Sixteen years' experience of counselling, diagnosis, and prenatal detection in one genetic centre: progress, results, and problems.

The work of one Genetic Centre over 16 years, covering about 14 000 kinships, is described. The numbers registered in a year increased from an average of 477 in the early 1960s to 1612 in 1976/1977. The increase is largely, but not entirely, attributable to the advent of prenatal diagnosis, and an account is given of our experience with this. In 1916 patients who had a successful amniocentesis, results indicative of fetal abnormality were found in 4.3% and a balanced translocation was found in an additional 0.9%. Results indicative of fetal abnormality were found in 3.5% of mothers referred because of a maternal age of 40 or more, 3.9% referred because of a high risk of neural tube defect, and 19.3% referred because of a high risk of an inborn error of metabolism. A number of cases with difficult diagnostic problems are described.


Congenital haemolytic anaemia resulting from glucose phosphate isomerase deficiency: genetics, clinical picture, and prenatal diagnosis.

Glucose phosphate isomerase (GPI) deficiency with severe haemolysis and hydrops fetalis was found in the first child of unrelated, healthy Caucasian parents. The child died at 3 hours. Both parents were found to have 50% of normal red cell GPI activity and qualitative tests on their red cells and white cells showed that each was heterozygous for a different GPI variant allele associated with enzyme deficiency. Tests on the placenta showed that the propositus was a 'compound' heterozygote. Examination of amniotic cells obtained by amniocentesis on the mother at 28 weeks in her second pregnancy led to the prenatal diagnosis of GPI deficiency. This second child, a 'compound' heterozygote at the GPI locus indistinguishable from the first, was successfully treated by immediate exchange transfusion and subsequent blood transfusions.


Inherited anaemias in the Greek community of Cape Town.

Cape Town has a Greek community of about 5000, of whom approximately 75% originate from the island of Lesbos. In a survey of inherited haematological conditions in this population, 250 unrelated volunteers were investigated. The prevalence of heterozygous beta-thalassaemia was found to be 6.4%, with a gene frequency of 0.033. G6PD deficiency was detected in 10 males and it can be estimated that the prevalence in the male members of this population is 6.7%, with a gene frequency of 0.067. Hereditary spherocytosis was found in three respondents and this represents a prevalence of 1.2%, with a gene frequency of 0.006. One subject was heterozygous for the sickle cell trait (HbS) and another volunteer had haemoglobin Lepore, which had already been diagnosed in Greece. Our findings with respect to beta-thalassaemia and G6PD deficiency are similar to those reported from regions in Greece where malaria is not highly endemic.


Hepatitis--Bs antigen in an isolated Indian population of southern Venezuela: a family study.

A genetic analysis of the presence of HBsAg in a population of which 7.2% of the members were positive is presented. Though the ratios of carriers: non-carriers were generally in good agreement with expectation if the carrier state were determined by homozygosity for a single recessive gene, the two examples of mating most critical to a test of the hypothesis, carrier X carrier, yielded 2 normal children among 4 in one family, and one normal child, the only offspring, in the second family. Other investigators have reported similar findings. We conclude that the hypothesis of simple recessive inheritance cannot be sustained.


Studies in mice on the mutagenicity of two contraceptive drugs.

An experiment is described which tests for visible and invisible mutants in mice treated with four different doses each of the contraceptives Gynanovlar and Lyndiol. The results show that there is no reason to suppose that either substance has an appreciable mutagenic effect, expressed as an increase of antenatal and postnatal lethals or visibles. The substrain CBA/CagCam, used throughout, has an incidence of 0.27% of singly occurring abnormalities, mainly of the appendicular skeleton, which distinguishes it from the parent CBA strain and its axial variation described by Gruneberg (1963).


No increased chromosome breakage in three Bloom's syndrome heterozygotes.

The frequency of chromosome aberrations in the lymphocytes of three established heterozygotes for the Bloom's syndrome gene (ages 67, 57, 46) was compared to that in controls (ages 68, 67, 61, 46, 34). The main part of the study was done on coded slides. No difference was found between the heterozygotes and the control group, except for one control (aged 46) who had a significantly higher number of chromosome aberrations than the others.


X-mapping in man: evidence against measurable linkage between anhidrotic ectodermal dysplasia and G6PD deficiency.

A Sardinian kindred segregating for X-linked anhidrotic ectodermal dysplasia (AED), glucose-6-phosphate dehydrogenase (G6PD) deficiency of Mediterranean type, and Xga blood antigen provides evidence against a measurable linkage between the loci for AED and G6PD. Moreover, from the segregation of the combined phenotypes in four scorable sons from two triple heterozygotes with phase known, it seems highly probable that the AED locus is nearer to the centromere than is the G6PD locus.


Additional pedigree supporting the frequent origin of XXYY from consecutive meiotic non-disjunction in paternal gametogenesis.

A 48,XXYY Sardinian patient, born to a 46,XX mother heterozygous for the Gd Mediterranean mutant, and to a 46,XY father hemizygous for the same mutant, was found to have a mosaic distribution of G6PD(+) and G6PD(-) peripheral red blood cells. The most likely interpretation of this finding is that the propositus is an additional example of an XXYY zygote derived from a consecutive meiotic non-disjunction during paternal gametogenesis.


Trisomy 20p from maternal t(3;20) translocation.

A case of trisomy 20p resulting from a maternal translocation t(3;20) is described. QM and BUdR banding techniques were used for its identification. A round face with oblique palpebral fissures, strabismus, cardiac and vertebral abnormalities, mild psychomotor retardation, together with poor coordination and speech impediment, are the most typical features of the proband.


Triple mosaicism 45,XY,--18/46, XY/47,XY,+18.

A patient with symptoms clinically resembling Edwards's syndrome is presented. Cranial asymmetry, thoracic and lumbar hemivertebrae, and an additional rib were the unusual features. The cytogenetic studies revealed the coexistence of three separate cell lines with 45,XY,--18/46,XY/47,XY,+18 complement.


The Prader-Willi syndrome with a 15/3 translocation.

A de novo translocation of 15q to 3p with complete monosomy of 15p and partial monosomy of 15q was detected by trypsin banding on peripheral lymphocytes of a 5-year-old boy with Prader-Willi syndrome (severe mental retardation, dyslalia, cryptorchidism, and muscular hypotonia). The pathogenic role of chromosome 15 abnormalities in the aetiology of this syndrome is discussed.


Priorities of nutritional concepts assigned by health professionals and students.

Medical faculty, practicing physicians, medical students, and dietitians/nutritionists rated nutritional concepts as to their importance for inclusion in the medical school curricula and indicated the best method of accomplishing this. Ten concepts were rated "essential." They related to biochemical and physiological aspects of nutrition; nutrition in pregnancy, lactation, growth, development, maturity, and old age; nutritional management in disease; drug and diet interrelationships; and critiques of popular dietary regimens. Ranked as "important" were eight concepts regarding sources of nutrition information; evaluation of nutritional status; recommended dietary allowances; and food additives, naturally occurring food toxins, and nutrient composition of foods. Based on results of this study, the authors make recommendations regarding nutritional concepts that should be included in medical school curricula and how these concepts should be incorporated.


The house officer as a teacher: what schools expect and measure.

Teaching is generally regarded as an important function of the house officer not only from a practical viewpoint but also as an integral part of the training of a professional. A survey by the Association of American Medical Colleges shows, however, that unlike other competencies, the house officer's teaching is not explicitly evaluated in most graduate training programs. Furthermore, it appears that the teaching role itself is not always well defined. It is urged that, if the teaching role is regarded as an important element in graduate medical education, earlier and more gradual preparation of the medical student for that role is needed.


Medical student attitude toward seeking professional psychological help.

To explore the antecedents of emotional distress among physicians, the authors investigated the relationship between year in medical school and student attitude toward seeking professional psychological help. The sample consisted of 489 students at the University of Southern California School of Medicine. Since a cross-sectional approach was employed a classical regression analysis was used to control for possible differences in the variables of sex, age, contact with psychotherapy, and specialty choice. Differences in male and female responses prompted separate analyses. For women, no attitudinal changes were noted during medical school. For men, a significant positive change in attitude was noted between the students of years one and two, as compared with students of years three and four. Results were contrary to findings in the literature. Several possible explanations are discussed.


Teacher-student interaction in a medical clerkship.

Seventeen randomly selected clinical teaching sessions in a medical school clerkship were videotaped during a one-month period, including teaching rounds, working rounds, morning report sessions, lectures, patient management conferences, grand rounds, and journal clubs. Using a verbal behavior classification schedule, the investigators analyzed the videotapes in terms of the proportion of talking done by clerkship instructors, medical students, residents, and others. The nature of the verbal interaction was examined by assessing the proportion of time devoted to giving information versus asking questions. The proportions on these dimensions were further analyzed according to the cognitive level of the verbal interaction. The data suggest that the teaching observed was not optimal for promoting problem-solving ability, since students were placed in a very passive role in which they received a preponderance of low-level, factual information.


The magnitude of declining psychiatric career choice.

Previous studies are reviewed and new data are reported which document a decline in the percentage of American medical graduates choosing psychiatric careers. Data on absolute numbers are conflicting. While 7 percent of graduates from 1945 to 1964 and 6.4 percent of graduates from 1965 to 1970 chose psychiatry, only 5.3 percent of graduates of the classes of 1975 and 1976 did so. Available data for more recent medical classes indicate that further decrements will occur. Possible explanations and strategies for research are briefly outlines.


Reducing ward-clinic conflicts by rotational scheduling of house staff.

Many internal medicine residency training programs are being modified to permit each resident to gain more outpatient experience, including providing continuous care to a defined panel of patients for three years. Increasing emphasis on these outpatient responsibilities and education, however, places demands on the resident that conflict with his responsibilities on the inpatient wards. In this paper the authors describe the development and implementation of a rotational scheduling system aimed at substantially alleviating the conflict between inpatient and outpatient responsibilities. During the first year of operation 84 percent of house staff members indicated their preference for continuing the system in future years.


Teaching medical gerontology: utilization of a psychiatry consultation program.

This is a report of a pilot project designed to explore the feasibility of using the clinical Adult Service Psychiatry Consultation-Liaison Program at the University of Michigan as the locus for teaching medical gerontology to psychiatric and medical/surgical house officers and medical students. The goals, general techniques, educational content, and implementation procedures are described. Evidence was obtained that teaching medical gerontology through the program is both feasible and effective. Since a nonphysician gerontologist implemented the clinically based teaching program, the project is an example of the possibilities inherent in a multidisciplinary clinical teaching program.


Passive protection by human serum in mice infected with encapsulated Staphylococcus aureus.

The occurrence and nature of passive protective antibody in 100 samples of human serum was investigated in mice challenged with strains of Staphylococcus aureus capsular types A (Smith diffuse strain) and B (strain NS58D). Sixty of the sera passively protected mice against the capsular type-A strain, three against type B, and one against both types. Rabbit antisera against human IgG, IgA and IgM could remove the protective activity from a human serum of high potency, and the activity was also sensitive to 2-mercaptoethanol. Absorption with Smith surface antigen removed protective activity and reduced the concentration of IgG 7-fold, IgA 2.7 fold and of IgM 3-fold more than in a non-protective serum. Consequently, the protective activity of human serum is believed to be associated with antibodies to the S. aureus capsular antigen in the three immunoglobulin classes.


Inhibition by amoeba-specific antiserum and by cytochalasin B of the cytopathogenicity of Naegleria fowleri in mouse embryo-cell cultures.

Inhibitors of trophozoite motility and phagocytosis were used to investigate the mechanism of Naegleria fowleri cytopathogenicity in mouse-embryo (ME)-cell cultures. Amoebae that were immobilised and agglutinated by specific antiserum exhibited no cytopathic activity, although they remained alive and were in constant contact with the ME cells. Mammalian-cell damage occurred only when the organisms recovered pseudopodium function and began to migrate over the monolayers as they overcame the inhibitory effects of the antiserum. Cytochalasin B at a concentration of 10 microgram/ml, shown to prevent the engulfment of chick erythrocytes by amoebae, also inhibited the cytopathogenicity of Naegleria when incorporated in ME-cell culture medium. Despite repeated contact with active trophozoites, the ME cells showed only those morphological changes characteristically induced by cytochalasin B itself. The amoebae in turn showed signs of starvation after 3 or 4 days' incubation, suggesting that the feeding activity of trophozoites was suppressed. Colchicine, on the other hand, inhibited neither the ingestion of erythrocytes nor the destruction of ME cells by amoebae. It was concluded that the cytopathogenicity of N. fowleri in ME-cell cultures was due to physical rather than biochemical or cytotoxic mechanisms and was associated with the phagocytic activity of trophozoites.


Adherence of Enterobacteriaceae to human buccal cells.

A preliminary examination has been made of the adherencae isolated from sputa. The radioadherence method was found to correlate well with the conventional light-microscope adherence technique. Saturation of buccal-cell binding sites with bacteria occurred when less than 10% of the buccal-cell surface was occupied. The adherence of Enterobacter aerogenes to buccal cells was impaired by the prior adherence of bacilli of either the same strain, or of a strain of Klebsiella pneumoniae.


Electron microscopy of Campylobacter jejuni.

Stools from 56 patients with gastroenteritis were cultured for Campylobacter jejuni. The five strains isolated were examined by electron microscopy. The campylobacter cells were pleomorphic and most displayed appearances similar to those of V. fetus. Morphological changes were observed in cultures subjected to prolonged incubation.


A mathematical model of proximal tubule absorption.

A previous model of the mechanisms of flow through epithelia was modified and extended to include hydrostatic and osmotic pressures in the cells and in the peritubular capillaries. The differential equations for flow and concentration in each region of the proximal tubule were derived. The equations were solved numerically by a finite difference method. The principal conclusions are: (i) Cell NaCl concentration remains essentially isotonic over the pressure variations considered; (ii) channel NaCl concentration varies only a few mosmol from isotonicity, and the hydrostatic and osmotic pressure differences across the cell wall are of the same order of magnitude; (iii) both reabsorbate osmolality and pressure-induced flow are relatively insensitive to the geometry of the system; (iv) a strong equilibrating mechanism exists in the sensitivity of the reabsorbate osmolality to luminal osmolality; this mechanism is far more significant than any other parameter change.


Glycogen metabolism in the prelaid chick embryo.

Glycogen metabolism has been studied during the development of the early chick embryo, at the cytochemical and ultrastructural levels. Two waves of glycogen synthesis and breakdown have been found. In the first, free clusters of glycogen particles are synthesized at late oogenesis. These clusters are found later in invaginations of the membrane of vesicles containing a floccular material (FLOV). The glycogen clusters are degraded there during ovulation and the first hours in the oviduct. The second wave of glycogen synthesis begins before cleavage, reaching a maximum at mid-uterine age. This second wave occurs in another type of vesicle (GLYV), which eventually disintegrates releasing free clusters of glycogen granules. This glycogen is degraded in membranous structures containing a floccular material, as in the first wave of degradation. The degradation ends at the late uterine stages, and at the same time numerous ribosomes are formed. This period corresponds to area pellucida formation, which probably depends on the energy liberated during the second wave of glycogen degradation.


Environmental chemical carcinogens and liver cancer.

An appraisal is made of these chemical carcinogens available in the human environment that have been implicated in the etiology of liver cancer. The possible role of mycotoxins is discussed in detail, in particular the association between the aflatoxins and liver cancer in Africa and the Far East.


Distribution of glutamate in layers of the rabbit hippocampal fields CA1, CA3, and the dentate area.

The distribution of L-glutamic acid in single layers dissected from freeze-dried sections of the rabbit hippocampus was estimated by means of an enzymatic cycling procedure. Although the regional variation in glutamate content is less than that of other transmitter candidates, there were present significant differences in it between the projection fields of certain fiber connections. Glutamate concentration was highest in the termination areas of commissural fibers and Schaffer's collaterals.


Role of pesticides in hepatocarcinogenesis.

Pesticides are biologically active substances that are significant environmental contaminants. Only a few of the many pesticides have been subjected to short- or long-term carcinogenicity tests. To date, 16 of them have been identified as hepatocarcinogenic agents in animals, usually mice. However, their cancer-inducing effect in humans has not been completely proved. The use of short-term screening tests (first of all the Salmonella-microsome test) for routine screening of pesticides on a large scale is highly recommended. The herbicide 2,4,5-trichlorophenoxyethanol (TCPE) containing different amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was tested for carcinogenicity in Swiss mice. TCPE enhanced liver tumors in males but TCDD did not affect liver tumor incidence. The occurrence of liver tumors was shown to be dose-dependent. There was no correlation between the results of in vivo carcinogenicity studies and the induction of aryl hydrocarbon hydroxylase and biphenyl 2-hydroxylase activities.


Promotion of liver tumors by steroid hormones.

Corticosterone inhibits proliferation of rat liver cells, but it can be inactivated by blocking its cytoplasmic receptors in liver cells with other steroids (progesterone). High levels of progesterones in animals lead to stimulated proliferation in the liver. Abnormally high proliferation in the liver may promote malignant transformation or may make it possible for smaller amounts of hepatocarcinogenic substances to induce tumors in a shorter time than normal.


Mass spectrometric identification of Cu, Zn, Fe, Co, Mn, Mg, and Pb in mammalian brain.

Combining the techniques of thin-layer chromatography (TLC) and mass spectrometry, we unambiguously identified the trace metals Cu, Zn, Fe, Pb, Mn, Co, and Mg in the brain of a female human who had no evidence of any pathologic disease in the central nervous system, and in brains from mouse, rat, guinea pig, and rabbit. These trace metals were also found in anatomic regions of human brain: cortex (gray), cortex (white), caudate nucleus, putamen, hippocampus, and thalamus, and in anatomic regions of rat brain: hypothalamus, cerebellum, stem striatum, and "the rest." The metals were characterized from the color and Rf values of their tetraphenylporphyrin chelates on TLC and from the mass and pattern of molecule ion cluster of the mass spectrum. The unexpected presence of lead in the brain is discussed.


Soluble protein and peptide pattern from different regions of rat brain during pre- and early postnatal development.

Isotachophoretic pattern from phylogenetically different regions of rat brain during pre- and early postnatal development were studied. Four main observations were made: a) The patterns were greatly similar during maturation of the respective regions studied; b) One complex of peaks disappeared or decreased in quantity during the 2nd and 3rd weeks of postnatal development; c) New peaks appeared and accumulated during the same period; d) Slight differences were observable in the different regions studied.


Importance of hepatic neoplasms in lower vertebrate animals as a tool in cancer research.

Hepatic tumors were induced in medakas (Oryzias latipes) by the addition of diethylnitrosamine (DEN) to their aquarium water. Medakas are useful for study because they are highly susceptible to the carcinogenic effect of DEN and the time for tumor induction is relatively short. Tumors had a histological pattern similar to that of mammalian hepatic tumors. The medaka seems to be susceptible to water-soluble carcinogens.


Relative normophagia and organ growth in growth-retarded weanling rats with dorsomedial hypothalamic lesions.

Weanling rats with ventromedial (VMNL) and dorsomedial (DMNL) hypothalamic lesions and sham-operated controls were maintained up to 198 days after operation. Food intake was measured throughout the experiment and organ weights were recorded at various periods of sacrifice. Comparisons were made between controls and VMNL and DMNL rats, respectively. Food intake and organ weights were expressed in absolute terms and relative to body mass and Kleiber's "metabolic size." VMNL rats were always normophagic and showed lower organ weights, regardless of manner of computation. Rats with DMNL, on the other hand, were absolutely hypophagic but relatively normophagic for considerable periods of time when food intake was referred to body mass. A similar relationship obtained for organ weights. The data fit well with previous results and with a hypothesis that holds that DMNL bring about a "resetting" of some central nervous control system that not only allows the rat so operated to subsist on lower substrate levels but also regulates normal growth in relation to body mass.


Effect of steroid hormones on liver cells in culture.

A variety of liver and hepatoma cell lines were incubated in the presence of corticosterone. DNA synthesis was inhibited in some but not all cell lines. One of them, the Fu 5a clone of the Reuber hepatoma cell line, was subjected to corticosterone for 48 h. Incorporation of labeled thymidine into DNA was inhibited up to 10%. Afterward, corticosterone was removed. DNA synthesis then increased 16-fold relative to controls. It was concluded that corticosterone blocks these cells in late G1 phase of the cell cycle and thus leads to synchronization.


Mesencephalic lesions in female rats resulting in normophagia and reduced body weight.

The effects of bilateral mescencephalic lesions in the area of the ventral noradrenergic bundle (VNA) were studied in immature and mature female rats. The food intake consumption of the immature lesioned rats did not differ from sham operated controls whether fed a chow or high fat diet. However, after the surgery the body weights of the two groups began to diverge with the immature lesioned rats obtaining a significantly lower body weight. By the end of the study the immature lesioned rats were also significantly shorter than the controls. Both groups showed normal body composition throughout the measurement period. Upon refeeding after a one day fast the immature female rats defended their lower than normal pre-fast body weight. These data are in good agreement with our earlier findings using immature male rats. The mature lesioned animals also showed normal food consumption when fed a chow type diet. However the lesioned animals did show a brief hyperphagia when placed on a high fat diet. Unlike the immature lesioned rats the body weight of these lesioned animals did not differ from their sham operated controls. It is suggested that lesions in the area of the VNA may result in hyperphagia or, in no effects on food intake or body weight as reported by others or normophagia with reduced body weight. Exact lesion placement may be responsible for these divergent findings.


Effects of the lateral septum and latent inhibition on successive discrimination learning.

Damage to the lateral nucleus of the septum in the rat resulted in atypical learning to a previously meaningless stimulus. Nonreinforced preexposure to a stimulus normally makes more difficult subsequent use of that stimulus for learning. The effect of this preexposure on learning is termed latent inhibition and was demonstrated in sham operated animals. Rats in which the lateral septum was damaged demonstrated a paradoxically smaller learning deficit in the presence of a conditioned stimulus that was previously presented without reinforcement, when compared to the performance of both septal lesioned rats no receiving nonreinforced preexposure and sham operates receiving preexposure. The interaction of nonreinforced preexposure and lateral septal lesions can be explained using a proposed sensitization hypothesis.


Effects of anoxia and depolarization on the movement of carbon atoms derived from glucose into macromolecular fractions in rat brain slices.

Incorporation of U-14C-glucose into macromolecules (lipid, protein and nucleic acid fractions) of rat brain cortex slices was studied in vitro under conditions of anoxia and reoxygenation. Additionally, the influence of depolarization on control and postanoxic U-14C-glucose metabolism was investigated. Postassium-induced depolarization of the slices lowered their capacity to incorporate 14 from U-14C glucose into proteins and nucleic acids without any changes in the labeling the lipids. Fifteen and 30 minutes of anoxia depressed the rate of 14C incorporation into each of the above macromolecules was partly restored compared to the control. Excess of potassium in the medium during the reoxygenation period inhibited restoration of the synthetic capacity of the slices execpt lipids, into which incorporation of 14C was even stimulated under depolarizing conditions. The influence of anoxia and depolarization were investigated also in different classes of lipids and proteins. 14C incorporation into SDS-extractable and residual proteins and phospholipid fraction containing phosphoinositol was closest to the control during reoxygenation which suggests the relatively highest resistance of these fractions of anoxia.


High-energy phosphate compounds and some glycolytic substrates in the rat brain during hypoxia.

The influence of acute and prolonged (with resuscitation) hypoxia, upon some glycolytic substrates and high energy phosphate compounds in the rat brain, was studies. Acute hypoxia decreased the content of glucose and glucose-6-phosphate as well as of high energy phosphate compounds. Stimultaneously, an increase of lactic level was recorded. Some adaptation features could be observed, when 30-minute hypoxia with resuscitation was studied. Brain content of high energy compounds returned to the normal value, while that of glucose increased twice over control. However, the level of lactic acid was still increased.


A model of GABA transport by cortical synaptosomes from the Long-Evans rat.

The initial velocity of uptake of GABA by cortical synaptosomes from the Long-Evans rat has been measured as a function of both sodium and GABA concentration. These data were then fitted to the rate equation for each of several possible models, and the models giving least error were identified. Although one cannot unequivocally distinguish between two of the models on the basis of the goodness of fit, deductions based on the fits of subsets of the models point to one of the two models, The major predictions from this model are as follows: 1) Uptake of GABA is totally sodium-dependent. 2) Although plots of 1/v versus 1/[Na]2 are nonlinear, the coupling ratio for transport (Na/GABA) is 2. 3) For transport to take place, the order of combination with carrier must be Na, Na, GABA. 4) Maximal velocity will occur only at infinite Na and GABA concentrations. 5) There is a sigmoidal relationship between apparent maximal velocity (Va) and [Na]. 6) Kt, the [GABA] that gives a velocity equal to Va/2, rises and then falls as [Na] is increased from zero, passing through a maximum at 33.52 mM [Na]. 7) The relationship between initial velocity and [Na] is sigmoidal. 8) Jm, rate of uptake with infinite [Na], is hyperbolically related to [GABA]; Jm approaches Vmax as [GABA] becomes very large. 9) kappa Na, the [Na] giving a velocity equal to Jm/2, declines rapidly from 10(-7) M to 10(-5)M GABA, but is essentially constant at 10(-4)M above. 10) One GABA molecule is translocated per carrier molecule. The model is consistent with observations in the literature concerning the effects of sodium on the kinetics of transport.


Cerebral amino acid levels and uptake in rats after portocaval anastomosis: I. Regional studies in vitro.

Uptake of various amino acids was studied in slices from brain regions of rats four weeks after portocaval anastomosis. No differences of the inulin compartment were observed between control and experimental animals. After 60-minutes incubation, uptake showed an overall pattern of diminution. This was more evident for some amino acids: valine, methionine, and lysine exhibited a lowering of about 30%, which was fairly uniform in the four tested regions; others showed a regional decrease-- alanine in pons-medulla, phenylalanine in cerebellum, histidine and GABA in mesodiencephalon. This decrease did not seen to be related to transport classes. The restricted entry of amino acids into brain cells in portocaval encephalopathy is somewhat difficult to explain; a decreased rate of protein synthesis may be of some importance, but other factors, such as a "carrier" impairment, effects on release and on amino acid metabolism, may also be involved.


Cerebral amino acid levels and uptake in rats after portocaval anastomosis: II. Regional studies in vivo.

Amino acid levels have been determined in plasma and in four cerebral regions of rats one month after portocaval shunt. Many plasma amino acids are significantly lowered (asparagine, glutamine, theonine, serine, alanine, valine, leucine, isoleucine, cystine, lysine), while others remain unchanged (taurine, glycine, proline, tryptophan, ornithine, histidine, arginine). Asparagine and glutamine levels are significantly higher than in normal rats, and a net increase of tyrosine (100%), phenylalanine (50%) and citrulline (50%) is evident. In the shunted rat brain the most prominent feature is a very large rise (up to fivefold) of tyrosine, phenylalanine, histidine, citrulline, tryptophan, and glutamine uniformly in the tested regions. Other neutral amino acids are slightly increased. Lysine and arginine are decreased in cerebellum and pons-medulla; taurine, in forebrain and cerebellum. Cerebral permeability to L-amino acids was studied in vivo. Neutral amino acid permeability is greatly increased, whereas basic amino acids show a net decrease in their rate of passage from blood to the brain. No changes are observed for GABA and glutamic acid. These data suggest an altered permeability of the cerebral capillary membranes, which seems to be selective for the different amino acid transport classes. Competitive inhibition experiments demonstrated that the increased brain permeability to neutral amino acids after portocaval shunt is due to an enhancement of the saturable transport. The sharp rise in the brain of some essential neutral amino acids (phenylalanine, tyrosine, trytophan, histidine), largely exceeding their changes in plasma, and the slight cerebral increase of other neutral amino acids despite their lowered level and the rise of competing amino acids in the plasma, is consistent with our observation of enhanced transport for the neutral class. In hepatic encephalopathy, correction of the altered plasma amino acid levels has been reported to improve the clinical status. If this result is connected to the concomitant correction of the brain amino acid levels, carefully selected competitive inhibition among various plasma amino acids could be a useful therapeutic tool in this pathologic condition. However, the increased activity of the neutral amino acid transport system adds a new factor to the problem, since it probably implies that the competing amino acids will accumulate to unphysiological levels in the brain.


Accidental injury in childhood: a literature review on pediatric trauma.

This article reviews the literature on accidental injury in childhood, summarizing incidence rates and outlining the factors which have been cited as affecting pediatric trauma: the host, the agents, and the environment. During childhood, age and sex differences for rates of accidental injury are frequently reported. Vehicular accidents, falls, drownings, burns, and ingestions are found to be common agents of injury to pediatric patients. The home affords a virtual breeding ground for accidents to children; however, parents also play an important role in the child's environment, with their illnesses, preoccupations, or dispositions to (in)action having consequences which may eventuate in injury.


Quality of life after major burns.

The only presently available method of measuring the outcome of major burns is the mortality rate. We have developed a scale, administered by interview and physical examination, with which the quality of life in survivors may be measured. In an initial group of 32 patients, we took each patient's own preinjury level of performance as a baseline. The size of the burn had no significant effect on the postburn score achieved. Substantial numbers of patients achieved levels superior to their preburn score. Improvement in scores did not begin until 12 months had elapsed from the time of injury. We feel that scales such as this will help determine what happens to patients after their injury, pinpoint areas of weaknesses in the burn program, and enable better comparison of performance between clinical facilities.


Superior mesenteric artery syndrome in thermally injured patients.

In a 12-year period, 37 of 3,536 burn patients developed acute obstruction of the duodenum by the superior mesenteric artery. Nasogastric decompression and intravenous fluids were required initially in all 37 patients. Twelve patients received no further therapy, with resolution of the obstruction in six and death of the other six from burn wound sepsis or pneumonia. Ten patients underwent operative treatment consisting of either duodenojejunostomy (eight) or vagotomy and gastroenterostomy (two), with resolution in seven and three postoperative deaths. Fifteen patients were treated with intravenous hyperalimentation and gastric decompression, with resolution in 12 patients, one required operative intervention, and two died of complications. A high degree of suspicion followed by prompt diagnosis and treatment of the SMA syndrome are required in all critically ill patients with unexplained bilious vomiting. Gastric decompression coupled with aggressive use of intravenous hyperalimentation recently has reduced the need for operative treatment (42% versus 11%).


Posterior fracture-dislocation of the hip: an epidemiologic review.

A retrospective study of 46 posterior fracture-dislocations of the hip showed that reduction of the dislocation within 24 hours was the most important initial treatment. Open reduction and fixation of the fracture could be delayed up to 4 weeks to allow associated injuries to be treated, and this technique was indicated to remove intra-articular bone fragments or for residual instability. Long-term disability resulted in every patient, regardless of the severity of the initial injury or the method of treatment. Half of the patients never returned to work. Of the 46 patients 43 were unrestrained occupants in vehicular accidents. Multiple injury occurred in 75% of the patients.


Subtrochanteric fractures of the femur: a review of 130 patients.

A review of 130 patients with subtrochanteric fractures of the femur has led to a new classification based upon fracture pattern. Type I is a short oblique, Type II a long oblique, and Type III any comminuted fracture of the subtrochanteric area. Twenty-two patients were treated with traction and 108 patients treated by surgical operation. Stable fractures treated in skin traction did well and extensively comminuted fractures appeared to be best treated with 90-90 skeletal traction. In the Type I and Type II fractures, it was determined that these fracture patterns were stable and any strong nail-plate device will provide adequate fixation. The Type III fracture may be converted to Type I or Type II by lag screw fixation and then fixed accordingly but if stability cannot be obtained by this method, a sliding screw type of device appeared to offer the best fixation. Supplementary bone graft where necessary to restore the medial buttress offered singularly better healing. Delayed weight bearing until fracture healing was secure gave the best chance of primary bone healing without deformity.


Fractures of the distal tibial metaphysis with intra-articular extension--the distal tibial explosion fracture.

In a study of 26 distal tibial explosion fractures in 24 patients two fracture patterns were identified: Type A, a rotational pattern; and Type B, a compressive fracture pattern. The rotational pattern was found to be less common than the compressive fracture and to have a substantially better prognosis. Operative treatment of the Type A pattern led to an overall acceptable result of 84%, while the Type B patients had 53% acceptable results. The results of operative treatment were however, superior to the results of nonoperative treatment in both fracture groups. Adequate treatment consists of anatomic reconstruction of the distal tibia, rigid internal fixation, early active motion, and nonweight bearing in 3 to 5 months.


Management of portal vein injuries.

Injuries to the portal vein are associated with a high mortality because of a high incidence of concomitant injury to surrounding structures and refractory shock. Repair of the portal vein injury is often difficult or impossible because of massive hemorrhage. The key to successful management of a portal vein injury is rapid blood volume resuscitation and obtaining rapid and adequate exposure. The optimal exposure for repair consists of reflection of the hepatic flexure of the colon with mobilization of the root of the mesentery, pancreas, and duodenum. Lateral venorrhaphy is the preferred method of management, but in hemodynamically unstable patients, ligation of the portal vein is an acceptable method of treatment.


Correlations between metabolic and cardiopulmonary measurements in patients after trauma, general surgery, and sepsis.

Simultaneous longitudinal hormonometabolic-physiologic (cardiopulmonary) profiles were measured in 14 nonseptic trauma/general surgery (T/GS) patients and in ten patients with Gram-negative abdominal surgical sepsis. The physiologic state classification system was used as the frame of reference. There were no response differences between the T and GS groups: they had A State responses. The sepsis (S) patients initially had exaggerated A State responses with significant changes in glucose, fat, amino acid, and glucagon plasma levels relative to T/GS. The S patients who survived (four) demonstrated profiles as in T/GS. The S patients who expired (six) progressively evolved an unbalanced, hyperdynamic B State response with progressive elevations of glucose, lactate, aromatic and branched-chain amino acids and glucagon, and low ketone bodies. There is definite correlation over time between metabolic and physiologic responses; the physiologic responses reflect the metabolic responses; the metabolic responses are consistent with a peripheral energy-fuel deficit.


Cervical osteomyelitis complicating transpharyngeal gunshot wounds to the neck.

Four cases of cervical osteomyelitis complicating transpharyngeal gunshot wounds to the neck are discussed. Thorough debridement of bone and soft tissue, adequate drainage, broad-spectrum antibiotics, and rigid immobilization of the cervical spine are essential for the successful treatment of this complication. Inadequate or delayed treatment may result in prolonged hospitalization, the need for multiple surgical procedures, and possible neurologic deficits.


Complete disruption of axillary artery caused by severe atherosclerosis and trivial nonpenetrating trauma.

Complete disruption of the axillary artery related to relatively trivial nonpenetrating trauma in a 67-year-old male is reported. The injury occurred in relation to severe circumferential atherosclerosis of the vessel. Successful revascularization was accomplished with salvage of the extremity and normal function.


Salmonella gastroenteritis in Hong Kong--a clinical review of 200 patients.

A sudden increase in Salmonella gastroenteritis affecting infants and children in Hong Kong in 1971 prompted a clinical review of 200 such patients seen over a 6 year period. It showed unprecedented prevalence of Salmonella johannesburg infections and unusually protracted diarrhoea. Only 3.5 per cent of patients were breast fed. Factors causing this chronicity are discussed. All 8 fatal cases were under 7 1/2 months old, with protracted diarrhoea starting within 1 month after birth in 7. The invasiveness of Salmonella johannesburg is low although its infectivity high. Bacteraemia occurred in only 1 patient and focal infections other than gastroenteritis in none. Antibiotics did not improve diarrhoea nor eliminate faecal excretion in the majority of those treated. Prolonged and intermittent faecal excretion of Salmonella was common. Nineteen per cent of patients acquired diarrhoea in hospital; some after a course of antibiotics given for other infections. Experience from this series does not recommend administration of antibiotics to patients with uncomplicated Salmonella johannesburg gastroenteritis. As chronicity of diarrhoea seemed to be the major prognostic factor with regard to mortality and morbidity in this series, further search for causes and control measures of this chronicity is required.


A school survey of tinea capitis in Benghazi, Libya.

A school survey of Tinea capitis in Benghazi revealed an incidence of 4.49 per cent. The commonest clinical type which accounted for 87.7 per cent of the cases, resembled Seborrhoea capitis more than with any classical type described so far. T. schoenleinii and T. violaeceum were the most frequent isolates.


Evaluation of the tuberculin sensitivity test in a healthy Sudanese population.

Three-hundred and seventeen healthy individuals were investigated on a volunteer basis for tuberculin sensitivity using the dual-intradermal tuberculin test technique. 251 of them were in contact with dairy animals and 64.9 per cent of such people were found specific reactors. Those who were not in contact with dairy animals (66 persons) gave 65.2 per cent rate of specific reactivity. To interpret the tuberculin sensitivity reaction, non-specific reactivity must be excluded, especially in tropical countries. Positive tuberculin reaction is defined when the diameter of induration is 10 mm or more for persons in contact with dairy animals and tuberculous patients or consuming raw milk and 5 mm or more for other persons.


Primary amoebic meningoencephalitis in Nigeria (report of two cases in children).

Two cases of PAME in children occurring during dusty harmattan period in Northern Nigeria are reported. In the absence of history of swimming or any other water related sport, and as suggested in our two previous reports, a dustbone infection as an important route of infection in PAME in this area is stressed. A need to fully investigate any atypical case of meningitis and meningoencephalitis in this area is emphasised.


Uncoating of adenovirus type 2.

The uncoating of adenovirus type 2 and a temperature-sensitive mutant, tsl, was studied. HEp-2 cells were infected with 32P- OR 125I-labeled purified virions for various lengths of time, and the nuclear and cytoplasmic fractions were analyzed by sucrose gradient velocity sedimentation and sodium dodecyl sulfate-polyacryl-amide gel electrophoresis. Within 1 h of infection, virions were converted into three subviral structures: (1) subviral structures in the cytoplasm with a density greater than virions but which qualitatively still contained all virus polypeptides; (ii) corelike structures associated with both the nuclear and cytoplasmic fractions and composed of viral DNA and polypeptides VIa2, V and PVII; and (iii) putative DNA-terminal protein complexes in the nuclei. The kinetic and compartmentalization studies suggested that the DNA-terminal protein complex is the end product of uncoating. The virions which were synthesized by tsl at the nonpermissive temperature and contained the precursor polypeptides PVI and PVII were found to be blocked in uncoating at the corelike stage. This block in uncoating provides the explanation for the lack of infectivity of these virions. A model for the uncoating of adenovirus is proposed.


Cell wall lysin as a component of the bacteriophage phi 6 virion.

Cell wall lytic activity was found in particles of the lipid-containing bacteriophage ø6. The activity can be extracted from the virion with Triton X-100 in the presence of salt. This treatment removes the membrane-like envelope of the virion which includes five proteins. The lysin requires detergent for in vitro activity. Virus particles formed in nonsuppressor cells by several classes of ø6 nonsense mutants contained the lysin activity; however, particles formed by a mutant (unable to make proteins P5 and P11) had very low activity; high activity was produced when particles were formed in a suppressor host. A study of the time course of the appearance of the lysin during infection showed that it appeared and increased in cells infected with wild-type virus and in suppressor cells infected with a mutant of class 511, but it did not increase in nonsuppressor cells infected with the class 511 mutant. It is concluded that protein P5 is a component of the lysin and that the role of its activity is in both early and late stages of infection. In particular, the lysin may be necessary for the passage of the infecting core of the virion through the cell wall of the bacterium, as well as in the final lysis necessary for the liberation of progeny phage. A mutant of the virus that produces a larger-than-normal protein P10 does not induce normal lysin activity in host Pseudomonas phaseolicola HB10Y, although it does in strain ERA Pseudomonas pseudoalcaligenes. This indicates that protein P5 is probably not sufficient for lysin activity, but the nature of the interaction between P5 and P10 is unknown.


Differential translation in normal and adenovirus type 5-infected human cells and cell-free systems.

When uninfected or adenovirus 5-infected KB cells are exposed to hypertonic medium, the incorporation of radioactive amino acids into protein decreases in both, but more severely in the uninfected cells. Although the effect of hypertonic medium on the synthesis of specific polypeptides varies, the translation of viral polypeptides as a class is less inhibited. The same patterns of proteins are synthesized regardless of the solute used in the hypertonic medium. The mechanism by which hypertonic conditions exert their effect on whole cells was investigated in K cell-free systems. It was possible to simulate the differential patterns of protein synthesis obtained in whole cells in hypertonic medium by increasing ion concentrations in cell-free extracts which are capable of initiating polypeptide chains on exogenous templates. However, in cell lysates which only elongate proteins, the same patterns were not obtained. Certain host and viral polypeptides displayed striking responses to increased ionic conditions in whole cells and cell-free systems. The synthesis of a host 44K protein, actin, appeared to be most sensitive; lower-molecular-weight proteins were fairly resistant. Among the viral proteins, the synthesis of 100K was inhibited, but most notable was the marked resistance of the synthesis of polypeptide IX. Possible mechanisms for differential synthesis and their significance are considered.


gag-Related polyproteins of Moloney murine leukemia virus: evidence for independent synthesis of glycosylated and unglycosylated forms.

Immunoprecipitation of labeled extracts from murine leukemia virus-infected cells with antisera specific for internal structural (gag) proteins yields three major gag-related polyproteins with molecular weights of 180,000 (Pr180gag-pol), 80,000, and 65,000 (Pr65gag). It has been shown by others that Pr65gag is the immediate precursor of the internal structural (gag) protein, and that Pr180gag-pol is the precursor to reverse transcriptase. In studies reported here, the 80,000-dalton gag-related polyprotein from Moloney strain murine leukemia virus (M-MuLV)-infected cells was found to be glycosylated by the following criteria: (i) incorporation of [3H]mannose, (ii) a change in electrophoretic mobility upon digestion with endoglycosidase H, and (iii) a change in electrophoretic mobility when glycosylation was inhibited by treatment of the cells with tunicamycin during labeling. The 80,000-dalton gag polyprotein has therefore been designated GpP80gag. The unglycosylated form of GpP80gag was a polypeptide of 75,000 daltons. A comparison of [3H]mannose and [3H]galactose labeling experiments suggested that GpP80gag is further glycosylated to yield a glycopolypeptide of 95,000 daltons. This 95,000-dalton polypeptide is relatively rapidly cleaved to yield two glycopeptides of 55,000 and 40,000 daltons which are released into the cell culture fluid, as soluble proteins. Cell-free translation of M-MuLV genomic RNA resulted in two major gag-related products of 75,000 and 65,000 daltons. The 65,000-dalton gag-related cell-free translation product comigrated with Pr65gag, and the 75,000-dalton cell-free product comigrated with the unglycosylated form of GpP80gag. Both of the gag-related cell-free translation products could be labeled with [35S]formyl methionine, which is incorporated only as the N-terminal amino acid during translation. Other investigators have shown that GpP80gag and Pr65gag differ at their N-termini, and these results combined with those reported here suggest that GpP80gag and Pr65gag are translated from two separate initiation sites in M-MuLV RNA.


Glycoprotein encoded by the Friend spleen focus-forming virus.

The Friend spleen focus-forming virus (F-SFFV) released from cultured erythroleukemia cells (cell line F4-6/K) was cloned free of its helper lymphatic leukemia virus (F-MuLV). After allowing adsorption to Sc-1 fibroblasts at a low multiplicity of infection, the cells were seeded individually into wells of a microtitier test plate and the resulting colonies were grown into large cultures. Among 14 of these cell cultures that have been analyzed thoroughly, 6 contained F-SFFV alone, 1 contained F-MuLV plus F-SFFV, and 7 were uninfected. Each of the Sc-1 cell lines which had been infected with cloned F-SFFV contained a glycoprotein with an apparent molecular weight of 55,000 (gp55) that was absent from the cell lines that lacked F-SFFV. gp55 was also present in Friend erythroleukemia cells and in fibroblasts infected with an F-SFFV that had been doubly cloned in another laboratory. These results indicate that gp55 is encoded by the F-SFFV genome. gp55 has the following additional properties. It can be immunoprecipitated with antiserum made to the F-MuLV virion envelope glycoprotein (gp75). Its unglycosylated polypeptide, formed in cells treated with 2-deoxy-D-glucose, has a molecular weight of approximately 45,000. Its tryptic peptide map contains peptides in common with F-MuLV gp75 but it also contains unique peptides. It appears to be absent or present in only low concentrations in erythroleukemia cell plasma membranes as determined by lactoperoxidase-catalyzed iodination, and it accumulates intracellularly in large amounts. In addition, it is absent from released virions. The majority of the cellular gp55 has an isoelectric point of 8.5 to 9.0. These results are consistent with the idea that an env gene recombination event was involved in the origin of F-SFFV.


Tryptic peptide analysis of gag and gag-pol gene products of Rauscher murine leukemia virus.

[3H]tyrosine-labeled viral precursor polyproteins and known mature viral proteins derived from the Rauscher murine leukemia virus gag and pol genes were examined by two-dimensional tryptic peptide mapping. Pr200gag-pol was found to contain peptide sequences of the viral core proteins p30, p15, p12, and p10, as well as peptide sequences found in the cell-associated reverse transcriptase. Intermediate reverse transcriptase precursor Pr125pol lacked peptide sequences of the four-core proteins but contained reverse transcriptase-specific tryptic peptides plus two additional tyrosine-containing tryptic peptides not related to gag or pol gene products. Methionine-containing tryptic peptide analysis also suggested the presence of additional protein material in Pr125pol (Kopchick et al., Proc. Natl. Acad. Sci. U.S.A. 75:2016-2020, 1978). Pr200gag-pol, although containing both viral core and reverse transcriptase-assoicated methionine and tyrosine tryptic peptides, also contained additional tryptic peptides. Thes are of two classes: (i) tryptic peptides associated with the Pr125pol but not Pr80pol and (ii) tryptic peptides not found in Pr125pol or in any known viral protein. One interpretation of these results is that Pr200gag-pol contains additional gene products aside from the gag and pol genes. Pr80gag and Pr65gag peptide maps were also examined and found to have sequences of all four core proteins. Pr65gag was found to contain two p30 tyrosine tryptic peptides that were absent in Pr80gag, suggesting that Pr80gag may not be the precursor to Pr65gag. Pr80gag, as expected from its larger size, also contained tryptic peptides not found in Pr65gag. Two of these additional Pr80gag tryptic peptides were found in Pr80pol as well but not in any of the viral core proteins, suggesting that Pr80gag and Pr80pol may have overlapping peptide sequences. Consistent with this finding is the conclusion that Pr80gag terminates within the pol gene. A model that describes the relationship of these recent findings to viral gene products is presented.


Normal saline slush preparation for renal surgery.

We describe a simple, rapid method to prepare normal saline slush with commercially available slush mugs that are gas-sterilized in routine fashion and stored in freezer. Slush can be prepared intraoperatively in 10 minutes with this method.


Prevalence rate of renal stone disease in Forsyth County, North Carolina during 1977.

A count of all recorded hospitalized cases of Forsyth County, North Carolina residents with a primary discharge diagnosis of renal (kidneyand/or ureteral) stone in 1977 is obtained by age, race and sex, and used in conjunction with the census data to estimate age-adjusted prevalence rates. The over-all prevalence rate is 2.08 per thousand population, which agrees well with results of earlier investigations. For white male subjects the age-adjusted prevalence rate is 3.64 per thousand, for white female subjects 1.44, for non-white male subjects 0.97 and for non-white female subjects 0.34. The white to non-white ratio and the male to female rates are compared with earlier published values. For all groups the prevalence rate increases with age, attaining a maximum in the 40 to 60-year category for whites and somewhat later for non-whites. Beyond age 60 prevalence drops, reaching 0 or near 0 in the 80 to 89-year range. A simple phenomenological model is suggested to explain the observed race and sex differences in the prevalence rates.


The detection and clinical significance of antibodies to tumor-associated antigens in patients with renal cell carcinoma.

Antibodies against renal carcinoma cells were detected by a microcomplement fixation assay in the sera of 94 per cent of 75 patients with recently resected, localized or metastatic disease, and in 20 per cent of normal controls. Absorption of sera with pooled normal kidney cells abrogated reactivity against normal kidney cells but did not decrease reactivity significantly against the renal carcinoma cells. Analyses of sequential serum samples revealed that after nephrectomy in 9 of 10 patients free of tumor but a high risk for recurrence antibody levels decreased or disappeared by 1 year. However, these levels remained elevated in 2 patients who subsequently were found to have occult persistent tumor. Antibody titers in patients with metastatic renal cell carcinoma declined as the disease progressed. Patients with persistently elevated titers had the longest survival. Although the antibodies detected by this assay may not be specific for renal cell carcinoma, their detection may be of clinical significance with regard to the prognosis of the disease.


Congenital megaureter.

Megaureter is the descriptive term applied to the large, wide, dilated and often tortuous ureter, which is usually congenital. Megaureter may result from a number of causes and an accurate diagnostic classification, such as refluxing, obstructed or non-refluxing, non-obstructed, is essential for appropriate management. The 52 consecutive patients with the various forms of megaureter presented typify the various causes of the entity. Surgical intervention virtually is universal and factors bearing upon recoverability and prognosis have been analyzed.


The prevalence and significance of Brunn's nests, cystitis cystica and squamous metaplasia in normal bladders.

The frequency of Brunn's nests, cystitis cystica and squamous metaplasia was studied by multiple histologic sections in 100 grossly normal bladders obtained at postmortem examination. Of the 100 bladders 93 per cent had at least 1 of the 3 proliferative changes. Brunn's nests and cystitis cystica were seen in 89 and 60 per cent of the bladders, respectively, most often at the bladder neck and trigone. Non-keratinizing squamous metaplasia of the vaginal type was seen almost exclusively on the trigone and bladder neck in 46 per cent of the premenopausal and postmenopausal women but in only 7 per cent of the men. There was no satisfactory evidence that inflammation was casually associated with these changes. These findings suggest that Brunn's nests, cystitis cystica and squamous metaplasia of the vaginal type in women are normal variants of bladder urothelium and have no precancerous potential.


The survival of patients with bladder tumors treated by surgery: comparative results of an old and a recent series.

A review of a large number of patients with bladder tumors treated primarily by an operation during approximately 4 decades indicates that survival of patients with papillomas and superficial carcinomas essentially was unchanged. Recently, patients with invasive cancers who have been treated have enjoyed a modest improvement in the 5-year survival rate, which was at least in part the result of a diminished postoperative mortality rate.


Urolithiasis associated with pregnancy.

Of 34,081 deliveries in a 12-year period 20 were complicated by urinary calculi during the pregnancy. Of the 20 deliveries 3 required intervention either during pregnancy or immediately postpartum. There were no maternal deaths and only 1 stillborn secondary to erythroblastosis. Analysis of symptoms, findings, procedures and outcome is presented in this uncommon but serious problem.


High frequency current effects during transurethral resection.

Transurethral resection has been simulated electrically to detect the current pathways and locations of heat production inside the patient. Different electrical behavior was noted with instruments using electrically insulated or metal sheaths. Conductive lubricating jelly should be used with the metal sheath and non-conducting jelly should be used with the insulated sheath.


Vesicourethral dysfunction in multiple sclerosis.

Urodynamic evaluation was done 45 times on 41 consecutive patients with multiple sclerosis. Bladder symptoms correlated poorly with any single urodynamic finding and, accordingly, a comprehensive evaluation was necessary to define the underlying pathophysiology. Only 63 per cent of the patients with symptoms of urgency, frequency and urge incontinence actually were found to have uninhibited bladder contractions, while 73 per cent of the patients with obstructive symptoms had detrusor areflexia. Six patients (15 per cent) had a marked change in urodynamic findings upon repeat examination either because of a change in symptomatology or poor response to treatment. An additional 6 patients had vesicoureteral reflux. Bladder symptoms in multiple sclerosis patients should serve more to alert the clinician to the need for urodynamic testing than to mandate specific treatment.


The value of sphincter electromyography in urodynamics.

Multichannel urodynamic evaluation combined with sphincter electromyography was done on 102 patients. Normal and abnormal activity was defined. When detrusor hyperreflexia occurred in patients with obstruction, idiopathic detrusor hyperreflexia and upper motor neuron disease there was a reflex relaxation of the pelvic floor in 52 per cent of the cases. Electromyographic evidence of dyssynergia was associated with other evidence of sphincter obstruction in 50 per cent of the patients who voided by detrusor contraction and in 9 per cent of the patients who voided by Valsalva's maneuver. A diagnosis of dyssynergia should not be made from the electromyographic evidence alone, especially if the patient strains to void.


Electrodiagnosis of striated urethral sphincter dysfunction.

In many centers urethral striated sphincter electromyography has become an essential component of urodynamic testing. The urologist who uses this modality of investigation in an attempt to understand the pathophysiology of striated sphincter dysfunction must have some basic knowledge of electromyography. Attempts have been made to provide such basic information, especially relating to the methods of evaluation and interpretation. We also have incorporated our own views based on our experience with more than 200 subjects with neuropathic vesicourethral dysfunctions.


Low spinal anesthesia for the prevention of autonomic dysreflexia in the spinal cord injury patient.

Twenty-five patients with traumatic spinal cord injuries above T7 have been managed with low spinal anesthesia during endoscopic urologic procedures. The technique has been completely successful in preventing autonomic dysreflexia and has not been associated with hypotension.


A one-stage surgical approach to ectopic ureterocele.

Whenever a ureterectomy for treatment of ectopic ureterocele is appropriate total extravesical excision avoiding a ureteral stump is the preferred approach to avoid a pyoureter or alternating diverticulum and possible surgical complications from an intravesical procedure in small infants and children with large and distorting ectopic ureteroceles.


Upper tract management when posterior urethral valve ablation is insufficient.

Of 105 boys with posterior urethral valves managed during a 10-year period most were managed by primary valve ablation. However, 39 of these boys required concomitant or additional procedures to 71 massively dilated ureters because of azotemia, infection and/or progressive upper tract deterioration. In 17 boys 25 ureters could be reconstructed primarily by varying degrees of ureteral tailoring. When there was severe infection, azotemia and/or doubt as to the function of the affected renal unit, staged reconstruction was initiated by cutaneous ureterostomy. One-fourth of these ureterostomy diverted children died of azotemia despite free urinary drainage. Those who went on to have staged reconstruction, despite multiple surgical procedures, retained intact urinary systems with acceptable function.


Association of urinary tract infection and reflux with uninhibited bladder contractions and voluntary sphincteric obstruction.

We studied 53 neurologically normal children with recurrent urinary tract infection who were found to have bladder-sphincter incoordination characterized by voluntary sphincteric constriction during involuntary uninhibited bladder contraction. Increased intravesical pressure was documented during these events and was associated with vesicoureteral reflux in nearly 50 per cent of the children and with abnormalities of the ureteral orifice in 30 per cent of those without reflux. We hypothesize that increased intravesical pressure causes urinary infection in these children and produces a spectrum of intravesical anatomic distortion that predisposes to vesicoureteral reflux. In a prospective uncontrolled study treatment of the uninhibited bladder contractions allowed 58 per cent of the patients to maintain sterile urine without subsequent antimicrobial therapy after cure of the initial infection.


Nephrotic syndrome during treatment with alpha-mercaptopropionylglycine.

We report 2 cases of cystinuria in which a nephrotic syndrome developed during treatment with alpha-mercaptopropionylglycine. This syndrome resolved after withdrawal of the drug and it did not recur when the alpha-mercaptopropionylglycine was given again in lower doses. The hypothesis is made that the nephrotic syndrome was dose-related. The alpha-mercaptopropionylglycine must be used in doses less than 50 mg./kg per day with regular monitoring of 24-hour urinary protein in cystinuric children.


Management of infected polycystic kidneys.

We report 5 cases of severe uncontrolled infection of polycystic kidneys. Retrograde pyelography antedated infection in 2 of the patients. Difficulty in establishing the diagnosis was demonstrated in all cases. Each patient was treated initially with antibiotics but definitive therapy required an operation in 4 cases.


Acute reversible renal failure secondary to renal candidiasis.

A diabetic patient presenting with bilateral enlarged kidneys and acute renal failure was found to have renal parenchymal candidiasis without obstruction. Treatment with amphotericin B resulted in return of renal function and decrease in renal size.


Successful treatment of a renal arteriovenous fistula with a Fogarty catheter.

A large renal arteriovenous fistula developed in a 71-year-old patient after percutaneous needle biopsy. Attempts to control the fistula with autologous clot were unsuccessful. A Fogarty catheter placed fluoroscopically was used to obliterate the feeding vessel. This is the first case reported in which this technique was used to control a renal arteriovenous fistula. This method of treatment offers the advantage of avoiding major surgical intervention with precise control of the fistula.


Hypertension in childhood from renal vein thrombosis.

A case is presented of a 1-year-old boy with hypertension resulting from abnormal renin production by the right kidney. The kidney had undergone infarction and atrophy secondary to renal vein thrombosis. The left kidney remained normal despite inferior vena cava thrombosis because of the development of collateral venous circulation. The hypertension was cured by right nephrectomy. The child remains normotensive and with a normal serum creatinine at 1-year followup.


Two-stage procedure for the management of massive hydronephrosis.

A case of congenital unilateral massive hydronephrosis containing 42.5 l. clear urine is reported. Treatment consisted of a 2-stage procedure that is described. The consequences of sudden decompression, which occurs after a 1-stage operation, are discussed. The rationale of the 2-stage procedure is that gradual decompression helps to restore the normal anatomical and physiological base lines so that the definitive operation of removal of the sac can be accomplished with minimum risk to the patient. This 2-stage technique is a relatively safe procedure based on sound principles.


What about the other kidney?

Sophisticated diagnostic techniques have made the isolation of renal lesions more accurate. However, it must be remembered that simultaneous bilateral kidney pathology can exist in any patient. The most obvious lesion may not be the most important. Four cases are presented to illustrate this point.


Renal metastasis of adenocarcinoma of the lung: massive hematuria managed by therapeutic embolization.

The rare complication of massive hematuria secondary to metastatic infiltrating adenocarcinoma of the lung to the kidney was managed with steel coil therapeutic embolization. The angiographic and pathologic picture as well as the advantages of this therapeutic modality in this clinical setting are discussed.


Stones in orthotopic, non-obstructing ureteroceles.

A case is presented in which stones were found bilaterally in orthotopic, non-obstructing ureteroceles in a child. This is apparently the first reported instance of this condition occurring in the presence of sterile urine. A review of related literature gives clues to the possible etiology of such an occurrence.


Idiopathic retroperitonial fibrosis misinterpreted as lymphoma by computed tomography.

Two cases of idiopathic retroperitoneal fibrosis that were mistaken for lymphomas on a computed tomography scan are presented. The similar densities and anatomical appearances on cross section scans of these diseases probably account for this misinterpretation.


Ureterosigmoidostomy: a 59-year followup and review of long-term urinary diversion.

This case report documents the efficacy of urinary diversion by ureterosigmoidostomy. Our patient has suffered minimal complications with the added advantage of urinary continence for nearly 60 years. While we would not advocate the Coffey I technique for creation of ureterosigmoidostomy, this case does illustrate the longest survival after any form of diversion with normal urinary function reported in the literature.


Simultaneous traumatic bladder perforation and disruption of the prostatomembranous urethra.

The simultaneous occurrence of disruption of the prostatomembranous urethra and traumatic perforation of the bladder is seldom diagnosed before operation for the urethral injury. The presence of posterior disruption can make radiological diagnosis of the concomitant bladder perforation difficult. Lack of a palpable bladder a few hours after urethral injury should arouse suspicion of a combined injury. Careful bladder examination is indicated at the time of operation for all cases of posterior urethral injury to eliminate possible bladder perforations and the significant increase in morbidity and mortality associated with their presence.


Bilateral testicular dislocation with unilateral rupture.

A case of bilateral luxation of the testes associated with testicular rupture is presented. Bilateral traumatic dislocation of the testes is uncommon and its association with testicular rupture has not been reported previously. The etiology, classification and treatment of testicular luxation are reviewed briefly. Reports in the literature have indicated initial non-operative management but our case demonstrates the need for early surgical exploration.


Abdominoscrotal hydrocele in infant with hydronephrosis.

A case is presented of an unusually large abdominoscrotal hydrocele with secondary left ureterohydronephrosis owing to contiguous pressure. The technique that made the preoperative diagnosis apparent is described.


The increasing importance of polymicrobial bacteremia.

Polymicrobial bacteremia increased from 6% in 1970 to 13% in 1975 in patients with bloodstream infections. This type of serious infection most commonly complicated genitourinary (27%) and gastrointestinal (26%) conditions, frequently followed invasive procedures (68%), was more common in hospitalized patients (73%), and was often associated with malignancies (25%) or immunosuppressive or cancer chemotherapy (34%). Although polymicrobial endocarditis was more commonly encountered in recent years, this infection accounted for only 4.5% of patients with multiple organism bacteremias. Gram-negative aerobic bacteria were isolated from 62% and anaerobic bacteria in 39% of patients with polymicrobial bacteremia compared with 37% and 14%, respectively, in patients with monomicrobial bacteremia. In the 88 patients with polymicrobial bacteremia, the mortality was 44.5%, compared with 18.0% in patients with monomicrobial bacteremia.


Prenatal diagnosis of propionic acidemia.

Prenatal diagnosis of a fetus with propionic acidemia has been accomplished by the detection of methylcitrate, a unique metabolite, in the amniotic fluid by liquid partition chromatography and gas chromatography-mass spectrometry. The diagnosis was confirmed by demonstration of deficient activity of propionyl-CoA carboxylase in cells cultured from the amniotic fluid and in fetal tissues. In two subsequent pregnancies, methylcitrate was not present in amniotic fluid. Enzyme assay indicated that one fetus was heterozygous and the other was normal, and healthy infants were born at term. The analysis of organic acids in amniotic fluid permits very rapid prenatal diagnosis, usually within 48 hours after obtaining the fluid. It may provide a general method in conditions in which an unusual metabolite can be identified.


The autopsy. Past, present, and future.

The autopsy appears to be on the way to assuming an increasingly important role in patient care, continuing education, education of medical students and house staff, research in environmental pathology, and more fundamental aspects of disease. This trend needs to be nurtured. Not only pathologists but all physicians need to plan carefully to utilize autopsies to the fullest possible extent. Interest will continue to grow only if autopsies are performed or are closely supervised by highly motivated and experienced pathologists asking critical questions of current medical, scientific, and social concern. New, imaginative approaches are needed to develop the data necessary to address these questions.


Hypoxemia after thoracentesis. A predictable and treatable condition.

Hypoxemia was observed at 20 minutes and two hours postprocedure in 15 patients who had a thoracentesis. The hypoxemia resolved after 24 hours. No effect on pH, PaCO2, or bicarbonate ion was observed. The degree of hypoxemia was correlated directly with the volume of fluid removed. Oxygen therapy was found to reverse this effect. Hypoxemia that follows thoracentesis may be caused by several factors, the most important being frank pulmonary edema.


Limitatoins of surgical methods of pericardial drainage. Echocardiographic observations.

To assess the efficacy of surgical methods of pericardial drainage in preventing the accumulation of pericardial effusion, we performed M-mode and cross-sectional echocardiograms in 26 patients before and one week after the creation of a pericardial window or leaving the pericardium open after cardiac surgery. A pericardial window was created in six patients (group 1) who had pericardial effusions. Group 2 consisted of 20 patients who had heart surgery. Echocardiography disclosed moderate or large pericardial effusions preoperatively in all group 1 patients but in one of the group 2 patients. Following operation, three of the group 1 patients had complete clearing of pericardial effusion, while three showed reaccumulation. In group 2, thirteen patients had either no effusion or a small effusion. Seven patients had moderate or large pericardial effusions that were located posterior to the heart; only one had an anterior pericardial effusion. Cross-sectional echocardiography showed posterior loculation of effusion in six of the seven patients. Pericardial drainage is not always effective in preventing accumulation of pericardial effusions.


Roentgenographic evaluation of cervical spine trauma.

A practical approach to the roentgenographic assessment of a patient suspected of having a cervical spine injury is described. Once positioned, the patient is not moved until substantial bony injury has been excluded. The major roentgenographic signs with differential diagnosis are briefly discussed using some illustrative roentgenograms.


Continuing medical education.

1. Continuing medical education is unquestionably a worthwhile goal. Knowledge or exposure to information, however, does not ensure competence in medical care; nevertheless, without knowledge there is no possibility of true competence. 2. Continuing medical education should not be judged by recall knowledge but should ensure exposure to current and acceptable medical knowledge. 3. Because all licensed physicians have unrestricted licenses regardless of their specialty, they all should benefit from a comprehensive type of CME. 4. An open-book examination with reference sources appended to the questions would expose the physician to current and acceptable medical knowledge. 5. Recall types of examinations have no place in practical CME.


Serum alkaline phosphatase determination. Value in the staging of advanced breast cancer.

A retrospective study of 146 patients with metastatic disease was undertaken to verify the clinical impression that radionuclide scanning rarely, if ever, discloses hepatic metastases in breast cancer patients with normal serum alkaline phosphatase (AP) levels. Only two of 39 patients with abnormal liver scans had normal AP levels, and we conclude that liver scans are not necessary as a routine screening method for liver metastases when the AP level is normal. In contrast AP levels were not predictive of bone scan results. All patients with a twofold or greater elevation of the AP level had abnormal bone, liver, or bone and liver scans. Routine AP determinations provide accurate staging information, and their proper use can decrease the cost of initial and follow-up examination of patients with breast cancer.


Risk of vascular disease in women. Smoking, oral contraceptives, noncontraceptive estrogens, and other factors.

We investigated the relation in women of various factors to risk of myocardial infarction, subarachnoid hemorrhage, other strokes, and venous thromboembolism. Smoking significantly increased risk of all four diseases, whereas oral contraceptive use was associated with an increase only in risk of subarachnoid hemorrhage and venous thromboembolism. Use of noncontraceptive estrogens was not associated with increased risk of any of these diseases. Hypertension, hypercholesterolemia, obesity, gallbladder disease, and nondrinking of alcohol were all associated with increased risk of myocardial infarction, whereas only hypertension and hypercholesterolemia were associated with increased risk of other strokes. Cigarette smoking was overwhelmingly the most important risk factor for vascular disease in women. Smoking should be considered a contraindication to oral contraceptive use, or at the very least, women wishing to use oral contraceptives should be strongly urged not to smoke.


Erythema and conjunctivitis. Outbreak caused by inadvertent exposure to ultraviolet light.

During August to November 1977, fifty-eight episodes of erythema or conjunctivitis or both occurred among nursing-service employees at a large state hospital. Epidemiologic investigation implicated an ultraviolet-light-producing germicidal bulb in a nursing station's desk lamp as the causative agent. Removal of the lamp from the nursing station controlled the outbreak. Analysis of the spectral irradiance from the bulb suggested that the National Institute of Occupational Safety and Health exposure standards were exceeded in five to 20 minutes, depending on the individual's distance from the lamp.


Health effects of urban air pollution. Special consideration of areas at 1,500 m and above.

Urban air pollution, when sufficiently severe, can cause death in humans; these deaths occur preponderantly among those with increased susceptibility. Pollution--carbon monoxide and oxidants in particular--is capable of aggravating preexisting chronic heart and lung diseases. Pollution and tobacco (especially cigarette) smoke act synergistically in a causative role in chronic bronchitis and in an aggravating role in emphysema. Susceptibility to the effects of urban air pollution varies widely, with the most susceptible being fetuses, the newborn, the elderly, the infirm, those with chronic heart and lung diseases, and those who smoke. The carbon monoxide standards for sea level are probably too lenient for an altitude of 1,500 m and above. Using a broad definition of health, which takes into account concepts such as quality of life and social and mental well-being, few metropolitan residents would deny that their health is compromised by air that is malodorous, that irritates mucous membranes, and that obscures beautiful scenery.


A field study of the stress response syndrome. Young women after hysterectomy.

The symptom pattern previously delineated as the stress response syndrome in a mental health setting was hypothesized to be useful in conceptualizing reactions to a traumatic event in a nonpsychiatric patient population. The experience of loss resulting from nonelective hysterectomy for benign disease in women of childbearing age was selected as a relevant field study model. Twenty-eight women were studied one year after hysterectomy, using extensive psychological interviewing by women clinicians and experiential rating scales. Twelve subjects had a mild stress response syndrome, and five subjects had a serious level of intrusive and avoidant symptoms. Increasing severity of response was associated with persisting child-wish, deterioration in sexual functioning, and change in self-concept. Women who did well postoperatively generally had no future wish for children and were actively committed to achievement outside of the home.


Psychological coping mechanisms and survival time in metastatic breast cancer.

Thirty-five women with metastatic breast cancer received a battery of baseline psychological tests; results were correlated with length of survival. Patients who died in less than one year from baseline were categorized as short-term survivors, while patients who lived for one year or longer were assigned to the long-term survivor group. The long-term survivors were more symptomatic overall, with particular elevations on measures of anxiety and alienation, and substantially higher levels of dysphoric mood (eg, depression, guilt) than the short-term survivors. Short-term survivors revealed significantly lower levels of hostility, with higher levels of positive mood. Treating oncologists perceived the long-term survivors to show significantly poorer adjustment to their illnesses than the short-term survivors, and an interviewer's ratings indicated that long-term survivors had significantly poorer attitudes toward their physicians. Measures of clinical status and demographic data revealed few differences between the two groups.


Postoperative adjuvant chemotherapy with fluorouracil, doxorubicin, cyclophosphamide, and BCG vaccine. A follow-up report.

Two hundred twenty-two patients with stage II or III breast cancer following regional therapy were treated with a combination of fluorouracil, doxorubicin hydrochloride (Adrimycin), cyclophosphamide, and BCG vaccine. At 54 months of study (median follow-up, 30 months), the estimated proportions remaining disease-free two and three years after surgery were 83%and 78%, respectively, in the chemotherapy group and 64% and 55%, respectively, in 151 historical control patients. Estimated two- and three-year survival rates were 93% and 89%, respectively, in the chemotherapy group and 84% and 58%, respectively, in the control patients. Congestive heart failure has developed in three patients, possibly related to the use of doxorubicin. Adjuvant chemotherapy with these drugs was effective in prolonging the disease-free interval and survival of patients irrespective of menopausal status, degree of nodal involvement, or stage of the disease.


Viral hepatitis associated with day-care centers.

From September 1976 through March 1978, we investigated 11 outbreaks of non-B viral hepatitis associated with Louisiana day-care centers. The outbreaks included 168 cases, most of which were erroneously considered "sporadic" cases of non-B viral hepatitis prior to the investigations. Thirteen percent of all non-B viral hepatitis cases reported in the New Orleans metropolitan area during 1977 were associated with one of the outbreaks. Most of the cases in each outbreak and 85% overall were in older, usually adult, contacts of children attending the day-care centers. Within the household, parents appeared to be at greatest risk, particularly those who had 1- to 2-year-old children in the day-care center. Day-care center outbreaks of non-B hepatitis are easily overlooked and may be more widespread than is currently appreciated.


Effect of allopurinol (zyloric) on patients undergoing open heart surgery.

We observed previously that allopurinol, which was used for the treatment of gout, had a life saving effect after experiment on traumatic shock rats and hemorrhagic shock rabbits. To evaluate the effect of allopurinol fifteen patients undergoing open heart surgery who were considered to have similar metabolic derangement in shock patient were examined. Allopurinol was given orally 2 mg per kg body weight twice before the start of nitrous oxide, oxygen and halothane anesthesia. In the control group of ten patients who were not treated with allopurinol, serum uric acid increased, the lactate/pyruvate ratio rose and beta-glucuronidase activity increased respectively after open heart surgery as in shock. But the metabolic changes of the fifteen patients pretreated with allopurinol were less significant, although same tendency was observed. The heart beat of all patients except one case in the allopurinol group, started spontaneously after extracorporeal circulation without using DC counter shock. In the control group all patients needed DC counter shock. We concluded that allopurinol was effective in preventing damage of cellular structures and derangements of metabolism of patients undergoing open heart surgery.


Rate related block in the canine His-Purkinje system after ligation of the anterior septal artery--observation by His bundle electrocardiography.

In order to investigate the pathophysiology of tachycardia and bradycardia dependent block in the His-Purkinje system, anterior septal artery was ligated and the effects of vagal stimulation and atrial pacing were serially checked in 26 dogs. Tachycardia dependent intra-His bundle block or H-V blocks developed in all cases following ligation of the anterior septal artery and bradycardia dependent block ensued in 3 cases. The latter appeared only in the form of split His bundle or lengthening of the H-V intervals. Spontaneous second or third degree AV block appeared thereafter. Bundle branch block appeared in 19 cases after ligation of the artery. Rate dependent bundle branch block was observed before the development of stable bundle branch block. Frequently, a very long pause was necessary to produce bradycardia dependent block. On the other hand, bradycardia dependent H-V blocks by vagal stimulation were not necessarily dependent upon cardiac cycle length alone. Tachycardia dependent paroxysmal A-V blocks were induced in 7 cases by atrial pacing, soon before or after the onset of spontaneous second degree A-V block. In addition, this block was induced in the very early phase after ligation of the artery in one case. This repetitive intra-His bundle block or H-V block was induced not only by progressive increase in pacing rate but also by gradual decrease in pacing rate after a Wenckebach type of second degree A-H block.


Epidemiology of rheumatic fever in Japan.

The number of patients with the first attack of rheumatic fever reached a peak in 1960, decreased remarkably until 1968, then has remained unchanged for the last nine years. Approximately 10% of rheumatic patients still develop recurrences.


Clinical aspects of nonrheumatic myocarditis in children.

Sixty-eight patients of clinically diagnosed myocarditis, 0--15 years of age, were followed up and analyzed. Forty (58.8%) were males. The majority were older than 5 years. Clinical courses were rather mild, chronic and self-limiting at large. Only 1 case had a relation to chronic cariomyopathy. Exertional symptoms (chest pain, chest distress, syncope) were seen in 25 (36.8%). ECG changes were very common: the majority were nonspecific ST elevation, depression or both, mainly in leads II, III, V5 and V6. Positive Master' test, prolonged QTc, widened mean spatial QRS-T angle and various arrhythmias were also observed. Cardiac performance, estimated by echocardiogram and phono-mechanocardiogram was lowered in 41 (60.3%). Large IV sound and large A wave in apexcardiogram were also frequently found. All but 3 patients showed continuous elevation of serum enzymes, namely, LDH, LDH-1/LDH-2, CPK, CPK-MB, HBD and GOT. Etiological evidences were obtained by serological study in 11 cases (16.2%): 2 of Coxsackie B-1, 3 of Coxsackie B-2, 1 of Coxsackie B-4, 2 of mycoplasma pneumoniae, 1 of cytomegalovirus, 1 of ECHO-7 and 1 of rubella. We proposed a criteria for diagnosis of myocarditis as follows: (1) Exertional symptoms. (2) ECG findings. (3) Serum enzyme abnormality. (4) Lowered cardiac performance. (5) Cardiomegaly. (6) Changing character of all signs and symptoms.


Experimental cryptococcal myocarditis.

Rabbits and rats developed myocarditis on the 16th, 30th, and 60th day after intrarenal inoculation with Cryptococcus neoformans. The cardiac lesions consist of focal necrosis with infiltrations of small round cells in the myocardium. Cryptococcal antigens were demonstrated by a direct immunofluorescent antibody method in the damaged myocardial lesions. Cryptococcus neoformans itself was found by periodic acid-Schiff stain in the damaged myocardial lesions.


Rheumatic heart disease in childhood: comparative study between Japan and Thailand.

This report showed the comparative study of the rheumatic fever and rheumatic heart disease in Japan and Thailand. At first, there is remarkable difference about the incidence of the rheumatic heart disease. The incidence of the rheumatic heart disease in Thailand was one hundred times that in Japan. Secondly, there is particular difference about the course of mitral stenosis in childhood. In Japan common pattern of rheumatic heart disease was slight mitral insufficiency and mitral stenosis was seldom. In Thailand mitral stenosis was observed in 5% on rheumatic heart disease, and mitral stenosis developed early following an attack of rheumatic fever. These differences were supposed due to the socio-economic state in each country.


Ultrasonodiagnosis of subclinical heart failure by increasing afterload with angiotensin II.

In an attempt to diagnose latent heart failure, a transient increase of afterload to left ventricle was produced by angiotensin II, and the ventricular movement was assessed by echocardiography. Angiotensin II was administered in a dose of 0.075 micrograms/kg body weight. Blood pressure was elevated by 40.5 +/- 14.5 mmHg in 38 cases with latent heart failure and by 41.2 +/- 4.5 mmHg in 30 normal subjects. Yet, only in the former group, posterior wall excursion of left ventricle reduced from 11.4 +/- 2.4 mm to 7.3 +/- 2.3 mm and mean posterior wall velocity from 41.4 +/- 10.1mm/sec to 26.5 +/- 8.8 mm/sec. The rates of these reductions were inversely correlated to the rate of elevation of left ventricular endodiastolic pressure as determined in 5 cases by cardiac catheterization. There was no change in 30 subjects. The data indicate the usefulness of angiotensin-induced echocardiographic changes in detecting latent cadiac failure.


Presystolic pulmonary valve opening in constrictive pericarditis.

Right heart pressure tracings were studied in 5 cases with constrictive pericarditis. The pressure of the A-wave in the right atrium of these cases was higher than the pulmonary arterial diastolic pressure. In addition, a presystolic wave appeared in the pulmonary arterial and the right ventricular pressure tracings, in coincidence with atrial systole. The pressure of this presystolic wave was similar to that of the right atrial A-wave. This suggests that the pulmonary valve opens following atrial systole, and then the blood flows into the pulmonary artery in the presystolic phase in patients with constrictive pericarditis. In 2 cases, pulmonary valve echograms were recorded. The a-dip in these 2 cases was as deep as 8.4 mm and 9.6 mm (1.8-4.1 mm with a mean of 2.80 mm for normal men), and its duration was prolonged to 0.17 sec and 0.18 sec (0.10-0.13 sec with a mean of 0.115 sec for normal men). In conclusion, such a deep and prolonged a-dip on pulmonary valve echogram is presumably a sign of presystolic pulmonary valve opening.


Non-invasive determination of left ventricular diastolic compliance.

The log-log relationship between the instantaneous height of A wave obtained from apexcardiogram and the diameter of minor axis of left ventricle obtained by echocardiography has been calculated. The log-log slope was considered to be an indicator of ventricular stiffness. The slope was significantly higher in different subgroups of cardiac patients compared with normal subjects. This points to its possible value in the study of cardiac function.


Glycyl-prolyl-p-nitroanilidase (GPNAase) activity in cardiovascular diseases.

We have studied serum glycyl-prolyl-p-nitroanilidase (GPNAase) activity and its distribution in various parts of the body in patients with acute myocardial infarction, chronic ischemic heart disease, valvular heart disease with or without congestive heart failure and essential hypertension. Serum GPNAase activity in patients with acute myocardial infarction was significantly lower as long as 12 days after the onset as compared with normal controls. The serum enzyme activity in patients with congestive heart failure was also significantly lower than that of controls and there was a tendency of its gradual decrease with the progress of the disease. There was no significant difference between the activity in control group and that in age-matched patients with essential hypertension. There was no significant change of the activity in patients with chronic ischemic heart disease. The GPNAase activities in sera obtained from various parts of the body by cardiac catheterization were essentially similar.


Changes of ventricular monophasic action potential duration by stellate ganglion stimulation in dogs.

Left or right stellate ganglion stimulation resulted in changes of ST segments and T waves of electrocardiogram. The present experiments were performed in an attempt to elucidate alpha-and beta-adrenergic actions, and calcium action on the monophasic action potential duration (APD), that is, the repolarizing phase of myocardium. During experiments in open-chest dogs, right ventricular pacing was performed for avoiding the acceleration of heart rate by stellate ganglion stimulation. Administration of phentolamine, propranolol or D600 prolonged APD, while hydrazine shortened it. However, stellate ganglion stimulation caused a prolongation of APD after infusion of propranolol or hydrazine, and a shortening of APD after infusion of phentolamine, D600 or hydrazine. These results indicate that alpha-and beta-adrenergic actions as well as calcium ions can be related to APD in the ventricular myocardium of dogs; apparently, alpha-adrenergic action prolongs APD and beta-adrenergic action shortens it.