Fluorescent lighting and epilepsy.

Fluorescent tubes flash at twice the mains frequency (100 Hz in Europe). With aging, 50-Hz brightness modulation appears. A survey of tubes used in our institute showed that 42% exhibited brightness modulation up to a depth of 20% or occasionally 30%. The effects of fluorescent lighting on the EEGs of 20 patients with photosensitive epilepsy have been studied. In no patient did the 100-Hz flicker of normally functioning tubes elicit paroxysmal activity. In 8 of 13 subjects sensitive to 50 Hz, IPS paroxysmal discharges were evoked by 50-Hz brightness modulation, but only at modulation depths of 50% or more. It is concluded that as paroxysmal activity could not be elicited by normally functioning tubes nor at those depths of modulation occurring in practice, fluorescent lighting is unlikely to present a hazard to photosensitive patients.


Remission of seizures and relapse in patients with epilepsy.

In a longitudinal study of patients with epilepsy in Rochester, Minnesota, we found that the probability of being in remission (at least 5 consecutive years seizure-free, and continuing) at 20 years after diagnosis was 70%. The rates for remission we encountered were generally higher than those previously reported. We believe that the better prognosis in our series results from inclusion of all incidence cases in a defined population, beginning at the initial diagnosis of epilepsy. Prognosis for remission of epilepsy is poor in patients with associated neurologic dysfunction identified from birth. Patients with idiopathic seizures and survivors of postnatally acquired epilepsy have better prospects for eventual remission. The probability of remission is highest in patients with generalized-onset seizures diagnosed before 10 years of age. Prognosis is less favorable for those with partial complex seizures and adult-onset epilepsy.


Radiation-induced nondisjunction.

The methodology and results of epidemiological studies of the effects of preconception diagnostic x-rays of the abdomen on chromosome segregation in humans are described. Many studies have been conducted in a number of different countries. The vast majority show the same positive, though not significant, trend to increased nondisjunction among the offspring of irradiated women. The results of the various studies, however, cannot be pooled because of differing methodologies used. A worldwide co-operative project with standardized methodology is recommended. Such a study should identify the parental origin of the nondisjunctional event before etiological factors are investigated. Abnormal chromosome segregation during mitotic division has been inducted experimentally by the in vitro exposure of human lymphocytes to a low dose of 50 R gamma irradiation. First meiotic nondisjunction has been successfully induced by whole body exposure of female mice to a low dose of radiation. Further experiments are being conducted to try to induce abnormal segregation during second meiotic division. Because of difficulties encountered in trying to estimate total gonad doses resulting from differing techniques employed by radiologists and other health personnel, no attempt has been made to estimate the doubling dose nor minimum safe dose regarding the effects of radiation on chromosome segregation in humans. The question of time-related repair of the mechanism involved in chromosome segregation is raised.


Proximal chiasma localization within an interstitial chromosome segment, a likely correlate of adjacent-2 segregation of translocation causing multivalents in the mouse.

Two T7OH/+ translocation-carrying male mice were used in an investigation into the relation between the segregation pattern of the translocation caused multivalent at anaphase I and the position of the only chiasma in a long interstitial segment. Moreover, the relation between meiotic stage (from early diakinesis to metaphase I) and chiasma movement was assessed. It appeared that pronounced movement of a chiasma within the multivalent was linked with chiasma terminalization in an adjacent segment, either on the same side of the translocation breakpoint or on the other side. On summing the CIV and CIII+I configurations (making up 97.9% of all configurations found) and focusing on the multivalents from late meiotic cells, 41.3% had a proximal chiasma in the long interstitial segment of the multivalent. In total, a percentage of 33.5% of all secondary spermatocytes were characteristic of adjacent-2 segregation (i.e., homologous centromeres move to the same pole at anaphase I). Results obtained with T7OH translocation trisomics, which are briefly discussed in this paper, confirm the tendency of proximal chiasma frequencies in late meiotic cells to coincide with the frequency of absence of homologous centromere separation within the T7OH translocation multivalent. The importance of this phenomenon for normal bivalent behavior during anaphase I is considered.


Analysis of pediatric blood lead levels in New York City for 1970-1976.

A study was completed of more than 170,000 records of pediatric venous blood levels and supporting demographic information collected in New York City during 1970-1976. The geometric mean (GM) blood lead level shows a consistent cyclical variation superimposed on an overall decreasing trend with time for all ages and ethnic groups studied. The GM blood lead levels for blacks are significantly greater than those for either Hispanics or whites. Regression analysis indicates a significant statistical association between GM blood lead level and ambient air lead level, after appropriate adjustments are made for age and ethnic group. These highly significant statistical relationships provide extremely strong incentives and directions for research into casual factors related to blood lead levels in children.


New translocations in human lymphocytes: a mutagen monitoring system.

The human lymphocyte is a premier cell for monitoring chromosome aneuploidy. The lymphocyte is easily obtained, can be studied before and after culture, and has been extensively investigated. Assays available for lymphocytes include the scoring of chromosome breaks (subjective and laborious), the analysis of chromosome abnormalities such as increase or decrease in number (versus normal background), dicentrics etc., and the micronucleus test (presumable end-state phenomena). We propose the monitoring of somatic chromosome translocations in human lymphocytes. Background data available from North America indicate that the frequency of de novo chromosome translocations in Halifax, Portland, Denver, and Atlanta is about 1.7 x 10(-3). The most common translocation arising in lymphocytes is between chromosomes 7 and 14 (with a frequency of 4 x 10(-4). All translocations occurring de novo in human lymphocytes tend to appear balanced with no evidence for loss or gain of chromosome material. Cytogenetic laboratories are processing lymphocytes daily. The resultant photographs and karyotypes are all scorable for de novo translocations. Suitable data on exposure to possible mutagenic agents could be collected in advance of these chromosome studies. This would provide a new method for monitoring chromosome changes in the population. The cost of monitoring lymphocyte chromosomes for somatic translocations would be small, since numerous laboratories study lymphocytes rountinely for clinical diagnostic purposes. There may be merit in availing ourselves of easily available data from a very available species: man.


Measuring the public health impact of the aneuploidies.

If the protection of man against mutagenic agents in general, and against those that cause aneuploidies in particular, is to have an increasingly rational basis with the passage of time, quantitative or at least semiquantitative assessments of risks are needed. These should take into account both the likely numbers of induced cases and the likely severities of the different conditions. In the past, quantitative data relating to severity have been limited or nonexistent, but the data sources exist by which follow-up studies may be carried out to determine age-specific and cumulative risks of hospitalization and death, the durations of hospital stays, and the economic burden to society which these represent. To illustrate the use of such sources, the cumulative risks of death in children with anomalies of the autosomes and of the sex chromosomes, over the first 19 years of life, are compared with those for other kinds of hereditary and environmentally caused handicaps that are reported in that age group.


Origin of meiotic nondisjunction in Drosophila females.

Meiotic nondisjunction can be induced by external agents, such as heat, radiation, and chemicals, and by internal genotypic alterations, namely, point mutations and chromosomal rearrangements. In many cases, nondisjunction arises from a reduction or elimination of crossing over, leading to the production of homologous univalents which fail to co-orient on the metaphase plate and to disjoin properly. In some organisms, e.g., Drosophila and perhaps man, distributive pairing (i.e., a psot-exchange, size-dependent pairing) ensures the regular segregation of such homologous univalents. When a nonhomologous univalent is present, which falls within a size range permitting nonhomologous recognition and pairing, distributive nondisjunction of the homologues may follow. Examples of nondisjunction induced by inversion heterozygosity, translocation heterozygosity, chromosome fragments, radiation, heat, and recombination-defective mutants are presented.


Mechanisms of nondisjunction induction in drosophila oocytes.

Quantitative and qualitative studies on the induction of no-disjunction and related phenomena can be carried out using the germ cells of Drosophila. X-Irradiation breaks chromosomes and cold-shock disrupts spindles, these two treatments producing different spectra of nondisjunction in oocytes.


Chemical induction of nondisjunction in drosophila.

Tests for chemically induced nondisjunction and loss of the sex chromosomes in Drosophila were performed. Of 31 compounds tested four gave rise only to an increase of XO exceptions, indicating the induction of chromosome loss. Six compounds, all known spindle inhibitors (colchicine, organic mercury, lead, and tin compounds) gave rise to an increase both of XXY and XO or of only XXY. The effect by metalloorganic compounds of which methylmercury was studied particularly closely, follows a peculiar pattern. In females with structurally normal X chromosomes only an increase of XX gametes is obtained, while with X chromosomes heterozygous for long inversions only O gametes are increased. The data indicates that the effect of the metal compounds occurs at first meiosis and that the process is connected with a meiotic drive, giving rise to a preferential segregation of the two X chromosomes to the functioning pole. The increase only of O gametes with structurally heterozygous X chromosomes can tentatively be explained by a loss due to crossing over within the inversion. An increase of the effect of methyl mercury was obtained where the normal pairing of the X chromosomes was interfered with by means of autosomal inversions. Likewise a synergistic increase of nondisjunction was obtained when a temperature chock of 10 degrees C was applied together with treatment with methylmercury. It is concluded that chemical induction of nondisjunction can be studied in Drosophila, but the sensitivity of the test is rather low and large amount of material is required.


Activities of hepatic enzymes related to ethanol oxidation and effects of ethanol on hepatic metabolites in rats with chronic liver injury.

To study the effects of ethanol on liver chronically injured by CCl4, activities of hepatic enzymes related to ethanol oxidation, influences of ethanol on hepatic metabolites, and blood ethanol disappearance were observed. (1) Activities of alcohol dehydrogenase, low- and high-Km aldehyde dehydrogenase, microsomal ethanol-oxidizing system and drug-metabolizing enzyme were remarkably decreased in the injured liver. (2) Increases in lactate/pyruvate and beta-hydroxybutyrate/acetacetate ratios were shown in control liver 2 h after ethanol ingestion. Similar but less pronounced effects of ethanol on the 'redox state' were also seen in rats with chronic liver injury. (3) Delay in ethanol disappearance was not observed until 12 h after ethanol ingestion. The ethanol-induced changes in the redox state in the injured liver were similar to those in controls. Higher ethanol concentrations in blood from rats with chronic liver injury could be related to potentiate the injured liver.


Isatin inhibition of rat testicular alkaline phosphatase. A non-allosteric phenomenon.

Isatin has been found to inhibit rat testicular alkaline phosphatase (EC 3.1.3.1) uncompetitively. The hyperbolic curve relating inhibition as a function of substrate concentration; the persistence of inhibition after the tertiary structure of the enzyme has been altered by heat denaturation, exposure to urea or papain digestion; the small changes in entropy, free energy and enthalpy in the presence of isatin, and the number of isatin molecules (n = 1.29) combining with one molecule of enzyme indicate the non-allosteric nature of inhibition.


Inhibition of delta-aminolevulinic acid dehydratase in human red blood cells by lead and activation by zinc or cysteine.

Inhibition of blood delta-aminolevulinic acid dehydratase(ALA-D) activity by lead was studied in vivo and in vitro. In vivo, a negative linear correlation (r = -0.85) was found between the logarithmic values of ALA-D activity and blood lead levels. In vitro the inhibitory effect of lead on blood ALA-D activity increased both with contact time and contact temperature of lead with blood before ALA-D assay. Maximum enzyme inhibition occurred after 14 h of contact at 25 degrees C. Inhibition of ALA-D activity by lead, in vivo as well as in vitro, is suppressed by the addition of zinc or cysteine. The logarithmic values of the activity ratios increase linearly with blood lead concentrations. The increase in ALA-D activity brought about by the addition of zinc or cysteine can be used to identify cases of low enzyme activity with no lead intoxication involved. The same technique can also detect cases in which ALA-D inhibition may be concealed by a presumably high initial enzyme activity as observed in some patients.


The presence of serum creatine kinase 2 (MB) in hypokalemic familial periodic paralysis.

We recently found 17 U/l of isoenzyme creatine kinase (CK) 2 (MB), or 3.2% of total 533 U/l CK activity, in a patient with hypokalemic familial periodic paralysis who did not show clinical or EKG evidence of acute myocardial necrosis. The myopathy associated with hypokalemic familial periodic paralysis is thus another cause for the presence of CK 2 (MB). CK 2 (MB) is not a specific isoenzyme for myocardial damage since it may be identified in the serum of patients with skeletal muscle conditions.


Long-term effect of glucagon administration on rat liver L-type pyruvate kinase.

After 5 h of treatment with glucagon, liver L-type pyruvate kinase (ATP: pyruvate 2-0-phosphotransferase; EC 2.7.1.40) showed a significant decrease of K0.5 and the Hill coefficient (nH) in the absence of fructose 1,6-diphosphate. However, in the presence of fructose 1,6-diphosphate, liver enzymes from treated rats showed a slight decrease of K0.5 but nH remained unchanged. In both circumstances, no changes of Vmax were observed after treatment. These changes in the kinetic properties of liver L-type pyruvate kinase are consistent with the dephosphorylation of the enzyme caused by insulin release in response to treatment with glucagon.


Particle-bound glutathione-S-transferases.

The incubation of liver microsomes or mitochondria with glutathione, in the presence of electrophilic compounds, decreased the glutathione concentration in the incubation medium. Product analysis revealed that glutathione conjugates were formed.


Crabtree effect induced by fructose in hepatocytes isolated from developing rats.

The inhibition of respiration caused by fructose is investigated in hepatocytes isolated from fetal and developing rats. The respiration rate of the hepatocytes increases in the early days after birth. Adult values for oxygen uptake are reached by hepatocytes isolated from 14-day-old rats. After weaning, the Crabtree effect induced by fructose appears simultaneously with changes in energy metabolism.


Time course of O2-pulse during various tests of aerobic power.

The purpose of this study was to test the hypothesis that oxygen pulse typically reaches a maximum before maximal oxygen consumption by observing the time course of oxygen pulse throughout exercise to maximal stress and to discern those physiologic variables which might predispose an individual to reach a peak in oxygen pulse before achieving maximal oxygen consumption. Thirty male volunteers ranging in age from 18-25 (X = 20.5) years were recruited for this study. Maximal oxygen uptake was assessed on both bicycle ergometer and treadmill. Based upon the results of the exercise tests, subjects were classified into subgroups as a consequence of whether or not a maximal oxygen pulse or a plateau in oxygen pulse was demonstrated during submaximal exercise. The results indicate that submaximal peaking or at least the achieving of plateau values of oxygen pulse does in fact occur in some but not all indivuals. It was observed that this phenomenon occurs at a relatively high percentage of maximal heart rate and maximal oxygen consumption. It appeared that individuals who demonstrate low heart rates at low-work intensities, high maximal heart rates, and a disproportionate increase in R for a given ventilation are most likely to reach a submaximal peak in oxygen pulse. Oxygen pulse during submaximal exercise appears to provide a good indication of cardiorespiratory fitness.


Aerobic performance of female marathon and male ultramarathon athletes.

The aerobic performance of thirteen male ultramarathon and nine female marathon runners were studied in the laboratory and their results were related to their times in events ranging in distance from 5 km to 84.64 km. The mean maximal aerobic power output (VO2 max) of the men was 72.5 ml/kg . min compared with 58.2 ml/kg . min (p less than 0.001) in the women but the O2 cost (VO2) for a given speed or distance of running was the same in both sexes. The 5 km time of the male athletes was closely related to their VO2 max (r = -0.85) during uphill running but was independent of relative power output (%VO2 max). However, with increasing distance the association of VO2 max with male athletic performance diminished (but nevertheless remained significant even at 84.64 km), and the relationship between %VO2 max and time increased. Thus, using multiple regression analysis of the form: 42.2 km (marathon) time (h) = 7.445 - 0.0338 VO2 max (ml/kg . min) - 0.0303% VO2 max (r = 0.993) and 84.64 km (London-Brighton) time (h) = 16.998 - 0.0735 VO2 max (ml/kg . min) - 0.0844% VO2 max (r = 0.996) approximately 98% of the total variance of performance times could be accounted for in the marathon and ultramarathon events. This suggests that other factors such as footwear, clothing, and running technique (Costill, 1972) play a relatively minor role in this group of male distance runners. In the female athletes the intermediate times were not available and they did not compete beyond 42.2 km (marathon) distance but for this event a similar association though less in magnitude was found with VO2 max (r = -0.43) and %VO2 max (= -0.49). The male athletes were able to sustain 82% VO2 max (range 80--87%) in 42.2 km and 67% VO2 max (range 53--76%) in 84.64 km event. The comparable figure for the firls in the marathon was 79% VO2 max (ranges 68--86%). Our data suggests that success at the marathon and ultramarathon distances is crucially and (possibly) solely dependent on the development and utilisation of a large VO2 max.


Electrophysiological correlates of local muscular fatigue effects upon human visual reaction time.

A study of the neurophysiological basis of reaction time change was undertaken as a means of exploring the physiological mechanisms of local muscular fatigue effects upon sensorimotor performance. The identification of electrophysiological indices of central and peripheral processes within the human electroencephalogram and electromyogram, enabled a fractionation of total reaction time into component latencies measuring sensory reception time, sensorimotor integration time, central motor outflow time and peripheral motor contraction time. Simple foot dorsiflexion reactions to visual stimuli were observed in 18 male college students. Foot responses under one condition were performed against a resistance which necessitated a moderate degree of muscular tension before movement could occur while a second condition required normal unresisted responses. Two intensities of serial isometric work resulting in the order of a 38% decrement in maximum voluntary contractile capability (MVC) were performed by each subject. While the rate and extent of MVC decrement varied with the inherent strength of the subject and the intensity of the exercise performed, unconditional changes were observed in the spatiotemporal dimensions of reaction time performance following exercise-induced fatigue. The quality of total reaction time was found to deteriorate, particularly when responses were resisted. Peripheral deficiencies, suggestive of a decreased rate of tension development, were evidenced by a marked elongation of resisted motor times, and less vigorous and extensive unresisted responses. Insofar as the energy of response electromyograms was also diminished, central mechanisms were implicated, possible due to a shift in motor unit recruitment. Concomitant changes were also observed in central processing.


Physiological effects of dynamic work on a bicycle ergometer combined with different types of static contraction.

The effects on heart rate, oxygen uptake, and pulmonary ventilation of muscular exercises, including both dynamic contractions, either simple or combined, were studied in 4 male subjects, aged 21 to 23 years. The dynamic work consisted in cycling on an ergometric bicycle at three power levels: 40, 80, and 100 W. The static work consisted in pushing against, pulling and holding with the arms a 6, 9, 12, or 18 kg load. The physiological effects are expressed as cardiac cost (delta HR), oxygen cost (delta VO2) and ventilation cost (delta V). The physiological cost of the combined work increases according to the cycling power and to the isometric load developed. A statistical analysis shows that the costs of combined work are not different from the sum of the costs of the static and dynamic contractions measured separately. Thus, the physiological responses to the combinations investigated are of an additive type.


Mechanical power and segmental contribution to force impulses in long jump take-off.

Changes in total mechanical work, its partitioning into different energy states, mechanical power, force-time characteristics, force impulses of body segments and mass center's pathway characteristics during long jump take-off were investigated on four national and six ordinary level athletes. Both cinematographic and force-platform techniques were used. The data showed that the national level jumpers had higher run-up and higher take-off (release) velocities in horizontal and vertical directions. In addition, they were able to utilize efficiently the elastic energy stored in the leg extensor muscles at take-off impact. This was seen in high support leg eccentric and concentric forces, which were produced in short contact times. The ordinary level athletes had greater variability in the investigated attributes, and they reached their maximum length of jumps in many different ways. Cinematically the greatest difference between the subject groups was observed in the timing of the various body segment movements. In better athletes all the body parts (arms, trunk, and legs) had decelerating horizontal impulses, but in all ordinary level athletes the horizontal impulse of the swing leg was accelerating during take-off.


Mechanical characteristics and fiber composition of human leg extensor muscles.

To investigate the influence of skeletal muscle fiber composition on the mechanical performance of human skeletal muscle under dynamic conditions, 34 physical education students with differing muscle fiber composition (M. vastus lateralis) were used as subjects to perform maximal vertical jumps on the force-platform. Two kinds of jumps were performed: one from a static starting position (SJ), the other with a preliminary counter-movement (CMJ). The calculated mechanical parameters included height of rise of center of gravity (h), average force (F), net impulse (NI) and average mechanical power (W). It was observed that the percentage of fast twitch fibers was significantly related (p less than 0.05--0.01) to these variables in SJ condition and also to h and NI of the positive work phase in CMJ. It is concluded that skeletal muscle fiber composition also determines performance in a multijoint movement. The result is explainable through the differences in the mechanical characteristics of the motor units and their respective muscle fibers.


ADH and thermal sweating.

Sweating responses to heat exposure were compared in healthy subjects pretreated with pitressin or alcohol and in the control group. Between the three groups, there were no consistent differences in the rate of sweating expressed both as a total body weight loss during 2-h heat exposure and in mg of sweat per skin area covered by a paper disc. Likewise, there were no differences in the sweat osmolality or electrolyte concentration. There was also no evidence of inverse correlation between plasma ADH level and rate of sweat secretion or its concentration when pooled data of all subjects were analyzed. It was concluded that ADH did not substantially affect thermal sweating in men.


Effects of exercise on the serum concentrations of FSH, LH, progesterone, and estradiol.

The effects of 30 min of exercise (74.1 +/- 3.0% (VO2), on the responses of progesterone (P), estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were investigated in 10 women. With such exercise significant increments occurred in P (37.6 +/- 9.5%) and E2 (13.5 +/- 7.5%) (P less than 0.05), whereas no changes were observed in FSH and LH (p greater than 0.05). Exercise in the luteal phase and during menses provoked similar changes in P, but E2 concentrations remained unchanged when exercise occurred during menses (p greater than 0.05). With 8-11 weeks of training the menstrual cycles were quite irregular and retesting of subjects in the same phase of the cycle was not possible. Yet, when subjects were retested after training, no changes occurred in P, E2 or LH (p greater than 0.05) but a decrement did occur in FSH (p less than 0.10). Thus, heavy exercise in untrained subjects provokes significant increments in ovarian hormones, whereas no such increments are observed in trained subjects exercising at the same absolute workload.


The significance of the aerobic-anaerobic transition for the determination of work load intensities during endurance training.

Anaerobic and aerobic-anaerobic threshold (4 mmol/l lactate), as well as maximal capacity, were determined in seven cross country skiers of national level. All of them ran in a treadmill exercise for at least 30 min at constant heart rates as well as at constant running speed, both as previously determined for the aerobic-anaerobic threshold. During the exercise performed with a constant speed, lactate concentration initially rose to values of nearly 4 mmol/l and then remained essentially constant during the rest of the exercise. Heart rate displayed a slight but permanent increase and was on the average above 170 beats/min. A new arrangement of concepts for the anaerobic and aerobic-anaerobic threshold (as derived from energy metabolism) is suggested, that will make possible the determination of optimal work load intensities during endurance training by regulating heart rate.


Age-related differences in lactate distribution kinetics following maximal exercise.

Lactate concentrations were determined at 3, 5, and 7 min of recovery following maximal, continuous, multi-stage treadmill work in 180 men, aged 20-80 years, who were participants of the Baltimore Longitudinal Study of Aging. Each subject was placed into one of six age groups, e.g., 20-29, 30-39, etc. As expected, average concentrations decreased consistently with age. All three sampling times were similar in characterizing maximal lactates for the youngest men. For each older group, except for the oldest, the later values were significantly (p less than 0.01) higher than the 3-min values. For subjects in their 50's and 60's mean concentrations continued to rise through the 7th min. These data suggest that in man there is a progressive, age-related diminution of ability to diffuse lactate from muscle and/or distribute it into its space. This may result in decreased endurance and work capacity and a prolongation of recovery. As an alternative to multiple sampling and analyses for maximal lactate, single blood samples should be obtained no sooner than 5 min of recovery for men up to age 50, and at 7 min for those between 50 and 70 years. Variability among the men over 70 years of age was large enough to preclude single-sample alternatives.


EMG frequency spectrum, muscle structure, and fatigue during dynamic contractions in man.

Fatigue of the vastus lateralis muscle was studied in healthy well-conditioned students, who differed considerable regarding their muscle fibre type distribution. Muscle force decline during repeated maximum voluntary knee extensions at a constant angular velocity (180 degree X s-1 or rad X s-1), using isokinetic equipment, was taken as the criterion for the degree of fatigue. In an attempt to study quantitative as well as qualitative changes in the EMG pattern, integrated EMG (IEMG) and the frequency of the mean power (MPF), computed from the power spectral density function (PSDF), were analysed. It was found that individuals with muscles made up of a high proportion of fast twitch (FT) muscle fibres demonstrated higher peak knee extension torque, and a greater susceptibility to fatigue than did individuals with muscles mainly composed of slow twitch (ST) muscle fibres. An IEMG decline (p less than 0.01) was demonstrated during 100 contractions in individuals rich in FT fibres. Only a slight, but not significant, reduction in IEMG occurred in individuals with high percentage of ST fibres. Concomitantly, MPF decreased (p less than 0.001) in individuals with a high percentage of FT fibres, while their opposites demonstrated only a slight decrease (non-significant). It is suggested that muscle conctraction failure might also be related to qualitative changes in the motor unit recruitment pattern, and that these changes occur more rapidly in muscles composed of a high proportion of FT muscle fibres than in muscles composed to a high proportion of ST fibres.


Oxygen dissociation curves in trained and untrained subjects.

Oxygen dissociation curves (ODC) in whole blood and organic phosphate concentrations in red cells were determined in 10 highly trained male athletes (TR), 6 semitrained subjects (ST) who played sports regularly at low intensities and 8 untrained people (UT). In all groups standard ODCs (37 degrees C, pH 7.40, PCO2 approximately 43 Torr) at rest and after a short exhaustive exercise were nearly identical, but PO2 values measured immediately after blood sampling and corrected to standard conditions tended to fall to the right of the in vitro ODC. Elevated P50 in the physically active [28.65 +/- 1.4 Torr (3.81 +/- 0.18 kPa) in ST, 28.0 +/- 1.1 Torr (3.73 +/- 0.15 kPa) in TR, but 26.5 +/- 1.1 Torr (3.53 +/- 0.15 kPa) in UT] were partly caused by different [DPG] (11.9 +/- 1.3 mumol/GHb in UT, 13.3 +/- 1.5 mumol/GHb in TR, 13.8 +/- 2.2 mumol/gHb in ST). There were remarkable differences in the shape of the curves between the groups. The slope "n" in the Hill plot amounted to 2.65 +/- 0.12 in UT, 2.74 +/- in ST and 2.90 +/- 0.11 in the TR (2 p against UT less than 0.001), leading to an elevated oxygen pressure of about 2 Torr (0.27 kPa) at 20% saturation and an augmented oxygen extraction of 5--7 SO2 at a PO2 of about 15 Torr (2kPa), which might be favorable at high workloads. The reason for the phenomenon could be an increased amount of young red cells in the blood of TR, caused by exercise induced hemolysis.


Resting heart rate in apparently healthy middle-aged men.

Resting heart rate (fcrest) was measured by a standardized technique in 2,014 men aged 40-59 years during a cardiovascular survey. All men were thought to be healthy prior to the survey examination. According to the survey findings, the material was subdivided into 5 clinical subgroups, according to survey findings of coronary heart disease (CHD), or suspect symptoms, or signs. Coronary angiography was performed in 105 subjects with particularly strong suspicions of CHD. FCrest varied between 61-63 among the 5 groups (p greater than 0.10). In 1832/2014 defined as "normals" the following findings were made: 1. Mean fcrest 61 (SD 9.7), and almost identical values obtained by auscultation and from resting ECGs in the same persons. 2. Linear drop in fcrest by age (-0.126 beats/year, p less than 0.001). 3. Increase in fcrest with increasing systolic blood pressure. Since there is no generally accepted technique for measuring fcrest it is suggested that the wide variation in fcrest reported in the literature at least in part may be due to differences in techniques.


Protein synthesis in imbibing wheat embryos.

Polypeptides synthesized by imbibing wheat embryos have been compared with those made by cell-free extracts programmed with bulk poly(A)-rich RNA from dry wheat embryos. Newly synthesized polypeptides, labeled with [35S]methionine, were resolved by one-dimensional and two-dimensional electrophoresis and then records of the separations were prepared by fluorography. When programmed by bulk poly(A)-rich RNA from dry wheat embryos, a nuclease-treated rabbit reticulocyte lysate synthesizes an array of polypeptides which is broadly similar to that formed when a wheat germ extract is programmed with the same RNA. Polypeptides made in both homologous and heterologous cell-free systems, under the direction of bulk poly(A)-rich RNA from dry wheat embryos, are broadly similar to those formed during early (0--40 min) imbibition of dry wheat embryos. As imbibition progresses beyond 40 min, there are profound changes in the one-dimensional and two-dimensional electrophoretic distributions of newly made polypeptides present in the 23 000 x g supernatant fraction of cell-free homogenates; characteristically, low-molecular-weight and basic polypeptides comprise a diminishing proportion of the total polypeptides as imbibition progresses beyond 40 min. Ribosomal proteins are conspicuous among the proteins formed during early imbibition and especially prominent among the products formed when homologous cell-free polypeptide synthesis is programmed by bulk poly(A)-rich RNA from dry wheat embryos.


Characterization of pre-messenger-RNA-containing nuclear ribonucleoprotein particles from avian erythroblasts.

Ribonucleoprotein particles have been isolated from duck erythroblast nuclei using a procedure designed to produce maximal cytoplasmic dispersion with minimal release of endogenous hydrolytic enzymes. The RNA extracted from the purified nuclear ribonucleoprotein fraction is shown to contain globin messenger RNA sequences at a concentration comparable to that present in total nuclear RNA. The polypeptide composition of this fraction revealed by electrophoresis in two dimensions is complex, consisting of at least 65 acidic species and 21 basic species. Several lines of evidence suggest that these are authentic components of nuclear ribonucleoprotein. The so-called 'core' proteins of nuclear ribonucleoprotein which were previously shown to migrate as a single band on low-pH urea gels, and as six bands on sodium dodecyl sulphate gels are here shown to be considerably more complex being resolved by two-dimensional electrophoresis into a group of 15 basic and 6 more and less neutral polypeptides. Isoelectric focusing of nuclear ribonucleoprotein under non-denaturing conditions suggests that these latter species are not uniformly distributed along the pre-messenger RNA molecule.


Two-dimensional analysis of proteins associated with heterogenous nuclear RNA in various animal cell lines.

The protein complement of heterogenous nuclear RNA . protein particles from human HeLA, mouse L and Chinese hamster (CHO) cells has been analysed by two-dimensional gel electrophoresis using the two techniques described by O'Farrell [J. Biol. Chem. (1975) 250, 4007--4021 and Cell (1977) 12, 1133--1142]. Over a hundred individual spots habe been reproducibly detected both L-[35S]methionine. Large similarities, especially in the 25 000--40 000 Mr cluster of basic protein, were found among these three mammalian species. As far as phosphoproteins are concerned, it was observed that the bands already described by one-dimensional gels [Eur. J. Biochem. (1978) 86, 301--310] with Mr values of 28 000, 30 000, 37 000 and 52 000 are resolved into about 15 individual spots, suggesting a corresponding number of distinct states of phosphorylation. It was also clearly demonstrated that phosphoproteins are unrelated to the major basic protein species. Particles of different size classes were analysed with respect to their content of individual proteins, both non-phosphorylated and phosphorylated. The most salient feature observed was that phosphoproteins become progressively more abundant with particles of increasing size. This raises the possibility that at least some of these phosphoproteins might belong to a nuclear structure to which hnRNA is normally bound.


The primary structure of the ovine beta-caseins.

Ovine whole casein contains 2 multiphosphorylated beta-casein components designated as beta 1 and beta 2-caseins. The complete sequence of beta 1-casein and the partial sequence of beta 2-casein have been determined from cyanogen bromide and tryptic digests. The ovine beta 1 and beta 2-caseins have the same polypeptide chain and appear to differ only in that they contain 6 and 5 phosphates respectively. The amino acid composition of ovine beta 1-casein can be written as: Asp4, Asn4, Thr10, ThrP1, Ser9, SerP5, Glu19, Gn21, Pro34, Gly5, Ala4, Val21, Met6, Ile9, Leu22, Tyr3, Phe9, Trp1, Lys12, His5, Arg3. Compared to bovine beta-casein A2, which is made up of 209 residues, ovine beta 1-casein has a deletion of 2 residues (either Pro-179--Tyr-180 or Tyr-180--Pro-181) and 20 largely conservative amino acid substitutions. Although 20% of the substitutions involve proline residues, the proline contents of ovine beta 1 and bovine beta A2-caseins are very similar, around 16%. The average hydrophobicity, calculated according to Bigelow, is 5.51 kJ/residue, which is similar to that calculated for bovine beta-casein A2. The cluster of 4 phosphorylated serine residues and the highly charged nature of the amino terminal region observed for bovine beta-casein are conserved in the ovine beta-caseins. The substitution from Ile-12 (bovine) to Thr-12 (ovine) results in a new phosphorylation site, according to the phosphorylation code proposed for caseins. This site is only partially phosphorylated hence the occurrence of both beta 1 and beta 2-caseins in ovine milk.


Identification of the C-1-phosphate-binding arginine residue of rabbit-muscle aldolase. Isolation of 1,2-cyclohexanedione-labeled peptide by chemisorption chromatography.

The arginine-specific reagent 1,2-cyclohexanedione reacts selectively with the arginine residue of the C-1-phosphate-binding site of aldolase and inactivates the enzyme. The labeled peptide isolated from tryptic digests of inactivated aldolase was found to correspond to the sequence Leu-43 to Arg-56, the residue modified by cyclohexanedione being Arg-55. This peptide was absent form digests of aldolase treated in the same way but protected from inactivation by the presence of substrate, thus correlating modification of Arg-55 with loss of activity. Selective isolation ofthe peptide containing the modified arginine residue was effected by chemisorption chromatography on boric acid gel, a procedure exploiting the specific interaction of matrix-bound boric acid groups with vicinal cis-hxdroxyl groups of cyclohexanedione-modified arginine side chains.


Fluorescently labelled histones as probes of nucleosome structure. Preparation and general properties of methionine-labelled histone H4.

A fluorescent derivative of calf thymus histone H4 has been prepared by the reaction of methionine-84 with N-(iodoacetylaminoethyl)8-naphthylamine-1-sulfonic acid at pH 2.4 in 8 M urea. The preparation and characterization of this labelled histone is described. Fluorescence emission measurements indicate that the label on H4 undergoes a 3--5-fold increase in emission intensity when H4 self-interacts or binds to DNA alone or is incorporated in a synthetic nucleosome. The changes observed are consistent with the formation of varied apolar environments around methionine-84, due most likely to histone-histone rather than histone-DNA interactions. Preliminary experiments indicate that the precise emission intensity of labelled H4 in the nucleosome is quite sensitive to conditions of ionic strength and histone integrity.


Synthesis and characterization of a DNA complementary to pre-uteroglobin mRNA.

Uteroglobin, a progesterone-induced uterine protein of the rabbit, is synthesized in cell-free systems as a precursor containing 21 additional amino-acids at its N-terminal end. The mRNA for pre-uteroglobin has been purified from the membrane-bound polysomes of induced endometrium and used as template for the synthesis of a full copy complementary DNA. Final purification of the cDNA was based on hybridization to the template mRNA up to a low value of r0t (0.01 M . s) and digestion of the non-hybridized cDNA by S1 nuclease. A comparison of the hybridization kinetics of the pre-uteroglobin cDNA and rabbit globin cDNA to their respective templates indicates a nucleotide sequence complexity of 650 for pre-uteroglobin mRNA, in agreement with the values obtained by sucrose gradient centrifugation and polyacrylamide gel electrophoresis in formamaide. The melting temperature of the hybrids of pre-uteroglobin cDNA to its template reflects the absence of mismatched sequences. This cDNA has been used to quantify pre-uteroglobin mRNA sequences in the endometrial RNA from control animals and from animals treated sequentially with estradiol and progesterone. In agreement with the induction of uteroglobin-synthesizing activity, there is a dramatic increase in the uterine content of pre-uteroglobin mRNA after hormonal treatment. Part of this effect can be accounted for by hormonally induced cell proliferation. When expressed on a DNA basis there is a 50--100-fold increase in the cellular content of pre-uteroglobin mRNA following hormonal treatment.


Netropsin . dG-dG-dA-dA-dT-dT-dC-dC complex. Antibiotic binding at adenine . thymine base pairs in the minor groove of the self-complementary octanucleotide duplex.

The structure of the netropsin . dG-dG-dA-dA-dT-dT-dC-dC complex (one antibiotic molecule/self-complementary octanucleodide duplex) and its dynamics as a function of temperature have been monitored by the nuclear magnetic resonances of the Watson-Crick protons, the nonexchangeable base and sugar protons and the backbone phosphates. The antibiotic forms a complex with the nucleic acid duplex at the dA . dT-containing tetranucleotide segment dA-dA-dT-dT, with slow migration amongst potential binding sites at low temperature. The downfield shifts in the exchangeable protons of netropsin on complex formation demonstrate the contributions of hydrogen-bonding interactions between the antibiotic and the nucleic acid to the stability of the complex. Complex formation results in changes in the glycosidic torsion angles of both thymidine residues and one deoxyadenosine residue as monitored by chemical shift changes in the thymine C-6 and adenine C-8 protons. The close proximity of the pyrrole rings of the antibiotic and the base-pair edges in the minor groove is manifested in the downfield shifts (0.3--0.5 ppm) of the pyrrole C-3 protons of netropsin and one adenine C-2 proton and one thymine N-3 base-pair proton on complex formation. The internucleotide phosphates of the octanucleotide undergo 31P chemical shift changes on addition of netropsin and these may reflect, in part, contributions from electrostatic interactions between the charged ends of the antibiotic and the backbone phosphates of the nucleic acid.


A membrane glycoprotein of aggregating Dictyostelium cells with the properties of contact sites.

Aggregating cells of Dictyostelium discoideum form EDTA-stable contacts which are blocked by a Fab (antigen-binding fragment) preparation from antisera raised against membranes. The target site of the blocking Fab fragments has been identified as a specific glycoprotein. In this paper its purification, carbohydrate and amino acid composition are described. Purification was 800-fold, starting with cells lysed by digitonin. The plasma membranes, preserved as ghosts by this treatment, were purified in a two-phase system and extracted with butan-1-ol. The water phase contained predominantly concanavalin-A-binding glycoproteins and was particularly rich in contact sites A. These were further purified on DE-cellulose and sucrose gradients. Sodium dodecylsulphate/polyacrylamide gel electrophoresis of the purified material revealed one major glycoprotein band in the molecular weight region of 80 000 to 90 000, depending on the acrylamide concentration. The sugars found in contact sites A were mannose, N-acetylglucosamine, fucose, and possibly glucose. The protein moeity contained 8% proline and was particularly rich in hydroxy amino acids.


Determination of the hydrophobic binding site of phosphatidylcholine exchange protein with photosensitive phosphatidylcholine.

1-Acyl-2-(7-(4-azido-2-nitrophenoxy)-[1-14C]heptanoly)-sn-glycero-3-phosphocholine was synthesized in order to study the lipid-binding site of the phosphatidylcholine exchange protein from bovine liver. Photosensitive phosphatidylcholine was incorporated into the protein by incubation with vesicles of this phosphatidylcholine derivative. The lipid-protein complex was separated from the vesicles by chromatography on Biogel A-0.5m. Photolysis of the complex by irradiation with light of a high pressure mercury lamp at a wavelength above 340 nm generated the highly reactive nitrene. Sodium dodecyl sulfate gel electrophoresis of the photolysed complex indicated that 30% of the endogenous 14C-labeled phosphatidylcholine was covalently linked to the protein. Peptides were isolated after digestion of the photolysed complex with protease from Staphylococcus aureus and trypsin. It was determined that the 2-acyl chain of the phosphatidylcholine molecule was linked to the peptide segment -Gly-Ser-Lys-Val-Phe-Met-Tyr-Tyr-. This segment was part of a protease peptide of about 65 residues of which the sequence was determined by Edman degradation for the first 38 residues. This peptide contains a cluster of apolar residues -Val-Phe-Met-Tyr-Tyr-Phe with an extremely high hydrophobicity index and with a predicted beta-sheet conformation. It is concluded that this hydrophobic cluster forms part of the binding site.


Postsynaptic effects of crotoxin and of its isolated subunits.

Crotoxin is a potent neurotoxin from the venom of Crotalus durissus terrificus. It is composed of two subunits: a basic phospholipase A2 with low toxicity (component B) and an acidic protein seemingly devoid of intrinsic biological activity (component A). Crotoxin and its isolated phospholipase subunit block the depolarisation caused by cholinergic agonists on the isolated electroplaque from Electrophorus electricus. The other component, which is inactive when applied alone, enhances the pharmacological activity of the phospholipase when the two components are used together. Crotoxin also blocks the increase of 22Na+ efflux caused by carbamylcholine from excitable microsacs prepared from Torpedo marmorata electric organ. Crotoxin therefore acts postsynaptically, but does not interfere with the binding of alpha-toxin from Naja nigricollis to the nicotinic cholinergic receptor site. Instead, like local anesthetics, it stabilizes a desensitized form of the acetylcholine receptor characterized by its high affinity for agonists. The phospholipase component B binds in a non-saturable manner to receptor-rich membranes. In contrast, component A does not bind to acetylcholine receptor-rich membranes, but completely prevents the non-saturable binding of component B. When the two components are applied together, a saturable binding of the latter is observed with the acetylcholine receptor-rich membranes.


Role of the mitochondrial anion transporters in the regulation of ammoniagenesis in renal cortex mitochondria of the rabbit and rat.

The purpose of this study was to investigate factors which may regulate ammoniagenesis in the kidney cortex. Emphasis was placed on the segment of the pathway by which the carbons derived from glutamine must exit from the mitochondrion. These pathways were compared in the rat with high rates of ammoniagenesis and the rabbit which has a low rate of ammoniagenesis. The dicarboxylate transporter, which is essential for ammoniagenesis, has a maximum velocity which was much lower in the rabbit. The malate concentration required for half-maximal rates of transport was 14 nmol/mg mitochondrial protein and similar in both species. There was no effect of chronic metabolic acidosis on dicarboxylate transporter activity. The tricarboxylate transporter activity with phosphoenol pyruvate as substrate also had a low activity in the rabbit kidney-cortex mitochondria. The maximum velocity of phosphate dependent glutaminase, glutamate dehydrogenase and phosphoenolpyruvate carboxykinase were all much greater than the maximal rate of ammoniagenesis observed in vivo in the rabbit. Therefore, the low rates of ammoniagenesis and the failure to adapt to acidosis in the rabbit are best explained by factors influencing the dicarboxylate transporter.


Interaction of non-histone proteins with DNA and chromatin from Drosophila and mouse cells. Specificity, isolation and analysis of complexes.

The specificity of the binding of purified non-histone proteins to DNA has been investigated through two types of experiments. Using a nitrocellulose filter assay at a low protein/DNA ratio, the binding of mouse non-histone proteins to mouse DNA was twice as great as the binding of mouse non histone protein to Drosophila DNA. The reverse experiment using Drosophila non-histone protein confirmed the interpretation that some protein . DNA complexes were specific. Protein . DNA complexes isolated by gel filtration chromatography indicated that 20% or 10% of the non-histone protein was bound to homologous or heterologous DNA respectively. Purified non-histone proteins bound with lower efficiency (15%) than unpurified but with higher specificity to soluble chromatin than to naked DNA. This binding did not result from an exchange between chromatin non-histone proteins and purified non-histone proteins added in excess. DNA-bound and chromatin-bound proteins were analysed on polyacrylamide gels. Whereas no major qualitative differences were observed with DNA-bound proteins, some proteins bound to homologous mouse chromatin were different from those bound to heterologous Drosophila chromatin. These results suggest a possible role of DNA-bound non-histone proteins in the regulation of gene expression.


Macromolecular complexes of aminoacyl-tRNA synthetases from eukaryotes. 1. Extensive purification and characterization of the high-molecular-weight  complex(es) of seven aminoacyl-tRNA synthetases from sheep liver.

Starting from homogenates of sheep liver, extensive co-purification of seven aminoacyl-tRNA synthetases to high specific activities was achieved by a three-step procedure involving fractional precipitation by poly(ethylene glycol) 6000, gel filtration on 6% agarose and chromatography on Sepharose-bound tRNA. The purified material is composed of nine major protein components as revealed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and has an apparent molecular weight of about 10(6) estimated by gel filtration on 6% agarose. It contains aminoacyl-tRNA synthetase activities specific for methionine, lysine, arginine, leucine, isoleucine, glutamine and glutamic acid. The rigorous co-elution of these seven enzymes at each chromatographic step suggests, but does not conclusively prove, that they are physically associated within the same complex. The enzyme composition of the high-molecular-weight complex purified from sheep liver is identical to that of the complex previously isolated from human placenta by Denney in 1977 (Arch. Biochem. Biophys. 183, 156--167).


Metabolism of isolated kidney tubules. Interactions between lactate, glutamine and oleate metabolism.

Kidney-cortex tubule suspensions were prepared by collagenase treatment of kidney cortex from fed and starved rats. This preparation, consisting mainly of proximal convoluted tubules was incubated with three major renal substrates, L-lactate, glutamine and oleate to study the dose dependence of substrate uptake rates from medium substrate combinations. All three substances, when added at near physiological concentrations, modified the uptake rate and fate of the other substrates. In accordance with previous observations, oleate inhibited lactate uptake, and lactate decreased glutamine metabolism. Glutamine on the other hand led to a marked increase in lactate uptake. Both, glutamine and lactate increased oleate metabolism. Glucose was the main product of lactate and glutamine metabolism, lactate being preferentially taken up for this process. Oleate led to a net synthesis of triglycerides in the tubules, which was stimulated by the addition of lactate and glutamine. More than 75% of the oleate taken up was recovered as triglycerides. In the absence of fatty acids, triglyceride content of tubules decreased. The results indicate that oleate is taken up in preference to lactate and glutamine when all three substrates are offered to the tubule. Glucose and triglycerides are the main metabolic products of tubular substrate metabolism. Whereas glucose is released into the medium, triglycerides are stored in the tubule cell.


Cleavage of elongation factor G into compact domains.

A limited trypsinolysis of native elongation factor G results in the formation of two large fragments resistant to further proteolysis. The fragments were isolated in homogeneous state in conditions when their native structure is retained. According to circular dichroism and scanning calorimetry data the formed fragments retain the stability and compact structure that they had in the whole protein.


Mechanistic and stereochemical studies on the glycine reductase of Clostridium sticklandii.

Clostridial glycine reductase multienzyme complex which catalyses the reaction: Glycine + ADP + Pi + 2H leads to Acetate + ATP + NH3 was solubilised and fractionated essentially according to the method of Stadtman [T.C. Stadtman (1970) Methods Enzymol. 17A, 956--966] into two components: protein A and 'glycine reductase' fraction. A reconstituted system obtained by combining the two components in the presence of dithiothreitol catalysed the conversion of glycine into acetate concomitant with the phosphorylation of ADP to ATP. Using the reconstituted system, in which the unwanted enzyme activity catalyzing an exchange of the alpha hydrogen atoms of glycine with the protons of the medium had been greatly reduced, it was found that the conversion of (2RS)-[2-14C, 2-3H1]glycine (3H/14C = 7.16) into acetate (3H/14C = 7.03) was attended by the retention of both the C-2 hydrogen atoms of glycine. Conversion of (2S)-[2-2H1, 2-3H1]glycine and (2R)-[2-2H1, 2-3H1]glycine by the reconstituted system gave (2S)-acetate and (2R)-acetate respectively showing that the reductive deamination of glycine occurs through an inversion of configuration. The cumulative information available on the glycine reductase reaction is embodied in a hypothetical mechanism of action for the enzyme.


Measurement of colloid clearance rate as an adjunct to static liver imaging.

A technique for the measurement of the rate of uptake of 99mTc labelled sulphur colloid in the liver using a gamma camera and computer is described. The mathematical model showing the factors affecting the rate of uptake, and the results of the measurements in a series of normals and patients with a variety of liver diseases are presented. The range in cirrhosis was found to be significantly lower than normal and the range in acute liver injury significantly higher. The technique can easily be incorporated into a standard colloid liver imaging procedure and is considered to be a valuable adjunct to diagnosis using the static images.


Assessment of the extent of bone marrow haemopoietic activity in normal subjects.

A method, introduced by the authors, for assessment of the extent of bone marrow haemopoietic activity in normal subjects is reported. 99mTc-sulfur colloid is injected, and the bone marrow visualized on gamma camera, type Phogamma-HP, which is equipped with 4096 channel analyzer (Nuclear Chicago). By use of a standard and by registering the activity in "zones of interest" from the arm, forearm, thigh and lower leg bones, indices and mean normal values in 26 normal subjects were calculated and reported.


Application of ferrokinetic investigation for differential diagnosis in bone marrow hypoplasia and their clinical relevance.

In this study, erythropoietic activity of bone marrow has been evaluated by ferrokinetics. For that purpose, the data of radioiron disappearance from plasma and its ultimate incorporation in red blood cells after the injection of about 10 muCi of 59Fe tagged autologous plasma, were analysed and fitted to the sum of three exponentials, using a non-linear least square SAAM-25 program on UNIVAC-1108 computer. A function representing time-activity relationship, was constructed. The functional physiological model of iron metabolism, proposed by Cavill and Ricketts, was used to calculate various ferrokinetic parameters in terms of coefficients and exponents of the time-activity function. After identifying the parameters that could be used as indices of erythropoietic activity of bone marrow, the study was repeated in six patients after they had undergone myelostimulative therapy. A distinct correlation was found between ferrokinetic observations and clinical and biochemical findings. It has been demonstrated that in histologically diagnosed cases with bone marrow hypoplasia, a further differentiation between pure aplasia and those with hypoplasia together with ineffective erythropoiesis was possible. This discrimination which is clinically very important, is only possible by means of kinetic investigations.


Value of additional lateral scans in renal scintigraphy.

Although it is common to perform scintigrams in multiple projections this technique has not yet been generally accepted for kidney scintigraphy. By performing additional lateral scans using an Anger camera and with patients sitting we found at least three advantages: 1. Better Visualisation of Kidney Lesions: 7 (13,5%) of 52 cases with lesions could be detected in lateral projection only, in all other cases we obtained better information concerning location and size of lesions. 2. Determination of Real Kidney Size: Of 62 patients with kidneys appearing reduced unilaterally in the dorsal projection, additional lateral recordings demonstrated that 24 (39%) seemed diminished because of tilting. 3. Better Interpretation of Renograms: Demonstration of different depths of kidneys facilitates interpretation of renograms with different peak heights. Additional lateral scans thus can provide--at least if dorsal recordings are inconclusive--further information.


I-125 photon absorptiometric analysis of bone density in patients with regular dialysis treatment.

The density of bone in the distal third of the radius is measured by I-125 photon absorptiometry in 38 RDT (Regular Dialysis Treatment) patients (19 mean and 19 women, age range from 17 to 65 years). In the majority of patients the bone density (BMC/W) is reduced. The clinical follow-up of dialysis patients demonstrates that the incidence and severity of clinical symtpoms do not always correlate closely with the bone density values, nor with the biochemistry and histopathological findings of bone disease associated with dialysis. Despite control of calcium and phosphorus metabolism, decreased mineralization of the appendicular skeleton persists. The advantages as well as disadvantages of bone density measurements in RDT patients are discussed.


89Strontium therapy of bone metastases of carcinoma of the prostatic gland.

Following a firm diagnostic and therapeutic schedule for patients with prostatic carcinoma. 89Strontium therapy was introduced for multiple metastases. Positive skeletal scintigraphy with 99mTc-EHDP induced check for affinity to Sr using 85Sr scintigraphy. Of 80 patients, multiple metastases were found in 26. Therapy with 1 mCi of 89Sr-chloride was started in 20 cases. In 8 patients, relief from severe pain appeared shortly afterward, and a further 8 it was possible to prevent the development of pain. Moderate success in 3 cases and a failure to provide relief in 1 were observed.


Thyroid imaging with iodine-125 and technetium-99m.

Eighty-eight patients referred consecutively for thyroid imaging were studied. Each patient was scanned with a 3'' rectilinear scanner using both 125I and 99mTc. The paired scans were evaluated independently by two physicians experienced in thyroid evaluation and image analysis. The images were ranked on a scale from 1 to 5 as follows: 1) 125I scan much better than the 99mTc scan, 2) ..., 3) 125I scan and 99mTc scan the same, 4) ..., 5) 99mTc scan much better than 125I scan. The scores were statistically analyzed by the sign test and transformed normal score methods. Categories analyzed were: A. Hypothyroid, B. Euthyroid, C. Hyperthroid, (A-C based upon RAIU measurements), D. Cold Nodules, E. Graves Disease, F. Hot-Nodules, G. Multinodular Nontoxic Goiter, H. Miscellaneous and I. Normal. The significance of this study is that regardless of the classification we used, in no category was the 99mTc scan considered better than the 125I scan. This finding is at variance with the observations of some others comparing 99mTc with other iodine radioisotopes. 99mTc may have some procedural advantages and does deliver a lower radidation dose to the thyroid.


The indeterminate lung scan: its characteristics and its association with pulmonary embolism.

In an unselected series of patients whose only perfusion abnormalities on lung scan matched abnormalities on chest radiograph, the prevalence of pulmonary embolism ranged from 8 to 15%. These estimates depended upon whether only angiographic and autopsy-proven diagnoses were allowed or whether clinical diagnoses were also considered correct. Physical findings and laboratory data, in general, did not contribute to an elucidation of the cause of an indeterminate lung scan. Several radiographic findings with associated perfusion abnormalities (atelectasis alone, multiple infiltrates, bilateral effusions) were not seen in patients with pulmonary embolism. The probability of pulmonary embolism in patients with subsegmental defects alone and matching radiographic findings is about 9%; angiography in these patients would require that nearly two-thirds of the initial patient population undergo this procedure. Patients with larger defects (segmental or lobar) had a higher probability for pulmonary embolism (20--30%) and in these patients angiography is recommended.


Localization of 99mTc-diphosphonate in a surgical scar: a speculative case report and a review of the literature.

This communication reports a presumed increased localization of 99mTc-diphosphonate in a surgical scar 5 months post-op at the site of a medium sternotomy incision. The possible mechanisms for this observation are commented on and a brief review of the observed sites of soft-tissue uptake of 99mTc-labeled bone imaging agents is given.


Iodine 131 labelled ioglycamic acid (Biligram) for scintiscanning in hepatobiliary disorders.

Iodine-131 labelled Biligram has been evaluated as a radiopharmaceutical for dynamic scintiscanning of the liver and biliary tract. In 10 normal subjects there was good visualisation of the liver and gallbladder. In 18 patients 131I Biligram was found to be unsatifactory for differentiating parenchymal liver disease from biliary tract obstruction owing to inability to demonstrate the gallbladder when liver function was more than mildly deranged. Quantitative analyses of blood clearance and hepatic activity curves for 131I Biligram were not clinically helpful. Urinary excretion of 131I Biligram increased with the degree of hepatic dysfunction.


Liver scanning for amyloid.

Subsequent liver scans with both 99mTc-colloid and 99mTc-diphosphonate in a patient with biopsy proven liver amyloidosis are described. The colloid liver scans demonstrated the variable pattern which can be obtained at different stages of the disease, whereas, the absence of Tc-diphosphonate uptake, by the infiltrated liver, did not confirm previous suggestions about the amyloid seeking properties of this material.


The distribution of 75Se-adenosyl selenomethionine in the rat with observations on its potential as a prostate scanning agent.

The preparation of 75Se-adenosyl selenomethionine is described. Following injection into male rats 63% of the administered label was excreted in 24 h, predominantly in the urine. The remaining activity appeared to have joined the S-adenosyl methionine pool residing mainly in the liver and kidney. The maximum incorporation into the ventral prostate was 2 to 4 h after injection at 0.7% injected dose/g wet weight. These results indicate that 75Se-adenosyl selenomethionine is not a suitable radiopharmaceutical for diagnostic scanning of the prostate.


Radionuclide fetal imaging: radio-activity in the fetal bladder confirmed by ultrasound after maternal hepato-biliary scanning.

Hepato-biliary scanning with 99mTc-P.G. demonstrated in a jaundiced patient at 31 weeks pregnancy the filling of the fetal bladder 6 h after injection. This finding was confirmed by ultrasound. Fetal urinary bladder activity was seen until 33 h after injection. Fetal hepatic radio-activity could not be displayed although the localisation of the fetal liver was marked by ultrasound.


The significance of the abnormal rest thallium-201 myocardial image in coronary artery disease.

Rest Thallium-201 myocardial images were abnormal in 20 out of 40 patients with arteriographically proven coronary artery disease. The myocardial image appearances did not accurately reflect the extent of coronary artery disease present. However, in 35 of the 40 patients (88%) the presence or absence of abnormalities on the rest myocardial image correleted respectively with the presence or absence of abnormal wall motion at left ventriculography. Most rest image abnormalities could be attributed to previous myocardial infarction, but in six patients myocardial ischaemia was possibly the cause. These results suggest that though myocardial fibrosis is usually the cause of rest myocardial image abnormalities in coronary artery disease, this is not invariably so. The possible therapeutic implications are discussed.


An evaluation of six kits of technetium 99m human serum albumin injection for cardiac blood pool imaging.

We have investigated the suitability of five different commercially available kits which provide human serum albumin (HSA) labelled with technetium 99m (99mTc) for cardiac blood pool imaging. Four of these products were one-step processes using stannous chloride as the reducing agent; the fifth was based on an electrolytic reduction. In addition, we also assessed our own modification of the electrolytic method. We measured the radiochemical purity by precipitation with trichloroacetic acid and by gel filtration on a Biogel P4 column. In addition, we measured the clearance of radioactivity from the blood at frequent time intervals after intravenous injection. Each product was assessed in separate groups of six patients. The labelling efficiency of the one-step kits varied between 73 and 93% compared with 94 and 98% for the electrolytically labelled albumin. The blood clearance for all one-step kits was significantly faster than that obtained for the radiopharmaceuticals prepared by the electrolytic method. We conclude that HSA labelled with 99mTc by the electrolytic method is to be preferred.


Specificity of immunoassays. II. Heterogeneity of specificity of antibodies in antisera used for steroid immunoassay and the selective blocking of less specific antibodies, including a new method for the measurement of immunoassay specificity.

Practical aspects of the measurement of the specificity of immunoassay are reviewed. Antibody heterogeneity in an antiserum makes a pragmatic rather than a theoretical approach necessary. A new method for the measurement of immunoassay specificity is described. This method is based on the errors caused by the cross-reacting antigens and is directly relevant to the validity of results obtained by immunoassay methods. The effect of selectively blocking the least specific antibodies in antisera raised against steroid haptens is tested. The practical consequences of these considerations are tested using steroid radioimmunoassay and enzyme-immunoassay.


Specificity of immunoassays. III. Use of two antisera of differing specificities to improve the specificity of steroid immunoassay.

The specificity of immunoassays can be improved by using a second antiserum to bind substances that cross-react. Both theory and practice show that the effectiveness of the procedure is dependent of the complex interplay of the concentrations of the two antibodies, the concentrations of the three antigens involved (the labelled tracer, the antigen whose concentration is to be measured and the substance that cross reacts) and the affinities of the antibodies for these antigens. Measured cross-reactions can frequently be reduced to zero in the most important concentration ranges thereby enabling one to perform assays upon unpurified materials which other wise would not be possible. Limitations of the method are discussed.


Accumulation of radioiodinated tyrosine derivatives in the adrenal medulla and in melanomas.

Because tyrosine and dopa can be regarded as precursors of adrenomedullary hormones and melanin, radioiodinated derivatives of these compounds were tested for their accumulation in the adrenal medulla and in melanomas of various animal species. The highest level of accumulation in the adrenal medulla was attained in mice and rats with iodinated beta-hydroxy-alpha-methyltyramine, and in melanomas of mice with iodinated alpha-methyltyrosine. The results could not be reproduced to the same extent in other species.


An ultrafiltration technique for labeling red blood cells with Tc-99m.

This method automates the preparation of autologous Tc-99m labeled red blood cells utilizing the Amicon on-line column eluate concentrator to separate the plasma from the red blood cells. The red blood cells were pre-tinned with stannous diphosphonate and continuously recirculated over a 0.6 mu filter until all of the plasma was removed and the red blood cells remained suspended in a solution of 0.9% sodium chloride. Once the plasma has been removed the red blood cells are incubated with Tc-99m pertechnetate. The above Tc-99m red blood cells were compared to Tc-99m red blood cells produced in a similar manner except that centrifugation was used to separate the red blood cells from the plasma. Both preparations had a tagging efficiency of 98% or greater and rat distribution studies demonstrate that both preparations are equally stable as an in vivo intravascular agent.


Hepatic reticuloendothelial function in the sub-totally nephrectomized rat model of chronic uremia.

The chronic uremic condition was induced in male Wistar rats by long term maintenance of the animals following sequential sub-total and contralateral nephrectomies. Hepatic reticuloendothelial (RES) activity was estimated by non-invasive measurement of blood clearance rates and hepatic uptake of 99Tcm sulfur colloid administered intravenously. The blood half-time, and the blood clearance rate constants for normals and chronic uremics were 78 +/- 10 s and 49.5 +/- 5 s, and 7.51 +/- 1.04 x 10(-3) s-1 and 10.81 +/- 1.17 x 10(-3) s-1 respectively. The normal hepatic uptake rate constant was 9.03 +/- 1.25 x 10(-3) s-1, compared with a uremic uptake rate constant of 14.34 +/- 1.51 s-1. Measurement of total liver radioactivity upon termination, 15 min after injection, showed significantly increased total uptake in uremia, whereas no change in spleen radioactivity was observed. The clinical implications of these data are discussed.


Uptake of 67Ga-6-mercaptopurines in Morris hepatoma-3924 A.

67Ga-chloro-6-mercaptopurine and 67Ga-citrato-6-mercaptopurine complexes have been prepared and their distribution in Morris-hepatoma-3924 A-bearing rats studied. The tumour affinity of the gallium-67 compounds varies in the order: 67Ga-chloro-6-mercaptopurine greater than 67Ga-citrato-6-mercaptopurine greater than 67Ga-citrate greater than 67Ga-chloride.


Quantitative organ-uptake measurement with a gamma camera.

A study was carried out to investigate the use of a gamma camera for quantitative measurement of the absolute radioactivity in internal organs. Phantoms simulating different patient conditions were used to derive the attenuation correction factor and the conversion factor which relates a known radioactive dose to organ activity. The delimitation of the source image was established by means of an isocontour of maximum count rate. A mathematical approach was used for achievement of isosensitivity with depth of the organ and for correction for background. The accuracy of the procedure was proven by the recovery over the stomach area of the ingested activity. The method is applied to the quantitative assessment of the splenic red-cell volume.


The role of lysosomal enzyme activity in the localization of 67 gallium citrate.

The distribution of 67Ga citrate at 24 h post injection has been studied in the normal tissues of the mouse, rat and dog; 13 transplantable mouse tumours and 7 rat tumours have also been examined. The total activities of four lysosomal enzymes, aryl sulphatase, beta-glucuronidase, acid phosphatase and cathepsin-D were measured as well as the incorporation of thymidine-3H and leucine-14C ad indicators of DNA and protein synthesis. The results show a close correlation between 67Ga uptake and lysosomal enzyme activity in the tumours studied, which is an extension of the same relationship for normal tissues. It is suggested that the reported correlation between the uptake of 67Ga and the rate of cellular proliferation is secondary to the primary function of the lysosome in the localisation of the nuclide, lysosomal enzyme activity also being enhanced in situations of increased metabolic activity. A similar relationship appears to occur following administration of 111IN-Bleomycin and 99mTc-Citrate.


The mechanism of the localization of 67gallium citrate in experimental abscesses.

67Ga accumulation in turpentine-induced abscesses, from 5 h to 20 days old, in the rat has been investigated, and the results indicate that this is dependent on polymorphonuclear leukocyte (PMN) infiltration of the inflamed site. 67Ga concentration 24 h after injection correlates well with the activities of the lysosomal enzymes, aryl sulphatase and beta-glucuronidase, P less than 0.001, and with the DNA content of the tissue. There is no direct relationship with the rate of DNA synthesis. The mechanism of lysosomal incorporation into PMNs is consistent with the factors involved in 67Ga uptake into tumours and normal tissues.


The urinary excretion of gallium-67 citrate in patients with neoplastic disease.

The urinary excretion of gallium-67 has been studied in twenty-nine patients with considerable variation, ranging from 2.71 to 35.21 per cent of the injected dose in the first twenty-four hours. The data was analyzed to determine whether differences in excretion could be related to sex, age, plasma level, site or extent of disease but no significant relation could be found. While chemotherapy or radiotherapy has been shown to affect both the plasma clearance and protein binding they have no influence upon the urinary excretion of the isotope in this study. This study shows that all patients with high urinary excretion had bone metastasis from various types of primary tumour. Not all patients with bone metastasis have high urinary excretion of gallium-67. It would appear, however, from our limited series that patients with bone metastasis and normal urinary excretion of gallium-67 show a good response to treatment.


Tumour uptake of thallium-201 chloride.

The uptake of 201Tl-chloride in tumours has recently been investigated in several authors' laboratories. We are reporting studies on the uptake in malignant melanoma in mice. Generally, we confirm the published data qualitatively in finding higher uptake in tumour than in muscles. We confirm the rapid blood clearance and high kidney concentration, but we did not measure the myocardial uptake. We observed the concentrations in kidney muscle and tumour to rise during the first four hours while that in the liver fell from one hour onwards. We did not observe markedly higher uptake in melanin rich tumour than in other tumours.


Semi-quantitative interpretation of the bone scan in metabolic bone disease: definition and validation of the metabolic index.

Certain easily recognisable features are commonly seen in the bone scans of patients with metabolic bone disorders. Seven such features have been numerically graded by three independent observers in the scans of 100 patients with metabolic bone disease and of 50 control subjects. The total score for each patient is defined as the metabolic index. The mean metabolic index for each group of patients with metabolic bone disease is significantly greater than that for the control group (P less than 0.001).


Radioisotope X-ray fluorescence technique in the study of joint inflammation.

An X-ray fluorescence technique was employed to study the clearance rate from the knee joint of an intraarticularly injected stable tracer. Clearance curves, determined in two normal volunteers and in three patients with various articular diseases, were found to be of the monoexponential type in agreement with results obtained by authors employing radioactive tracers. Clearance half-time values in basal conditions were higher in the normal knee joint than in the inflamed knee joint. The effect of a corticosteroid suspension injected into the knee joint was also studied. Preliminary results obtained indicate that the X-ray fluorescence technique can be employed, with some advantages compared with the radiotracer technique, for quantitative determination of spontaneous or pharmacologically induced changes in joint inflammation.


Principal components analysis as an aid to classification of renal dynamic studies.

Four hundred renal dynamic studies obtained using 99mTc-(Sn) DTPA were classified clinically into four classes (normal, pre-renal lesion, intrarenal lesion and urinary tract obstruction). Principal components analysis was then applied to the kidney activity/time curves and yielded good class separation using only three components. The separation of normal and obstructed or damaged kidneys using only the first component was better than that obtained using the calculated mean transit time.


Iatrogenic and transient hyperglycinemia in patients with phenylketonuria.

Two patients with phenylketonuria detected by newborn screening for inborn errors of metabolism were treated with low phenylanine formulae. Serum phenylalanine levels were well controlled, but serum glycine levels were elevated until 4 or 5 months of age. This was probable due to the high content of glycine in the formulae. Glycine level returned to be normal in these patients, even though they were kept on the same formula, suggesting, immature metabolism of glycine during this period. No clinical problems were encountered in either patient.


Reduction of adult height in tall girls.

Assessment of the results of treatment of tall girls with estrogens by comparing actual mature height with predicted mature height is unreliable, unless the accuracy of prediction has been tested in untreated tall girls. We report such an investigation in 14 tall girls who were treated with estrogens and in 14 untreated tall girls. Of the three prediction methods, those of Bayley and Tanner were reliable in our hands, whereas the method of Roche was less adequate. The mean reduction of height by treatment was about 7 cm using Tanner's method of prediction, 10 cm when Bayley's method was used. The standard deviation of the difference between actual and predicted height as found in untreated girls makes it hazardous to assess the amount of height reduction in the individual treated case with any certainty.


Neuroblastoma with a fulminant clinical course caused by tumor embolism.

The case of a 2 1/2-year-old girl with a well-nigh asymptomatic neuroblastoma of the left adrenal is described. In the final stage it gave rise to unusual clinical signs. The tumor had grown into the inferior vena cava via the left suprarenal and renal veins. Dissolution of the soft tumor mass in the vena cava caused fatal massive embolism of lungs and brain.


Plasma progesterone in the respiratory distress syndrome.

Seventeen newborns suffering from RDS (verified by X-ray and clinical parameters) had a mean plasma progesterone of 13.9 +/- 1.2 ng/ml (mean +/- S.E.) at 24h of age. This is only 62% of the normal level (22.6 +/- 1.5 ng/ml).


A case of biotin-responsive 3-methylcrotonylglycin- and 3-hydroxyisovaleric aciduria.

During selective screening for organic acidurias, a 10-week-old girl with muscular hypotonia and recurrent fits was shown to be excreting 3-methylcrotonylglycin and 3-hydroxyisovaleric acid. Besides these metabolites of leucine the presence of small but pathological amounts of propionic and methylcitric acids were demonstrable in her urine, pointing to a defect in the metabolism of biotin. On treatment with biotin (2 x 5 mg/day) the convulsions stopped at once, her clinical condition improved gradually, and the abnormal metabolites disappeared from the urine. Within 6 weeks the child was discharged in a good general condition without apparent signs of neurological damage.


Rheumatoid arthritis during the first year of life. A case report and review of the literature.

A 20-week-old female, first examined at 14 weeks of age for daily "spiking" fever and skin rash, subsequently developed signs of rheumatoid arthritis. The onset of rheumatoid arthritis during the first weeks of life is rare and its diagnosis may be difficult. It seems that onset during the later months of the first year is more frequently encountered. A review of the relevant publications in English disclosed that onset during first year was noticed in 1.02 percent of the patients, while in a study from Germany 6 to 9.9 percent of cases started during their first year.


Unusual roentgenographic presentation of a congenital cystic malformation of the lung.

We describe here an infant with a large, solitary, fluid-filled lung cyst and hyperinflation of adjacent lung tissue in the same lobe. The combination of a fluid-filled cyst and ectatic emphysema in the same lobe suggests bronchial collapse and airway obstruction as a contributory mechanism for this unusual roentgenographic presentation of a congenital cystic malformation of the lung.


Gastric function and absorption of vitamin B12 in children with celiac disease.

Gastric acid secretion in nineteen children with celiac disease remained almost unchanged and the level of fasting serum gastrin was comparable with that of a control group of the same age. The absorption of vitamin B12 was significantly decreased, most clearly in the infants with celiac disease as compared with their controls. The serum B12 level, however, was decreased only in the oldest children. The results suggest that the mucosal lesion in the small intestine is most extensive in the youngest children, but the absorption defect of vitamin B12 becomes clinically significant only after a long duration of the disease and not in childhood.


Oculo-neural involvement in an enzymatically proven case of Niemann-Pick disease type B.

Niemann-Pick disease type B was diagnosed clinically and enzymatically in a 4 years old girl presenting with hepatosplenomegaly, diffuse interstitial infiltrations of both lungs on chest roentgenograms, and foam cells in the bone marrow aspirate. Intelligence and neurological examinations were normal. Spingomyelinase activity was almost totally deficient in leukocytes and cultured skin fibroblasts. Unexpectedly, fundoscopy revealed oculo-neural involvement with a reddish-brown spot of the macula comparable to but differing in some respects from the classic cherry-red spot found in neurolipidoses. By definition patients with type B Niemann-Pick disease should have no cerebral or oculo-neural involvement. Two comparable cases have been described in the literature. The prognosis of this special type is not yet known. For classification--and especially for genetic counselling--it seems important to include the possibility of oculo-neural involvement in the diagnosis of Niemann-Pick disease type B.


Transient hypothyroidism associated with prematurity, sepsis, and respiratory distress.

Serial TSH and T4 determinations were performed in sixty neonates admitted to our hospital for neonatal intensive care within a period of three months. Seven patients (12%) showed transient hypothyroidism on the basis of low T4 and high TSH values. Only one of these patients, who had meconium aspiration and pneumonia, did not have the respiratory distress syndrome. In addition, 4 of these patients had sepsis. All of the patients were born before 37 gestational weeks and had birth weights under 2200 g. In addition, two patients of this gestational age and birth weight group had a progressive fall of T4 to extremely hypothyroid values without simultaneous elevation of TSH. Two of the 5 patients who died had histological studies of their thyroids. These revealed colloid-depleted vesicles, desquamated epithelium, and prominent vascularisation of the thyroid. The results of this study show that early recognition and therapy of transient hypothyroidism may be live saving.


Pathological and immunological observations in a case of Lesch-Nyhan-syndrome.

A patient with clearly developed features of the full Lesch-Nyhan syndrome and complete lack of activity of hypoxynthine-phosphoribosyltransferase is described. The clinical picture was characterized by absence of spasticity, good control of autoaggression by behavior therapy, and no signs of renal insufficiency. After death, which was caused by a viral infection, pathological examination and a search for material immunologically cross-reacting with hypoxanthine-phosphoribosyltransferase were possible. In spite of increased serum urate levels and raised urinary uric acid excretion there were no signs of urate deposits or damage in the internal organs, including the kidneys. Crossreactive material was found in the liver, kidneys and spleen, a relatively rare finding in the full Lesch-Nyhan-syndrome. The absence of any specific pathological changes in the brain of this patient is in agreement with earlier reports.


Amylase isoenzymes in mumps.

The amylase isoenzymes activities in serum and urine from 75 children treated for complications of mumps were evaluated. The clinical observations, especially in cases with suspected pancreatitis, were compared with the P- and S-type amylase activities. Increased total activity of serum amylase in 79% of patients was due to increased S-type amylase. However, in 39% of patients there was also a markedly increased P-type serum amylase. Amylase isoenzymes may offer a new insights into the relationship between the pancreas and the parotid glands in mumps.


Congenital absence of the pulmonary valve associated with imperforate membrane type of tricuspid atresia, right ventricular tensor apparatus and intact ventricular septum: a curious developmental complex.

We have presented the unique clinical and morphological features of 3 patients with an imperforate tricuspid valve and right ventricular tensor apparatus. Thus, despite valve tissue and apparatus, there was not a perforate atrioventricular connection. This most uncommon type of tricuspid atresia' was associated in all 3 cases with a congenitally absent pulmonary valve, an underdeveloped right ventricle, and a curious distortion of the ventricular septum. Indeed, 2 of these patients demonstrated severe disproportionate ventricular septal thickening, although histopathologic examination did not substantiate those features usually associated with a hypertrophic cardiomyopathy. Rather, microscopic examination revealed a sinusoidal malformation consisting of normal myocardial cells separated by branching ethothelial-lined channels which communicated with the right ventricular cavity. In addition, gross examination of these 3 specimens revealed an abnormally persistent right venous valve in 2, which subdivided the right atrium. Finally, these cases provide further evidence that the term 'tricuspid atresia' oversimplifies the observed morphological features.


2:1 and phase 4 peri-infarction block.

A patient with acute inferior and anteroseptal myocardial infarction initially developed a 2 : 1 AV block with alternate conducted ventricular complexes showing aberrancy, and later Wenckebach-type, 2nd-degree AV block with aberrancy of the beats following a long diastolic pause. Intracavitary recording suggested that aberrancy was related to an intraventricular block. ECG and VCG recordings excluded the site of block as being in the main bundles or in the fascicles of the left bundle. The patient therefore showed evidence for a 2 : 1 and later a phase 4 peripheral block, defined also as a peri-infarction block because of the underlying etiology of the block. The block could be localized in the posterior wall of the right ventricle, by the marked rightward and posterior orientation of the middle and terminal electrical forces evident in the vectorcardiogram.


Case report: left ventricular echinococcosis diagnosed by coronary cineangiography.

This report presents a case of echinococcosis of the left ventricle treated surgically with success. Coronary cineangiography showed a circular capillary blush. This supports the view that this sign might well prove to be pathognomonic of this condition, as has been recently pointed out in another similar case. The diagnostic value of coronary cineangiography in left ventricular echinococcosis is emphasized.


The therapeutic value of clonidine in patients with coronary heart disease.

11 coronary patients, 8 with mild hypertension, were treated with clonidine, at a dose of 75 micrograms b.i.d. per os for a week. The effect of the drug on coronary heart disease was assessed by means of a symptom-limited multistage exercise test on the cycloergometer. Clonidine was effective in reducing the exercise-induced increases in blood pressure (by 15.5 +/- 6.1%), the double product (by 34.8 +/- 20.8%) and the electrocardiographic ischemic changes. In 2/4 patients, effort related ventricular extrasystoles were reduced by greater than 50% after clonidine. The drug worsened the anginal pain in 3 and relieved the pain in 3 patients. However, it reduced the exercise-induced ST-T segment downsloping in 7 patients. The tolerance was good, since only 3/11 patients reported slight dry mouth, sedation and pyrosis. In view of the electrocardiographic effect, further studies with clonidine on myocardial ischemia should be performed.


Echocardiography in infective endocarditis. Lack of specificity in patients with valvular pathology.

59 patients with suspected infective endocarditis on a natural valve were studied by M-Mode echocardiography to determine the specificity of the ultrasonic technique in detecting valvular vegetations. All echocardiograms were read independently by two observers who were unaware of the final diagnosis. Among 40 patients who later proved not to have infective endocarditis, two (5%) were diagnosed by echocardiography as having either possible or probably vegetation by at least one observer. Both patients with a false positive diagnosis of vegetation had pre-existing valvular pathology, the presence of which greatly complicated the interpretation of the echocardiogram. Inter-observer disagreement occurred in 5 of the 59 studies (8.5%). The results of this study suggest that caution should be exerted in the echocardiographic diagnosis of vegetation in patients with pre-existing valvular pathology.


The interpretation of gross left axis deviation in the electrocardiogram.

In 94 patients with prominent left axis deviation, there was a marked disparity in the mean angles determined by the maximum magnitude of the deflections and that determined by areas. There was also considerable variation in the angle of the maximum vector in the frontal plane (frontal plane angle) and the angle of 50 msec vector in the frontal plane. Similar results were observed in 17 cases of ostium primum atrial septal defect. These differences contrasted with the findings in a normal group of 50 subjects where a close correlation was found. The initial vector was directed to the right in approximately 80% of normals and 60% of the patients with LAD indicative of conduction defects in the left anterior fascicular or its distal ramifications. We conclude that a rightward orientation of the 5--10 msec vector (i.e. causing a Q wave in lead 1) should not be required for diagnosis of left anterior fascicular block. The spatial orientation of the initial vector was always anterior in the control subjects. In these 'normals', as well as in the patients with left axis deviation, the initial vector varied markedly in its azimuth direction (right or left) when superiorly directed; but when inferiorly directed in the normal subjects it was virtually always directed rightward. From these data we were unable to construct rigid criteria which would reliably distinguish aberrant excitation patterns manifested by gross left axis deviation in the electrocardiograms of patients with established heart disease from subjects without defined heart disease. Old infarction patterns, anterior, inferior, and lateral were not obscured by the associated anterior fascicular block.


Anomalous origin of the left anterior descending coronary artery from the pulmonary trunk.

An extremely rare congenital abnormality is reported in which the anterior descending branch of the left main coronary artery arises independently from the pulmonary trunk in a young patient who presented with unstable angina. Its clinical presentation, angiographic identification and surgical treatment are described. It appears to be a distinct entity with few of the features of the classical form of anomalous origin of the left main coronary artery.


Improved oral glucose tolerance following antiserotonin treatment in patients with chemical diabetes.

The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.


Plasma theophylline level and effect on lung function after oral and rectal administration of aminophylline.

Twelve patients with partly reversible, chronic airway obstruction, according to a double blind randomized cross-over design, received on three consecutive days oral aminophylline 500 mg, a 500 mg aminophylline suppository and a placebo. The effects on ventilatory function were studied and the plasma concentration of theophylline was measured. After rectal administration, the plasma concentration of theophylline rose to 5 to 10 microgram/ml, and after oral ingestion the plasma level in most patients exceeded 10 microgram/ml. Administration of the aminophylline suppository resulted in moderate improvement in ventilatory function, and although the improvement was less pronounced than after oral administration, the use of a suppository in the treatment of patients with chronic obstructive lung disease should not be rejected.