory changes during spontaneous and controlled ventilation.

Disseminated intravascular coagulation (DIC) was induced in anaesthetized dogs by the infusion of a fibrinolytic inhibitor followed by thrombin. The occurrence of DIC was confirmed by haematological and histological examinations. After the thrombin infusion there was a progressive reduction in cardiac index and systemic arterial pressure, only four of the 14 dogs surviving for 4 hr. Pulmonary artery pressure increased after the thrombin infusion, but decreased subsequently in seven animals allowed to breathe spontaneously. In these animals, there was an increase in respiratory rate, minute volume and deadspace/tidal volume ratio, but there were no changes in the arterial-to-alveolar PCO2 difference. Arterial PCO2 and PO2 decreased, but there were no significant changes in total venous admixture. In seven dogs submitted to controlled ventilation, arterial PO2 decreased to the same extent, but there were no significant changes in arterial PCO2, deadspace/tidal volume ratio or venous admixture.


The effect of halothane anaesthesia on the uptake of oxygen and on the respiratory pattern in man.

Nine patients were anaesthetized with halothane in oxygen using a closed-circle circuit with a Benedict-Roth spirometer substituted for the reservoir bag. The movements of the spirometer were recorded to enable the oxygen consumption and respiratory pattern to be measured continuously before surgery commenced. Increasing concentrations of halothane produced progressive decreases in oxygen uptake and in the tidal and minute volumes, but an increase in the respiratory rate.


Systemic and coronary haemodynamic effects of ketamine in intact anaesthetized and unanaesthetized dogs.

Ten intact anaesthetized dogs breathing room air spontaneously (Group A) were compared with ten artificially ventilated dogs (Group B). All were given a bolus of ketamine 2 mg/kg followed by a 20-min infusion of ketamine 0.1 mg/kg/min. In Group A, coronary sinus blood flow, measured with a thermodilution flowmeter, increased by 90% while coronary vascular resistance decreased by 28% and coronary sinus oxygen content decreased by 27%. Heart rate increased by 47%, and arterial pressure by 9%. Cardiac output, calculated by the dye dilution method, increased by 29%, while the left ventricular work index decreased by 50%. Minute ventilation rate decreased by 55%. The Group B dogs were studied as described above, except that they were artificially ventilated. The haemodynamic ahanges were less in Group B, possibly because of improved arterial oxygenation. Heart rate increased by 24%, cardiac output by 21% and arterial pressure by 2%. The coronary sinus blood flow increased by 12% while coronary vascular resistance decreased by 11%. Coronary sinus oxygen concentration decreased by 15%. Five unanaesthetized dogs with electromagnetic flowmeter probes chronically implanted on the aorta and circumflex coronary artery, and an indwelling arterial catheter were studied before, during and after the intravenous administration of ketamine 2, 4, and 8 mg/kg. A dose of 8 mg/kg produced increases in cardiac output, heart rate and arterial pressure of 21%, 44% and 24%, respectively, while coronary blood flow increased 47%. We conclude that, in healthy dogs, ketamine produces an increase in heart rate and cardiac work. A significant increase in coronary blood flow appears to be insufficient to meet the metabolic demands of the myocardium, as the coronary sinus oxygen content decreased.


Growth hormone and blood-glucose concentrations during cardiopulmonary bypass.

Plasma growth hormone (plasma GH) and blood-glucose concentrations were measured in 23 patients undergoing open heart surgery with moderate hypothermia. A significant increase in blood-glucose concentration occurred with sternotomy and increased during bypass, partly as a result of the exogenous glucose load from the perfusate. Following bypass, the blood-glucose remained above the pre-anaesthetic concentration, and this elevation persisted into the period following surgery. Plasma GH also increased with surgery and remained elevated during perfusion. The highest concentrations occurred following bypass when normal temperature had been regained .


The use of propanidid and lignocaine to reduce suxamethonium fasciculations.

A technique of induction of anaesthesia using propanidid, lignocaine and suxamethonium is described, and the muscle fasciculations that follow it are shown to be significantly less than those accompanying induction with methohexitone and suxamethonium.