Dietary protein level and experimental aortic atherosclerosis. White Carneau pigeons were fed diets containing three levels of protein (compensated for by changes in the dextrin level); all other dietary constituents, including cholesterol, were at the same level, and these diets were fed for nine months, when the birds were killed and necropsied. Group A, which was fed the lowest level of dietary protein (10%), which is considerably less than that in Pigeon Chow Checkers, showed a high mortality rate (50%) and the survivors showed a significant loss in body weight. The birds in the other two groups, B and C (20 and 40% protein respectively) showed no significant changes in body weight during the experiment. When the mean serum uric acid values for the last four blood sampling periods, at two months intervals, in the last seven months of the experiment were compared with the values for A, only Group C showed a significant increase. There was no significant difference in serum total cholesterol concentrations, when compared in the same way. There were no significant changes in either the aorta atherosclerosis indices or the mean aorta cholesterol concentrations, determined after necropsy. If one compares the serum total cholesterol concentration for the groups of pigeons, of the blood samples drawn the day before they were killed, there were significant increases observed for Groups B and C. This work does not support the suggestion previously made that the dietary protein cholesterol interact in determining the concentration of aorta cholesterol and the atherosclerosis index in this breed of pigeon.


Scanning electron microscopy of arteries. The morphology of aortic endothelium in haemodynamically stressed areas associated with branches. The endothelial surface around branches of the normal rabbit aorta was examined by scanning electron microscopy (SEM). Focal endothelial damage was consistently found both on, and distal to, aortic flow dividers. In some case small areas were denuded of endothelial cover. Similar injury to endothelal cells was also occasionally observed proximal to the ostium of a branch. Haemodynamic forces, expecially high shear stress, may be responsible for these morphological changes. This altered endothelial integrity probably underlies the susceptibility of these sites to the formation of induced atherosclerotic lesions.


Influence of experimental stenosis on uptake of albumin by the abdominal aorta. The influence of abdominal aortic stenosis on the uptake of the protein-binding trypan blue dye and 131I human serum albumin (HSA) has been studied. The major change was a region of high uptake proximal to the stenosis, returning to normal by the level of the renal arteries. There was reduced uptake distal to the stenosis, apart from occasional small areas of high uptake probably due to turbulence. The increase in uptake immediately proximal to the stenosis was dependent on the severity and duration of the stenosis. Removal of the stenosis immediately before the injection of dye and 131I-HSA still resulted in elevated uptake in the proximal region. Some haemodynamic modifications resulting from a stenosis are described. It is suggested that the most satisfactory haemodynamic explanation of the observed uptake change is a proximal increase in oscillatory pressure/strain. The relevance of these findings to atherosclerotic development at and above arterial junctions is discussed.


Glucosamine and experimental atherosclerosis. Increased wet weight and changed composition of cholesterol fatty acids in aorta of rabbits fed a cholesterol-enriched diet with added glucosamine. Three groups of each 12 rabbits were fed a cholesterol-enriched diet. Glucosamine was added in amounts of 0.5% and 2.0% (w/w) to the diet of two of the groups, while the third group served as a control group. The amount of cholesterol in the diet was individually adjusted, so that all rabbits experimental period. Glucosamine did not affect the concentration response of serum cholesterol to dietary cholesterol or the amount of free and esterified cholesterol in the inner aorta. It did, however, cause an increase in the wet weight of the inner aorta with a corresponding decrease in the concentration of aortic cholesterol. Furthermore a decrease in the ratio between mono-unsaturated and di-unsaturated fatty acids of the cholesterol esters of serum and inner aorta were observed in the animals which received glucosamine.


Inverse effect of chronically elevated blood flow on atherogenesis in miniature swine. The effect of chronically elevated blood flow on the development of atherosclerosis in miniature swine was studied. Fistulas connecting the right external iliac artery and vein were surgically created in four swine, while three were not fistulated. Pulsed Doppler velocity detection cuffs placed around the abdominal aorta and both iliac arteries of all pigs permitted chronic measurements of blood velocity, blood velocity distributions, and blood flow. All swine were fed an atherogenic diet consisting of 20% beef tallow, 3% cholesterol, and 5% cholic acid for 6 months. This diet elevated the serum cholesterol to values exceeding 500 mg/100 ml. Creation of the arteriovenous fistula (AVF) markedly elevated blood velocity and flow in the abdominal aorta and in the shunted iliac artery. In the shunted animals the aortic blood flow was 42.1 +/- 2.0 ml/sec compared with 17.3 +/- 1.4 ml/sec in the unshunted swine. The velocity distribution pattern across the vessel was also indicative of an elevated wall shear stress. After 6 months, the animals were killed and the arterial vessels examined macroscopically and microscopically for the presence of atherosclerotic lesions. In the shunted pigs, 17 +/- 15% of the lumenal surface was occupied by sudanophilic lesions, whereas 80 +/- 8% of the surface was covered by lesions in the unshunted (control) pigs. From these studies, it is apparent that mechanical factors related to blood flow rates can influence the development of atherosclerotic lesions in swine.


Lecithin: cholesterol acyl transferase activity in the serum of rats fed saturated and unsaturated fats. Groups of rats were fed diets containing either butter, beef, fat or safflower oil. After 20 or 70 days of feeding, blood was taken from the animals in a postabsorptive state. Serum lipid levels and lecithin: cholesterol acyl transferase activity were measured. Feeding the different fats did not alter serum total cholesterol levels but free cholesterol and triglycerides were significantly lower in the safflower oil-fed group. Net cholesterol esterification in vitro was also significantly depressed in the safflower oil-fed group and this was shown to be due to the inability of the lipoprotein substrate to support the reaction rather than because of low LCAT enzyme activity.


Short-term effect of coffee on blood fibrinolytic activity in healthy adults. Ingestion of coffee was followed after one-half and one hour by shortening of whole blood fibrinolysis time. The amount of coffee was equivalent to a heaped teaspoonsful and a standard brand of instant coffee was tested. The effect was laregly lost when decaffeinated coffee was taken. It appears that the caffeine in the amounts of coffee ordinarily consumed stimulates fibrinolytic activity but 2 of the 12 subjects were resistant to the effect.


Anoxic-ischemic encephalopathy in the human neonatal period. The significance of brain stem involvement. Although the human brain stem is considered relatively invulnerable to ischemic anoxia, evaluation of 16 cases of a single acute asphyxial episode either at or following birth indicates that such involvement is a frequent and characteristic aspect of anoxic encephalopathy in the infant. Ischemic cell change, neuronal loss, and nuclear or reticular formation gliosis were present in the brain stem of all but one infant. At least two topographic patterns of anoxic encephalopathy exist: (1) a rostrocaudal pattern of decreasing vulnerability, with the cerebral cortex being most sensitive and the brain stem least sensitive, and (2) a pattern of brain stem and thalamic damage. Of the two, the latter pattern appears to follow most acute asphyxial episodes in the human neonate and infant.


[Morphological classification of oral leukoplakia (author's transl)]. 656 cases of oral leukoplakia were analysed according to macroscopic aspects, microscopic growth patterns and histologicalcytological differentiation, and the relationship to cancer of the oral cavity was studied. Homogeneous and speckled leukoplakia can be distinguished macroscopically, while flat (70%), papillary-endophytic (22%) and papillomatous-exophytic (8%) types can be distinguished by their growth pattern. Histological-cytological characteristics consist of epithelial hyperplasia (hyperkeratosis with ortho- or parakeratosis; akanthosis) and epithelial dysplasia (dyskeratosis, basal-cell hyperplasia, loss of polar arrangement of the basal cells, cell polymorphism, increased mitosis rate). No or little dysplasia was demonstrated in 74% of leukoplakias, moderate in 17% and marked in 6%. Carcinoma-in-situ, defined as high-grade dysplasia with additional loss of epithelial layering, was found in 3%. Precancerous leukoplakia (in almost 10% of cases, counting high-grade dysplasias and carcinoma-in-situ) must be delineated as a special group. Numerous correlations were found between dysplastic leukoplakias and oral cavity cancer as regards localisation, age and sex distribution. In the various leukoplakia forms there was an increased incidence of marked stroma reactions and of Candida colonisation with increased degrees of dysplasia.


[Results of resection treatment of chronic pancreatitis (author's transl)]. A total of 201 patients with chronic pancreatitis were treated surgically between 1964 and 1975. In 116 cases (57,7%) resection was done at operation: 44 partial and 18 total duodenopancreatectomies, 37 partial and 17 subtotal left pancreatic resections. The mortality rate of the operation was 12.9%. The late mortality was 9.4% based on an average observation period of 2 7/12 years. Three quarters of the patients became completely asymptomatic. Preoperative diabetes was observed in 21% rising to 38% postoperatively. Satisfactory long-term results were mainly seen after partial duodeno-pancreatectomy and subtotal left resection. However, continued alcohol abuse limits the success rate.


Inequivalent conformational response of Chironomus hemoglobins to ligation with O2 and CO. A circular-dichrosim and infrared-spectroscopic study. For the monomeric hemoglobins III and IV and the dimeric hemoglobins of Chironomus the tryptophan circular dichrosim reports different conformational response to binding of different ligands. The fine structure bands at 292 nm are most strongly developed in the unliganded state and considerably reduced in the oxy form. The spectrum of the CO derivative is intermediate but clearly more deoxy-like. This finding correlates well with the corresponding Bohr effect magnitudes determined by measuring proton release upon ligation. Infrared difference spectroscopy on O2 versus CO derivatives in aqueous solution shows a normal O2 stretching band position at 1107 cm-1 characteristic of asymmetric oxygen binding. The CO stretching band, however, is consistently blue-shifted by 11--13 cm-1 from the 1951 cm-1 position observed with mammalian hemoglobins, indicating reduced CO binding strength. Structural factors relevant to an explanation of the observed phenomena are discussed.


Lignoceric acid biosynthesis in the developing brain. Activities of mitochondrial acetyl-CoA-dependent synthesis and microsomal malonyl-CoA chain-elongating system in relation to myelination. Comparison between normal mouse and dysmyelinating mutants (quaking and jimpy). Age-related changes in the activities of microsomal and mitochondrial elongating systems have been determined in mouse brain from birth to maturity. In microsomes, the components necessary for behenyl-CoA (docosanoly-CoA) elongation have been found to be NADPH and malonyl-CoA. In mitochondria, both NADH and NADPH are used and acetyl-CoA is the only donor of two-carbon-atoms unit. The synthesised fatty acids were identified by thin-layer and gas chromatography. The specific activity is higher in microsomes than in mitochondria. In microsomes, the specific activity for malonyl-Co-A incorporation reached a maximum at 15 - 20 days of age; this peak was not obtained in the Quaking and Jimpy mutants. The increase in enzyme activity (specific activity and total activity per brain) paralleled the myelin deposition. The activity of the mitochondrial system increases regularly during development: it is not correlated to myelination and it is not affected in the Quaking mutant. The interplay between microsomal and mitochondrial elongation systems is studied.


Structural studies on the coat protein of alfalfa mosaic virus. The complete primary structure. The complete amino acid sequence of the coat protein of alfalfa mosaic virus (strain 425) is reported. Sequence determinations were mainly performed on peptides obtained from fragmentation by cyanogen bromide and trypsin. Both manual and automatic sequence methods were used. Some refinements of the solid-phase Edman degradation were introduced. The final alignment of the peptides was established by means of alternative cleavage methods, such as limited tryptic digestion of intact virus particles, tryptic digestion after blockage of lysine residues and chymotryptic digestion. The coat protein consists of 220 amino acid residues corresponding to a molecular weight of 24252. A remarkable clustering of basic residues occurs in the N-terminal part of the protein chain. Several internal hydrophobic clusters and a strongly acidic site at the C-terminus can be observed. Two regions of sequence homology (12 residues) were found. Some features of the secondary structure are predicted.


Biochemistry of development in insects. Triacyglycerol and phosphoglyceride biosynthesis by subcellular fractions. 1. A different biochemical behaviour has been previously shown during several stages of the development of the insect Ceratitis capitata; thus, the acyl transferase activity has a different participation in the pathways of synthesis of triacylglycerols and phosphoglycerides by either larval or pharate adult stages of development. The results reported here are concerned with the behavior of mitochondria and microsomes from larvae and pharate adults for the synthesis of triacylglycerols and phosphoglycerides. In all preparations of either mitochondrial or microsomal fractions the optimum protein amount, previously determined, has been used. 2. The highest incorporation of [14C]palmitate into triacylglycerols and phosphoglycerides was achieved by the microsomal fraction from the larval stage of development of the insect. However, mitochondrial fractions from pharate adults utilized higher levels of [14C]palmitate than the microsomal preparation. These differences were not correlated with the palmitoyl-CoA synthetase activity. 3. Glycerol 3-phosphate influenced the fatty acid incorporation in a different manner depending on the stage of development of the insect. Increasing concentrations of glycerol 3-phosphate stimulated the synthesis of triacylglycerols by microsomal and mitochondrial preparations. This effect was not exhibited by the subcellular preparations of pharate adults. 4. Double-label experiments using [14C]glycerol 3-phosphate and[3H]palmitate showed qualitative differences in the synthesis of triacylglycerols by mitochondrial preparations from either larvae of pharate adults. Incorporation of the labelled fatty acids to endogenous triglycerides was preferentially shown by the mitochondria larval preparations. The pathways of synthesis of triacylglycerols and phosphoglycerides by microsomal preparations showed only quantitative differences depending on the stage of development of the insect. 5. Acylation of 14C-labelled lyso-phosphatidylcholine and 14C-labelled lyso-phosphatidylethanolamine by [3H]olate was assayed in the presence of miochondrial and microsomal preparations from the different stages of development of the insect. Microsomal fractions showed an efficient acyl transferase activity mainly when lyso-phosphatidyl-ethanolamine was used as a substrate.


Uptake of D-glucose anomers by rat retina. Uptake of D-glucose anomers by isolated rat retina was studied. After 3 min incubation at 37 degrees C in the presence of alpha or beta anomer (750 mug/ml), a significantly greater uptake (1.32 mg/g wet tissue) of beta-anomer was observed compared with that of alpha-D-glucose (1.11 mg/g wet tissue). This result and other data suggest that the carrier for D-glucose transport in the retina prefers the beta-anomer stereospecifically.


N-(5'-Phosphopyridoxyl)-4-aminobutyric acid: a stabel bisubstrate adduct inhibitor of rat brain 4-aminobutyric acid aminotransferase. N-(5'-Phosphophopyridoxyl)-4-aminobutyric acid, a stable adduct of pyridoxal phosphate and 4-aminobutyrate acid, has been shown to be a potent inhibitor of rat brain 4-aminobutyric acid aminotransferase (GABA-T) with a K1 of 1.4 muM.


MAO inhibition, an unlikely mode of action for chlordimeform. Inhibition constants of several formamidines, their corresponding formanilides and other representatives of compounds derived from aniline, such as phenylureas, N-phenyl-carbamates and acylanilides, were determined for rat liver monoamine oxidase. The reversability of the inhibition and the lack of correlation between inhibition potencies and toxicities of the compounds tested add to the opinion that MAO inhibition is not a prominent factor in chlordimeform poisoning.


Mouse sex vesicle. C-band and pairing at the light and electron microscope. C banded mouse pachytene chromsomes were studied with the light and electron microscopes by the whole mount technique. The X and Y chromosomes show pairing by the long, by the short or by both long and short arms. Assuming Lyon's hypothesis, the latter suggests that the Y segment transferred to the X is intercalar. With the light microscope, a negative image of the synaptonemal complex is evidenced.


Physiological changes in hairless mice maintained on an antioxidant supplemented diet. Several physiological parameters were measured in hairless mice maintained on a diet supplemented with antioxidants. Comparisons to animals on control diet revealed higher water-soluble antioxidant content of skin and increased liver weight. Only small differences in body weight occurred and no distinct histological changes were observed in skin or liver.


Sensitivity of the developing chick myocardium to the positive inotropic effects of calcium and isoproterenol. The present results show that the sensitivity of the chick myocardium to the positive inotropic effect of Ca++ decreases during development and that the Ca++ concentration of the physiological solution used must be lowered below 'normal' to study the effects of positive inotropic agents in preparations from younger embryos. Isoproterenol elicits positive inotropic responses in 7-9 day embryonic ventricle and in newborn chick atria; however, the 4-day embryonic myocardium is unresponsive to isoproterenol.


The influence of N-methyl-N-beta-chloroethyl hydrazines on the mitotic index of Ehrlich ascites tumor cells and the leukopoiesis of the mouse. The cytostatic activity of N'-methyl-N'-beta-chloroethylbenzaldehyd hydrazone (B1) is at least equal to that of procarbazine when its effect is tested with the Ehrlich ascites tumor cells of the mouse and the Yoshida sarcoma of the rat. B1 causes a slighter decrease of mitotic cells and no shift from prophase to metaphase. These results suggest that the cytostatic effect of B1 is due to interference with cell metabolism or an effect at the cell membrane and not to an effect on cell proliferation. This assumption is supported by a considerable depression of lymphocytes and a minor effect on granulopoiesis, which is especially sensitive towards proliferation toxins. All these findings suggest a different mechanism of action of B1 and procarbazine.


The local anesthetic potency of norcocaine, a metabolite of cocaine. The local anesthetic effects of cocaine and one of its main metabolites norcocaine, were investigated comparatively on isolated ganglion cells of the marine gastropod, Aplysia californica. During a 4-hour-period, different action potential parameters such as amplitude, duration, maximum rate of rise were observed, which demonstrated that norcocaine exhibits a higher local anesthetic potency than cocaine.


Inhibition of DNA synthesis in BHK fibroblasts treated in vitro with potassium dichromate. Treatment of hamster fibroblasts with potassium dichromate in vitro stimulates tritiated thymidine uptake into the intracellular nucleotide pool. This effect is due to the oxidizing action of hexavalent chromium on the plasma membrane. Dichromate, induces also an inhibition of DNA replication, which is due to the interaction of reduced trivalent chromium with specific biological ligands on the DNA molecule.


Lack of correlation between structural features and function of synthetic agents tested for leukocyte chemotaxis. A number of proteins, poly-L-amino acids, oligopeptides and lipids were tested for neutrophil, eosinophil and macrophage chemotactic activity. One myoglobin preparation was active. Based on the negative findings for all other substances, primary structure, secondary structure, degree of hydrophobicity, size and charge of a molecule, could be ruled out as structural features recognized by chemotactically responding phagocytes.


Thermal effects from degranulation of mastcells in cutaneous mastocytosis. Small bipsies of the skin were taken from patients with papulo-cutaneous mastocytosis. The mast cell tumours were then degranulated with compound 48/80 (250 mug/ml in saline), and with a Sorption microcalorimeter, relatively strong exothermic reactions were measured, whereas normal skin showed only 1/10th the intensity. Disodium chromoglicate (1%) had no inhibitory effect on this thermal reaction.


Interstate migrants in the United States: some social-economic differences by type of move;. U.S. interstate migrants (over a five-year period) are separated into three groups: (a) those leaving state of birth; (b) those returning to state of birth; and (c) those outside state of birth at the beginning of the period and moving on to a third state by the end. Evidence is presented suggesting that the third group is particularly selective of persons with high social and economic status. The findings are linked to certain hypotheses about the changing role and function of migration in a highly developed country where the transition from a rural society based on agriculture has essentially been completed.


A model for estimating adolescent sterility among married women. A model to estimate adolescent sterility among married women is presented using the principle of convex combination of two or more probability density functions.


Trends in nonprinted U.S. census and survey data and some research implications. I have raised a number of issues related to research using computerized data, which must be considered by supplying agencies, libraries, funding agencies. and researchers. Before the 1980 census data are released, researchers should suggest ways in which the data could be made easier and more useful to work with, and data supplying institutions should both respond to and take a lead in finding new approaches that will allow scientists to take full advantage of the opportunities provided by computerized data.


The use of public transportation in urban areas: toward a causal model. In this study, using the statistical models recently introduced by Goodman, we analyze the reasons why individuals choose the car or public transportation for the journey to work and draw out some of the implications of our analysis for public policy. Building on the work of Schnore, we develop a model in which both structural and individual variables are interrelated and show that the structural contexts within which individuals make decisions about their choice are crucial. We also show that, while status differentials are largely accounted for by income differences, male preferences for the automobile tend not to be due either to the structural variables or to income differences. Our findings suggest that present policies designed to induce people to shift to public transportation for the journey to work are not likely to be effective, since they do nothing to alter present cost differentials between the two modes.


Cohort, age, and period effects upon the employment of white females: evidence for 1957-1968. The net effects of birth cohort, age, and period upon the employment of white women, 1957-1968, are estimated by a regression analysis of data from the Social Security Administration's continuous work history file. By conceptualizing period-specific effects as those associated with the business cycle, we avoid multicollinearity and succeed in performing an analysis faithful to the cohort concerns usual in fertility analysis and to the macro-economic concerns usual in employment studies. The age pattern of employment and the pattern of intercohort employment change are examined in some detail. The long-run (cohort) trend of increasing white female employment is compared with the estimated (short-run) effects attributable to the business cycle, and it is found that, while both are significant, the former exerted a stronger effect in the 1957-1968 period.


Wife's employment and cumulative family size in the United States, 1970 and 1960. Using a multiple classification analysis of the data from the 1 percent public-use samples of the 1960 and 1970 censuses of population, it is found that the negative relationship between wives' employment and their cumulative family size is stronger among whites than nonwhites and is strongest among women married less than 10 years, with 12 or more years of schooling, and who have no relatives living with them. Moreover, although there are many similarities in the pattern of the employment status/fertility relationship between the 1960 and 1970 data, the relationship is weaker in 1970 than in 1960.


Marital instability and the economic status of women. This paper uses longitudinal data from the Panel Study of Income Dynamics to examine the relationship between changes in marital status and economic status. Differences between men and women and between whites and blacks are also considered. A major finding is that, after adjusting for changes in family size, the economic status of divorced or separated men improves, while that of women declines. Components of income change are discussed, with special emphasis on changes in the labor force and welfare status of women who were divorced or separated during the analysis period. Finally, data on the magnitude and distribution of alimony/child-support payments are presented.


The stable equivalent population, age composition, and Fisher's reproductive value function. This paper deals with a further analysis of the stable equivalent population for human populations. It first shows that the arithmetic difference between the size of the stable equivalent population and the actual population captures the total prospective contribution of age composition to the growth of the present population" if fertility and mortality rates are held constant at their current levels. The second part of the paper examined Fisher's reproductive value function and investigates the location of maxima in relation to alternative values of the intrinsic growth rate. One conclusion which follows from this analysis is that, contrary to what has been discovered by others in specific examples, the reproductive value function can possess a global maximum in the first one or two years of life, provided the intrinsic rate of population growth is sufficiently negative. This principle is illustrated by reference to reproductive value functions calculated from the recent experience of U.S. females.


Methodological issues underlying multiple decrement life table analysis. In this paper, the actuarial method of multiple decrement life table analysis of censored, longitudinal data is examined. The discussion is organized in terms of the first segment of usage of an intrauterine device. Weaknesses of the actuarial approach are pointed out, and an alternative approach, based on the classical model of competing risks, is proposed. Finally, the actuarial and the alternative method of analyzing censored data are compared, using data from the Taichung Medical Study on Intrauterine Devices.


A new technique for measuring preferences in demographic studies. In this article, we introduce an alternative technique to the single-sentence question for measuring preferences for number of children, age at marriage, length of first birth interval, length of employment, and years of schooling. This new measurement procedure utilizes a graphic scale rather than verbal responses, and it places family size decisions within the context of several other major life cycle decisions. One month reliability data for the measurement technique were obtained from a sample of 107 school children. Reliability results are compared to data from a previous study of teenagers.


[Bladder dysfunctions years after radical hysterectomy without subsequent radiation therapy for cervical cancer. A urodynamic investigation. (author's transl)]. 52% (21/40) of patients treated for cervical cancer by a radical hysterectomy without subsequent radiation therapy, complained months and years later still about a significant bladder dystunction and about urinary incontinence. A urodynamic investigation of the urologically sumptomatic cases revealed a severe hypertonus of the detrusor muscle in 58% (10/17). Uninhibited detrusor contractions are not typical of the bladder dysfunction after radical hysterectomy. The urinary incontinence was in most cases a mixed one, where a hypertonic detrusor and a sphincter incontinence are both present.


[Hemoccult tests of the stool at the time of preventive gynaecological examination (author's transl)]. From January 1, 1977 on, the test for occult blood in the stool becomes, by law, part of routine preventive checkups in order to detect carcinomatous and precancerous lesions of the colon. The effectiveness and practical use of the hemoccult test in the routine gynaecological annual checkup was tested. From October 1975 to June 1976 the test was done in 1,017 women at the time of the preventive gynaecological examinations. The patients received three hemoccult test sachets. They contained guayac resin on filter paper. The stool sample is placed on the filter paper and later tested with peroxide. The patients were informed about the test. The high interest of the patients in the test was exemplified by the high return rate of 80.7%. In 29 patients at least one hemoccult test was found to be positive for a rate of 3.53%. In one of the 821 patients who returned the test a carcinoma of the rectum was discovered which was too high for digital rectal examination. An optimal test is obtained when a stool sample is placed on the filter paper on three consecutive days. When a test is positive the patient is subjected to rectal digital examination, sigmoidoscopy and air contrast barium enema. If the source of bleeding cannot be detected in this manner a coloscopy is done. If the patient followed a diet prior and during the test the rate of positive tests of 3.53% was not increased compared to the group without dietary measures. A special diet prior and during the test is therefore not necessary. The above study shows that the inclusion of the hemoccult test in preventive examinations is a rational extention of preventive testing. Combined with gynaecological preventive examinations, the additional testing for precancerous and carcinomatous lesions of the colon is of additional preventive value for the health of the women.


[Polyps of the uterine cervix during the hormonal resting phase in childhood (author's transl)]. The occurrance of polyps of the uterine cervix during childhood is described which is exceedingly rare according to the literature. A pediatric gynaecological outpatient department was established two years ago and among about 600 children examined by viginoscopy, nine children with polyps of the cervix were detected. All nine girls had similar symptoms and signs. There was vaginal bleeding with malodorous discharge which could also be characteristic of a malignant tumor. The vaginal introitus was rather larger with an almost absent hymen. It is important to recognize the conditions early and to treat it. The vaginal discharge was treated. The polyp was removed and the base of the polyp was coagulated to avoid a recurrence. It can be expected that polyps of the uterine cervix in childhood will be found more often as the interest in pediatric gynaecology increases.


The development of children born by vaginal or abdominal breech delivery (author's transl). The early and late development of children born by the breech either by vaginal breech delivery or by caesarean Section is compared. The early and late morbidity of the two groups is discussed in detail. Considering the recently published data by Hagberg (6) theinterpretation of findings classified as secondary morbidity is very dificult. There are numerous especially antenatal factors which interfere with the interpretation. The conclusion is presented that it is a present not possible to make a definite statement on the value of vaginal or Caesarean Section delivery in breech presentation. It is still considered to be safe to do Caesarean Section delivery in breech presentation. It is still considered to be safe to do Caesarean Sections in breech presentations on an individualized basis.


[Vulvovaginal mycoses-stort-term treatment with Econazole (author's transl)]. The short-term treatment (3 days) of mycologically demonstrated vulvovaginal candidiasis with econazole vaginal suppositories 150 mg was tested in a population of 194 women. Substancial prerequisites for thorough and complete performance of the therapy are high cure rates (93,3%), prompt therapeutic results, minor burden for the patient and good tolerability. In view of the vital danger for the newborn provoked by candidiasis morbidity, this short-term therapy is also indicated for prenatal prophylaxis.


[Intraepithelial carcinoma of the cervix uteri in young women (author's transl)]. 78 cases of cervical carcinoma in situ in women aged thirty years or less treated at the 1st Universitäts-Frauenklinik in Vienna in the period 1960-1974 are being reported. This number represents 10,7% of all 729 cases of cervical carcinoma in situ in this period. It was surprising to notice a distinct increase in the incidence of this disease in the last years. The amount of young women with cervical carcinoma in situ went up to 15.8% in the period 1972-1974.


[Epidural anaesthesia in obstetrics (author's transl)]. Review of 1400 epidural anaesthesias during labour and delivery. The single shot method resulted in complete analgesia in 83.8% of the cases. There were 2.8% failures. With longer duration of albour 13.4% of the epidural anaesthesias had to be repeated. Epidural anaesthesia was tolerated well by the women in labour. Hypotension occurred in 21.6% of the cases and was corrected by intravenous infusion and positioning of the patient on the side. No adverse effects on the fetus were found. The duration of labour and delivery was not prolonged. The caesarean section rate was not increased by epidural anaesthesia. Because of the more difficult bearing down reflux during the second stage of labour, the incidence of vacuum extractions was increased by 1 to 3%. The incidence of forceps deliveries remained stable. There was no significant increase of abnormal vertex positions. Postpartum headaches because of decompression by loss of cerebrospinal fluid was seen in 2.2% of the cases. The headaches subsided on complete bed rest. One case of total spinal anesthesia with respiratory arrest is reported which necessitated immediate intubation. Another dangerous complication was noted in a Para 2 who suffered a complete uterine rupture below the level of the epidural anesthesia without any clinical signs and symptoms. Therefore continual internal fetal monitoring is considered to be essential in all cases with epidural anaesthesias. Previous caesarean sections or uterine operations are no contra-indications to epidural anaesthesia.


Effects of ureteral obstruction on the renal metabolism of alpha-ketoglutarate and other substrates in vivo. The renal metabolims of alpha-ketoglutarate, glutamate, oxygen, carbon dioxide, and citrate during the infusion of beta-hydroxybutyrate and/or alpha-ketoglutarate was evaluated in vivo in the awake, resting dog after varying periods of unilateral ureteral obstruction. The induction of reversible renal damage by 2 weeks of obstruction was associated with (i) decreased utilization of alpha-ketoglutarate and oxygen; (ii) decreased production of carbon dioxide; (iii) elevated respiratory quotient; and (iv) nearly complete lack of citrate production. The induction of irreversible renal damage by 6 weeks of obstruction was associated with (i) a nearly total absence of alpha-ketoglutarate utilization; (ii) a markedly decreased amount of oxygen utilization and carbon dioxide production; (iii) a normal respiratory quotient; and (iv) a nearly total absence of citrate production. The metabolic changes observed after obstruction indicate that aerobic metabolism is inhibited by either reversible or irreversible renal damage. However, certain anaerobic reactions continued in the reversibly damaged kidney. Differences in the extent and character of metabolic changes may make it possible to predict the degree of renal damage.


Investigation of intrarenal blood flow and urine flow aspects by scintillation camera. In order to clarify intrarenal dynamic processes related to regional distribution in patients with unilateral renal disease, two radioactive tracers, 133Xe and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) were introduced into a renal artery and intrarenal blood flow and urine flow aspects were observed by scintillation camera. Cortical blood flow decreased and medullary blood flow relatively increased with the advance of renal damage. Urine flow curve from normal cortex showed two phasic patterns. One early phase might correspond to the appearance of the tracer through the proximal tubule and a second phase might correspond to the appearance of the tracer through the loop of Henle to the distal tubule. Under mannitol diuresis, two phasic urine flow curves from the cortex became obscured and the peak time of pelvic curve shifted to the earlier period. These studies were considered to be useful in evaluating unilateral renal function and might offer a good insight for intrarenal physiology concerning blood flow as well as urine flow.


Studies in ureteral regeneration: replacement of a large segment of ureter with an in situ pedicle graft of proximal ureter. The phenomenon of ureteral regeneration has been of interest to clinicians, anatomists, and physiologists for many years. The object of this investigation was to study the regeneration of a long pedicle graft of ureter. Regeneration of the pedicle graft over a stent took place in 4 to 5 weeks. At sacrifice 8 to 10 months postoperatively, 7 of 10 operations were completely successful with no evidence of hydronephrosis, obstruction, or pyelonephritis. Two animals exhibited slight dilation of the upper tracts, and one operation was a failure. It is evident from this study that a strip of ureter removed from the ureteral artery will regenerate over a stent in 4 to 5 weeks if the blood supply from the adjacent adventitia is left intact.


Oxalate absorption from intestinal segments of rats. An animal experimental model was used to study oxalate absorption from the gut. It was found that the initial rate of [14C]oxalate absorption is rapid (6.5 per cent per min), and that after 5 min the rate of absorption decreases to about 0.6 per cent per min. Absorption of [14C]oxalate was greatest in the jejunum and least in the colon. On the basis of linear coefficients derived from the data, it is estimated that at least 8.6 per cent of a challenge dose of oxalate should be absorbed from the small bowel during normal transit. The high absorption rate, compared with the normal absorption of oxalate, in this model is most likely attributable to the oxalate's being completely dissolved in the gut. Magnesium and calcium in the test solution did not cause large changes in the rate or amount of oxalate transfer in this experimental model.


Experimental transureteroureterostomy performed with tissue adhesive. Transureteroureterostomy was performed on 20 experimental animals by an adhesive technique with no sutures. Sixteen cases displayed very good results, two were only partly successful, and two others proved to be failures. The longest follow-up was 3 years. Results obtained are documented by excretory urography and pathologic examinations.


Ultrastructural stereology: a new approach to the study of prostatic function. Stereology is a method used to obtain quantitative information of structural changes at the light and electron microscopic level. The basic principles of stereology are outlined below. This paper shows how stereologic techniques can be used to obtain structural data from histologic and electron micrographs of intact tissue and cells. A morphometric model, which provides information on the structure of the prostatic gland has been developed for the rat prostate. The model consists of morphologically defined space and membrane compartments of the prostatic gland and the glandular cells. The alterations, induced in the glandular cells of the ventral lobe of rat prostate by the administration of a synthetic progestin (ethinyl-norgestrienone), were studied by electron microscopy. The results presented are relative to a cubic centimeter of prostatic tissue, a cubic centimeter of acinar parenchyma, and glandular cell cytoplasm. An attempt to relate stereologic and biochemical data is shown.


Ureteral function. IV. The urometrogram at increased urine output. In this study the shape of the urometrogram or ureteral pressure pulse is evaluated as a function of urine output. Using a simultaneous monitoring technique, the urometrogram, spurt volume, and wave speed, as well as various aspects of wave geometry, have been studied on dogs with explanted bladders during various stages of urine output. The qualitative shape of the urometrogram is discussed for urine flows ranging from less than 0.01 ml per min to about 6 ml per min. An explanation of the shape of the urometrogram is presented and shown to be related to urine output and to length of the bolus. Preliminary experiments using mannitol, Lasix, Hypaque, and saline were all shown to induce similar changes in the shape of the urometrogram; however, the rate at which the changes occur was a function of the specific drug.


The sympathetic innervation and adrenoreceptor function of the human lower urinary tract in the normal state and after parasympathetic denervation. Adrenergic innervation of the human urinary bladder was studied in vitro in specimens excised during operation from six neurologically normal bladders and from five parasympathetically denervated (lower motor neuron lesion) bladders. Using a specific histochemical fluorescence technique, it was found that the adrenergic nerve terminals of the detrusor of the patients with lower motor neuron lesions were thicker, had a stronger fluorescence intensity, and were in most cases also more densely distributed than those of any of the six neurologically normal bladders examined. By recording the changes in the isometric tension of detrusor strips after different pharmacologic treatments, the existence of alpha-adrenergic receptors could be demonstrated in the parasympathetically denervated detrusor but not in the normal detrusor. The influence of alpha-adrenolytic treatment (phenoxybenzamine) was studied in vivo in seven patients with lower motor neuron lesions. In the cystometrograms, the bladders were more hypotonic and the "autonomous waves" appeared at a higher level of filling or were totally extinguished after this pharmacologic treatment. With an isotonic volume registration method, a bladder volume increase was recorded after alpha-adrenergic blockade. Using sphincterometry or urethral pressure profile studies, a decrease in the urethral resistance was observed after alpha-adrenolytic treatment.


Ultramicro GC determination of amino acids using glass open tubular columns and a nitrogen-selective detector. A glass open tubular (capillary) column together with a nitrogen-selective detector were evaluated for the analysis of amino acids by gas chromatography. Test samples included normal and abnormal human sera and urine and several hydrolysates of pure proteins. Amino acids in the biological samples were isolated by ion exchange pretreatment and derivatized to the n-propyl, N-acetyl derivatives. Protein hydrolysates were derivatized without pretreatment. Compared with a flame ionization detector, the nitrogen-selective detector gave a sensitivity enhancement of 80x-180x for the amino acid derivatives, depending on the particular amino acid. Long-term stability of the detector was excellent. Reproducibility studies gave a long-term precision of about 6% for serum or urine samples while a precision of 5% was obtainable on a day-to-day basis when analyzing protein hydrolyzates. The experiments showed that amino acids at the picomole level could be reliably analyzed with the system. The open tubular column coated with a mixture of Carbowax 20M and Silar 5 CP and having a very thin liquid phase film gave greatly improved thermal stability compared with a previously used packed column.


A sample-bottle purging method for the determination of vinyl chloride in water at submicrogram per liter levels. Methodology is presented for the concentration, detection and measurement of vinyl chloride (VC) in water at a maximum sensitivity of 0.1 mug/1 by gas chromatography, using the halogen specific microcoulometric titration detector. The methodology eliminates cyanogen chloride (CNCI) as a potential interference by using a 180 mm X 4 mm i.d. GC column packed in the first one-third with Chromosorb 101, and in the second two-thirds with Chromosorb 102; a procedure for purging the sealed sample bottle itself is utilized as a means of analyzing larger samples, while at the same time avoiding the loss of VC by volatilization which occurred when the sample was transferred to a purging device. A method of verifying the accuracy of standard solutions that utilizes a new device called a "Reaction Coulometer," is also included and a detailed description of how to convert the inlet system of the Tracor MT 220 gas chromatograph to a desorbing device is provided.


High pressure liquid chromatographic analysis of Oryzalin and other selected herbicides. Procedures are described for the analysis of Oryzalin, Tebuthiuron, and several other selected dinitroaniline herbicides by high-pressure liquid chromatography (HPLC). Quantitation of Oryzalin and small concentrations of chemical impurities from the production process can be performed rapidly. Linearity and reproducibility are discussed and comparisons to other methods are made.


Drug effects on fixed-interval responding with pause requirements for food presentation. In pigeons performing under a multiple schedule of food presentation, low key-pecking rates (0.18 to 0.29 responses per second) were maintained during 3-min fixed-interval components by requiring a 4-, 5-, or 6-sec pause preceding the food-delivery response (tandem DRL), while higher rates (0.70 to 1.37 responses per second) were maintained in alternative fixed-interval components by requiring a pause of no more than 40 msec preceding the food-delivery response (tandem DRH). Thus, reinforcement density was equal but overall response rates markedly different in the two schedule components. Pentobarbital (3, 10 mg/kg) had effects on overall rates of responding consistent with a rate-dependency interpretation (low rates were increased while higher rates were decreased), but d-amphetamine (0.03 to 3 mg/kg) either failed to increase low overall rates in the tandem DRL components or increased them only slightly. Effects of both drugs on local responding within the fixed-intervals were always related in an orderly way to control response rate, but the extent of rate increases produced by d-amphetamine was modifed in some birds by pause requirements such that the drug increased comparable rates less when these occurred in the tandem DRL component than when they occurred in the tandem DRH components. Control rate is an important determinant of drug effects, independent DRH components. Control rate is an important determinant of drug effects, independent of reinforcement density maintaining rates, and independent of environmental influences, such as response-spacing requirements for food presentation, that can modify the extent of some drug-produced rate changes.


Graded group procedures for long term regressed schizophrenics. It has been suggested that a graded sequence of treatments might be the most efficacious approach to the rehabilitation of the regressed schizophrenic. To date, however, no research has been reported which examines the relative effectiveness of various treatment combinations with this difficult population. The present study is an investigation of the relative effectiveness of three treatment sequences in increasing social interaction among long term  regressed schizophrenics. In this study, 32 chronic schizophrenic patients were randomly assigned to one of three treatment sequences or to a control group. Each sequence began with six sessions of remotivation group therapy. Following, this, one group participated in four sessions of activities, another had social living discussions, and a third continued with remotivation therapy. Both the remotivation-activities sequence and the remotivation-only sesequence significantly increased social interaction relative to the remotivation-social living sequence and thecontrol group. Therefore it appears that both the activities groups and the remotivation groups are effective early components of a graded treatment program to increase social interaction among withdrawn schizophrenics.


Predicting outcome for mental hospital patients: who, what to ask. Outcomes for 62 hospitalized mental patients were predicted, utilizing various background information, diagnoses, and staff ratings of behavior, as independent variables. Diagnoses and previous admissions correlated weakly with the outcomes, viz., length of stay, subsequent readmissions, and post-hospital adjustment. Staff ratings were more reliable, and of these, the open ward aides' estimates generally were more effective than those of admission ward personnel or professionals. Staff predictions and judgments of patients' behaviors yielded multiple correlations explaining over 60 per cent of the variation in each outcome measure. In addition, the patient's judged competence and posthospital living situation were associated with his or her use of outpatient facilities.


WAIS and MMPI correlates of the Halstead-Reitan Neuropsychology Battery in normal male subjects. Two groups, each consisting of 24 normal young men, were given the Halstead-Reitan Neuropsychology Battery and additional tests of intellectual and personality functioning, the Wechsler Adult Intelligence Scale, the Minnesota Multiphasic Personality Inventory, the Taylor Manifest Anxiety Scale, and the Cornell Medical Index. The test (and subtest) scores were intercorrelated. No significant correlations were found between any of the personality tests and any of the subtests of the Halstead-Reitan Neuropsychology Battery. Most of the WAIS measures likewise failed to correlate with the Halstead-Reitan measures in the two samples. The exceptions were the Digit Span and Block Design subtests and the Performance Scale IG score on the WAIS which did correlate with some of the subtests from the  Halstead-Reitan Neuropsychology Battery. The findings with normal subjects reported in this paper, in contrast with findings with psychopathological and brain-damaged groups of subjects reported by others, indicate that for Ss in the top half of the population in education and WAIS FSIQ, individual differences in scores on the WAIS, the MMPI, TMAS, and CMI do not materially influence performance on the Halstead-Reitan Neuropsychology Battery Measures.


Handedness and the lateral distribution of conversion reactions. The purpose of this investigation was to determine whether the observation of Ferenczi and Purves-Stewart that conversion reactions occur with higher frequency on the left side of the body than on the right side could be confirmed. Both right-handed and left-handed patients experienced a higher proportion of left-sided symptoms (weakness or paralysis; sensory loss or numbness) than would be expected by chance, indicating a lack of support for the hypothesis that unilateral conversion symptoms occur most frequently on the most "convenient" (nondominant) side of the body. These findings and prior reports of left-sided lateralization of psychogenic pain were interpreted as support for the hypothesis that the right cerebral hemisphere is particularly involved in the mediation of affectively or motivationally determined somatic symptoms. The question of a possible link between these results and certain symptoms of disease of the right hemisphere was raised.


Platelet and plasma amine oxidase inhibition and urinary amine excretion changes during phenelzine treatment. The treatment of depressed patients with the monoamine oxidase (MAO)-inhibiting antidepressant, phenelzine, was found to be accompanied by an 82 per cent reduction in platelet MAO activity and a 91 per cent reduction in plasma amine oxidase activity. Maximum reductions in enzyme activity occurred after 7 to 14 days of treatment; recovery of enzyme activity posttreatment required an average of 14 days for the platelet MAO and greater than 6 weeks for the plasma enzyme. Marked elevations in urinary tryptamine excretion occurred in conjunction with MAO inhibition during phenelzine treatment, but the magnitidue of urinary tryptamine change in individual patients was not closely correlated with the magnitude of enzyme activity reduction. Changes in platelet serotonin content serotonin content and in urinary catecholamine metabolites also occurred in response to phenelzine treatment.


Facial recognition in "pseudoneurological" patients. A test of facial recognition was given to 44 patients whose symptoms raised a question of differential diagnosis between brain disease and functional psychiatric disorder. These "pseudoneurological" patients presented symptoms (e.g., memory impairment, headache, sensory disturbances) that were sufficiently suggestive of CNS disease to warrant thorough neurological evaluation. In each case, such evaluation disclosed no evidence of brain disease and the final diagnosis was some type of functional psychiatric disorder. Facial recognition performances of these patients were indistinguishable from those of medical patients without history or evidence of brain disease. The findings support the clinical application of this type of task in cases presenting problems of differential diagnosis.


Psychological effects of mastectomy on a woman's feminine self-concept. Previous literature on mastectomy indicates that the operation may be perceived by the patient as a threat to her feminity. Accordingly, the present study attempted to measure changes in body image, self-concept, and total self-image in mastectomy patients and two control groups (biopsy and surgical controls). Patients were given a questionnaire measuring the concepts in question three times: 1 day before surgery; 6 days after surgery; and 6 to 11 months later. There were distinctly different patterns of results for the three groups. Mastectomy patients did indeed evince a decline in body image and total self-image, but not until months after surgery. This was not unexpected in light of previous findings of massive denial in mastectomy patients. Immediately after surgery, this denial would be at its strongest, and it is feasible that it would take some months of reality testing until the denial is no longer a necessary defense. Biopsy patients showed a decline in body image and total self-image immediately after surgery, when their denial was no longer needed. Surgical control patients showed little overall change. Thus, mastectomy patients do appear to react to the operation with a decline in self-image, although this  does not appear until some time after the operation.


Dynamics of hypnotic analgesia: some new data. Following two surgical operations under hypnotic anesthesia, it was possible, during subsequent recall under hypnosis, to elicit a representation of the past operative experience. It would seem that under hypnosis there is a persistence of the preception of nociceptive information and of its recognition as such by the subject. From an analysis of these two experiments in recall, it is possible to formulate several hypotheses concerning the psychological processes involved in hypnotic analgesia. In consequence of an affective relationship, in which the hypnotist's word assumes a special importance for the subject, the latter has recourse to two kinds of mechanism: a) internal (assimilation to an analogous sensation, not, however, registered as dangerous-rationalization); and b) external (total compliance with the interpretations proposed by the hypnotist), which lead to a qualitative transformation of nocieceptive information, as also the inhibition of the behavioral manifestations normally associated with a painful stimulus.


In vitro stereoselective metabolism of the psychotomimetic amine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane. An apparent enantiomeric interaction. The stereoselective metabolism [R/S (metabolized) less than 1] of the psychotomimetic amine (R,S)-1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in 10 000g rabbit liver homogenate supernatant and 100 000g microsomal fractions has been demonstrated with the aid of the chiral reagent (S)-N-pentafluorobenzoylprolyl-1-imidazolide and GLC analyses. In contrast to the enantiomeric discrimination observed with racemic amine, the individual isomers were metabolized at approximately the same rate. This apparent enantiomeric interaction illustrates the fact that racemates should be viewed as unique chemical species with pharmacodynamic and toxicologic profiles potentially different from the individual antipodes.


Synthesis and antitussive activity of aminotetra- (and -hexa-) hydrodibenzofurans. The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with that of codeine, was found in the 4alpha-amino series. The 4-methylpiperazin-1-ylpropionamide (28) was found to be the most active of the compounds synthesized and was equipment with codeine. The effects of structural modification upon antitussive activity were investigated in numerous analogues but no enhancement of activity was achieved over that of 28.


Synthesis and structure-activity relationships of 5H,11 H-[I]benzopyrano[4,3-g]benzopyran-9-carboxylic acids. The synthesis and properties of the title compounds 1 are described. Many of these compounds are potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge. Structural variations include substitutions in the 2, 3, 4, 5, 7, and 12 position of the nucleus 1. A novel rearrangement from a compound of the related [3,4-f] series to this group is reported.


Derivatives of tetrahydro-1,4-benzodiazepines as potential antihypertensive agents. 4-Amidino derivatives and quaternary salts of tetrahydro-1,4-benzodiazepines were synthesized and evaluated for antihypertensive activity in conscious rats by the oral route. Included in this study were derivatives of 1,2,4,5,6,7-hexahydropyrrolo[3,2,1-jk][1,4]benzodiazepine and 1,2,3,4,8,9,10,11-octahydro[1,4]diazepino[6,5,4-jk]carbazole in which the 1 and 9 positions of tetrahydro-1,4-benzodiazepine are linked by an ethylene and a cyclohexenyl chain, respectively. Four compounds exhibited marked blood pressure lowering activity (greater than 50 mmHg) at doses of 75 mg/kg. Further study indicated that these compounds are effective by impairing transmission in the sympathetic nervous system.


Synthesis and topical antiinflammatory properties of 17,21-bis(acetyloxy)-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione and related 2-halogenated compounds. Introduction of a halogen atom at C-2 of steroid 3-ketofluorohydrins, obtained from the corresponding 5alpha,6alpha-epoxides by trans-diaxial opening with hydrofluoric acid, prevents the 6beta-fluorine atom from undergoing rearrangement to the more stable 6alpha configuration when the 5-tert-hydroxyl is split off to yield to yield a conjugated double bond. Two processes were investigated for the synthesis of 17,21-bis(acetyloxy)-6beta-fluoro-1,4,9(11)-triene-3,20-dione (24a) and the related 2-bromo compound 24b starting from the known 21-(acetyloxy)-6beta-fluoro-5alpha,11alpha,17-trihydroxypregnane-3,20-dione (13). Successive reaction with hypobromous acid, epoxidation, and fluorination converted 24a and 24b into the title compound 27a and the analogue 2-bromo compound 27b. In addition, a synthesis of 17,21-bis(acetyloxy)-2-chloro-6beta,9-difluoropregna-1,4-diene-3,20-dione (27c) is reported. The antiinflammatory activity of 17,21-bis-(acetyloxy)-6beta,9-difluoropregna-1,4-diene-3,20-dione (27a) and its 2-halogenated analogues 27b and 27c in comparison with the corresponding 6alpha,9-difluoro epimers was studied. Some 6beta-fluoro compounds displayed high topical antiinflammatory activity without systemic effects.


Potential hypolipidemic agents derived from 3-hydroxy-17,17-dimethylgona-1,3,5(10),8,11,13-hexaene. Numerous aryloxy derivatives containing a lipophilic group have been found to possess hypolipidemic activity. This has prompted the preparation of various derivatives of 3-hydroxy-17,17-dimethylgona-1,3,5(10),8,11,13-hexaene (6a). In 6a the lipophilic biphenyl group is incorporated into the steroid nucleus. A three-step synthesis of 6a from 17beta-methylestradiol methyl ether was developed. The derivatives prepared were tested in rats made hypercholesterolemic with propylthiouracil. Several were found active in this test.


Inhibitors of polyamine biosynthesis. 4. Effects of alpha-methyl-(+/-)-ornithine and methylglyoxal bis(guanylhydrazone) on growth and polyamine content of L1210 leukemic cells of mice. L1210 leukemic cells of mice were incubated for a period of two generations in the presence of either alpha-methyl-(+/-)-ornithine, an inhibitor of ornithine decarboxylase, or methylglyoxal bis(guanylhydroazone), an inhibitor of S-adenosylmethionine decarboxylase. alpha-Methyl-(+/-)-ornithine produced a 50% decrease in spermidine levels, reduced putrescine to nondetectable levels, and caused a slight increase in spermine levels of the cells. However, DNA content of the cell suspension was not altered by alpha-methyl-(+/-) ornithine. Thus putrescine and 50% of the cellular content of spermidine are not essential for DNA synthesis in these cells. Methylglyoxal bis(guanylhydrazone) produced a large increase inputrescine levels, the same decrease in spermidine levels as did alpha-methyl-(+/-)-ornithine, and approximately a 45% decrease in spermine levels. These changes were accompanied by a large decrease in the DNA content of the cell suspension. Since the two inhibitors caused a similar decrease in spermidine levels, it is unlikely that the inhibition of DNA synthesis by methylglyoxal bis(guanylhydrazone) is a result of a decrease in the cellular levels of spermidine. Rather, it seems likely that methylglyoxal bis(guanylhydrazone) inhibits DNA synthesis through a mechanism other than a decrease in polyamine levels.


Synthesis of [1-sarcosine, 8-O-methylserine]angiotensin II and 1-substituted analogues of [8-threonine]angiotensin II as antagonists of angiotensin II. [1-N-methylisoleucine,8-threonine]-(I), [1-dimethylglycine,8-threonine]-(II), [1-guanidineacetic acid,8-threonine]-(III), des-1-aspartic acid-[8-threonine]-(IV), and [1-sarcosine,8-O-methylserine]angiotensin II (V) were synthesized by Merrifield's solid-phase procedure to study the effect of (a) substituents in position 1 on the antagonistic activity of [1-sarcosine,8-threonine]angiotensin II, and (b) a change in size and branching in position 8 of [1-sarcosine,-8-O-methylthreonine]angiotensin II. The analogues I-V caused an initial rise in blood pressure (30 min of infusion, 250 ng/kg/min in vagotomized ganglion-blocked rats) of 8.05, 11.7, 3.50, 4.5, and 11.16 mmHg. The pA2 values (rabbit aortic strips) obtained were 7.68, 7.53, 7.23, 7.53, and 9.66, and the dose ratios (in vagotomized ganglion-blocked rats infused at 250 ng/kg/min) obtained were 2.37, 4.49, 1.02, 1.47, and 24.04, respectively. The results obtained indicate that (a) the nature of the substituent in position 1 has an important influence on the biological activity of these peptides, and (b) the potency of antagonists I-IV (all less potent antagonists than [1-sarcosine,8-threonine]angiotensin II) is very much influenced by the length and branching of the side chain in position 8. The in vivo antagonistic activity of [1-sarcosine,8-O-methylthreonine]angiotensin II is reduced considerably by shortening the chain length by one carbon atom as is in V.


A study of the mechanism of halothane-induced liver necrosis. Role of covalent binding of halothane metabolites to liver proteins in the rat. Various anesthetic and nonanesthetic doses of [1-14C]halothane were administered separately to normal and phenobarbital-pretreated (PBP) rats by ip route. The rats were sacrificed at 0.5-24 h after dosing, and livers were removed and examined histopathologically for tissue necrosis. Only PBP rats that received anesthetic doses of halothane (11.5 or 23 mmol/kg) and sacrificed 24 h after dosing exhibited liver toxicity. Determination of the radioactivity distribution among various liver macromolecules revealed that the protein fraction contained the highest activity at all time points in all animals. The lipid fraction showed some radioactivity during the initial 1-6 h period which disappeared after 6-8 h, while the DNA fraction was devoid of radioactivity in all animals injected with [14C]halothane. All the PBP rats that exhibited liver necrosis consistently attained higher covalent binding of halothane metabolites to liver proteins (2.13-2.20 nmol/mg of protein) when compared with the protein binding (1.12-1.41 nmol/mg of protein) observed among the rats that did not exhibit liver toxicity during the same time period. These results suggest a correlation between covalent binding of halothane metabolites to liver proteins and halothane-induced liver necrosis.


Antiarrhythmic activity of p-hydroxy-N-(2-diethylaminoethyl) benzamide (the p-hydroxy isostere of procainamide) in dogs and mice. p-Hydroxy-N-(2-diethylaminoethyl)benzamide (2), the p-hydroxy isostere of procainamide (1), shows antiarrhythmic activity against acontine-induced atrial arrhythmia and lowers mean arterial blood pressure after iv infusion in dogs. In isolated canine Purkinje fibers, phenolic 2 in a bath concentration of 20 mug/ml significantly reduced the rate of phase O depolarization, prolonged the repolarization time, and reduced automaticity. These in vitro and the above in vivo activities of phenolic 2 were similar to those observed for procainamide (1). Bioisosters, phenolic 2 and procainamide (1), have almost identical respective 13C NMR chemical shifts indicating that electron densities on the respective carbons are very similar. This may explain their similar antiarrhythmic and hypotensive effects. Phenolic 2 and procainamide (1) therapeutic ratios in ICR male mice (acute LD50/ED50 against chloroform hypoxia induced ventricular fibrillation) are 2.1 and 1.8, respectively. Procainamide analogues with electron-donating groups [OH, NH2, NHC(=O)CH3] on the aromatic ring possess more antiarrhythmic activity in mice than the analogue with an electron-withdrawing group (NO2). This indicates that a shift in electron density toward the amide region in the former analogues, as determined by 13C NMR spectroscopy, is one of the factors influencing antiarrhythmic potency in this series.


Biological significance of the electronic structure of alloxan and its tautomers. By means of a molecular orbital method which considers all valence electrons, INDO, we have calculated several electronic indices and determined the major tautomers in the lactan-lactim tautomerism of alloxan in the liquid and gaseous states. We have found that the principal tautomer, in both the gas phase and in solution, is the keto form; however, in solution, we have found a major contribution by the 2-hydroxy form. In addition, we have determined that the most reactive group, in all tautomers, to nucleophilic addition is the 5-CO group. We also made some observations concerning the effect of the electronic structure of alloxan on its diabetogenic activity.


Synthesis of analogues of N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea for evaluation as anticancer agents. The superior activity of N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea (MeCCNU) against advanced murine Lewis lung carcinoma in comparisons with the cis form and other nitrosoureas prompted the synthesis of a number of MeCCNU analogues, including several cis-trans pairs. The methyl group was replaced by a variety of substituents (CO2H, CH2CO2H, CO2Me, CH2OAc, CH2Cl, OMe); the trans-3-methylcyclohexyl, cis-2-methyl-1,3-dithian-5-yl, cis- and trans-2-methyl-1,3-dithian-5-yl-tetraoxide, and 1-methylhexyl (open-chain) analogues were also prepared. Preliminary tests against murine leukemia L1210 revealed therapeutic indices (ED50/LD10) ranging from 0.26 to 0.79; all but three analogues effected 50% cure rates at nontoxic doses, the open-chain analogue being one of the least active. In terms of therapeutic index, diequatorial (trans-4) isomers were, with one exception, as active as or, in four of the eight examples, somewhat more active than the corresponding axial-equatorial (cis-4) isomers. In this series, four of the five 2-fluoroethyl analogues prepared were clearly inferior to the corresponding 2-chloroethyl analogues.


Inhibition of solid tumors by nitrosoureas. 1. Lewis lung carcinoma. The utility of the Lewis lung carcinoma as a secondary screen for the evaluation of nitrosoureas as anticancer agents has been assessed. The activity of this series of compounds was determined against both the early (before metastasis) and late (after metastasis) forms of the disease. Although some exceptions were noted, compounds most active against the early form of the disease were most active against the established tumor. A differentiation in activity based on the Lewis lung system was evident with nitrosoureas equally active against leukemia L1210, although the significance of this differentiation with respect to the human disease has not yet been established.


Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogues. Replacement of the 4-methoxy of mescaline with higher alkyl homologues or with bromine led to increased activity at serotonin receptors in a sheep umbilical artery preparation. This activity appears correlated with lipophilicity, as measured by 1-octanol-water partition coefficients, but drops off when the 4-substituent is about five atoms in length. It is suggested that 3,4,5-trisubhe 2,4,5-substitution pattern.


Substituent constants for correlation analysis. Constants for pi and omega ahve been measured for a miscellaneous group of aromatic substituents of interest to medicinal chemists. Swain and Lupton's gamma and kappa values have been calculated from the omego constants. Values for molar refractivity are also given for each of the substituents.


Synthesis and structure-activity relationship studies of cytotoxic epoxide derivatives of 7-oxabicyclo[2.2.1]heptane. Dimethyl exo-5,6-oxido-7-oxabicyclo[2.2.1]hept-2-ene-2,3-dicarboxylate (1) and the 1-methyl homologue 2 were shown to exhibit significant cytotoxicity in the 9KB tissue culture assay. Several analogues of 1 were prepared and it was found that removal of the epoxide, or the oxygen bridge, or the 2,3 double bond from 1 resulted in loss of significant cytotoxic activity. One compound which lacked the epoxide moiety, dimethyl 1-methyl-7-oxabicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate (5), also exhibited marginal cytotoxic activity.


9-hydroxy-1,2,3,4,5,6-hexahydro-1,5-methano-3-benzazocine derivatives as analgesics. Three 1,3-dimethyl-9-hydroxy-1,2,3,4,5,6-hexahydro-1,5-methano-3-benzazocine derivatives (7-9) have been synthesized and tested as analgesics. The synthesis of these compounds involved conversion of 1-methyl-7-methoxy-beta-tetralone (1) by Mannich reaction with MeNH2 and HCHO to give the 11-ketone 2, from which 7,8, and 9, respectively, were obtained. These compounds have analgesic activity, and 7 was found to be comparable to codeine.


Synthesis and specific pressor activity of [1-aspartic acid,5-valine,9-serine]angiotensin I ("fowl angiotensin I"). [Asp1, Val5, Ser9]angiotensin I was synthesized by Merrifield's solid-phase procedure. The dansylated derivative of this angiotensin was cochromatographed on the TLC with the dansylated angiotensin decapeptide isolated from white leghorn fowl. Either angiotensin showed identical behavior. The per mole pressor activity of the synthetic decapeptide (in rats anesthetized with pentobarbital and treated with pentolinium) as compared to mammalian angiotensins, namely, [Ile5]angiotensin I, [Val5]angiotensin I, [Ile5]angiotensin II, and [Val5]angiotensin II, was 157, 181, 114, and 85%, respectively.


Estrogen potentiating activity of two spiro compounds having approximately similar molecular dimensions to stilbestrol. Pharmacological investigation of members of a series of synthetic spiro derivatives with similar molecular dimensions to stilbestrol revealed that two compounds, spiro[cyclohexane-1,2'-tetralin]-1,4'-dione and spiro[cyclohexane-1,2'-indan]-1,4'-diol, exhibited a marked ability to potentiate stilbestrol at doses which had no intrinsic estrogenic activity. It is postulated that such compounds may be of use in reducing the side effects associated with estrogen therapy.


"Normal" children, "abnormal" results.

"Normal" children, "abnormal" results. The relationship of sensitivity and specificity to disease frequency is considered in quantitative detail for typical screening situations. It is shown by illustrative examples that most screening procedures applied unselectively to total populations will yield a vast abundance of false positive results. The important role of prior probability in interpreting diagnostic test results is spelled out and applied to paradigms for screening.


Perinephric abscess: an unusual presentation of perforation of the colon. Perinephric abscess caused by spread of infection from an adjacent extrarenal focus is rare. Prior to diagnosis, several features of this case suggested such a pathogenesis: absence of an associated upper urinary tract infection or a distant focus for hematogenous seeding, and late recurrence of the abscess despite prompt clinical response following drainage and antimicrobial therapy. Specifically, the large bowel was suspected early on and subsequently documented as the source of infection because of the unusual finding of a polymicrobial perinephric abscess.


Ultraviolet air disinfection for protection against influenza. Three converging lines of evidence support the belief that it may be possible, under appropriate circumstances, to interrupt the airborne transmission of influenza by ultraviolet (UV) air disinfection. These lines of evidence are: (a) that influenza is airborne; (b) that UV irradiation of the upper air of a room can provide safe and effective disinfection of air in the lower part of the room; and (c) that epidemic spread of airborne viral infections in humans can be prevented if the population under consideration remains in the UV-protected environment.


The characteristics and mortality of outpatient-acquired pneumonia. One-hundred fifty-four cases of pneumonia occurring over a 6-month period were analyzed. Population characteristics, admission diagnoses, causative pathogens, frequency of associated illnesses, antibiotic usage and mortality were evaluated. Despite population characteristics known to predispose to a poor clinical outcome, the mortality was low, probably because of rapid institution of a single, appropriate antibiotic.


A migrant study of adopted Apache children. Reservation-born Apache children adopted into non-Apache homes off the reservation at an early age were studied for incidence of three illnesses common on the reservation--pneumonia, diarrhea and otitis media. The illness rates were compared with those of non-Apache siblings in the adoptive home and with those of reservation children. Adopted Apache children had more illness than their non-Apache siblings, but less than Apache children on the reservation. Particularly striking was the low rate of multiple episodes of illness for adopted Apaches compared with those on the reservation. Intensive programs are needed to improve living conditions on the reservation.


[Pathophysiology and diagnosis of autonomous adenoma (author's transl)]. From personal experience in 200 patients and after a careful review of the literature autonomous adenoma of the thyroid is discussed under three aspects: 1. Different ways of its pathogenesis are possible. None of them has been sufficiently proven. 2. Differentiation by scintigraphy into a compensated, partially decompensated and fully decompensated stage does not correlate sufficiently with the concentration of thyroid hormones in the blood and the overall clinical picture. The TRH test is negative in about 90% of patients independent of the stage evaluated by scintigraphy. 3. The diagnosis of the disease by modern tools is critically reviewed.


[Clinical feature, treatment and prognosis of carcinoid tumors (author's transl)]. 14 cases of carcinoid tumors over a period of 16 years are reported. There are 7 carcinoids of the vermiforme appendix, 3 of the small bowel, 1 of the rectum, and 2 carcinoids of the bronchus. No carcinoid syndrom was observed. Three patients with carcinoid tumors, localized in the small intestine died immediately post operationem. All others are still alife and followed up between 6 month and 13 years, are free of symptoms or rezidives. Poor prognosis of the carcinoids of the small intestine seems to depend on late diagnosis, complications already occured at the moment of operation, and advanced age of these patients. Different malignance is not considered to be an important factor of prognosis.


[Septic shock following abdominal operations (author's transl)]. Septic or toxic shock is a life threatening complication after abdominal operations. The etiologic analysis of our 102 patients showed the following conditions: 1. diseases, which have already preoperatively a high incidence of septic complications, 2. sepsis developing after primary aseptic diseases, 3. septis without any etiologic connection to the primary disease or operation. An initial standarised intensive therapy must start before any irreversible organ damage may occur. First aim of all surgical measures is the eradication of the source of infection. Early relaparotomy is the only possibility for correction of intraoperativ technical defects. Only by longstanding combination of intensive personal and technical support prognosis of septic shock after abdominal operations can be improved.


[Instrumental esophageal perforations--diagnosis and treatment (author's transl)]. In the last 6 years 16 patients with an iatrogenic esophageal lesion have been treated. Most frequently this lesion results from esophagoscopies and bouginages. Laying of a gastric tube, extraction of a foreign body or dilatation of a cardiospasm are rare reasons for a lesion. Only three patients suffered from cancer. The early diagnosis and immediately operation is decisive for the therapy's success. The operation with primary closure of the defect and drainage should be aspired. After this the best results are levelled. If the surgical operation is carried on after the 24-hours limit, the operation itself is of minor importance as the lethality of these patients is very high and does not depend on the kind of therapy.


[Postoperative alkaline reflux gastritis (author's transl)]. Postoperative alkaline reflux gastritis is a distinct clinical entity occuring after operations enlarging, bypassing or resecting the pylorus. Reflux of alkaline duodenal content into the stomach is the causative factor. Primarily bile acids have an aggressive effect and lead to a destruction of the gastric mucosal barrier. Epigastric pain, fullness after meals and bile vomiting are the main symptoms. Gastroscopy with biopsy reveals a severe chronic atrophic gastritis and bile reflux. In most cases an achlorhydria that can be histamin-resistant is present. For adequate treatment surgical procedures diverting the bile flow from the stomach should be performed.


Increased blood fibrinolytic activity after aspirin ingestion. Fibrinolytic activity of whole blood and of platelet-deficient plasma, measured by 125I-fibrin assay in four normal subjects before and after ingestion of 1.8 g of aspirin, increased 33 to 150 per cent at one to three hours, at plasma salicylate levels of 5 to 18 mg per 100 ml. In two, plasma activity also increased. Fibrinolysis in blood, but not in plasma, increased 66 per cent after sodium salicylate. Sodium salicylate increased fibrinolytic activities of blood and of purified polymorphonuclear leukocytes in vitro, whereas aspirin had little effect. These striking effects of aspirin on cellular and fluid phases of blood fibrinolysis are apparently distinct from known aspirin actions on platelets. Plasma fibrinolytic activity accounted for only 18.8 +/- 12.3 per cent (S.D.) and 17.4 +/- 10.4 per cent of the activity measured in the corresponding whole blood of 11 normal men and 10 normal women, respectively, indicating the importance of cellular elements in normal blood fibrinolysis.


Somatostatin in human cerebrospinal fluid. To determine whether somatostatin is found in the hypothalamus and extrahypothalamic brain, we studied autopsy brain tissue by specific immunoassay. The hypothalamus contained the highest concentration (16.7 +/- 2.4 S.D. pg per microgram of protein), with small amounts in brainstem, cerebral cortex, cerebellum, pineal gland and spinal cord. Cerebrospinal fluid of seven neurologically normal persons also contained somatostatin in concentrations ranging from 15 to 55 pg per milliliter. To determine whether brain disease leads to abnormal cerebrospinal-fluid somatostatin, we examined 30 patients with neurologic disease, of whom 20 of 24 with cord or cerebral disease had concentrations above the highest normal level. The wide variety of diseases with somatostatin elevation suggests nonspecific leakage from damaged brain tissue. Cerebrospinal-fluid somatostatin may provide a good index of brain damage. Although correlated statistically with cerebrospinal-fluid protein, somatostatin concentration in five of 24 cases exceeded the upper limit of normal by 3 S.D. while protein was normal.


Ultrasonic and radiographic cholecystography. To define the relative merits of radiographic and ultrasonic cholecystography, we studied 208 randomly selected patients with possible cholelithiasis. The patients underwent both procedures, and the results were interpreted in blind fashion. Two hundred patients had satisfactory confirmation of their diagnosis, by either a well visualized radiographic cholecystogram or operation or both. The overall accuracy of the ultrasonic examination was 93 per cent, with a false-negative rate of 11 and an indeterminate rate of 4 per cent. The indeterminate rate was 24 per cent for the single-dose oral cholecystogram and 8 per cent for the double-dose oral cholecystogram. Both ultrasonic cholecystography and radiographic cholecystography are useful to detect gallstones. Our findings support using single-dose oral cholecystography as the routine first examination. If the gallbladder is not satifactorily visualized, ultrasonic cholecystography can be performed immediately. In an emergency or for patients who might be pregnant, ultrasonic cholecystography is available as the initial examination.


["Paralytic shellfish poisoning" (author's transl)]. In October 1976 an epidemic of 120 cases of paralytic shellfish poisoning was recorded in western Europe. Analysis of the 23 cases seen in Swizterland shows the following data; paresthesia of mouth and lips (100%); cerebellar syndrome (86%) with giddiness, ataxia, dysmetry and floating sensation; paresia or paralysis (62%); digestive symptoms (14%); no death. The mean incubation time is 3 hs 30 min; mean duration of the symptoms is 2 days. Half of the patients complain of asthenia and moderate memory disturbance lasting up to 3 weeks. The severity of the illness is in relation to the amount of ingested neurotoxin. The epidemiologic study shows that all European cases were due to consumption of mussels from the Atlantic coast of Spain.


[The aminopyrine respiratory test under the acute effect of ethanol. Evaluation of a new method for the measurement of microsomal functions of the liver]. Microsomal demethylation, a partial function of the liver, can be estimated by the aminopyrine breath test. Both the determination of specific activity and the disappearance rate constant for 14CO2 in breath demand the assumption of rapid formaldehyde oxidation to CO2. Conversely, the disappearance of aminopyrine from plasma reflects microsomal aminopyrine metabolism only. Ethanol is known to affect both microsomal demethylation and formaldehyde metabolism. If in the presence of ethanol the latter process should become rate-limiting, a discrepancy between the data obtained in breath and in plasma could be expected. In order to investigate this possibility 10 fasting healthy male volunteers received 9 mg/kg (dimethylamine-14C)-aminopyrine (2 muCi) orally and, 3 hs later, 0.7 g/kg ethanol. Immediately following ethanol the specific activity of 14CO2 in breath decreased by 25% (p less than 0.005) and the disappearance of 14CO2 from breath was 31% lower than in 17 matched controls (p less than 0.005). The aminopyrine plasma disappearance rate, determined by GLC, decreased by 30% after ethanol (p less than 0.05). Since the decrease in aminopyrine plasma disappearance rate seems to account for the proportional decreases obtained by breath analysis, it is concluded that the aminopyrine breath test expresses the rate of microsomal demethylation even during altered formaldehyde metabolism, e.g. in acute ethanol intoxication.


[Experiences with the pneumatic drill for the taking of biopsy cylinders]. Surgical excisional biopsies, needle biopsies and aspiration biopsies are at present the most frequently used technical procedures in the diagnosis of tumors or other pathologic conditions. An additional, lesser known method of obtaining tissue for microscopic examination with a high speed pneumatic drill biopsy device is described. Over a period of 29 months 118 biopsies have been performed in 99 patients for histologic examinations limited to breast lymph nodes, skin and scars, thyroid gland, bone and parotic gland. Only 8 (6.8%) out of 118 biopsies were inadequate for microscopic evaluation. The 110 (93.2%) histologically adequate biopsies showed 76 (64.4%) specimens with pathologic changes and 28 (23.7%) were correctly negative. Consequently, 104 (88.1%) of the biopsies performed gave correct results. 6 cases (5.1%) were false-negative. False-positive cases were not obtained. In view of the number of successful examinations with adequate results, it can be concluded that the method presented is a useful diagnostic tool. The procedure involves little stress for the patient and can be performed under local anesthesia on an out-patient basis.


[Liver cirrhosis due to a breast neoplasm metastasis. So-called metastatic-carcinomatous cirrhosis]. A case is presented which, 9 years after surgical removal of a scirrhous breast cancer, exhibited morphologically atypical metastasis in the liver with fibrosis and reduction of liver parenchyma, as well as typical features of cirrhosis including portal hypertension and esophageal varices. Problems posed by the differential diagnosis and pathogenesis of this rare type of metastasis (known in the literature as metastatic carcinomatous cirrhosis) are briefly discussed.


Public health hazards from electricity-producing plants. When a new electricity-producing plant is to be built in a given locality it is natural to take into account the public health consequences of the normal operation of each type of plant contemplated. Here, the fossil-burning plants and nuclear facilities come under consideration. I have attempted to show that, in spite of the many important studies performed, there is currently no reliable methodology to estimate how many more cancer cases, and how many more heart attacks and other diseases have to be anticipated as a consequence of the normal operation of this or that type of electric generator. In part, this is because the currently available estimates of radiation effects on humans are based on extrapolations from studies of two kinds. Those of one kind may be exemplified by studies of atomic bomb casualties in Hiroshima and Nagasaki. The other kind are laboratory experiments with lower animals, frequently mice. The unreliability of both kinds of extrapolations is connected with the following circumstances: (i) The omnipresent troublesome phenomenon of competing risks. (ii) The dependence of health effects of a given noxious agent on the preexisting local pollution. (iii) The dependence of health effects not only on the "dose" of an agent, but also on the rate at which the agent is administered. (iv) The noted difficulties of making extrapolations from one mammal to another. Our obtaining reliable estimates of the public health effects of extra pollution from new industrial plants would seem to depend on a large multipollutant and multilocality epidemiological study being conducted--one requiring the cooperative effort of several governmental agencies. However, a much easier study of certain developments in the vicinity of Rocky Flats, Colorado, might provide important direct information on health phenomena as they occur in real life.


Migrating birds respond to Project Seafarer's electromagnetic field. Radar tracking of individual migrating birds flying over a large alternating-current antenna system showed that the birds turned or changed altitude more frequently when the antenna system was operating than when it was not. These results suggest that birds sense low-intensity alternating-current electromagnetic fields during nocturnal migratory flight.


Altered yolk structure and reduced hatchability of eggs from birds fed single doses of petroleum oils. Yolk deposited by Japanese quail was abnormal for 24 hours after the oral administration of a single capsule containing 200 milligrams of bunker C oil. Both the structure and the staining properties of the yolk were affected. Fewer eggs were laid during the 4 days after dosing, compared to controls, and hatchability was drastically reduced. Hatchability returned to normal in 4 days. Three other reference oils also affected yolk structure. Canada geese given 2 grams and chickens given 500 milligrams of bunker C oil produced eggs with abnormal yolk rings.


Rapid brain cooling in exercising dogs.

Rapid brain cooling in exercising dogs. In alert, resting dogs, the brain is warmer than arterial blood in the common carotid artery. When dogs run, brain temperature drops, despite a sharp rise in carotid blood temperature, and is maintained 1.3 degrees C below carotid temperature during exercise. This brain cooling apparently results from countercurrent heat exchange between warm arterial blood supplying the brain and cool venous blood draining the nose and mouth. The heat exchange occurs in the arteries at the base of the brain, which form a rudimentary carotid rete in the dog, and is greatest during exercise, when respiratory evaporation is at a peak. In animals with a carotid rete, the brain is protected against overheating during the severe thermal stress of exercise.


Hereditary hemolytic anemia with increased red cell adenosine deaminase (45- to 70-fold) and decreased adenosine triphosphate. Hereditary hemolytic anemia, a dominantly transmitted disorder, has affected 12 family members spanning three generations. The concentration of adenosine triphosphate in the red cells was about half that of comparably reticulocyte-rich blood. Since adenosine deaminase and adenosine kinase compete for a common substrate, the greatly increased activity of the former may interfere with nucleotide salvage via the latter.


Zinc binding: a difference between human and bovine milk. Gel chromatography indicated that most of the zinc in cow's milk was associated with high-molecular-weight fractions, whereas zinc in human milk was associated with low-molecular-weight fractions. A species difference in zinc-binding ligands may explain why symptoms of the genetic disorder of zinc metabolism, acrodermatitis enteropathica, can be alleviated by feeding human but not cow's milk.


Sexual calling behavior in primitive ants. The wingless virgin females of the ponerine ant Rhytidoponera metallica attract males by the release of a pheromone from the tergal gland, a hitherto unrecognized exocrine gland located between the last two abdominal segments. This is the first evidence for sexual chemical communication in the large and primitive subfamily Ponerinae.


Amygdaloid projections to prefrontal and motor cortex. Direct projections from the amygdala to the entire frontal cortex were demonstrated in the cat using the retrograde transport of horseradish peroxidase. Injections throughout the prefrontal cortex labeled neurons in the ipsilateral basal magnocellular amygdaloid nucleus; injections in the premotor and motor cortices labeled neurons in the same nucleus plus a few cells in the anterior amygdaloid area.


Differential sensitivity for smell: "noise" at the nose. The ability of subjects to resolve differences in concentration of chemicals in the vapor phase by smell rivaled the optimum performance of chromatographs. In some instances, subjects resolved a difference in concentration of only 5 percent. The reported inability of olfaction to register fine differences in intensity seems to be largely a result of fluctuations in the stimulus.


The practical training of New Zealand veterinary undergraduates in meat hygiene. Development of the veterinary undergraduate course in meat hygiene over a ten year period is discussed. Arrangements and supervision of students during a two week practical course at six specified centres of meat production, and the value of such training in an actual industrial environment are discussed. The timing of this course in relation to the veterinary curriculum and the seasonal nature of the meat industry in New Zealand creates some problems. Training centres must slaughter a variety of animals and have sufficient staff to effectively teach students. Adequate preparation of students and close co-operation with both the Ministry of Agriculture and the meat industry is essential for success.


Fetal electrocardiography in the mare as a practical aid to diagnosing singleton and twin pregnancy. Fetal electrocardiography (FECG) in the mare has been investigated by several workers (Holmes and Darke 1968, Kanagawa and others 1967). This short paper seeks to evaluate previous work, present new findings, and provide a practical technique enabling veterinary surgeons to diagnose singleton and twin pregnancies in the latter part of pregnancy.


[Two rare cases of neovascularity on coronary angiography (author's transl)]. The appearance of neovascularity on coronary angiography is described in two patients. A large thrombus was documented in one case at autopsy, whilst in the second case the presence of a thrombus was confirmed by two subsequent coronary arteriographic and ventriculographic studies. Thus, the observation of neovascularity of the left ventricle on angiography is indicative of thrombus formation rather than the presence of a neoplasm.


[The influence of somatostatin on serum gastrin concentrations in patients after total duodenopancreatectomy (author's transl)]. Serum gastrin concentrations were measured in insulin-dependent diabetics and in patients who had undergone total duodenopancreatectomy and gastrectomy. Administration of somatostatin markedly inhibited gastrin release in the diabetic patients with an intact gastrointestinal tract. This inhibitory effect of somatostatin, however, is not detectable in the group of operated patients, who display basically low plasma gastrin levels. A marked increase in the plasma gastrin level after withdrawal of somatostatin was observed in patients with a normal gastrointestinal tract. This rebound effect was only slight in the operated patients.


[Cefazolin content in the gall bladder (author's transl)]. The concentration of cefazolin in the bile obtained by means of duodenoscopy was determined and compared with the values published as results of sampling by gall bladder puncture and T drains. The results obtained using this endoscopic procedure accorded with the results in the literature. When 1 g cefazolin was administered intravenously, high biliary levels of this drug with antibacterial activity were achieved. Our preliminary studies show that not only highly-sensitive gram-positive organisms, but also most of the E. coli Klebsiella and indol-negative proteus bacteria were affected when 1 g cefazolin was administered 3-4 times daily. These results will be reported later. Cefazolin (Gramaxin) represents a valuable addition to the chemotherapeutic agents available in combating infections of the gall bladder and the biliary duct system.