Pulmonary edema due to tetrachloroethylene. A patient with massive exposure to tetrachloroethylene fumes presented with coma and severe pulmonary edema. Sequential blood gases, chest x-rays, and clinical findings showed dramatic improvement with conventional but aggressive management and the patient recovered completely. There was no evidence of permanent renal, hepatic, or central nervous system damage.


Chemical reactivity-absorption, retention, metabolism, and elimination of hexachlorocyclopentadiene. Hexachlorocyclopentadiene is eliminated from the body efficiently by urinary excretion. Although direct evidence is not available, it appears that expiration may be another important route of elimination. Of the administered dose 9% is excreted in the bile in 1 hr, approximately equal to the amount of fecal excretion in 7 days, suggesting enterohepatic circulation. After a single dose, HCPD decays from the blood biexponentially with a terminal phase half-life of 60 min. Of the tissues analyzed kidney, followed by liver, concentrate HCPD 1 hr or 7 days after exposure to any significant extent. Subcellularly, HCPD is predominantly associated with cytosol fractions of both kidney as well as liver, observations consistent with rapid elimination of HCPD after a single exposure. Preexposure to HCPD (50 mg/kg-day for 3 days) resulted in unaltered blood decay curves and biliary excretion, but increased the concentration in the kidneys after a single subsequent challenge.


Toxicology of the fluoroalkenes: review and research needs. In this review of the published literature on the toxicology of fluoroalkenes several features emerge and research needs are evident. The fluoroalkenes vary widely in acute inhalation toxicity. Those, such as perfluoroisobutylene, PFIB, the most highly toxic member, attacks the pulmonary epithelium of rats eventuating in edema and death after a delay of about one day. Other fluoroalkenes, such as hexafluoropropylene (HFP) or chlorotrifluoroethylene (CTFE), also cause pulmonary injury but at lower concentrations produce concentration dependent changes in the renal concentrating mechanism of the rat. Changes in the CNS of rats and rabbits have also been reported for CTFE. CTFE, in repeated exposures, has produced blood pressure changes in dogs, CNS effects and changes in the erythropoietic system. This variety of responses indicates the need for investigation. Chronic effects have not been sufficiently studied for PFIB and HFP. Thus pointing up the desirability for study. Mechanisms of action research for fluoroalkenes is an important area of need. While several ideas have been suggested, there are no data to support them. The nucleophilic sensitivity of the fluoroalkenes and the potential carcinogenic effects stemming therefrom suggests a need field for investigation. We also can readily perceive the needs for the evaluation of effects on reproduction (including mutagenesis and teratogenesis), metabolism pulmonary functions, cellular function and structure. Epidemiologic studies on occupationally exposed populations are desirable in order to adequately define human health hazard from these fluorocarbons.


Metabolism and toxicology of pyrethroids with dihalovinyl substituents. Replacement of the photolabile and biodegradable isobutenyl substituent of pyrethroids with a dihalovinyl group often leads to improved insecticidal potency and enhanced photostability. This type of structural modification does not greatly alter the ease of detoxification in mammals since other sites in the molecule undergo metabolic attack. The available toxicological information on dihalovinyl pyrethroids indicates that they are suitable replacements for other insecticides with less favorable persistence and toxicological characteristics.


Haloethylene-related compounds of industrial, environmental, and medical significance. A broad-based literature survey was made for chemicals that contain either a haloethylene or a related substructure. Two hundred and sixty-two compounds, including synthetic intermediates, pesticides, solvents, drugs, food components, natural products, and metabolites, are grouped by their structures. Some are in current use or are bioavailable while little exposure is expected from others. As more biologic-response information is reported for small compounds of these types, it should become possible to select others for research on additional questions of structure-activity relationships. Some of the compounds are widespread while others are not. Some are used or found in large amounts while others may be trace contaminants, minor or more major by-products of synthesis or isolation. The pesticides and solvents, for example, are knowingly and often deliberately released to the environment, sometimes in very large quantities. Inadvertent release also occurs, sometimes referred to as fugitive emission. Food contaminants and drugs are directly accessible to humans. Sparsely distributed natural products could be accessible to humans, for example, via the food chain. Some of the compounds in food may be formed during preparation, storage or metabolically. Last, the haloethylene function has often been synthesized into compounds in order to achieve desired biologic activities. There are many types and degrees of relatedness of structure, depending upon atomic dimensions and stereochemical, polar, resonance, and other factors. Furthermore, for some chemical series, biologic responses are continuously variable while, in other cases, it is not uncommon that qualitatively different types of response occur with apparently very close homologs. Genetic, metabolic, and behavioral factors affecting response must also be considered. Thus, safety or hazard cannot yet be predicted conclusively by apparent relatedness of structure alone. Also, since the tables are noncomprehensive, some relevant compounds have likely been omitted. The haloalkanes, for example, are not here because of their large number, despite the knowledge that some are either metabolized or nonbiologically converted to haloalkenes.


Interim results of two-year toxicological studies in rats of vinylidene chloride incorporated in the drinking water or administered by repeated inhalation. Male and female Sprague-Dawley rats were exposed to vinylidene chloride (VDC) orally or by inhalation in 2-year toxicological studies. Interim results are included in this report. VDC was given in the drinking water at mean +/- S.D. concentrations of 0, 68 +/- 13, 106 +/- 22, and 220 +/- 35 ppm which produced mean +/- S.D. dosage levels of 0, 5.9 +/- 0.6, 10.0 +/- 1.2, and 19.3 +/- 2.7 mg/kg for male rats and 0, 7.5 +/- 0.4, 12.6 +/- 1.1, and 25.6 +/- 2.4 mg/kg for female rats. Forty-eight rats/sex/VDC level and 80 rats/sex in the control group were used in the 2-year study with an interim kill of an additional 10 rats/sex/level at 90 days. In the inhalation study, rats were exposed to 0, 10, or 40 ppm of VDC vapor 6 hr/day, 5 days/week for 5 weeks, after which the exposure levels were changed to 0, 25, and 75 ppm of VDC. Exposure continued for a total of 18 months and the rats held for observation an additional 6 months. Interim kills occurred at 1, 6 and 12 months. A separate 90-day study using 20 rats/sex/level was conducted at 0, 25, and 75 ppm of VDC vapor. There were 86 rats/sex/level in the 2-year portion of the study. The parameters monitored were: body weight, food and water consumption (drinking water study only), hematology, clinical chemistries, cytogentics of bone marrow cells (inhalation study only), mortality, terminal organ weights, and gross and histopathology. Based on interim kills and gross pathologic observations, the main conclusions are: increased cytoplasmic vacuolation of hepatocytes was seen in the livers of rats given 200 ppm VDC in drinking water or 25 or 75 ppm VDC vapor by inhalation; based on gross tumor count, tumor incidence in VDC-exposed rats was not greater than controls.


Carcinogenicity studies on vinylidene chloride. Results of a study on Wistar rats regarding a possible carcinogenic effect of vinylidene chloride (VDC) were presented previously by one of the authors. Due to the unclear character of these results, a second inhalation study was initiated with Sprague-Dawley rats. Groups of 60 animals were exposed to 100 and 75 ppm VDC, along with one control group. A final report on the pathological results must await completion of the microscopic examination of the tissues and organs from all the animals. Nevertheless, it seems clear that there is no grossly observable interrelation between tumor production and VDC inhalation.


Chronic toxicity and reproduction studies of hexachlorobutadiene in rats. Hexachlorobutadiene (HCBD), while not produced commercially in the United States, may be encountered as an unwanted by-product of certain processes associated with the chlorination of hydrocarbons. Studies were conducted to assess the potential long-term toxicity of HCBD. In a reproduction study conducted in rats, dose levels of 20 or 2.0 mg/kg-day of HCBD induced slight maternal toxicity (primarily of the kidney) but caused no adverse effects on reproductive parameters-percent pregnancy and neonatal survival/development. A decreased neonatal body weight was noted at the highest dose level of 20 mg/kg-day of HCBD. No toxicologic effects were observed among the adults at a dose level of 0.2 mg/kg-day or among the neonates at dose levels of 0.2 or 2.0 mg/kg-day of HCBD. In a chronic toxicity study in rats, ingestion of 20 mg/kg-day for up to 2 years caused multiple toxicologic effects, primarily of the kidney, including the development of renal tubular adenomas and adenocarcinomas. Ingestion of the intermediate dose level of 2 mg/kg-day caused lesser degrees of toxicity, but no evidence of neoplasia. Ingestion of the lowest dose level of 0.2 mg/kg-day of HCBD caused no effects that could be attributed to treatment. These data indicate a dose-response relationship for HCBD-induced toxicity affecting primarily the kidney. HCBD-induced neoplasms occurred only at a dose level higher than that causing discernible renal injury.


Comparative mammalian metabolism of vinyl chloride and vinylidene chloride in relation to oncogenic potential. Elucidation of the role of vinyl chloride metabolites in the various reaction sequences which comprise the metabolic pathway, including the interaction of reactive metabolities with some purine and pyrimidine residues of target-organ DNA, provides some explanation for the (oncogenic) properties associated with the original substance. Comparative investigation of the biological fate of vinylidene chloride reveals an agent of low oncogenic potential which is likely to be damaging only under special circumstances, and species differences which suggest that the mouse is more susceptible than the rat towards vinylidene chloride oncogenicity.


Dominant lethal studies with the halogenated olefins vinyl chloride and vinylidene dichloride in male CD-1 mice. The mutagenic activity of vinyl chloride (VC) and vinylidene dichloride (VDC) at three exposure levels was assessed in fertile male CD-1 mice with the dominant lethal test. Each compound was assessed in a separate study. Male mice were exposed by inhalation to VC at 3000, 10,000, and 30,000 ppm and to VDC at 10, 30, and 50 ppm for 6 hr/day for 5 days. By comparison with control males exposed to air, no mutagenic effects on any maturation stage of spermatogenesis in treated males were detected. There was no significant increase in the number of postimplantational early fetal deaths as shown by the number of females with one or more early deaths or the number of early deaths/pregnancy or the number of early deaths/total implants/pregnancy. There was no evidence of pre-implantational egg losses as indicated by the total implants/pregnant female. There was also no reduction in fertility. (The reduction in fertility at 50 ppm VDC was unproven). The lack of effect was not due to the insensitivity of the system used, since both the VC and VDC study a mutagenic effect was clearly demonstrated in male mice dosed IP with the positive control compounds cyclophosphamide (CTX) and/or ethylmethane sulfonate (EMS). During dosing these animals were housed under similar exposure conditions to those animals exposed to the test substances but with a flow of air through the exposure chambers.Thus, neither VC nor VDC is mutagenic in the mouse at the stated exposure levels as measured by the dominant lethal test.


Preliminary report on the effects of totigestational exposure to ethchlorvynol. Ethchlorvynol, a sedative-hypnotic drug used clinically since 1955, has recently been the subject of renewed interest primarily because of its chemical relationship to vinyl chloride. In our totigestational studies, sperm-positive female rats were given a daily dose of ethchlorvynol dissolved in olive oil for 21 consecutive days. The dams were allowed to deliver and their offspring were observed for alterations in development by monitoring a number of gross behavioral, histological and biochemical parameters at newborn, weanling, puberty, adult and geriatric stages. Gross development appeared normal at time of weaning: however, offspring of treated dams showed increased behavioral activity in addition to alterations in a number of clinical chemistry parameters. The dose-response seen with most of the parameters suggests that the changes are drug related. However, the clinical pathological significance has not been ascertained.


Metabolism of halogenated ethylenes.

Metabolism of halogenated ethylenes. The metabolism of the chlorinated ethylenes may be explained by the formation of chloroethylene epoxides as the first intermediate products. The evidence indicates that these epoxides rearrange with migration of chlorine to form chloroacetaldehydes and chloroacetyl chlorides. Thus, monochloroacetic acid, chloral hydrate, and trichloroacetic acid have been found in reaction mixtures of 1,1-dichloroethylene, trichloroethylene, and tetrachloroethylene, respectively, with rat liver microsomal systems. Rearrangements of the chloroethylene, and glycols formed from the epoxides by hydration may also take place, but would appear, at least in the case of 1,1-dichloroethylene, to be quantitatively less important. The literature on the metabolism of chlorinated ethylenes and its relationship to their toxicity is reviewed.


Pharmacokinetics of vinylidene chloride in the rat. The metabolism of inhaled vinylidene chloride in rats represents a balance of biotransformation pathways leading to the formation of a reactive alkylating species which is normally detoxified by conjugation with glutathione. Detoxification of the reactive intermediate formed from inhaled VDC is dependent upon the availability of hepatic glutathione (GSH); as VDC exposure concentrations are increased, the fraction of the dose detoxified by conjugation with GSH decreases markedly, commensurate with depletion of hepatic GSH. This reactive intermediate in the absence of GSH alkylates hepatic macromolecules and causes cell death. Similarly, hepatic GSH plays a vital role in the detoxification of the reactive metabolite formed from inhaled vinyl chloride (VC). However, the dose--response relationships for the utilization of GSH and the accumulation of alkylating metabolites following inhalation exposure to either VDC or VC point to distinct differences which may explain the differing biological activities of the two materials. Finally, preliminary pharmacokinetic data for inhaled VDC in mice indicate an enhanced susceptibility to VDC by virtue of an increased ability for production of alkylating VDC metabolites over that observed in the rat. The importance of these findings in light of recent evidence for a carcinogenic effect of VDC in mice is discussed.


Reactions induced in vertebrates by invertebrate cell suspensions. I/Specific effects of sea star axial organ cells injection. Starfish axial organ cell suspensions injected subcutaneously into irradiated mice induce a characteristic angiogenesis reaction. The size of the reaction appears to be dependent upon the number of injected starfish cells. Axial organ cells also provoke a splenomegaly positive test in 16 day old chick embryos. No significant angiogenesis nor splenomegaly were induced by heat killed axial organ cells, ovocytes or branchial digestive organ cells. These results support our hypothesis that echinoid axial organ represents an ancestral primary lymphoid organ.


Reactions induced in vertebrates by invertebrate cell suspensions. II/Non adherent axial organ cells as effector cells. In contrast to starfish axial organ cells, coelomocytes of Asterias rubens do not induce a significant reaction of angiogenesis after subcutaneous injection into irradiated mice. Axial organ cells are separated into adhering and nonadhering cells by attachment ot plastic surface. Nonadhering cells consisting mainly of small lymphocyte-like cells appear to be effector cells in the reaction. Phytogenetic implications of these observations are discussed.


Electron microscopic studies of the developing amphibian thymus. Electron-microscopic studies of larval Xenopus laevis thymus at three different stages of development are presented. Studies of thymus from 5 and 8 day old larvae (ages when early thymectomy is performed) reveal a relatively undifferentiated rudiment composed of epithelial cells and lymphoid cell precursors. These findings are in marked contrast to ultrastructural observations of 30 day old larval thymus, where there exists a well defined corticomedullary differentiation with an abundance of small lymphocytes in the cortical region.


The fate of transplanted tails in frog larvae. Frog larvae recieved transplants of autografts, allografts, and xeonografts using Rana brevipoda and Rana japonica. Tail tip autografts heal rapidly, continue to grow but undergo degeneration at metamorphosis. Allografts and xenografts also heal but show signs of rejection by the host's immune system. Onset of rejection depends upon the stage when grafts were performed. If transplants were made during early stages, onset was late; if performed later, onset was early. Because frog larvae will eventually undergo metamorphosis as a result of thyroxine effects, they are excellent experimental models for correlating the immune and endocrine systems with differentiation, growth, and aging.


Antibody-dependent cellular cytotoxicity in poikilotherms. 51Cr-chromate labelled chicken red blood cells, treated with rabbit (anti-chicken red blood cell) serum, are lysed in vitro, in the absence of complement, by spleen cells from Xenopus laevis, Ambystoma mexicanum or Lacerta viridis. Optimal conditions for lysis by Xenopus spleen cells were determined. The phenomenon seems homologous with antibody-dependent cellular cytotoxicity (ADCC) mediated by mammalian or avian K cells. The phylogenetic significance of the finding is discussed.


Birth weight in relation to maternal socio-economic status. On an attempt to illustrate the influence of maternal socio-economic status on birth weight, this study was carried out on 689 full term new borns. The weight, age, parity, income and occupation of their mothers were compared to the birth weight. A correlation was also performed between birth weight and the presentation of the babies and the ante-natal care offered to their mothers. A positive correlation was only found to be present between birth weight and family income below 10 pounds/month. A similar correlation was noticed between birth weight and the interpregnancy interval up to 30 months. The presentation of the foetus might be of influence on birth weight only in cephalic and breeck presentation. The age of the mother, occupation, weight were negatively correlated with birth weight.


Effect of low-protein diet and its duration on hair composition. The effect of feeding rats a low-protein diet (1%) and its duration (4, 8, 12 and 16 weeks) on the protein content and the amino acids pattern of hair were studied. These variations were compared with control group fed an adequate protein diet (16%). Protein content of hair was diminished in the protein deficient rats after four weeks followed by a gradual decrease till the end of the experiment. Sulphur-containing amino acids cystine and cysteine were significantly reduced in the hair of the protein deficient rats when compared with the controls. The amino acids patterns showed significant differences from controls by the end of the whole experimental period.


Red cell membrane protein in thalassemia and glucose-6-phosphate dehydrogenase deficiency anemia. Twenty cases of thalassemia major and 20 children with glucose-6-phosphate dehydrogenase deficiency were studied for the protein content of their red cell membrane as well as for its fractions, compared to 20 normal controls. The results showed that the total membrane proteins per red cell and the various fraction percentages in both conditions were not significantly different from normal controls. Also the acrylamide gel electrophoretic studies of the red cell membrane proteins gave band patterns identical with those of normal controls. These results are discussed.


[Mapping of the c-region of phage phi80]. A set of c-mutants of the phage phi80 is isolated. These mutants fit into three genes. According to plaque morphology and frequency of lysogenization of mutants, the genes were named cI, cII and cIII as it was previously done for phage lambda. Their order, determinated by mutant phage crosses, is cIII-sus326-cI-cII-sus250. Sus326 is a mutation in the gene 15, so it is probably an analogue of the N gene of the phage lambda. Thermoinducible mutants of the phage phi80 cts11 and cts12 correspond to the mutant types cItsB and cItsA of the phage lambda and they complement each other. Thus, it is supposed that phi80 phage repressor molecules consist of few protein subunits.


[Characteristics of the mutants of the temporate actinophage phiC31 with a disordered lysogenicity and that overcome the immunity of lysogenic cultures]. The study of c- and cts-mutants of the temperate actinophage phiC31, affecting the lysogenization process in Streptomyces coelicolor showed the interallelic negative complementation. This fact implies the protein nature of the repressor synthesized under the control of gene C and its multiunit structure. Transdominant c- and cts-mutants were partly virulent being able to overcome the immunity of lysogens with effecting of plating (eop) about 5. Virulent mutants infecting lysogens with an eop 1 were detected. Differences in behaviour of virulent mutants isolated from transdominant mutant (v) stock and those containing a recessive mutation in the gene C (vd- and vdt-mutants) are shown. It is demonstrated that vd-mutants unlike v-mutants are not capable of growing without phage-helper (presumably prophage) and use many prophage gene products marked by ts- and host-range-mutations to form progeny. Common to all isolated virulent mutants are their ability to promote the prophage induction in lysogens and inability to display virulent phenotype in the absence of a mutation in the gene C.


[Frequency of chromosome aberrations in persons living in areas with a varying pesticide expenditure]. The frequency and types of chromosome aberrations in peripheral blood lymphocytes were studied in two groups of healthy pupils of 15--17 years old (55 persons) living in agricultural districts with three-fold difference in pesticides' application. 10096 metaphases were analysed. The average level of aberrant cells comprised 2.12% in experimental and 1.74% in the control zones; the difference between them being insignificant. In lymphocytes of people, living in both districts, chromatid types of aberrations (especially, single fragments) prevailed. The results obtained may serve as the base data for further investigation of the spontaneous mutagenesis of people living in these agricultural zones.


[Induction of gene mutations and the lethal action of ultraviolet rays in synchronized Chinese hamster cells]. Lethal and mutagenic effects of UV light were studied in two synchronized UV-sensitive Chinese hamster cell clones differing in the degree of sensitivity (CHS1, CHS2). It is shown that the phase of mitosis is most resistant to the lethal effect of UV. The sensitivity of both cell clones increases in the pre-synthetic phase and reaches its maximum during the phase of DNA synthesis. Positive correlation of cell sensitivity to mutagenic and lethal action of UV was observed when studying induced mutability in both cell clones during the phase of DNA synthesis. However, the study of the mutagenic effect of UV on different phases of the synthesis. However, the study of the mutagenic effect of UV on different phases of the cell cycle (M, G1, S) in the less UV-sensitive cell clone has revealed that the maximal mutation yield takes place when cells are irradiated at G1 (CHS1). The discrepancy observed may be due to different probability of the phenotypic detection of pre-mutational lesions, arising at different phases of the cell cycle. It is shown that only one cell generation is necessary for the expression of pre-mutational changes. These data allow to conclude that the increased mutation rate observed at G1 (as compared with S) reveals rather a probability of the expression but not of the occurrence of pre-mutational lesions. It is suggested that the fixation of mutations in the cells studied proceeds during the post-replication repair synthesis.


[Rate of spontaneous chromosome aberration occurrence in cultured Chinese hamster cells]. The spontaneous chromosome mutation rate was studied in cultured aneuploid Chinese hamster cells (clone 237(1)) using the method of slowing down the rate of cell division in a limiting medium containing 0.1% of serum. It was shown that during one cell generation (which lasted 14 days in limiting medium) the accumulation of chromosome aberrations with time took place. The data obtained are in keeping with the assumption of a linear dependence of this accumulation on time. The spontaneous chromosome rearrangement rate was 1.2 X 10(-2) mutations per cell per 24 hours. Proceeding from this value the spontaneous chromosome aberration rate in cells with a normal duration of the cell cycle was 0.6 X 10(-2) per cell per generation.


[Problems of the genetics of stress. III. The differential effect of stress on the fertility of mice of differing genotypes]. Pre- and post-implantation embryonic mortality and the litter size in intact females and in females stressed during pregnancy were studied. These mice were the progeny of full diallele cross of 4 inbred strains (BALB/c, C3H/He, C57BL/6 and AKR/J). No genetic effects of pre-implantation losses were observed in the control group, but in the stressed group significant genetic effects (both additive and non-additive) on this character were found. Females originating from the most emotionally reactive strain (BALB/c) had a greater value of pre-implantation losses than the other animals, while the progeny of the least emotionally reactive strain (C57BL/6) had a smaller one. The litter size in the latter females was larger than in the former, in spite of the fact that the number of ovulation in RALB/c progeny was higher than that in C57BL/6 progeny. Thus, differential effect of stress on fitness was demonstrated in these experiments.


[Mutagenic action of cadmium on the sex cells of male mice]. Possible mutagenic effect of cadmium chloride was studied by determining the frequency of dominant lethal mutations induced in germ cells of male mice. Water solution of CdCl2 was injected intraperitoneally to male mice at doses of 1.0, 2.0 and 4.0 mg/kg. The results obtained did not reveal any mutagenic effect of this compound. The dose of 4.0 mg/kg CdCl2 resulted in the death of spermatocytes and spermatogonia and the sterility of male mice. Cadmium chloride at a dose of 2.0 mg/kg did not affect the frequency of dominant lethal mutation induced by gamma-rays 60Co at a dose of 450 r in germ cells of male mice.


[Role of thymine dimers in the UV mutagenesis of bacteriophage sd]. The sensitized irradiation (lambda greater than 310 nm) with AcphiM induces plaque mutants of extracellular phage Sd. Thus, TT in phage Sd DNA are both lethal and mutagenic. The yield of plaque mutants is about 3-fold lower as compared with the yield after UV-irradiation (lambda = 254 nm). The theoretical analysis of UV-induced mutagenesis curves of phage Sd was carried out. It is concluded that the following photoproducts make a contribution in the mutagenic effect of near-UV (lambda = 254 nm): 1) lethal pyrimidine dimers; 2) other lethal photolesions; and 3) non-lethal mutagenic photoproducts of cytosine. The cytosine photohydrate contribution nearly twice exceeds the total contribution of lethal photoproducts. It is assumed that bacteriophages T4 and Sd have their own system of repair, like SOS-repair in bacteria.


[Multiple antibiotic resistance in actinomycetes]. Native strains of Actinomycetes from three systematic groups of Streptomyces (blue, gray and globisporine) have been characterized for their resistance to antibiotics and sulfamids. Most strains are found to possess stably inheritable multiple resistance to many antibiotics. The resistance of a number of strains to the aminoglycoside antibiotics and penicillins appears to be due to the presence of inactivating enzymes in these strains. The resistance to erythromycin, lyncomycin, tetracycline and ristomycin is likely to have an inducible nature in S. coelicolor A3(2). Linkage analysis for resistance determinants in pairs suggests random distribution of the majority of determinants among tested strains. Non-random distribution has been shown for determinants of resistance to tetracycline, chloramphenicol and ristomycin in Tc Cm, Tc Rm combinations.


[Nosological classification of bokhoror]. The results of neurological, pathomorphological and clinic-genealogical studies of vilyuisk encephalitis (VE), a chronic progressive disease of CNS, are presented. The disease is spread in Yakutija in Vilyui river basin (mainly in Vilyuisk and Kobyaisk regions) exclusively among native population and is known there since the middle of the last century. The results obtained suggest that VE (despite the existing opinion on its natural-focal virus etiology) is an ethnic hereditary disease with autosomal recessive type of transmission, is spread in a limited Yakut population by an ancestor effect and gradually gets out of the limits of this population at the expense of migration. According to its clinical symptoms and pathomorphological substrate of this main neurological syndrome (peculiar lower spastic paraparesis as a result of systemic ascending degeneration of lateral corticospinal tract of spinal cord), VE belongs to hereditary heterogenous group of diseases which are referred to Strümpell's spastic paraplegia. VE is different from the diseases of this group by the occurrence of cases with very rapid progressing and characteristic brain damages. To prevent further VE accumulation, it is necessary to concentrate efforts on biochemical and neurological studies in search of reliable tests for early detection of heterozygotes. Taking into account the hereditary nature of VE, its ethnic limitations and nosological self-dependence, it is expedient to designate the disease by its local name "bokhoroor".


[Genetic structure of an isolated native population group of northern Sibiria, the Nganasani (Tavgi) of the Taimyr. II. An analysis of intrapopulation variability]. Chi-square contingency table analysis of phenotypic (genotypic) and gene frequencies of erythrocyte and blood serum groups and enzymes in a group of reindeer hunter and fishermen revealed heterogeneity within the population studied. Four out of twelve loci which have been compared were found to be involved in the process of differentiation into two local subgroups (subpopulations). No statistical differences have been observed between samples arbitrarily representing three generations. The data obtained support the hypothesis that the whole population still preserves the state of the stability. Traditional migration from adjacent populations close to nganasans by language and culture has made an important contribution into heterogeneity found in nganasans.


Determinants of venous return in the fetal lamb. Measurements have been made of the peripheral vascular factors influencing venous return, and hence cardiac output, in the fetus. These measurements show the fetus maintains a high venous return by means of a high mean systemic pressure, or driving pressure for venous return, and a low resistance to venous return. Increases in fetal blood volume cause increases in mean systemic pressure with no change in resistance to venous return and, as a result, venous return is increased. These studies show the possible importance of peripheral vascular factors in the control of cardiac output.


Intrauterine pressure wave form characteristics of successful and failed first stage labor. A retrospective study was designed to contrast the intrauterine pressure wave form characteristics of hypocontractile labor in patients with and without obstruction and before and after oxytocin therapy. No differences were observed between the patient groups (vaginal delivery vs. cesarean section), either before or after oxytocin. Problems in defining adequate contractility in patients with possible obstructed labors are discussed, and new parameters of potential value are identified.


Galactosyltransferase activity of the microvillous surface of human placental syncytial trophoblast. The syncytial trophoblast has previously been shown to have minimal intrasyncytial galactosyltransferase activity at term. The biochemical and autoradiographic study reported here shows that the microvillous surface of term human placental syncytial trophoblast has a galactosyltransferase activity capable of transferring 3H-galactose from uridine diphosphate-D-galactose-1-3H to trichloroacetic-acid precipitable, endogenous acceptors. This capability of resynthesizing cleaved galactose moieties in the glycocalyx, without dependence on cytoplasmically located galactosyltransferases, would allow for reinstatement of the original surface molecular configuration without requiring synthesis and insertion of a completely new membrane molecule. It is suggested that the surface galactosyltransferase might function to repair damage to syncytial trophoblast glycocalyx induced by the enzymes in maternal blood.


Sequential evaluation of the supine hypertension or 'roll-over' test in a high risk population. The supine hypertensive or 'roll-over' test (ROT) was performed serially in 24 primigravid patients between 27 and 35 weeks of gestational age. Pregnancy-induced hypertension (PIH) developed in 3 women (12.5%). Test producibility one week to the next in the same patient was poor. A false-positive ROT was noted for 83% of our patients a false-negative test for 12.5%. We conclude that serial testing reveals marked variations in response that reflect inherent biologic fluctuations that limit the predictive value of the ROT for screening outpatients.


Fetal metabolism during recovery from surgical stress. 10 fetal lambs prepared with sampling catheters in the common umbilical vein and distal aorta were studied at 2 h, 2 and 4 days postoperatively. Umbilical blood flow was measured by a diffusion equilibrium method. Oxygen, lactate, pyruvate, glucose and alpha-amino nitrogen concentrations were determined on umbilical arterial (UA) and umbilical vein (UV) blood. Fetal oxygen consumption averaged 10.4, 10.6 and 1.0 ml.kg-1.min-1 for the three study periods. Lactate/pyruvate ratios were higher in UV than in UA in 17 of 20 experiments. Significant reductions (p less than 0.05) in (1) maternal mixed venous-UA glucose concentration difference, and (2) UA glucose concentrations occurred at 2 and 4 days compared to the 2-hour period. Fetal alpha-amino nitrogen balance was negative at the 2-hour period, but positive 2 days and 4 days postoperatively.


Vasodilating effect of estrogen on the human umbilical artery. The effects of estradiol, estrone and estriol on the tonus of the isolated vascular segments of human umbilical artery were studied by a perfusion technique. Estradiol (10 microgram/ml), estrone (10 microgram/ml) or estriol (2 and 10 microgram/ml) produce relaxation of the vascular bed which was reflected in a significant reduction in basal pressure of segments perfused at constant rate. A dose-dependent relationship was demonstrated for estriol. The time dependence and extent of relation were similar for all three natural estrogens.


A mechanism of action of phenylephrine on heart. Phenylephrine exerted a positive chronotropic and inotropic effect on isolated, spontaneously beating, atria of reserpinised rabbits. Addition of phenoxybenzamine and phentolamine resulted in a depression of control contractile amplitude. Practolol, however, was devoid of this effect. The positive inotropic response to phenylephrine was significantly antagonised by all the three blockers used, while positive chronotropic response was annulled by phentolamine and practolol, but not with phenoxybenzamine. It is, therefore, suggested that phenylephrine exerts its cardiostimulant effects through mediation of both alpha and beta-1 adrenoceptors. A probable mechanism of action could be, that phenylephrine acts on some specific chemical group, shared by alpha and beta1 receptors. This specific group is probably blocked by both alpha and betaceptor antagonists separately, so phenylephrine becomes ineffective in presence of these antagonists.


Exercise induced serum enzyme changes in untrained subjects. The serum enzyme values (GOT, GPT, LDH and Aldolase) of 13 fit healthy volunteers were determined before and after physical effort of a moderate grade of 3.9 Kcal/min. The pulse rate pattern of the subjects during the exercise of climbing up and down a staircase for 30 minutes and during a 10 minute recovery phase was also recorded. The pulse pattern was in no case in excess of 150 bpm and full recovery was achieved within 10 minutes indicating that the exercise was moderate. The serum enzyme values after the exercise were raised. The difference between the exercise and rest values of the four enzyme activities were significant at the 1% level. It was observed that the raised enzyme activity level dropped to normal levels within 24 hours after the exercise. Large individual variations in the rise of these enzyme levels after exercise were observed and hence it is difficult to quantitate the phenomenon. Consequently the value of serum enzyme levels after the exercise as a practical-index of physiological strain is limited.


Hypothermia and acetylcholine content of dog heart. The acetylcholine level of dog heart has been determined under hypothermia. It was increased at 28 degrees C, and decrease at 20 degrees C. Further, it was observed that the heart rate and blood pressure decreased with gradual reduction in the body temperature of the dog and ventricular fibrillation occurred in 50% of the animals at 20 degrees C. It is proposed that cholinergic agents may have a role as antifibrillatory agents in hypothermia.


Seminal fructose, citric acid and phosphatase levels and their relation to the sperm count in man. Seminal fructose, citric acid and phosphatase levels were estimated in 60 normal adults and compared with 60 oligospermic and 24 azoospermic Indian subjects. In normal group, the seminal plasma fructose level and acid phosphatase activity showed a fall as the sperm count increased. As compared to normals, significantly higher mean values for fructose and acid phosphatase activity were observed in oligospermic and azoospermic groups. Seminal alkaline phosphatase activity did not show any relationship with sperm count. Similarity in changes observed in seminal fructose and acid phosphatase levels with respect to seminal citric acid content and sperm concentration suggests that both these parameters are probably regulated by similar physiological mechanism.


Leucocyte phagocytic response in relation to abo blood groups. In vitro suspension technique was carried out in order to study the phagocytic activity of the leucocytes spun out from the blood of healthy young volunteers belonging to similar socio-economic group and having no history of recurrent infection, drug medication and chronic smoking. Saline suspension of Staphylococcus aureus was mixed with leucocyte rich cream and incubated at 37 degrees C for 1/2 hr. Films were stained with Leishman and leucocytes were examined under microscope for calculation of their phagocytic coefficients. Blood group O seems to have highest values, followed by A, B and AB in that order. It is likely that the phagocytic co-efficient is correlated to the presence or absence of specific blood group substances ABH (O) or their antibodies.


Modification of vascular response to synthetic oxytocin by oestrogen in rabbit. Intravenously administered oxytocin caused a dose-related fall in blood pressure of the rabbit. When oxytocin was administered in oestrogen-primed animals, the depressor response was converted to a pressor one "Oxytocin reversal". The "oxytocin reversal." was abolished after treatment with dihydroergotamine, hexamethonium or adrenalectomy. The "oxytocin reversal" did not appear in reserpinized animals.


Studies on the toxic effects of streptolysin 'O': electrocardiographic changes in mammals. The effect of streptolysin 'O' (a streptococcal exotoxin) on ECG in rabbits and mongrel puppys has been investigated. The intravenous administration of streptolysin 'O' (SLO) in doses of 0.5 to 2 U/kg in rabbits and 0.5 to 4 U/kg in puppys immediately caused transient sinus bradycardia, which was dose dependent. Intense sinus bradycardia followed by ST elevation and progressively increasing atrioventricular blocks in rabbits and nodal rhythm and intraventricular conduction defects in puppys, terminating in cardiac standstill were observed after a dose of 4 and 8 U/kg respectively. Pretreatment of rabbits with antistreptolysin 'O' completely protected them against the cardiotoxic and lethal effects of challenging doses of SLO. It is suggested that this streptococcal component may be involved in the causation of derangements of cardiac activity during acute rheumatic fever in man.


Central cholinergic mechanism for control of urine volume and electrolyte excretion. 1. Studies were conducted on urine volume and electrolyte excretion chiefly of Na and K in anaesthetized hydrated dogs. 2. Central injection of acetylcholine caused a dose dependent antidiuretic response but without any change in excretion of urinary Sodium (UNa) and Potassium (UK). 3. After central atropinization, antidiuretic response to acetylcholine was partially blocked without any effect on electrolyte excretion. 4. Intracerebroventricularly (I.C.V.) administered acetylcholine after vagotomy and spinalectomy, each done separately and together also elicited an antidiuretic response. There was no effect on electrolyte excretion. 5. It is thus suggested that acetylcholine may be acting on central cholinergic receptors concerned with A.D.H. release.


Methods of combining the correction of deformities of the knee with the use of the total condylar prosthesis. Study of post-operative stability. (1) Our Total Condylar knee prosthesis can be adapted to cases of severe deformity, either varus or valgus, and to flexion contracture. (2) The technique of mobilization and sliding of the capsulo-ligamentous structures on the contracted side is necessary in cases with severe deformity. (3) After mobilization of the contracted structures it is necessary, before sectioning the bone, to distract the joint in flexion as well as extension in order to achieve stability both in the sagittal and frontal planes. (4) Despite the removal of the cruciate ligaments and capsulo-ligamentous slide, no significant residual instability was found in either plane.


Results of manipulative treatment of congenital club foot. Review of seventy-six cases after more than six years. The authors draw the following conclusions from a long-term review (six to twenty-eight years) of seventy-six cases of congenital club foot, treated by the "classical" method of moulding therapy, sometimes in association with elongation of the Achilles tendon: --There was a high percentage of poor and moderate results (32.7 per cent), though this is lower than the average values reported by other authors (fifty to sixty per cent); --Elongation of the Achilles tendon (performed late, between the ninth and fourteenth month of life) still significantly reduced the percentage of unsatisfactory results (twenty-four per cent in the cases operated on); --Residual deformities between fairly well-marked limits were well tolerated. --The "classic" moulding therapy should and can be modified in the interests of improving our results, (earlier or more radical surgery where indicated) but does not deserve to be abandoned completely.


Paralysis of the trapezius associated with myogenic torticollis. A report of 6 cases. The authors report the follow-up results of forty-three patients operated on for myogenic torticollis between 1965 and 1975. The surgical treatment consisted of distal tenotomy in eight cases, distal and proximal tenotomy in twenty-three cases, tenomyomectomy in eight cases. The results were subdivided into three groups: excellent twenty-two, (57 per cent); good , fourteen (38 per cent); poor, two (five per cent). The most interesting finding that emerged was the association of paralysis of the trapezius muscle with myogenic torticollis: this was observed in six cases, three after and three before operation. Preoperative investigations, including an EMG test and confirmation at operation, appeared to show that the paralysis was secondary to compression of the accessory nerve in its passage through the sternocleidomastoid muscle. Neurolysis, performed in three cases, led to recovery of the paralysis. Compression of the accessory nerve is slowly progressive, and paralysis or paresis of the trapezius muscle therefore occurred late. In fact, the patients who presented with both lesions were well beyond infancy. The authors emphasize the importance of being aware of the association of this lesion with myogenic torticollis so that operation for the latter may complemented by neurolysis of the accessory nerve.


The importance of the acetabular rim in the genesis of congenital hip dysplasia. Experimental research. The posterior aspect of the cartilaginous acetabular rim was surgically removed in very young rabbits in order to study its effect on the further development of the acetabular cavity. A dysplasic change was produced which led to posterior hip dislocation. Through an analysis of the morphological, radiographic and histological findings, and comparison with human congenital hip dislocation, the acetabular rim is considered to be physiologically responsible for the development of the retaining properties of the acetabular cavity. Moreover, a genetic abnormality altering the physiological development of the cartilaginous acetabular rim, is responsible for the non-retaining power of the acetabulum which leads to congenital hip dislocation.


Acceptance of the rights of homosexuals: a social profile. The relationships between attitudes toward homosexuality and sociodemographic and attitudinal variables were explored, using the data from a nationwide opinion survey in the United States. Individuals who were willing to grant such rights to homosexuals as teaching in college, speaking in a local community, and removing a book from a local library written by a homosexual and favorable to homosexuality, tended to be well educated, young, Jewish or nonreligious, from urban areas, raised in the Northeast or Pacific states, and willing to provide freedom of expression to people with nonconformist political ideas. "Erotophobia," which was not related closely to the rights issue, was associated with moral judgments about homosexual acts.


Attitudes, opinions, and sexual development of 205 homosexual women. Two hundred and five homosexual women, aged 15 to 50, were surveyed as to their attitudes and experiences in the areas of education, religion, family experiences, marriage, friendship, personal happiness, sexual development and satisfaction, psychological adjustment, and occupational status. The investigation discovered a high rate of only-child status among lesbian women, a tendency toward ambivalence of opinion on many issues, and a general lack of insight into self and others. Comparisons with other research on female homosexuality were made.


Role expectations and definitions: a comparison of female transsexuals and lesbians. A new study on female transsexuals and lesbians is reported. A matched-group comparison of 15 women in each sample suggests that the two groups do not differ in overall intelligence, although lesbians, unlike female transsexuals, tended to have a significantly higher verbal IQ than performance IQ. Both groups showed a similar response pattern on the Embedded Figures Test but differed on the Draw-A-Person Test, The Guilford-Zimmerman Temperament Survey, and the Bem Androgyny Scale. Whereas the female transsexual group reflected a more rigid gender role stereotype, the lesbians saw their options as more androgynous.


Media mating I: newspaper "personals" ads of homosexual men. Based on a design used in previous research with heterosexuals "Personals" advertisements, this study reports a content analysis of 359 ads placed by male homosexuals. Following exchange theory, it was hypothesized that, as with heterosexuals, a favorable presentation of self would characterize the advertisements. Further hypotheses predicted that homosexual ads would be more frank than are heterosexual ads and more specific about goals for desired relationships, and that homosexual ads would reflect the "virilization" of the male homosexual subculture. All predictions were strongly supported. The overtly sexual explicitness of many of the advertisements was explained on the basis of differences between same- and cross-sex relationships, and male/female differences in conceptualizing "love."


Teaching assertive skills to a passive homosexual adolescent: an illustrative case study. Social skills training was used to alter the socially inappropriate and ineffectual behavior of a 17-year old homosexual male. Target behaviors selected for treatment were the subject's effeminate mannerisms and lack of assertiveness in conflict situations, especially those involving other persons making derisive comments to him. A multiple baseline design was used to increase the patient's (a) eye contact, (b) rate of making appropriate requests for behavior change in others, and (c) general level of assertive affect. Six training and six generalization role-played interpersonal scenes were used. Results indicated significant improvement on trained social skills components with generalization to nontrained scenes as well. Implications of these findings are discussed, particularly with respect to social skills and assertion training for effeminate homosexuals.


An evaluation of the validity of the Freudian theory of paranoia. This paper evaluates the validity of the Freudian theory of paranoia on the basis of the available research evidence. This theory essentially states that delusional thinking arises as a result of the reaction-formation and projection of threatening unconscious homosexual wishes. It is concluded that a positive association between paranoid and homosexual tendencies has been found, but only for the case of male paranoid patients. The research leading to this conclusion has not, however, demonstrated that a defensive attempt against unconscious homosexual impulses causes delusional thinking. Rather, the argument is made that it is more parsimonious to assume that only the second step in the Freudian etiological mechanism, a continuous tension-reducing projection of the patient's threatening and intense hostility, need be invoked to account for paranoia.


Rational design of arabinosyl nucleosides as antitumor and antiviral agents. The rational design of antitumor and antiviral agents must ultimately take advantage of biochemical differences between normal host cells and transformed cells. The initial experiments must be performed with subcellular or cellular model systems. For the studies with arabinosyl nucleosides we have chosen those enzyme systems, synthesizing DNA and RNA; being precursor analogues, the different arabinosyl nucleosides have been added in the triphosphate state to the different DNA- and RNA polymerase assays. 1-beta-D-Arabinofuranosylcytosine-5'-triphosphate has been found to inhibit the RNA-dependent DNA polymerases (isolated from oncogenic RNA viruses) 200-fold more sensitively than viral and cellular DNA-dependent DNA polymerases. Recent results, showing that RNA-leukemia-virus-related sequences are present in DNA of some human leukemia patients might support the assumption that the efficacy of this antimetabolite in the treatment of acute leukemia is due to its, at least relative selective inhibitory activity on reverse transcriptase. 9-beta-D-Arabinofuranosyladenine-5'-triphosphate is a strong inhibitor of cellular DNA polymerases with the cytological consequence of an inhibition of cell proliferation. The clinical benefit of the compound in treatment of tumors is dependent on their levels of adenosine deaminase. The triphosphate of this compound is a 100-fold more sensitive inhibitor of the herpesvirus DNA polymerase compared to the cellular replicative DNA polymerase. In addition the analogue, incorporated into herpesvirus DNA, acts as chain terminator. These effects are the biochemical basis for the highly selective antiherpesvirus activity of this antimetabolite. The anomer 9-alpha-D-arabinofuranosyladenine-5'-triphosphate only inhibits cellular replicative DNA polymerase and has no effect on herpesvirus DNA polymerase. Consequently this agent acts only cytostatically and not antivirally. Concerning 1-beta-D-arabinofuranosyluracil and 1-beta-D-arabinofuranosylthymine no pronounced antitumor or antiviral effect is known.


Enzyme inhibitors in relation to cancer therapy. In the last 11 years the authors have succeeded in isolating nearly 40 enzyme inhibitors of small molecular size from microbial origins. These inhibitors proved to be not only useful tools in analyses of homeostasis of living organisms but also promising agents for cancer chemotherapy. Leupeptin was originally isolated as an inhibitor against serine or thiol proteases such as trypsin, plasmin, papain and cathepsin B. And soon it was demonstrated that leupeptin suppressed chemical carcinogenesis in rats. Pepstatin has an extremely strong activity to inhibit pepsin and cathepsin D. It also inhibits ascites accumulation caused by neoplastic diseases. Bestatin is a specific inhibitor against aminopeptidase B and leucine aminopeptidase. The enzymes are located on the surface membrane in various kinds of cells including lymphocytes. Bestatin was shown to enhance not only blastogenesis of lymphocytes in vitro but also establishment of delayed-type hypersensitivity in vivo. Combined use of bestatin and other antitumor agents gave promising results in animal experiments. Studies on enzyme inhibitors have provided us a new approach to cancer chemotherapy.


Modern instrumental methods for identification of antibiotics. Modern screening for antimicrobial agents and the characterization of their transformation products are not only extremely competitive but highly labor intensive activities. The use of specialized instrumental techniques for rapid identification of molecular species shows promise of becoming an essential part of this process. At the earliest stages, microseparation methods coupled with modern methods of ion production are particularly useful. Applications of various methods of chromatography, including high performance liquid chromatography, with various methods of ion production using mass spectrometers, particularly under computer control, are exceptionally powerful, though expensive, means of addressing this problem. Some present and potential uses of this technique are discussed along with a consideration of the strengths and weaknesses now apparent and a projection is made of the future of this method. A brief review of the use of a variety of physical methods of structural characterization for a variety of specialized purposes is also given along with a bibliography of recent applications to specific antibiotics. The scope and limitations of these methods is also treated.


Some observations on biodegradation of pollutants in aquatic systems. The biodegradability of pollutants introduced into aquatic environments is subject to many variabilities characteristic of microbial processes. Some observations have been reported on studies with p-cresol, methyl parathion, benzo[b]thiophene, dibenzothiophene, 9H-carbazole, quinoline, benzo[f]quinoline, benz[a]anthracene, benzo[a]pyrene, 7H-dibenzo[c,g]carbazole, Mirex, 2,4-dichlorophenoxyacetic acid, Lindane and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane analogs. Water reservoirs included a eutrophic stream, a eutrophic pond, an oligotrophic lake and effluents from waste-water treatment plants. The first ten of the above compounds were studied only in aerobic mixed-culture systems, and Mirex was studied with mixed cultures under both aerobic and anaerobic conditions. Examples were presented of the significance of cometabolism, diauxic processes, film fermentations and microbial interactions in biodegradation studies. Caution is advised in protocols regarding biodegradability of pollutants in aquatic environments.


Antitumor screening procedures of the National Cancer Institute. From the time of its inception in 1955, the Drug Development Program of the National Cancer Institute has relied primarily on transplanted rodent tumor systems in vivo for the evaluation and selection of potential antitumor agents. Although greater emphasis has been placed in recent years on rationally designed drugs, the major effort throughout the history of the program has involved the empirical screening of a wide variety of chemical structures and natural products of varying sources. The initial screening spectrum consisted of three mouse tumors, Sarcoma 180, Carcinoma 755 and Leukemia 1210, based on the retrospective analysis presented in the GELLHORN-HIRSCHBERG Report. As a result of further expermental studies and analyses, the screens changed successively to (1) L1210 plus a spectrum of mouse, rat and hamster tumors, (2) L1210 plus the rat tumor, WALKER 256, (3) L1210, plus P388 for natural products and B16 melanoma and LEWIS lung carcinoma for special studies, and finally (4) P388 as a pre-screen followed by a panel of transplanted tumors and xenografts representing the major tumor sites. The rationale underlying each of the successive changes, and results obtained with each approach, will be discussed.


New anthracycline antibiotics.

New anthracycline antibiotics. A number of anthracycline antibiotics have been found in Streptomyces cultures. Among them, adriamycin and daunomycin have been studied most in detail, because these compounds have exhibited a strong antitumor activities 1, 2). However, their clinical usefuleness is limited by side effects, particularly by bone marrow suppression and cumulative dose-dependent cardiac toxicity. 3 approximately 5) By the collaboration with Prof. H. UMEZAWA and Dr. T. TAKEUCHI, Institute of Microbial Chemistry, for the studies to find out new anthracycline antibiotics that may have lower cardiac toxicity and the same degree of the antitumor activity, we found 32 new anthracycline compounds in Streptomyces cultures and aclacinomycin A is under the phase II clinical study. Anthracycline compounds can be classified depending on the structures of their aglycones as shown in Table 1. These compounds have a linear tetracyclic polyhydroxy anthracyclines, and can be grouped into seven groups. Biologically active anthracycline antibiotics have various sugar moieties at C-7 and/or C-10 position of the anthracyclinones. In 1951, H. BROCKMANN6) discovered rhodomycins A and B in the culture of a new species of Streptomyces purpurascens. Since then, he found numerous anthracycline compounds such as rhodomycin-, isorhodomycin- and pyrromycin-types in Streptomyces and elucidated their structures. All of these anthracyclines are red pigments. In 1964 and 1969 new group of orange-red anthracycline antibiotics: daunomycin10) and adriamycin11) was reported by DiMARCO and F. ARCAMONE. Moreover, aklavin12, 13) which has yellow aklavinone as aglycone and citromycinone aglycone14) which is also yellow have been isolated in the Streptomyces cultures. Aclacinomycin A15), which we found in Streptomyces galilaeus MA144-M1, has aklavinone aglycone and is becoming more interesting in its low cardiac toxicity.


Mycophenolic acid and its mechanism of action in cancer and psoriasis. Mycophenolic acid is active against fungi, bacteria, and viruses in vitro and is active against some viruses and tumors in experimental animals. Mycophenolic acid is not effective in the treatment of cancer in man, but it is effective in treating psoriasis. In all of the various diseases MA presumably inhibits the synthesis of GMP resulting in decreased synthesis of RNA and DNA. The direct inhibition of GMP synthesis is the result of MA activity against the IMPDHase and GMP synthetase as determined in experimental tumors. The inhibition of GMP synthesis can be circumvented by the guanine salvage pathway which is controlled by PRTase activity. PRTase may be the sole factor in preventing the inhibition caused by MA in the biosynthesis of GMP (Fig. 3). However, before MA can stop GMP synthesis, MA must enter the cell. The current data show that MA is almost completely detoxified in man and circulates in the plasma as the glucuronide, MAG, Glucuronides are normally inactive forms of active drugs. Due to their bivalent and non-lipophilic nature, glucuronides do not normally cross the cell membranes. Therefore, MAG is extracellular and beta-Gase intracellular, and this prevents hydrolysis of MAG to the active MA in cancer patients.


Adaptive properties of the b-wave and the PIII in the perfused isolated carp retina. 1. Perfusion of isolated carp retina with a pure oxygen saturated standard solution used in this experiment permitted several continuous hours of ERG recordings showing a distinctive b-wave as well as the PIII isolated by sodium aspartate. 2. The dark-adapted threshold for the PIII required an absorption of 5 to 6 quanta per rod. The 'rod-cone break' in the increment threshold curve for the b-wave was induced at a background intensity of about 2.0 X 10(-2) muW/cm2. 3. Both the b-wave and the PIII showed rapid and complete recovery of sensitivity after exposure to dim adapting lights. After bright light adaptation, the sensitivities went through a short 'fast phase' followed by a prolonged 'slow phase' of recovery. The rate of recovery during the fast phase was significantly faster for the PIII than for the b-wave. Neither a lowered temperature (9 degrees C) nor the application of ouabain (10(-6) M) influenced the fast phase. This seems to prove that the visual pigment, photoproducts and the active transport hardly participate in its mechanism, if at all. 4. The prolonged slow phase that followed the fast phase was distinguished by the recovery of the rod activity, even in isolated retinas.


Inhibitory action of dantrolene sodium on the activation of excitation-contraction coupling in frog skeletal muscle. Effect of dantrolene sodium on the activation of potassium contracture in single fibers of frog semitendinosus muscle was studied. Dantrolene shifted the activation curve to the right without changing the depolarization produced by a given K+ concentration. The shift of mechanical threshold by dantrolene was dependent on the concentration of calcium in the medium and the effects of dantrolene and Ca++ are additive to each other. On the other hand, the action of dantrolene is antagonized by Ca++ with respect to the peak tension in 190 mM K+. In addition, dantrolene did not release 45Ca from the self-exchangeable Ca fraction and did not affect the exchange of 45Ca in the self-exchangeable Ca fraction with 40Ca. It was also observed that dantrolene had no appreciable influence on the ultrastructure of muscle fibers under our experimental conditions. On the basis of these results, the mechanism of action of dantrolene on the activation of excitation-contraction coupling, the relation between the drug and calcium actions and the drug effect on the Ca movement in T-system membranes were discussed.


On the roles of calcium ion during potassium induced contracture in the smooth muscle cells of the rabbit main pulmonary artery. The half decay time of the K-induced contracture of rabbit main pulmonary artery following pretreatment with Ca-free EGTA containing solution was 110 sec. A Ca-free K-solution did not generate contraction while noradrenaline, acetylcholine and prostaglandin F2alpha-containing solution did evoke contracture. The decays of the chemically induced mechanical response in Ca-free solution against the exposure times could be classified into three components (2 min, 28 min and over 100 min, respectively). When the membrane depolarization produced by excess K+ was simulated in Krebs solution by application of current, the generated mechanical response was smaller than that produced by 118 mM K+. When the membrane potential was clamped at the resting level before, during and after application of the excess K+, and excess K+ still evoked contracture. The amplitudes of contracture depended on [K]o. The effects of various [K]o on the length constant of the tissue were also observed in relation to the clamping condition. It is postulated that the mechanical response of the pulmonary artery induced by excess K is mainly due to influx of Ca++ and the depolarization plays only a minor role. This means that release of stored Ca by depolarization is not an essential factor in generation of K-induced contracture in this tissue.


Possible functioning of active ion transport mechanism in the mucous epithelial cells of newt stomach at low temperature. The membrane potential of mucous epithelial cells of isolated newt stomach was -23 mV on the average at 7 degrees C. The potential decreased when the temperature was lowered further, the normal external solution was replaced with K+-free solution, or ouabain or DNP was applied. The decreased membrane potential level of the cells in K+-free solution was not changed any more by adding ouabain to the solution. The membrane potential increased transiently beyond the control level when the stomach was returned to the normal solution after being exposed to isotonic NaCl solution with EGTA. The transient potential increase was blocked by ouabain. These results suggest that, even at such a low temperature as 7 degrees C, the active ion transport mechanism(s) of mucous epithelial cells in the newt stomach is still capable of functioning to some extent.


Effects of cord section and pithing on spontaneously hypertensive rats. In spontaneously hypertensive rats and normotensive control rats the spinal cord was transected between the vertebrae C7 and Th 1 under ether anesthesia. When the animals recovered from anesthesia in two hours, the blood pressure was significantly higher in the hypertensive rats, indicating that the hypertensive factors are not confined to the supraspinal centers. The blood pressure was also significantly higher in spontaneously hypertensive rats than in normotensive control rats even after pithing the spinal cord below the vertebra of Th 1. In either case subsequent pentobarbital anesthesia abolished the significant difference in pressure between the two groups of rats. The blood pressure after either cord section or pithing tended to increase with age in spontaneously hypertensive rats but not in normotensive control rats. These findings indicate the presence of certain age-dependent peripheral hypertensive factors which are susceptible to pentobarbital and probably myogenic in nature.


A circumferentially-sensitive miniature pressure sensor for study of human esophageal motility. Manometric systems in current use for study of human esophageal motility consist of sensors with a restricted radial disposition. Since both upper and lower esophageal sphincters are asymmetrical structures, such sensors are not ideal for sphincteric pressure measurements. In this report, we describe a circumferentially sensitive sensor (MT) which consists essentially of a miniature transducer mounted within a sealed fluid-filled chamber, surrounded by a pressure-sensitive silastic diaphragm. This device is accurate and sensitive. It was compared in 10 young healthy men with a standard perfused catheter system (PC) composed of three catheters, whose side openings were at the same axial level, connected to external transducers. Pressures recorded from the lower esophageal sphincter were significantly higher with the MT than with the PC; and in the upper esophageal sphincter, the rapid pressure changes associated with deglutition were far more faithfully reproduced with the MT. Contractile pressures recorded after swallowing from the body of the esophagus were similar with the two systems, provided that catheters were perfused at a rapid rate (approximately 8 ml/min for each catheter). This preliminary evaluation indicates that this MT has significant advantages as compared with currently available systems.


Some questions concerning electroretinographic response and its variability. Changes in retinal potential take place when the eye is adequately stimulated. This evoked response, the electroretinogram (ERG) is recorded in vivo by placing an electrode on the cornea, while the reference electrode is grounded elsewhere. In spite of a great deal of work in this field, the very meaning of ERG, in the frame of visual process, is not yet wholly understood. The present paper produces some data which show that the plot of visual performance vs. time, during the course of the day, runs parallel to that of the size of ERG. The meaning of this finding is discussed, by making reference to the electrical analog of the recording circuit, in terms of lumping approximation.


Hodgkin's disease: results of treatment with combination chemotherapy. Combination chemotherapy, which consisted of nitrogen mustard, a vinca alkaloid, procarbazine, and prednisone, was given to 60 patients with disseminated or recurrent Hodgkin's disease. A complete remission of disease was observed in 41 patients, with a median duration of 35+ months. The longest continuing remission was 89 months, and 52% of patients who achieved a complete remission were alive five years from the start of treatment. In contrast, patients who only had a partial remission (11 patients), or failed to respond to therapy (8 patients) fared badly, with a less than 50% survival rate at one year. Response to drug therapy could not be predicted on the basis of sex, age or tumour histology, but patients who had previously received both radiotherapy and chemotherapy had a poor prognosis. Drug toxicity was substantial, but was considered acceptable in view of the clear benefit of treatment to most patients. Further improvement in the outlook of patients with advanced Hodgkin's disease is likely to result from modifications of current drug regimens, possibly combined with non-radical radiotherapy.


Bioavailability evaluation of an enteric-coated phenylbutazone formulation, and cross-over comparison with a sugar-coated product. The relative bioavailability of enteric-coated, and commercially available sugar-coated tablets of phenylbutazone (PBZ) was studied in eight healthy volunteers. Each subject received a single oral dose of 400 mg of each preparation in a cross-over sequence. Blood samples were taken for assay of unchanged drug at intervals up to 360 hours. In an attempt fully to characterize the absorption and elimination profiles, three bioavailability parameters were evaluated; peak plasma level of PBZ, time taken to achieve peak level, and area under the plasma level-time curve. Peak plasma levels of PBZ, and area under the plasma level-time curves were not significantly different for the two products, which indicated their bioequivalence. A statistically significant (P is less than 0.001) difference in the rate of absorption of the two products was apparent, since the mean time of occurrence of the peak plasma level of PBZ for the enteric-coated tablets was 9.0 hours compared with 3.9 hours for the sugar-coated formulation. No subjective effects from the two products were noted by any of the subjects, nor were there any alterations in haematological or biochemical parameters.


Effects on humans of bites of Australian non-bloodsucking reduviid bugs. Occasional reports are received of painful bites inflicted on humans in Australia by predatory bugs of the family Reduviidae. A compilation is made here of such reports, which were obtained from published sources and from the files of the School of Public Health and Tropical Medicine, and is accompanied by available data on the circumstances of the attack and the symptoms produced in the victim. Particular attention is given to two recent cases of reactions to bites of species of Piestolestes, an otherwise obscure endemic genus. It is suggested that the nature of reported reactions to bites of non-bloodsucking Reduviidae raises the possibility that they are a response to the injection of a toxin, and note is made of a study of an Israeli non-bloodsucking reduviid which produces a venom suggested to be potentially harmful to humans.


The laboratory report: a problem in communication between clinician and microbiologist? When writing a laboratory report, the microbiologist often makes certain assumptions as to the clinician's understanding of laboratory procedures and reporting practices. The effect of these assumptions on the interpretations of the reports is discussed, with data from a survey of general practitioners. Possible ways of improving communication between the laboratory and the clinician are suggested.


Retrieval of the critically ill in South Australia: a coordinated approach. A system is described for the stabilization and evacuation of the critically ill in South Australia, with a discussion of experience in 278 patients. The integration of activities of peripheral medical practitioners, major teaching hospitals, and the ambulance transport authority (St John Ambulance Council) is paramount. Modes of communication are by "urgent line" telephone and radio. Advanced life-support equipment is portable, may be placed in any ambulance vehicle, and is used and maintained principally by the staff of intensive care units. The design characteristics of a suitable road vehicle and fixed-wing aircraft are considered, with emphasis on dimensions for the particular needs of advanced life-support. The cost of transporting such a patient is approximately two-thirds of an average bed day cost in a public hospital, plus the basic ambulance charge. The number of patients who need such measures is 0.2% of the total number of patients carried by ambulance per annum.


Some aspects of the computed tomography of the head. Computed tomography demonstrates intracranial neoplasms so clearly that nearly all early work in this field was limited to descriptions of the appearance of various lesions. Only recently have investigators directed their attention to the medical implications of the physical and pathophysiologic phenonmena that characterize this remarkable new technique. This paper will discuss recent work in these two areas and its clinical implications, and will examine the application of computed tomography to the evaluation of the postsurgical and postradiation patient.


Animal models of brain tumors.

Animal models of brain tumors. Although no single model of the numerous animal models of brain tumors developed in recent years perfectly represents the spontaneous human tumors, different ones do have specific advantages for certain types of studies. Chemical induction in adult animals, transplacental chemical induction, viral induction, and transplantation are effective methods that allow choice of numerous histologic types of tumors which, to a greater or lesser extent, simulate human tumors. Reproducibility of location, cell type, and time of tumor appearances; expense; ability to grow in tissue culture; safety for personnel; trauma to brain; nature of vasculature, and amount of brain and tumor tissue available for examination are among the variables to be considered in choosing a model appropriate for a particular study.


Cerebrospinal fluid sterols in the evaluation of patients with gliomas. This study was an effort to obtain a marker indicative of the biologic activity of human gliomas. Sterol levels in the cerebrospinal fluid (CSF) were evaluated. Studies were conducted longitudinally during the course of tumor therapy. The evidence indicated that desmosterol levels in the CSF may reflect the growth potential of these neoplasms.


Chemotherapy of human nervous system tumors: influence on cerebrospinal fluid sterols. The cerebrospinal fluid levels of cholesterol, desmosterol, and the ratio 100 D:C taken from a study of 59 patients are reported. The patients, who had tumors of the nervous system, underwent neurosurgery, radiotherapy, and chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea or 1-(2-chlororethyl)-3-cyclohexyl-1-nitrosourea. The relationships among the levels of these three parameters and the clinical and neuroradiologic evolution are discussed.


Surgical management of malignant brain tumors. Data are presented to support the contention that aggressive surgical management of malignant brain tumors, both primary and metastatic, is valuable in terms of quality and length of survival. Metastatic brain tumors must be solitary in a patient whose primary is either asymptomatic or under good control to justify surgical removal. Primary malignant gliomas are surgical candidates when the core of tumor can be excised, thus increasing survival after radiation and chemotherapy.


Chemotherapy studies of various nitrosoureas: prevention of development of ethylnitrosourea-induced tumors in the nervous system. Of four nitrosoureas administered to F344 rats that were offspring of mothers treated with ethylnitrosourea during pregnancy, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and its methyl derivative were particularly effective in blocking tumor development.


Conventional methods of diagnosis using nuclear scan and recent progress with radionuclide transaxial tomography. Radionuclide brain imaging, a simple, noninvasive test for evaluating patients with suspected cerebral pathology, has a high degree of accuracy when compared with more complex neuroradiologic procedures such as angiography and pneumoencephalography. The detection of brain tumors with use of radionuclide scans is related to the tumor cell type and their location in the brain. Transmission computed cranial tomography (CCT) offers another simple procedure for evaluating cerebral pathology. Even though CCT gives more anatomic detail than the radionuclide study, the two procedures are often complementary. Radionuclide transaxial tomography appears promising as a means of evaluating cerebral metabolism and metabolic changes associated with cerebral pathology.


Cancer incidence in the Mexican American. Mexican Americans of Los Angeles County, both those born in Mexico and in the United States, were at lower risk to all sites of cancer combined, than other whites. These Mexican Americans were at increased risk to some specific cancers, including those of the stomach, gallbladder, and cervix. For those tumors for which racial differences existed, clear migrant patterns were present.


Rationale and methods for an epidemiologic study of cancer among Seventh-Day Adventists. Considerable evidence was found that Adventists are a low-risk population to develop cancer of many sites. Adventists have numerous unique life-style and dietary habits with great variability within the population in adherence to these practices as well as considerable variation in duration of exposure to these characteristics. Thus this study population will likely be extremely productive in identifying dietary habits or other life-style characteristics that are etiologically related to various cancer sites.


Papanicolaou testing and hysterectomy prevalence in low-income communities: a survey in Los Angeles County. A survey of the prevalence of Papanicolaou (Pap) testing and of hysterectomy and a feasibility study were conducted in low-income communities with high rates of cervical cancer, identified by an analysis of mortality and case rates. Although about 90% of the women reported having had a Pap regular testing. For example, in the 5 years preceding the study (1971--75), about a quarter of the women had been tested only once and about a third not at all. No evidence of a secular change in hysterectomy prevalence in these communities was found.


Histocompatibility leukocyte antigen patterns and nasopharyngeal carcinoma. Incidence patterns indicated the prominent role of genetic factors in this type of cancer. A histocompatibility leukocyte antigen (HLA) profile of A2 and B-locus antigen, Singapore 2 (Sin 2), was identified. An association between these genes and increased risk for nasopharyngeal carcinoma (NPC), was confirmed. The risk was restricted to the "co-occurrence" of A2, B-Sin 2, suggesting that the genotype predisposing to the development of NPC was the A, B-Sin 2 haplotype. Similar associations were found to exist in Malaysian and Hong Kong Chinese so the A2, B-Sin 2 phenotype is a feature common to Asian Chinese in at least three locations. Preliminary HLA studies of medium NPC incidence in Tunisians and Malays indicated that patients with NPC of both ethnic types have altered HLA antigen profiles. If the findings of a locus-B antigen deficit in Tunisians and the role of A9 with B-locus antigens in Malays can be confirmed and clarified, the histocompatibility genetic hypothesis of NPC predisposition would be substantially strengthened.


Immunogenetic aspects of nasopharyngeal carcinoma. V. Confirmation of a Chinese-related HLA profile (A2, Singapore 2) associated with an increased risk in Chinese for nasopharyngeal carcinoma. Histocompatibility locus A typing of 43 Malaysian Chinese and 51 Hong Kong Chinese patients with nasopharyngeal carcinoma (NPC) confirmed the association between the occurrence of A2-Sin 2 and the increased risk for NPC that was previously demonstrated in Singapore Chinese. The results support the previous interpretation that the histocompatibility locus A genotype of importance in NPC predisposition is the A2-Sin 2 haplotype. The histocompatibility locus A-linked, genetically determined NPC risk is common to Asian Chinese from at least three geographic locations.


Histocompatibility leukocyte antigen patterns in nasopharyngeal carcinoma cases from California. Histocompatibility leukocyte antigen (HLA)-A2 in the first locus and less than two antigens in the second locus were found to be significantly associated with an increased risk to nasopharyngeal carcinoma in Chinese. HLA-A2 in the first locus alone was responsible for the increased risk. No significant HLA patterns were found to be associated with the Caucasian population.


Breast cancer among American Japanese in the San Francisco Bay area. The Japanese-American population was particularly well suited for the study of cancer occurrence because: 1) An American-born population as well as the immigrant Japanese-American population could be studied; 2) good cancer incidence and mortality data from Japan could be compared with data from the United States; and 3) some differences in the rate of occurrence of several specific cancer sites in Japan as compared with the United States were striking. The most significant of these involved the gastrointestinal tract and sex organs. Data were presented concerning cancer incidence rates for the Japanese-American population of the San Francisco Bay area. The high gastric rates for the Japanese in Japan were reduced in a stepwise fashion in the immigrant Japanese-American population to the American-born Japanese who were approaching the low rate of the United States. Colon cancer rates, which were low in Japan, approached the rates in the United States in both the immigrants from Japan and in Japanese Americans. The low rates of cancers of the breast, uterine corpus, and ovary of Japanese women in Japan and for prostate cancer among men rapidly approached the higher rates for these cancer sites that existed in the United States. A study of nutritional factors related to the increase of cancer of the breast in Japanese Americans is being conducted.


Breast secretory activity in nonlactating women, postpartum breast involution, and the epidemiology of breast cancer. We found an association between the secretory activity of the nonlactating breast and genes related to apocrine function. Based on these findings, we developed a biologic model that relates epidemiologic evidence for an association of reproductive experience with risk of breast cancer to our findings of genetic variation of breast secretory activity and the fact that exogenously derived substances are secreted into breast fluid. The turnover rate of secreted substances was a primary determinant of exposure of the breast epithelium to environmental and endogenous carcinogens and promoters.


Diet and exogenous estrogens in three populations at different levels of risk for breast cancer. A case-control study is being conducted in which a questionnaire is used to collect information on past history of drug usage (including menopausal estrogens) and the normal weekly dietary intake. Breast cancer cases from 3 selected populations (ages 45--74) are identified: 1) the Caucasians in Hawaii, at high risk for breast cancer; 2) the Japanese in Hawaii, at intermediate risk; and 3) the Japanese in Fukuoka, Japan, representing a low-risk population. For each case, a neighborhood and hospital control matched by race and age is interviewed. Attempts are made to verify the drug history with the subject's personal physician, and a subsample of the study population received a repeated dietary interview to assess its reliability. Pathologic slides of the breast cancer cases are reviewed by three consulting pathologists to confirm cancer diagnosis and to identify possible histologic differences in the 3 populations. In all, 200 cases and 400 controls will be interviewed from each study population.


Colon and rectum cancer in the New Zealand population. To test the hypothesis that the high rates of large bowel cancer in New Zealand were attributable to geographic location, occupation, or country of birth, we reviewed 4,760 cases registered in that country between 1964 and 1968. Analyses demonstrated that significantly high rates existed for certain rural populations, for small subsections of the immigrant population, and for certain occupations. However, the number of persons-at-risk represented in these groups collectively were not large enough to account for the high New Zealand rates.


Gastrointestinal carcinoma in the Japanese of Hawaii: a status report. The primary aim of the Japan--Hawaii Cancer Study was to identify factors that could explain the changes in cancer risk experienced by Japanese who migrated to Hawaii. Many investigations were conducted in this long-term prospective study since its inception in 1971. Among the findings that relate to gastrointestinal carcinoma were the following: 1) Bowel transit time does not appear to be related to the occurrence of large bowel cancer or to any of the benign conditions with which it is associated; 2) adenomatous and hyperplastic polyps, as well as diverticula, are much more prevalent among autopsy specimens from Japanese who had lived in Hawaii than of those in Japan; 3) adenomatous polyps and diverticula are positively associated with atherosclerosis in the necropsy population in Hawaii; 4) although the incidence of the diffuse histopathologic type of gastric cancer does not differ appreciably among the Japanese in Hawaii and Japan, the migrants have a significantly lower incidence of the intestinal type of stomach cancer; and 5) case-control studies indicated that the two conditions frequently associated with gastric carcinoma, i.e., gastric ulcer and intestinal metaplasia of the stomach, are associated with high salt intakes and adherence to the traditional Japanese diet.


Role of the cancer registry.

Role of the cancer registry. The cancer registry can be defined as a facility for the collection, storage, analysis, and interpretation of data on persons with cancer. The possible range of registry activities was discussed in relation to the population-based cancer registry. These activities included service to the medical profession and hence the cancer patient, the provision of information for planning control measures, the evaluation of treatment and of screening programs, the conduct of epidemiologic studies, either directly or indirectly, and the education of the public and the medical profession. The resources of the cancer registry can be used in follow-up for industrial and other cohorts exposed to a variety of agents. Registries must be prepared to meet the problem of confidentiality that might arise when information in the registry is linked with other data sets. The value of a cancer registry increases when it becomes possible to examine and assess time trends. Unfortunately, many cancer registries were not adequately funded or staffed to exploit usefully the data already collected at considerable expenses. The three types of staff required to ensure full utilization were discussed.


Cancer registries in Australia.

Cancer registries in Australia. Cancer registries are at an early stage of development in Australia. Population-based registries are located in New South Wales Registry and Western Australia, and of these, only the New South Wales Registry is fully functioning. A hospital-based registry is maintained in Victoria. We have a national cancer registry in principle but it will not be functional for many years. Preliminary statistics for New South Wales indicate a cancer pattern similar to Caucasian populations. Some epidemiologic surveys have been undertaken.


Lymphoproliferative and myeloproliferative disease in Tasmania. Tasmania, an island state of the Australian Commonwealth with a population of 400,000 of predominantly Anglo-Saxon heritage, has relatively centralized oncology services. A study was undertaken of all patients known in December 1971 and of all new cases diagnosed since January 1972 with all forms of leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, myeloma, and other myeloproliferative and lymphoproliferative disorders. Data were obtained with respect to lifetime residential and occupational history, schools attended, and known familial cases of any of the myeloproliferative and lymphoproliferative disorders.


Cancer registry in New Zealand.

Cancer registry in New Zealand. Cancer registration, introduced in New Zealand in 1948, evolved from a clinically oriented to a population-based collection scheme. The registry, located within the National Health Statistics Centre, can draw on a wide range of other health data reported to that office. New Zealand has a population of 3 million, 8% of whom are Maoris. Findings indicated that cancer is the second leading cause of death and that Maori women have a much higher overall cancer death toll than other New Zealand women. Significantly higher incidence rates for cancers of the stomach, pancreas, lung, thyroid gland, and uterus and lower rates for cancer of the large bowel and melanoma of the skin were found in Maoris.


Cancer epidemiology in the Philippines.

Cancer epidemiology in the Philippines. Based on 16,492 cancer cases recorded at the Central Tumor Registry of the Philippines from July 1968 to June 1973, an epidemiologic analysis was conducted. Age-adjusted incidence rates for cancer of all sites in the Philippines, the United States, and Japan were similar. Cancers of the lung and breast were the leading sites in males and females, respectively. Age-specific incidence rates by each site were compared for the Philippines, the United States, and Japan. Cancers of the oral cavity, nasopharynx, liver, lung, breast, cervix, ovary, and thyroid and malignant lymphoma occurred with higher frequency in the Philippines. The more education people had, the more likely they were to develop cancers of the lung, pancreas, bladder, prostate, breast, and ovary, whereas cancers of the stomach, skin, esophagus, oropharynx, tongue, and mouth were more common in individuals who had not completed high school. Among smokers, neoplasms of the lung, larynx, tongue, mouth, liver, esophagus, and oropharynx occurred with significantly higher frequency. Epidemiologic implications and significance of these results for cancer control were discussed.


Current status of the Cancer Registry and population-based studies in Hong Kong. Despite the handicaps of shortage of staff, lack of a broad health insurance program, and the apathy of most of the medical profession, we managed to establish a Cancer Registry that is achieving near completeness in registration of cancers at certain sites. These cancers are among the most common types occurring in the population.


Current status of cancer studies in the South Pacific. An analysis of cancer incidence and mortality data indicated that cancer has become one of the five leading causes of death in many of the republics and territories in the South Pacific. The most developed areas had rates that exceeded world averages for malignant neoplasms of the lung, breast, and cervix uteri. The two existing cancer registries are in the Papua New Guinea and Fiji. These registries have documented a number of unusual patterns of cancer incidence that allow casual inferences to be made. Among these are the association of chewing betel nut and cancer of the mouth, and the finding of Burkitt's lymphoma in Papua New Guinea with the same epidemiologic features as in West Africa. These and a number of other unusual patterns of cancer occurrence underline the need and the special opportunities for cancer research in the South Pacific.


Epidemiologic cancer research programs of the Cancer Center of Hawaii. Ongoing epidemiologic cancer research programs are described. These programs were developed by the Epidemiology and Demography Unit, Cancer Center of Hawaii, established in July 1974. During the 15-month period prior to the Pacific Basin Conference, many epidemiologic projects were initiated. Major descriptive, epidemiologic studies were undertaken: a) cancer mortality among the Japanese in Hawaii, adjusted by prefecture-of-origin; b) time trend of mortality rates for 80 causes between 1910--70; c) evaluation of race classification in Hawaii; d) survival analysis; and e) increased lung cancer rates among Japanese migrants in relation to smoking. Major analytic, epidemiologic studies were as follows: a) an international case-control study on breast cancer in relation to diet and exogenous estrogens; b) association between height and weight and various types of cancer; c) a follow-up study of about 9,000 shipyard workers exposed to asbestos; d) an epidemiologic survey on a 2- to 3-% sample population of Hawaii; and e) a follow-up study on leprosy patients in relation to their risks for cancer.


Cancer epidemiology in the San Francisco Bay Area. The Third National Cancer Survey of 1969--71 included the five counties of the San Francisco--Oakland Standard Metropolitan Statistical Area. The complete cancer reporting for this area, begun by the Third National Cancer Survey, was continued by the California Tumor Registry as part of the San Francisco Bay Area Resource for Cancer Epidemiology. The population-based cancer-reporting system provided an excellent data base for epidemiologic studies, a number of which (planned or in progress) were described briefly. Those in progress include: cancer of the ovary, corpus uteri, and breast as related to child bearing, fertility, exogenous hormones, etc.; the relationship of diet to breast cancer occurrence among Japanese; diet and colorectal cancer among blacks; and the relationship of cervical cancer to cytology in Alameda County. Other study proposals are under consideration.


Cancer surveillance program in Los Angeles County. A system of rapid surveillance for cancer in the population of Los Angeles County was studied, and the methodology was compared with traditional population-based registries. Comparisons with the Third National Cancer Survey were also made, and the pattern of malignant melanoma occurrence in Los Angeles residents was described.


[Tomodensitometry in stereotaxic conditions (possibilities and limitations in the diagnosis and treatment of brain lesions)]. The stereotaxic approach of cerebral lesions for diagnostic (biopsies) and/or therapeutic purposes (interstitial radiotherapy) has been well documented. These techniques depend on an exact spatial definition of the tumoral volume, which is often difficult to obtain through conventional neuroradiology, stereoencephalography, rheography... The use of tomodensitometry in this context is obviously of upmost interest if, and only if, the scan itself is obtained in stereotaxic conditions. The authors present a stereotaxic system with which all the diagnostic data, including CT scan itself, are recorded and matched within the same stereotaxic space. This method achieves an exact mapping of lesions within the actual stereotaxic brain space. Hence any further stereotaxic gesture can be calculated and controlled with a suitable accuracy. The interest of these procedures in the management of brain lesions is demonstrated through an experience of 52 supra tentorial tumors. 13 cases of lesions under 20 mm in diameter are especially discussed.


[Craniosynostoses (17 years of experience with a new surgical technic)]. In the treatment of craniosynostosis methods have been proposed to prevent craniectomies from early reclosure. New bone is formed at the edge of the craniectomy but particularly at the outer surface of the dura. The author has developed a method to separate the edges from each other and to stop osteogenesis inside the craniectomy. The outer layer of the dura is dissected free from the inner layer, folded over the edge of the groove and sutured to the outer periosteum. The operative technique and the results in 40 patients with a follow up of up to 17 years are described.