Studies on reproduction in the camel (Camelus dromedarius) V. morphology of the testis in relation to age and season. Quantitative and qualitative changes in the morphology of the camel testis were studied in relation to age (6 to 18 years) and season. The diameter of the seminiferous tubules increased up to the age of 9 years. There was little variation in the number of germinal cells (spermatogonia, primary spermatocytes and spermatids) with the advancement of age. The number of spermatozoa increased up to the age of 10 years and decreased thereafter. Khe number of Sertoli cells was almost constant. Significant monthly and seasonal changes were observed in the criteria studied. The largest seminiferous tubule diameters and the greatest numbers of spermatogonia, spermatids and spermatozoa were found in the material collected during the spring. The numbers of mature Leydig cells, compared to the numbers of pre-Leydig and immature Leydig cells, increased by the end of winter so that, during the spring, the interstitial cells were mainly of the mature type. Degenerative changes with diminished numbers of mature cells were seen in the summer and this trend continued into early and mid-autumn.


Vitamin A in bovine sperm acrosomes.

Vitamin A in bovine sperm acrosomes. Bull semen was collected artifically and vitamin A was determined in the intact spermatozoa, the acrosomes and the sperm tails. The results show that over 90% of the total vitamin A in the spermatozoa was present in the acrosomes and that the sperm tails were completely devoid of vitamin A. The concentration of vitamin A varied from 224 to 364 ng/10-9 spermatozoa.


Autoimmune human sperm antibodies and age in males. The incidence of autoimmunization to spermatozoa, investigated by means of the Kibrick technique, increased with age in 913 males unselected with regard to fertility. By contrast, the incidence of sperm agglutinin-postive sera decreased with age in 1600 male partners in sterile couples. The increasing incidence of autoimmunization to spermatozoa offers one explanation of the lowering of fertility with increasing age, but sperm antibodies seem to be more important as a cause of sterility at younger ages. The presence of spermatozoa may not be necessary for immunization since sperm agglutinins were found in a 9-year-old boy.


Induction and inhibition of implantation in lactating rats. The interrelationship between prolactin and LH in the maintenance of pregnancy during lactation was studied. The reduction of suckled young from eight to two or less, as late as on the morning of Day 4 of pregnancy, resulted in normal implantation. Reintroduction of eight young on Day 4 to lactating pregnant rats deprived of their litters on Day 1 resulted in an inhibition of implantation, but reintroduction on Days 5 or 6 did not inhibit implantation. If oestrogen, HCG or PMSG was given on Day 4 of pregnancy, implantation was induced at the normal time in rats suckling large litters. When LH antiserum was given on the morning of Day 4 or Day 8 to pregnant rats suckling two young each, it blocked implantation and postimplantation survival of blasto-cysts, respectively. When the number of suckling young was increased from two to eight on Day 6, however, LH antiserum blocked pregnancy only to the extent of 70%. Prolactin administered during the preimplantation phase inhibited implantation in pregnant rats suckling a minimum number of young, but had no effect when given during the postimplantation phase. Progesterone failed to block implantation. Prolactin had no inhibitory effect on implantation in the absence of the suckling stimulus or in non-lactating pregnant rats. The inhibition of implantation by prolactin in rats suckling two young could be effectively reversed by the administration of oestrogen, PMSG or HCG on Day 4 of pregnancy.


The effect of copper on the distribution of elements in human spermatozoa. Examination of intact individual human spermatozoa by X-ray microanalysis revealed that there was a correlation between particular elements in differnt regions of the cell. There was a constancy in the ratios of sodium to potassium in the head and mid-piece and of calcium to phosphorus in the mid-piece in any one sample, though the ratios varied between samples. This may have reflected the external environment since immersion in culture medium or cervical mucus had little effect on motility, yet markedly altered the sodium: potassium ratio. Incubation with copper wire in semen or cervical mucus significantly reduced the subcellular levels of both sodium and potassium inspermatozoa but did not affect the ratio between these two elements. The metal also displaced zinc from the head region, possible replacing it by copper. This may account for the decreased motility of spermatozoa in contact with copper ions. The observed toxicity of copper for human sperm cells lends support to the theory that part ofthe mode of action of the copper IUD may be due to an alteration in sperm fertilizing potential. Although the level of copper released by IUDs containing 200 mm-2 ofcopper wire exerted a minor toxic effect on spermatozoa, the elemental changes observed here may have great significance in the development of more efficient copper-releasing IUDs or an intracervical device whose action would depend on its spermatotoxiceffect.


Histochemical observations on the lipid changes in rat corpora lutea during various reproductive states after treatment with exogenous hormones. Lipid changes were studied histochemically in rat CL during the oestrous cycle, pregnancy and lactation after treatment with oestradiol benzoate (EB), LH and prolactin. A single injection of 50 mug EB given on any day during the first half of the oestrous cycle, pregnancy and lactation caused a heavy accumulation of lipid droplets, which consisted mainly of cholesterol and/or its esters, triglycerides and some phospholipids. If the treatment with EB was followed by a single injection of 20 i.u. prolactin, droplet accumulation either did not occur, or was greatly reduced. During the second half of pregnancy, a massive accumulation of cholesterol- and triglyceride-positive lipid droplets occurred in the CL of untreated rats, and prolactin was equally effective in reducing, or preventing the storage of cholesterol-positive lipid droplets. Prolactin was more effective if two injections of 10 i.u. were given daily after an interval of 11 to 12 hr. No appreciable lipid change in the CL was caused by injection of 100 mug LH on any day during the first half of the oestrous cycle and pregnancy, but during lactation the same amount caused a heavy accumulation of lipid droplets, consisting mainly of cholesterol and/or its esters, triglycerides and very little phospholipid. Persisting CL of pregnancy and cyclic CL seen during lactation and pregnancy, respectively, were unresponsive to exogenous hormones, apparently due to ageing as no lipid changes occurred in the CL after hormonal treatment. The results are discussed in relation to previous histochemical and biochemical studies and suggest that both LH and prolactin regulate the lipid and cholesterol metabolism in the luteal cells of the rat.


Inhibition by aspirin and indomethacin of uterine hypertrophy induced by an IUD. An IUD inserted into one uterine horn caused an increase in its weight when this was compared with that of the contralateral control horn in rats. Such an increase could be partly prevented by treating the animals with indomethacin and aspirin. It is suggested that the IUD-induced increase in weight is at least in part mediated by release of prostaglandins.


Concentrations of free and esterified cholesterol in the testes of maturing rabbits. Levels of cholesterol and cholesterol esters were established in the testes of maturing New Zealand white rabbits. Free cholesterol levels remained relatively constant throughout pre- and post-pubertal development. The total cholesterol, cholesterol esters and percentage esterified cholesterol values were highest during the prepubertal period and decreased steadily thereafter, reaching their lowest after 90 days of age. Correlations of these findings with hormonal and morphological changes during testicular development are discussed.


Stimulation of repoduction in captivity of the wild rabbit, Oryctolagus cuniculus. Female wild rabbits which failed to breed under laboratory conditions were treated with gonadotrophins and artificially inseminated with epididymal spermatozoa. The fertilized eggs so obtained were transferred to synchronous domestic rabbits. Altogether, 185 eggs were transferred to thirty-six recipients. Thirty-three of the recipients maintained pregnancy to term and nearly half of the transferred eggs developed into normal young. Birthweights ranged from 45 to 59 g. Postnatal survival was excellent. Females born in captivity remained sexually immature in spite of attaining normal adult body weights. Sexual development was apparently normal in the males, although most remained shy breeders. Incidental observations on ovarian response, egg size and rate of development are presented.


Epididymal carbohydrate metabolism. III. Metabolism of the caput and cauda epididymidis after separation from the testis in the rat. After unilateral separation of the rat epididymis from the testis, the metabolism of various substrates in vitro by tissue from the attached and separated caput and cauda epididymidis at 7 and 28 days after surgery was determined by radiorespirometry. Hourly collections of 14-CO2 were made during 5-hr incubations. The patterns of 14-CO2 evolution from glucose indicated that most of the metabolic activity followed the Embden-Meyerhof glycolytic and the Krebs cycle respiration pathways. The alteration of the rate of glycolysis was always greater than that of respiration. In all samples, the metabolism of (2-14C) glucose was approximately equal to that of (6-14C) glucose (G-6)and less than that of (1-14C) glucose (G-1). Pentose cycle activity was indicated in all tissues from the caput and cauda epididymidis by the preferential utilization of G-1 over G-6. At 7 and 28 days after surgery, respectively, the G-1:G-6 ratios of 14-CO2 evolution after incubation for 2 hr were 9.75 and 7.79 for the separated caput, 5.17 and 2.66 for the intact caput, 3.11 and 2.52 for the separated cauda and 3.73 and 2.84 for the attached cauda epididymidis. Although epididymal separation did not effect the metabolism of (U-14C) glucose or (U-14C) fructose, glucose appeared to be a more important epididymal substrate than fructose.


Antisera to gonadotrophins and placental function in mice. I. Effect on polyamine content. The effect of antisera to ovine LH and ovine prolactin was studied on polyamine levels in the mouse placenta. The antisera were administered on Day 11, 12 or 13 of pregnancy and the mice were killed 24 hr later. The polyamines (spermine, spermidine and putrescine) in the placentae were estimated. Polyamine levels were reduced after treatment with anti-LH on any of the 3 days and after treatment with anti-prolactin serum on Days 11 or 12. Only the spermidine content was reduced when anti-prolactin serum was injected on Day 13 of pregnancy. Placental DNA and RNA levels paralleled those observed for polyamine content. The changes in polyamine content and nucleic acid levels indicate that these antisera to LH and prolactin interfere with placental function.


The entry of alpha-chlorohydrin into body fluids of male rats and its effect upon the incorporation of glycerol into lipids. The rate of entry of alpha-chlorohydrin into rat rete testis fluid has been studied using the 14-C and 36-Cl-labelled compounds. The alpha-chlorohydrin crosses the blood-testis barrier and the concentration of radioactivity in rete testis fluid attained blood levels within 45 min. Within 3 hr of a single injection of [14-C] alpha-chlorohydrin, radioactivity was widely distributed in body fluids, and was present in the lipids of the brain, testis, epididymis and epididymal fat pads. No radioactivity was found in tissue lipids following the administration of [36-Cl] alpha-chlorohydrin, which suggests that dechlorination of this compound occurs before its incorporation. Neither a single high dose nor repeated low doses of alpha-chlorohydrin induced changes in the incorporation of [14-C] glycerol into lipids of the brain, testis, epididymis and epididymal fat pads.


Electroejaculation of Australian marsupials and analyses of the sugars in the seminal plasma from three macropod species. Electroejaculation of a variety of Australian marsupials was attempted in this study. The animals used were conscious, sedated, anaesthetized or recently shot. Electroejaculation proved to be a satisfactory means of obtaining seminal plasma but not spermatozoa. The largest volumes of seminal plasma were collected from animals shortly after death. Anaesthetized animals also provided useful volumes of seminal plasma but only insignificant amounts were obtained from conscious and sedated animals. Quantitative analyses of N-acetylglucosamine, glucose and anthronereactive material were made of deproteinized, deionized, water extracts of seminal plasma from electroejaculates obtained from wallabies and kangaroos shortly after death. The major seminal sugar of the three macropod species was N-acetylglucosamine and glucose was also present in quite large concentrations. These observations show that the pattern of sugars in the prostate gland of marsupials is reflected in the semen.


A preliminary assessment of the source of oestrogen within the ovary of the domestic fowl Gallus domesticus. Oestradiol was measured by radioimmunoassay in blood draining individual preovulatory follicles and in different ovarian tissues of the hen. The concentration of oestradiol in blood from follicles 20 to 50 hr before ovulation ranged from 66 to 264 pg/ml and was less than that in peripheral blood collected concurrently, suggesting a net uptake rather than secretion of oestradiol by the follicle at these times. In one bird approximately 6 hr before ovulation, the highest content of oestradiol in tissue (35 ng) was in the small (less than 5 mm) follicles and ovarian stroma; this represented 87.5% of the total ovarian content. Only 0.86 to 1.02 ng oestradiol (2.0 to 2.5) was found in the large preovulatory follicles and 2.22 ng (5.5%) in the postovulatory follicles. High concentrations of oestradiol (2.4 ng/g) were also found in the liver. These results suggest that the small follicles and/or ovarian stroma are the main site of oestradiol production in the fowl; they do not exclude the possibility that oestradiol is secreted at a high rate by the mature follicle for a short period immediately before ovulation, thus influencing the release of LH.


Effect of 4-chloromethyl-2-methyl-2-pentyl- 1,3-dioxolane (AY-22,352) on the fertilizing ability of hamster epididymal spermatozoa. Fertile male hamsters were injected subcutaneously with AY-22,352 to determine the minimal antifertility dose, the site of action and the onset and duration of infertility. Fertility tests showed that 37 mg AY-22,352/kg/day induced sterility within 4 days. None of the males became infertile within the first 2 days but marked loss of sperm fertilizing ability had occurred by 24 hr from the second injection; all males were sterile after the fourth dose. Comparable daily treatment procuded the same antifertility effect subsequent to bilateral ligation of the corpus epididymidis and fertilization did not occur after artificial insemination with spermatozoa from the cauda epididymidis of such animals. The prompt recovery of fertilizing ability of spermatozoa in males which receoved four daily doses of AY-22,352 (37 mg/kg) and had ligated ductuli efferentes shows that transport of epididymal spermatozoa and their acquisition of fertilizing ability are not influenced by the drug.


Physical complaints of patients with sickle cell trait. Prospective and retrospective experience with physical complaints of 112 oral contraceptive and 67 intrauterine device Black family planning patients with sickle cell trait was evaluated by comparing their cumulative complaint rates with a randomly selected control group of non-sickle cell trait family planning patients having the same method, age and parity distribution as the sickle cell trait patients. Physical complaints considered are: dysmenorrhea, mental depression, vaginal discharge, fatigue, headaches, and nausea-vomiting. No evidence of a significant difference at level .05 is found between cumulative complaint rates of sickle cell trait and control patients for either oral or intrauterine device users for any of the complaint types. Further clinical research may be desirable in this area for dysmenorrhea and mental depression.


Trypsin-mediated activation of the alpha-haemolysin of Staphylococcus aureus. Alpha protoxin of Staphylococcus aureus "Wood 46" was activated by trypsin which had been coupled to carboxymethylcellulose, as indicated by the toxin's ability to hydrolyse tosyl-arginine methylester (TAME). A Lineweaver-Burk plot of the degradation of TAME by toxin and trypsin showed that toxin had a greater affinity for the substrate than had trypsin. N-terminal amino-acid analyses of activated toxin suggested that leucine or isoleucine is the N-terminus, in contrast to protoxin, the N-terminus of which is histidine.


Evidence for Ca-2+ control of the transducer mechanism in crayfish stretch receptor. Recording from the dendrite membrane indicated a resting potential of minus-51.6 mV, which was reduced by inhibition of the Na+/K+ pump. Voltage clamp at rest revealed a small inward current between minus-50 and minus-80 mV and a larger outward current at clamp potentials of minus-40 to +30 mV. Using ramp-changes of muscle tension as stimuli a time-variant tension-induced inward current (TIC) became apparent, the amplitude of which decreased towards larger depolarizing voltages until at +18 mV the current reversed the direction. The time course of the conductance changes corresponds to similar phases in the generator potential. The outward current only responded to fast reductions in tension, decreasing transiently. A contribution of the active Na+/K+ pump to the hyperpolarizing potential response is suggested by the effects of K-removal or Na-substitution by Li+. In Na-free choline chloride media the generator potential and the TIC was depressed by 70-85%. Additional removal of Ca-2+ abolished the TIC. In contrast, lowering the Ca-2+ level in presence of Na+ decreased the membrane resistance and markedly enhanced the TIC (maximally eightfold at 10-minus 5M Ca-2+) while 75-150 mM Ca-2+ or intracellular application of a Ca-ionophore had the reverse effect.


Ionic permeabilities of an Aplysia giant neuron. In a giant neuron of Aplysia californica, permeabilities and conductances obtained by measuring net fluxes of Na+, K+  and Cl-minus with ion-specific microelectrodes were compared with those obtained by measuring transmembrane current and potential changes when the three ions were varied in the external solution. Net fluxes were measured with ion-specific microelectrodes, after blocking metabolic processes, thus allowing movement of ions down their electrochemical gradients. Premeabilities and conductances obtained from the "chemical" measurements (i.e., ion-specific electrodes) were generally comparable to the values obtained from "electrical" measurements (i.e., ion-specific electrodes) were generally comparable to the values obtained from "electrical" measurements. Where discrepancies occurred, they could be explained by showing that some of the assumptions necessary to use the "electrical" method were not quantitatively true in this system. The absolute magnitudes of the permeabilities are significantly less than those found in many axonal preparations. There is also a relatively high PNa/PK ratio. The selectivity of the membrane against ions such as Tris" and MeSO3-minus is not good, Tris+ being nearly as permeable as Na+ and MeSO3-minus about one-half as permeables as Cl-minus. These properties may be characteristic of somal membranes.


Sugar transport by renal plasma membrane vesicles. Characterization of the systems in the brush-border microvilli and basal-lateral plasma membranes. Uptake studies of D-and L-glucose were performed on vesicles derived from brush-border and basal-lateral membranes. The uptake of the sugars into the vesicles was osmotically sensitive and independent of glucose metabolism. In brush-border vesicles D-glucose but not L-glucose transport was Na-+-dependent, wn the presence of an initial Na+gradient. Basal-lateral membranes take up D-glucose faster than L-glucose, but the D-glucose uptake is significantly less sensitive to sodium removal and only moderately inhibited by phlorzin as compared to the prush-border fraction.


A comparison of the rate equations, kinetic parameters, and activation energies for the initial uptake of L-lysine, L-valine, gamma-aminobutyric acid, and alpha-aminoisobutyric acid by mouse brain slices. At substrate concentrations, in medium, of 0.2 to 20 mM and at temperatures of 25 and 37 degrees C, the initial concentrative influx of the amino acids L-lysine (30 and 37 degrees C), L-valine, and gamma-aminobutyric acid into incubated mouse-cerebrum slices follows the rate equation for the initial influx of alpha-aminoisobutyric acid (Cohen, J. Physiol. 228:105, 1973), v equals Vmax/(1+Kt/S)+kuS. Kinetic constants at 37 degrees C are: Vmax equals 0.089 mumoles/g final wet wt of slices, min, Kt equals 0.69 mM, ku equals 0.037 mumoles/g final wet wt, mM-substrate, min for L-lysine; Vmax equals 0.60, Kt equals 1.30, ku equals 0.067 for L-valine; and Vmax equals 1.71, Kt equals 1.58, ku equals 0.094 for gamma-aminobutyric acid. The linear term, kuS, is due to an unsaturable process of concentrative uptake, not diffusion. Comparison of temperature coefficients reveals a "reference" pattern for typical low affinity transport of amino acids into brain slices. Its characteristics are: Activation energies associated with Vmax and ku are in range 14 to 20 kcal/mole; K, varies only slightly with temperature, L-Lysine and alpha-aminoisobutyric acid fit this pattern; L-valine and gamma-aminobutyric acid deviate in part. The Akedo-Christensen plot (J. Biol. Chem. 237:118, 1962) does not distinguish between the rateequation v equals Vmax/(1+Kt/S)+kuS for saturable uptake plus first-order unsaturable concentrative uptake, and the rate equation v equals Vmax/(1 + Kt/S)+kd(S minus Si) for saturable uptake plus first-order nonconcentrative "passive diffusion".


The mechanism of electrical breakdown in the membranes of Valonai utricularis. The dielectric breakdown in the membranes of cells of Valonia utricularis was investigated using intracellular electrodes and 500 mu sec current pulses. Electrical breakdown, which occurs when the membrane potential reaches a well-defined critical value, is not associated with global damage to the cell or its membranes (the membrane reseals in smaller than 5 sec). It was thus possible to investigate the effect of temperature on dielectric breakdown in single cells. It was found that the critical potential for breakdown was strongly dependent on temperature, decreasing from similar to 100 mV at 4 degrees C to similar to 640 mV at 30 degrees C. The decrease in the breakdown potential with increasing temperature and the very short rise-time of the breakdown current (similar to 1mu sec) suggests that the Wien field dissociation does not play a major role in the breakdown process. It is shown that the nonlinear I-V characteristics observed at different temperatures can be accurately accounted for with no adjustable parameters, by considerations of the mechanical compression of the membrane due to stresses induced by the electric field. Electrical breakdown on this scheme results from an electromechanical instability in the membrane. On this basis the present results indicate that the elastic modulus of the region of the membrane where breakdown occurs, decreases by a factor of 2 with increasing temperature from 4 to 30 degrees C. On the assumption of a thickness of 4.0 nm and a dielectric constant of 5, the elastic modulus is estimated to have a value of 5 times 10-6Nm- minus 2 at 20 degrees C.


The form and function of retractile claws in the Felidae and other representative carnivorans. Recent behavioral studies have  shown the primary organ of prehension used in capturing prey to be the claw equipped forelimbs. In light of its functional importance, the claw retractile mechanism for 15 felid species is described and its function studied . The anatomy of the claw retractile mechanism for felids is then compared to that of other carnivorans. For felids,claw retraction is mechanically possible due to the unique shape of the middle and distal phalanges. Claw retraction, however, is a function of the dorsal elastic ligaments and not of the forearm extensor muscles. The resistance provided by these ligaments allows for flexion of the wrist and digital joints without claw protrusion. Moreover, co-contraction of both forearm flexor and extensor muscles is necessary to produce claw protrusion. The functional anatomy of claw retraction for felids differs considerably from that of most other carnivorans. However, the claw retractile mechanism for some advanced viverrids is structurally similar to that of the felids. For these viverrids prey  seizing, as in the felids, has become a function of the forelimbs. For the other families of carnivorans, the jaws and not the forelimbs are used as the primary organ of prehension and the anatomy of the claw retractile mechanism reflects functional demands placed on it other than grasping and holding prey.


The suprarenal glands of a prosimian primate, the lesser bushbaby (Galago senegalensis). The gross relationships and light microscopic anatomy of the suprarenal gland of a prosimian primate, Galago senegalensis, is described. The left gland is located medial to the pole of the left kidney in a fascial compartment of its own. The right suprarenal is located medial to the pole of the right kidney in intimate apposition to the liver and inferior vena cava. The capsule of the right gland blends with the capsule of the right lobe of the liver and is also contiguous with the adventitia of the inferior vena  cava. The histologic appearance of the gland is similar to that of other primate genera. The zona glomerulosa is poorly developed; the zona fasciculata is composed of cell cords and is relatively well developed and the zona reticularis shows no unusual characteristics. The organization of the lipid content of the various cortical zones show a considerable different pattern than previously reported. The zona glomerulosa contains numerous large lipid droplets. In contrast to the bi-laminar pattern of lipid deposition seen in other primates, the Galgo shows three distinct layers of lipid droplets in the zona fasciculata. The zona reticularis has a moderate population of lipid droplets essentially similar to that reported in most other forms. The medulla, except for a sparse number of centrally displaced zona reticularis cells, is completely devoid of lipid deposits. The  junction of the zona reticularis and medulla is distinct, although a connective tissue capsule is not present.


A fluorescence microscopic study of the distribution of monoamines in the hypothalamus of the cat. Three distinct groups of monoamine (MA)-containing nerve cell bodies have been visualized in the hypothalamus and preoptic area of the cat by means of the Falck-Hillarp fluorescence histochemical technique. First, numerous small-sized catecholamine (CA) type neurons were disclosed within the ventral half of the periventricular area in the supraoptic and middle hypothalamic regions. The round to oval neurons of this medio-ventral group were more especially abundant around the base of the third ventricle, within the arcuate and supraopticus diffusus nuclei. Numerous medium-sized CA perikarya identified as the dorsal group, were also mapped out in the dorsal and posterior hypothalamic areas. Finally, a small population of both CA and serotonin (5-hydroxytryptamine, 5-HT)-containing neurons was disclosed within the lateral area of the middle and mammillary hypothalamic regions. These multipolar or elongated neurons which compose the lateral group were lying either along the ventrolateral surface of the hypothalamus or around the ventrolateral aspect of the fornix. In addition to these three MA cell groups, a few cells displaying a fluorescence of the CA type were also visualized in the so-called "dorsal chiasmatic nucleus" after alpha-methyl-dopa treatment. High density of CA axon terminals were found, on the other hand, in the extrenal layer of the median eminence, in the dorsomedial, paraventricular supraoptic and suprachiasmatic nuclei, and also within nucleus interstitialis of stria terminalis. In the present study, however, it was possible to identify with certainty any concentration of 5-HT axon terminals in the cat hypothalamus. Therefore, except for the lateral cell group which could be peculiar to the cat, the topographical distribution of MA nerve cell bodies and axon terminals in the hypothalamus of the cat appears similar to the morphological organization of the MA neuronal elements in the hypothalamus of the rat.


The cardiac muscle in the pulmonary vein of the rat: a morphological and electrophysiological study. The pulmonary veins of albino Wistar rats were studied by means of light and electron microscopy. The media of larger veins consists of cardiac muscle fibers which extend until the vessels attain about 100 mu in diameter. This coat consists of external longitudinal fibers and internal circular fibers. The vasa vasorum are well developed and the capillaries show pseudofenestrations. The numerous adrenergic and cholinergic nerve endings do not form typical motor end-plates as seen in skeletal muscles. The ultrastructure of these media muscle fibers is similar to that of the rat hearts. The smooth muscle layer of larger pulmonary veins is not continuous as it is in smaller veins where it forms cushions. Comparison of albino rats and other rodents reveal striking differences. Action potential shape and propagation velocity (0.5-1.2 m/s) along the myocardial coat of the pulmonary vein were similar to those observed in the left atrium and so was their sensitivity to locally applied acetylcholine. The physiological direction of propagation in rat pulmonary veins is toward the lung. This fingind lends support to the hypothesis of a rhythmic, valve-like action of the striated musculature of the pulmonary venous wall during the systole and a possible role in the capacitance of the pulmonary circulation.


Cytological examination of reduction bodies of Corvomeyenia carolinensis Harrison (porifera: spongillidae). Freshwater sponges, Corvomeyenia carolinensis Harrison, were placed into tap water to induce degenerative reduction body formation. Reduction bodies were examined using light and electron microscopy in order to define their histochemical and ultrastructural characteristics. The reduction body of freshwater sponges is an extremely simple developmental system consisting primarily of an archeocyte reserve delimited by a simple squamous pinacoderm. The freshwater sponge reduction body displays many similarities to overwintering phases of marine sponges. The system presents an unusually straightforward vehicle for investigations of degeneration and regeneration as processes in developmental biology and may represent a reasonable vehicle in which to examine the process of the genesis of lysosomes.


Zinc suppression of initiation of sarcoma 180 growth. Subcutaneous administration of 80 mug zinc daily to mice that had received an intraperitoneal inoculation of 1 times 10-6 sarcoma 180 cells within the preceding 2 days resulted in protection of up to 60% of the hosts. In animals in which tumors grew, daily injections of zinc did not alter the rate of tumor cell growth. We hypothesized that the metal suppressed initiation of tumor cell reproduction, possibly by stimulation of host defense cell mechanisms.


Inhibition of dimethylhydrazine-induced neoplasia of the large intestine by disulfiram. Disulfiram added to the diet of female CF1 mice inhibited large-bowel neoplasia produced by repeated subcutaneous administrations of dimethylhydrazine (DMH). The mice on a control diet all showed multiple tumors of the large bowel after DMH treatments, whereas there was no evidence of neoplasia in mice given disulfiram.


Nuclear magnetic resonance studies on human breast dysplasias and neoplasms. The ability of nuclear magnetic resonance (NMR) spectroscopy to distinguish normal, diseased non-neoplastic, and neoplastic human breast tissues was investigated with T1 and T2 relaxation times used. The results indicated that NMR relaxation times could distinguish between the mean values of breast neoplasms and other diseased or normal tissues, with P values less than 0.001. Given a single sample, the probability of classifying it nonneoplastic or carcinoma could be accomplished with 85% confidence. For human breast tissues, the relaxation time T2 may be more discriminating that T1. These results support the view that the use of NMR spectroscopy in cancer detection may be of significant value and warrants considerable more interest and effort to determine the beneficial applications and limits of this technology.


Magnesium oxide as carrier dust in benzo(a)pyrene-induced lung carcino-genesis in Syrian hamsters. The neoplastic progression induced by intratracheal instillation of benzo[a]pyrene (BP) and magnesium oxide (MgO) was compared with that induced by intratracheal instillation of BP and ferric oxide (Fe2O3). BP and MgO produced squamous cell carcinomas and papillomas in the larynx with a latent period as shor as 9 weeks. They also induced many papillomas as well as squamous cell carcinomas and adenocarcinomas in the trachea and a papilloma, squamous cell carcinomas, adenocarcinomas, adenosquamous lesions, and peripheral adenomatoid lesions in the bronchi. They rarely caused tumors in other organs; only a few forestomach papillomas, one melanoma on the dorsal skin, and one ovarian carconoma were seen BP, with Fe2O3 as the carrier, induced a comparable number of histologically similar tumors; however, tumors developed more frequently in the main bronchi. Thus MgO strongly facilitated the tumor-inducing effects of BP, causing tumors in different areas of the respiratory tract, and was as effective as Fe2O3 as a carrier agent in the experimental induction of respiratory tumors.


An epizootic in hamsters of lymphomas of undetermined origin and mode of transmission. An epizootic of lymphomas arose spontaneously on three occasions in a facility containing both inbred and randombred Syrian hamsters. These tumors developed in approximately half the colony-born hamsters and were horizontally transmissible to those brought into the colony.


Nonspecific  Immunotherapy of Murine Solid Tumors With Corynebacterium granulosum. A single intraperitoneal (ip) or intravenous (iv) injection of Corynebacterium granulosum into C3Hf/Bu mice shortly after subcutaneous (sc) injection of cells from a strongly antigenic syngeneic fibrosarcoma induced by 3-methylcholanthrene caused complete and lasting regressions of 100 and 70% of resulting tumors, respectively. Treatment with this bacterium sc only slightly inhibited the growth of some tumors. C. granulosum given iv to mice 3 days after the sc injection of fibrosarcoma cells caused complete regressions of 39 of 45 tumors; two iv injections with this immunostimulant given 1 month apart were no more effective than a single injection. Intralesional treatment of fibrosarcomas 8 mm in diameter induced complete regressions of tumors in 30% of the animals, whereas sc treatment contralateral to the growing tumor only slightly reduced tumor growth. Intraperitoneal growth of a fibrosarcoma was efficiently controlled (58-80% survival of mice) if C. granulosum was given ip, but not iv, 3 days after inoculation with tumor cells. Again, two injections of C. granulosum (given ip 4 days apart) were only as effective as a single injection. Treatment with C. granulosum iv at 3, 7, 14, or 21 days after sc inoculation of a weakly antigenic, spontaneously arising mammary carcinoma (MC-1) strongly inhibited tumor growth. Three complete but temporary tumor regressions were observed. The subcutaneous growth of another spontaneous mammary carcinoma (MC-2), which contained fairly strong tumor-specific antigen(s), was also significantly inhibited if C. granulosum was given 3,7, or 14 days after, but not 7 days before, tumor cell inoculation. However, pretreatment of mice with the immunostimulant significantly protected the mice against artifically induced pulmonary metastases of this tumor.


Antigenic changes in cultured murine lymphomas after retransplantation into syngeneic hosts. When cultured murine lymphomas were retransplanted into syngeneic hosts, the quantitative representation of H-2 antigens and Moloney leukemia virus-determined cell-surface antigens tended to revert to the antigenic pattern characteristic of the corresponding lines propagated in vivo. In some instances, a complete reversion of both the virus-specific and H-2 antigens was observed after a single passage of cultured lymphoma cells in syngeneic hosts.


Mouse skin tumorigenesis and induction of aryl hydrocarbon hydroxylase by tobacco smoke fractions. Ten fractions separated from the neutral portion of cigarette smoke condensate (CSC) were tested on mouse skin for tumor-initiating activity and for their capacity to induce the enzyme aryl hydrocarbon hydroxylase (AHH). Tumor-initiating activity was confined primarily to the fraction containing more than 90% of the polynuclear aromatic hydrocarbons (PAH) in CSC. One other PAH-containing fraction was active. The combined initiating effect of these fractions was comparable to that of a 40-ppm solution of benzo[a]pyrene (BP), which is about 40 times the BP content of CSC. Some of the neutral fractions that have been demonstrated to cause tumor promotion in mice pretreated with 7,12-dimethylbenz-[aA1ANTHRACENE sere inactive as tumor initiators. The fractions that contained aromatic hydrocarbons induced mouse skin AHH levels twofold to sixfold after a single topical application. AHH-inducing activity was not, however, a reliable indicator of the carcinogenic potential of a fraction.


Embryonic inductive tissues that cause histologic differentiation of murine mammary carcinoma in vitro. A murine mammary tumor was cultured in vitro for 14 days, either in direct combination with various embryonic murine inductive tissues or separated by a Millipore filter from these tissues. From 456 test cultures and 269 control cultures of tumor alone, morphologic, histochemical, and autoradiographic evidence for cytodifferentiation was obtained in the tumor after exposure to inductive tissues directly or through the filter. There appeared to be a gradient in potency of the inductive tissues; embryonic mammary mesenchyme was the most active of the tissues tested. Tumor growth was not different from that of controls, however, when the cultured, inductive tissue-exposed neoplasm was returned to the murine host.


Prolonged inhibition of mouse epidermal DNA synthesis by dexamethasone. The effect of dexamethasone, an anti-inflammatory agent that inhibits skin carcinogenesis, on DNA, RNA, and protein synthesis in mouse epidermis was investigated. Within 1 hour after the topical application of 75 mug dexamethasone to the skin of mice, epidermal DNA synthesis was inhibited drastically and lasted for approximately 5 days, followed by a biphasic stimulation at 7 and 10 days after treatment. Histologically, the skin after dexamethasone treatment revealed only subtle quantitative changes. The dermis was not altered. The epidermal thickness was unchanged, but the nuclei of the epidermal cells were more densely stained and the chromatin was more densely clumped. These changes were present by 12 hours and persisted for 10 days. Both epidermal RNA and protein syntheses were stimulated early, reached a peak of around 180% of controls at 1 hour, but returned to control levels by 3 hours. They were slightly inhibited between 3 and 12 hours after treatment and then returned to control levels. This prolonged inhibition of DNA synthesis by dexamethasone may be related to its anticarcinogenic effect.


Carcinogenic effects of Di-n-propylnitrosamine, beta-hydroxypropyl-n-propylnitrosamine, and methyl-n-propylnitrosamine on Sprague-Dawlay rats. The carcinogenic effects of di-n-propylnitrosamine and its two related compounds, beta-hydroxypropyl-n-propylnitrosamine (HPPN) and methyl-n-propylnitrosamine (MPN), were tested in rats and compared. All three substances induced neoplasms in the nasal and paranasal cavities, esophagus, and liver. MPN treatment caused the highest tumor incidence in the esophagus, whereas HPPN induced the most hepatic tumors.


Carcinogenicity of the antineoplastic agent, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide, and its metabolites in rats. Chronic oral administration of the antineoplastic agent, 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388, DTIC), induced predominantly thymic and mammary tumors as demonstrated previously. Male and female Sprague-Dawley and female Buffalo rats were susceptible to the carcinogenicity of DTIC. A 50% incidence of mammary adenocarcinomas was induced in males within 18 weeks. Type of tumor and tumor incidence were dose dependent. Single and multiple intraperitoneal injections of DTIC did not alter organ specificity. DTIC-induced thymic lymphosarcomas and mammary adenocarcinomas were transplantable. Tissue distribution studies revealed no correlation between uptake of DTIC by a given tissue and its susceptibility to carcinogenicity. Metabolites of DTIC were tested for carcinogenic activity. Animals administered 5-diazoimidazole-4-carboxamide orally, intraperitoneally, or intragastrically developed low incidences of thymic, stomach, bladder, or mammary tumors. A low incidence of mammary tumors developed in rats fed 2-azahypoxanthine. A variety of tumors, including several ependymoblastomas, were induced in rats that received 5-aminoimidazole-4-carboxamide orally. 5-(3-Methyl-1-triazeno)imidazole-4-carboxamide (MTIC), when fed or given in single or multiple intraperitoneal injections, induced a high incidence of mammary adenofibromas and a low incidence of uterine leiomyosarcomas. Control rats had low incidences of mammary adenocarcinomas and adenofibromas after 52 weeks. These data show that the carcinogenic properties of DTIC resemble those of carcinogenic N-nitroso compounds, hydrazine, azo, and azoxy-alkanes and aryltriazenes and thus suggest similar mechanism(s) of action. These data also indicate that MTIC is involved in the induction of mammary adenofibromas and uterine leiomyosarcomas by DTIC.


Sequential studies of serum blocking activity in rats bearing chemically induced primary bowel tumors. Colon and small-bowel tumors were induced in WF rats by treatment with one of three chemical carcinogens. Tumor occurrence and growth were monitored by multiple double-contrast examinations. Roentgenologic diagnoses and histologic examination of tumors were verified at tumor resection or autopsy. Serial serum samples from each of 11 rats were tested in microcytotoxicity assays for their ability to block the cytotoxicity of lymph node cells from rats with isografts of colon carcinoma NG-W1 against NG-W1 target cells. Sera from all tumor-bearing rats demonstrated specific blocking activity. With two exceptions, serum blocking activity preceded roentgenologic evidence of tumor. Sera of the 2 exceptional rats lacked blocking 2 and 8 weeks before tumor detection, respectively. The sera of only one animal specifically inhibited lymphocyte cytotoxicity despite consistently negative double-contrast examinations. At autopsy this rat was found to have an adenocarcinoma of the distal rectum, impossible to visualize by the roentgenologic technique used. In serum samples obtained from animals after successful tumor excision and with no radiologic evidence of recurrence, blocking activity could no longer be demonstrated. Rats that had received carcinogen but developed no tumor and had no abnormalities on double-contrast examination demonstrated no serum blocking activity.


Carcinogenicity of three dose levels of 1,4-Bis(4-fluorophenyl)-2-propynyl-N-cyclooctyl carbamate in male Sprague-Dawley and F344 rats. Feeding 1,4-bis(fluorophenyl)-2-propynyl-N-cyclooctyl carbamate to F344 or Sprague-Dawley male rats at 125-500 ppm in the diet led to many carcinomas of the small intestine and ear duct (Zymbal's gland tumors) in addition to lymphomas and leukemias. A high incidence of mammary adenocarcinomas was found in the Sprague-Dawley rats. Only a few colon or liver tumors were observed in each strain.


Cytotoxic and oncogenic activities of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane and metabolites to mouse embryo cells in culture. The cytotoxic and oncogenic activities of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), and its metabolites 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), and bis(p-chlorophenyl)acetic acid, were studies at various equimolar concentrations in an in vitro mouse embryo cell culture system that was malignantly transformable. DDD was the most active compound in producing transformation, whereas DDT and DDE showed slight activity. However, none of the transformed foci had the typical malignantly transformed morphology produced by 7,12-dimethylben[a]anthracene and did not produce tumors when inoculated into syngeneic mice.


Aryl hydrocarbon hydroxylase induction in rat tissues by naturally occurring indoles of cruciferous plants. A phytochemical investigation to identify inducers of increased aryl hydrocarbon hydroxylase (AHH) activity from three cruciferous vegetables, Brussels sprouts, cabbage, and cauliflower, resulted in the identification of indole-3-acetonitrile, indole-3-carbinol, and 3,3'-diindolylmethane as naturally occurring inducers. These compounds are produced during the hydrolysis of indolyl-methyl glucosinolate by the plant enzyme myrosinase.


Tumor suppression by pyran copolymer: correlation with production of cytotoxic macrophages. Intraperitoneal administration of pyran copolymer (pyran-2-succinic anhydride-4,5-dicarboxytetrahydro-6-methylanhydride polymer) protected C3H/HeN male mice against tumor development after intradermal challenge with cells of the transplantable, methylcholanthrene-induced, syngeneic fibrosarcoma 1038. Peritoneal cells from pyran-treated but not from normal animals suppressed tumor development in local passive-transfer experiments. Adherent peritoneal cells from pyran-treated mice were cytotoxic in vitro to several syngeneic murine tumor cell lines including 1038.


Inhibitory effect of interferon on multiplication of Friend leukemia cells in vivo. The multiplication of Friend leukemia cells in the spleens of irradiated or nonirradiated histocompatible DBA/2 mice was determined by the uptake of 125-5-iodo-2'-deoxyuridine. The multiplication was inhibited by daily treatment with mouse interferon preparations or the interferon inducer, Newcastle disease virus. Since, under the experimental conditions used, the proliferation of the Friend leukemia cells was independent of the replication of the Friend virus, the inhibitory effect of interferon might not be mediated by an antiviral effect but by some other mechanism.


Inhibition of metastasis in rats immunized with xenogenized autologous tumor cells after excision of the primary tumor. Subcutaneously transplanted 3-methylcholanthrene-induced KMT-17 tumor in WKA rats yielded not only a local solid tumor but also frequent metastases in regional lymph nodes. Neither active immunization with xenogenized identical tumor cells nor surgical excision of the solid tumor prohibited the metastases when each treatment was given 4 days after tumor transplantation. However, immunization combined with surgery significantly decreased the metastases and prolonged survival.


Hormonal  status of breast cancer. I. Thoretical basis for the analysis of steroid profile. Gas-liquid chromatography was applied to the analysis of urinary steroids of women. In the statistical analysis, quantitation of all steroid excretions and ratios among them were transformed to give a normal frequency distribution. The influence of the host's age and the menstrual cycle on 24 hours' excretion was investigated for each of 14 identified neutral steroids, of which four  in our fraction 2 (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, and pregnanetriol) were menstruation dependent. The 14 neutral steroid excretions were generally correlated with one another within the host, and the use of a steroid ratio rather than quantitation of steroid excretion was often more sensitive in the characterization of the hormonal status.


Social class differences among patients with large-bowel cancer in Cali, Colombia. The incidence of large-bowel cancer in Cali, Colombia, for 1962-71 shows the upper socioeconomic classes to be a higher risk. This is the first report of a socioeconomic gradient in risk for this site. The gradients were most marked for cancer of the ascending through rectosigmoid colon and were minimal for cancer of the cecum and rectum. The Cali experience presents several parallels with information derived from comparisons of developed and developing countries and also appears consistent with recent information on the possible role of dietary factors in bowel cancer.


Characterization of human maligant melanoma cell lines. I. Morphology and growth characteristics in culture. Seven human malignant melanoma lines were maintained in vitro for various periods of time. One line, established in this laboratory from a metastatic solid tumor by repeated treatment of the primary outgrowth with 0.02 percent EDTA, allowed a continuous culture of melanoma cells free of fibroblasts. By light microscopy, cells in each line could be classified into one of three morphologic types: elongated dendritic, cuboidal, or triangular dendritic. Four of the seven lines exhibited various degrees of pigmentation. The growth pattern was determined by plating efficiency and saturation density for each line. Cytogenetic analysis with the fluorescent banding technique revealed only human chromosomes with gross aneuploidy. Major marker chromosomes specific for each line were identified. None of the parameters studied showed any correlation or interdependence with one another, except for an association of elongated dendritic morphology with poor plating efficiency and low saturation density.


Circulating interferon in man after administration of exogenous human leukocyte interferon. Interferon was measured at different intervals after the iv, sc, and im application of exogenous human leukocyte interferon to patients with various virus diseases or neoplasms. Interferon injected iv into patients had a half-life of about 15 minutes in the 1st hour and of about 90 minutes in the next 3 hours. Six hours after iv injection of 30 million U, no serum interferon was detectable. With a continuous iv infusion, a relatively high serum interferon level was reached. By the im administration of 1 million U interferon, a peak level of serum interferon (mean value 107 U/ml serum) occurred after 2 hours and was fairly stable for about 6 hours. Twenty-four hours after im application, a low level of serum interferon was still detectable. Similar results were found after sc interferon injections. In a patient with subacute sclerosing panencephalitis, no interferon was found in the cerebrospinal fluid at the time of the highest serum interferon level and 24 hours after two im interferon injections. Only minimal side reactions resulted from sc and im interferon injections. In one patient, a shock reaction occurred after iv application. For therapeutic trials, about 1 million U exogenous human interferon should be injected twice daily im or sc.


Tryptophanase of fecal flora as a possible factor in the etiology of colon cancer. Twenty-three strains of intestinal anaerobes obtained from two laboratories were examined for indole production from tryptophan. Among the 23 isolates tested, three of Bacteroides fragilis thetaiotaomicron and one Citrobacter sp. were indole positive. The tryptophanase of the indole-positive strains of intestinal anaerobes was inducible by tryptophan and was susceptible to glucose repression. The products of tryptophanase activity were formed in stoichiometric amounts by dialyzed, freshly prepared extracts. The tryptophan concentration and tryptophanase activity in feces from rats on an all-meat diet were significantly higher than those in feces from rats on a normal diet. The results indicated that the higher tryptophanase activity in the feces of rats fed an all-meat diet is due to the inducibility of this enzyme by tryptophan and is not due to any inhibitor in the feces of rats on a normal diet. The results also suggested that a population with a diet rich in meat has a greater chance for exposure to possible carcinogens such as indole and other tryptophan metabolites. This agrees with the hypothesis, based on epidemiologic data, that a high intake of meat may be related to the development of colon cancer in man.


In vitro culture of cells isolate from dimethylnitrosamine-induced renal mesenchymal tumors of  the rat. I. Qualitative morphology. The in vitro morphology of cells isolated from renal mesenchymal tumors induced in rats by a single ip injection of dimethylnitrosamine was followed in short- and long-term culture. The morphology of cells isolated from normal rat-kidney cortex was studied for comparison. Primary tumor-cell isolates consisted of a range of mesenchymal cell forms interspersed between discrete, homogeneous islands of cohesive epithelium-like cells. The latter were presumably derived from renal parenchyma that had been engulfed within the in vivo neoplasm by proliferating tumor cells, since this epithelial component did not survive serial subculture. Established tumor cell lines consisted of a pleomorphic range of mesenchymal forms resembling the descriptions of various cell types in vitro, including fibroblasts, smooth muscle cells, and endothelial cells. A range of mesenchymal cell forms in culture therefore correlated with the heterogeneous histologic nature of the in vivo neoplasm in which fibroblasts, smooth muscle fibers, and endothelium-like cells were also represented. Multinucleate or polymorphonuclear giant cells were characteristic of tumor cell cultures, whereas large, expanded polygonal cells with longitudinal striations were characteristic of normal kidney cell cultures. Some tumor cell cultures were typified by cells with cytoplasmic vacuolation and some by the acquisition of an epithelioid form at high cell density, a change not preceded by islands of cohesive, epithelium-like cells at preconfluent stages.


Morphology and morphogenesis of experimental epithelial tumors of the intestine. In a morphogenetic study of experimental tumors of the intestine, 556 male noninbred albino rats were given weekly sc injections of 21 mg 1, 2-dimethylhydrazine dihydrochloride/kg body weight and were killed at different intervals (10-70 rats/wk) after the beginning of treatment. Intestinal carcinomas developed in almost all rats surviving 5 months after the beginning of the experiment. In addition, intestinal tumors induced in 800 rats  of both sexes were examined. Tumor development began with a widening of the proliferative zone within the crypts, an indication of enterocyte differentiation disorders. The ensuing in situ carcinoma became superficial cancer capable of invading the lamina propria of the mucosa. Its continued growth caused the tumor to penetrate the tunica muscularis mucosae into the underlying layers of the intestinal wall. Thus experimental intestinal adenocarcinomas developed de novo or, at least, were not preceded by adenomatous polyps. Signet-ring cell carcinomas began with the accumulation of goblet cells in cells of signet-ring appearance; later they ruptured the basal membrane and infiltrated the surrounding tissues. The proposed scheme of morphogenesis of experimental tumors was correlated with current concepts of rectal tumor development in man.


Foreign-body tumorigenesis by vinyl chloride vinyl acetate copolymer: no evidence for chemical cocarcinogenesis. We investigated whether vinyl chloride monomers, released from implants of vinyl chloride vinyl acetate copolymer (VCA), exerted cocarcinogenic activity and added thereby to the mechanism of foreign-body (FB) tumorigenesis. CBA/H and CBA/H-T6 mice were used. No evidence was found to indicate that chemical carcinogenic activity partakes in tumorigenesis by VCA implants. Hence it was concluded that VCA plastic is not suitable for the study of the combined process of FB/chemical cocarcinogenesis. Furthermore, experimental results obtained with VCA film implants were representative of FB tumorigenesis in the absence of demonstrable chemical carcinogenic activity.


Valley triage: an approach to mass casuality care. Organizations prepared to respond to war, fire, flood, earthquake, or attack are essential for effective disaster control. "Valley Triage" the San Fernando Valley Medical Triage Team in Los Angeles, was formed to meet this need. The team is a mobile medical unit staffed by physicians and coordinated with civilian and military emergency services. It incorporates innovative means of communication, transportation, equipment, and training. The primary aim of Valley Triage is to provide on-site medical attention to disaster victims, and to coordinate their transfer to adequately staffed and equipped hospitals. Valley Triage offers a new approach to disaster management and can serve as a model for the development of other teams throughout the nation.


Spontaneous delayed splenic rupture--case report of a five-year interval between trauma and diagnosis. A 27-year-old white man was admitted in shock with a tender distended abdomen 5 years following significant thoraco-abdominal trauma. Immediately following resuscitation he had an emergency exploratory laparotomy because of his critical condition. At operation 3 liters of old and fresh blood were present intraperitoneally and the spleen was ruptured. The spleen was surrounded by and adherent to the omentum and adjacent viscera. Splenectomy was performed and recovery was uneventful. Histologic examination of the spleen confirmed the 5-year interval between injury and rupture. Delayed splenic rupture accounts for 14% of all splenic injuries and has a high mortality. This case represents the longest reported delay between splenic trauma and delayed rupture.


Disruption of the renal pelvis by blunt trauma. Blunt trauma to the renal pelvis is exceedingly rare and such trauma of the ureter is only slightly more common. A tetrad of radiologic findings should suggest the diagnosis when there is a high index of suspicion. It would seem that early surgical treatment would be the preferred program but in the face of serious associated trauma there is little lost by waiting. Nineteen days elapsed between injury and repair in this case. That duration may be excessive, but as shown in this case the result was excellent and the patient's retroperitoneum was never infected. We do not advocate a purposeful delay of this duration but on the other hand there is no reason to assume that it is particularly harmful.


Hepatostomy for central hepatic hematomas. Two patients with central hepatic hematomas are presented. Hepatostomy tube drainage provided prompt healing of the cavities without complications. The technique is presented as a safe and effective alternative to hepatic resection without compromising the established principles of management.


Diazepam hypnosis for orthipaedic manipulations. In this study, intravenous diazepam was a convenient, safe, and entirely adequate replacement of anesthesia for orthopaedia manipulations. It was administered in the hospital emergency room to both healthy and ill patients. A wide age range of patients was treated, and many very difficult reductions were accomplished. It is the author's firm opinion, however, that the physician using this technique should be capable of using emergency respiratory resuscitation equipment and that such equipment should be immediately available. Close attention should be paid to the recomended method of drug administration and the physician should be congnizant of potential complications.


Electrical burns of the mouth in children; a method for assessing results. A retrospective study has been reported of a 15-year experience with electrical burns of the mouth in children. Addtionally, a method has been described by which the surgical results to date can be measured. It seems that the means of initial treatment (excision vs. conservative) does not influence the final results, but rather the extent of injury is probably the crucial factor. Because of a high incidence of significant bleeding from the labial artery, and the concept of early wound excision to diminish late scaring, we continus to favor initial delayed primary excision.


Thoracic aortic clamping for prophylaxis against sudden cardiac arrest during laparotomy for acute massive hemoperitoneum. Experimental studies in dogs were performed to develop a model simulating clinical patients with penetrating wounds of the major abdominal vessels who develop sudden cardiac arrest following laparotomy and decompression of an acute massive hemoperitoneum. Hypovolemic dogs with a saline-distended tense abdomen and major arterial bleeding after laparotomy develop a sudden deterioration of cardiac function despite raped blood infusion, thus simulating the clinical problem. However, thoracic aortic occlusion before laparotomy and until control of distal arterial bleeding prevented such a cardiovascular collapse. Increased intra-abdominal pressure it itself was determental to cardiovascular function; its sudden release by laparotomy was associated with an improvement in cardiovascular function. An approach of thoracic aortic control before laparotomy is recommended in patients with acute massive hemoperitoneum who remain hypotensive before laparotomy.


The effects of methylprednisolone on oxygenation in experimental hypoxemic respiratory failure. Methylprednisolone administration in dogs with oleic acid-induced pulmonary edema increases survival rate, cardiac output, oxygen delivery, and peripheral capillary Po2 compared to untreated dogs with edema. In addition, there is evidence that steroid treatment brings about a more favorable relationship between ventilation and perfusion but this effect takes a longer time than those dependent on cardiac output. There is mounting evidence from this and other studies that steroids represent a rational form of treatment at least for some forms of hypoxemic respiratory failure.


Vertebral column injuries and seat belts. It is obvious from the above that there are several independent mechanisms in the production of the various types of lumbar fractures. The details of these mechanisms must be fully understood in each case of lumbar vertebral injury. The cases reviewed in the present paper show that similar if not identical lumbar injuries can occur in car occupants wearing or not wearing lap belts at the time of the crash. Thus, cauxally relating a lumbar injury to the lap seat belt is in error. Only distraction injuries located between 1-2 and 1-4 with no evidence of either compression or anterior wedging can be causally related to a lap belt. Even some injuries with this typical confuguration have been observed in persons who were not belted (10). Thus, without knowledge of details of the crunch, lumbar fractures could mistakenly related to use of the lap belt. Thoraculumbar injuries have been senn in patients who were ejected from the car some time during the crash event. Relating the ejection event to the lumbar fracture must be done with great caution. As has been shown by Roaf (48) and by Kaufer and Hayes (33), the type and location of the lumbar spine injury can frequently and indicatory of load application. Other body injuries, or lack thereof, are often good clues to determine the point of load application causing lumbar injury. In addition, it has been recomended that additional details of the injury and of the accident be obtained for accuracy reporting of seat belt injuries.


Nasal fractures.

Nasal fractures. Although diagnosis and treatment of acute nasal fractures are usually relatively simple, they often go undiagnosed and untreated because of frequent dependence on the reports of facial-bone X-rays taken through the emergency room. A routine method of managing displaced nasal fractures has given excellent results with almost no complications. This techiniqe, along with our approach to the managemnet of healed nasal fracture deformities, is presented. Salient statistical information regarding etiology, associated injuries, and complications included.


The immediate circulatory response to high-velocity missiles. The immediate hemodynamic response to a high-velocity missile wound was studied in the hind legs of dogs. A spherical missile of constant mass and velocity was used. The immediate effect after the shot was a marked transient peak flow, which may be due to the effects of the pressure wave on the vascular bed, with a release of constrictor tone. The subsequent more constant increase of blood flow in the traumatized leg is of the same character as that seen following extensive soft-tissue contusion trauma. In addition to these local changes there was also a generalized effect with decreased blood pressure without a compensating increase in hear rate. This may be explained by the specific character of the trauma that a high-velocity missile produces.


Early intracranial pressure studies in gunshot wounds of the brain. Intracranial pressure (ICP) was recorded following gunshot wounds of the brain in 20 patients, and in 11 of them within an hour of injury, during resuscitation. In six who were bleeding profusely, both ICP and blood pressure were low, and they required massive transfusion, with successful outcome in two. Four others presented with small wounds and high ICP. Others, with minimal damage, had "normal" pressures, but this could be affected adversely by coughing, struggling, and minor degrees of respiratory obstruction. Immediate endotracheal intubation, muscle relaxation, and mechanical ventilation prevented such deterioration. Controlled ventilation was continued postoperatively and seemed to control ICP in survivors. It is suggested that the very labile post-traumatic condition of such patients can be improved by adequate resuscitation, immediate intubation, and controlled ventilation; ICP monitoring is valuable pre- and postoperatively in assessing treatment.


Ten years' experience with femoral shaft fractures. One hundred one patients with femoral shaft fractures treated by open reduction and intramedullary fixation have been presented. The results demonstrated no nonunions in nonpathologic bone; less than 2% infection; clinical union in 4 to 6 months; radiologic union at 6 to 8 months; excellent range of knee motion in more than 90% of patients; unsupported full weight-bearing usually present by the eighth postoperative week, and an average hospital stay of 6 to 7 weeks. The advantages and disadvantages of the most common methods of treatment of femoral shaft fractures have been reviewed. The non-operative approach of cast-bracing has yielded encouraging results in the hands of those well-trained in its application. Weighing the advantages and disadvantages of the operative and nonoperative  techniques, as described, we feel that open reduction and internal fixation with an intramedullary rod is still the treatment of choice for most femoral shaft fractures, in the hands of most orthopaedic surgeons.


An appliance to prevent and treat microstomia from burns. The development and use of a dynamic splint, Microstomia Prevention Appliance, is described. It is effective in preventing microstomia as a consequence of burns and is capable of enlarging a contracted mouth if used before maturation of the scar.


Traumatic arterio-ureteral fistula: "hematuria" without urine. A case is presented in which a patient with a gunshot wound in the abdomen sustained a traumatic arterio-ureteral fistula with resultant continual output of bloody fluid from the urethral catheter in the absence of any real production of urine. It is important to recognize the possibility of false reassurance regarding the patient's general status by supposing fluid thus produced to be an indication of actual urine formation.


Traumatic arteriovenous fistula of the kidney; an unusual cause of hypertensive encephalopathy. A patient with a traumatic arteriovenous fistula of the kidney developed encephalopathy with seizures and was unconscious for 48 hours before undergoing a left nephrectomy, excision of a false aneurysm of the left renal artery, and colostomy closure. He has remained in good health for two years following the final operative intervention.


Proximal interphalangeal joint injuries and their initial treatment. Many PIP joint injuries which appear to be innocuous are actually very severe injuries to this small hinged joint and carry a high percentage of disability for the hand as well as the individual digit. A flexion contracture of the PIP joint of one digit may significantly reduce the functional capacity of the entire hand. To prevent such physical impairment, the type of PIP joint injury must be defined and the proper treatment for the particular injury must be initiated. Second, it is paramount that prolonged immobilization of this joint be prevented. It has been found, through clinical experience and experimental projects, that the early healing process is complete by 3 weeks and active motion may then be initiated without any detrimental effects. Extensor and flexor contractures of this joint are apt to occur in digits which have been immobilized for significantly longer than 3 weeks. Finally, the well-publicized "position of function" for the hand is not necessarily the ideal position for the rehabilitation of the hand. The "intrinsic plus position" is the position of choice for immobilization of the MP and PIP joints to prevent contractures. This concept has been confirmed by our clinical experience and the biomechanical studies performed in the laboratory.


Vitamin A assay in burned patients.

Vitamin A assay in burned patients. A study of serum vitamin A levels in burned patients at the Vancouver General Hospital (1972-1973) is reported in an attempt to relate hypovitaminosis A to acute stress erosions in the gastrointestinal tract. Thirty-one patients were studied, of whom 10 had moderate to severe burns. Vitamin A levels of normal males and females at the Vancouver General Hospital averaged at 35 mug/100 ml. Patients with burn indices of less than 12 did not show any significant fall in serum vitamin A levels. The fall of vitamin A levels was greater as the burn index increased, and the fall of vitamin A level was noticed within 48 hours postburn and returned to normal by the second week postburn. In patients with severe burns and gastrointestinal bleeding with stress ulcers, the serum vitamin A levels fell more profoundly (e.g., 18 mug/100 ml). Four patients with gastrointestinal bleeding were detected, of whom three had acute gastric erosions with low serum vitamin A levels. The possibility that hypovitaminosis A is a contributing factor in acute gastric erosions of the gastric mucosa in severely burned patients is suggested.


Diagnosis and management of abdominal gunshot wounds during pregnancy. The literature on gunshot wounds of the gravid uterus is reviewed, and three new cases reported. Clinical management is discussed, with emphasis on the condition of the abdominal wall and other connective tissue during pregnancy, the contraindications for paracentesis, the changes during pregnancy in blood volume, central venous pressure, white blood count, and GI and GU tracts, and indications for celiotomy or cesarean section.


ECG changes after experimental head trauma. ECG changes have been recorded in 11 monkeys following experimental head injury. The principal changes include bradycardia, shortening of the Q-Tc interval, prolongation of the Q-T interval, and alterations of rhythm. The changes last from a few seconds to approximately 2 hours. It is concluded that the changes result from a massive autonomic out-flow from the injured brain and in occasional instances may result in death due to cardiac arrest.


Changes in the serum alpha glycoprotein distribution in trauma patients. Serum electropherograms of trauma patients, when stained for glycoproteins, show striking changes in the alpha glycoproteins of these patients which revert to normal if and when they recover. Thus monitoring of the glycoprotidograms of trauma patients (contrary to ordinary protidograms) is likely to afford important information on the course of these patients' recovery. Of two glycoproteins that have been more closely studied, one, alpha1A acid glycoprotein, is a phagocytosis inhibitor; it is increased in the sera of trauma patients. The other, alpha2HS glycoprotein, is a phagocytosis promotor (or opsonin); it is decreased in the sera of trauma patients. Both the increase of the first and the decrease of the second glycoprotein may thus contribute to the known increased proneness to bacterial infection among these patients.


Measuring the emergency surgical care of auto-accident patients. A series of 2,389 Emergency Department surgical admissions was assessed for quantitative indices of actual services rendered and time spent. Auto accident-related patients were compared to other Emergency Department surgical patients. The average diagnostic index for auto accident patients was 48 units compared to 25 units for all patients. Their workload for Emergency Department personnel was twice the average for non-automobile accident patients. Although they made up to 7.9% of all patients, they accounted for 15% of the total diagnostic services, 12% of the total therapeutic services, and 14% of the overall services rendered during the period of study. These data suggest strongly that auto accident-related patients are different from the average Emergency Department surgical patient and are quantitatively treated differently from other surgical patients.


Fractures of the scapula: a review of 53 fractures. A series of 53 fractures of the scapula has been reviewed. Almost three fourths of our patients were injuried in automobile or motorcycle accidents in which severe force was applied to the shoulder region. There is rarely a problem in diagnosis, but one may need to take special roentgenographic views to delineate the extent of the fracture clearly. A geographic classification of these fractures was used, and it was found that 66% occur in the region of the scapular neck. It was emphasized that 81% of these patients had other associated injuries, many of which were life threatening. Symptomatic immobilization of the scapular fracture seems to be adequate for the vast majority, if not all, patients.


A survey of motor vehicle burn accidents in children: report of 45 cases. The association of burns with motor vehicles was reviewed from the records of 1,532 children treated at the Galveston Shriners Burns Institute since 1966. Forty-five children were burned in or about a motor vehicle. The most common causes were gasoline spillage in moving vehicle accidents, and small children playing with matches unattended in a stationary vehicle. Motor vehicle burn patients had more serious and larger burns than in the general burn population. Of the 34 children burned within the confined space of a motor vehicle, 94% suffered face and/or hand burns. There was a high incidence of respiratory problems. In the moving motor-vehicle fire accident group there were 13 major injuries seen in 17 patients. Of the total motor vehicle occupancy in 38 separate accidents, 19 people died and 66 were hospitalized at the SBI or elsewhere.


Clostridium sordelli infection.

Clostridium sordelli infection. A case of human Clostridium sordelli soft tissue infection is presented. Analysis of this patient's course led to the use of a mouse experimental model for examination of this organism's potential for toxin production. Data thus obtained correlated with that seen in this instance of human infection, indicates that the lethal effects of this organism may be related to the ability to Clostridium sordelli to produce a widespread "toxin-mediated" edema with subsequent marked "third-space" sequestration of fluid.


Traumatic hemipelvectomy: case report and literature review. A case of traumatic hemipelvectomy with survival is presented, apparently the sixth reported case in the literature. Following complete left hemipelvectomy and fracture of the right acetabulum, the patient recovered, demonstrated voluntary bowel and urinary control, was full weight bearing on crutches (against advice), and refused a bucket seat or prosthesis, as well as neurosurgical consultation. The patient was then unfortunately lost to followup.


Renal perfusion/excretion determination renogram: a new tool in the diagnostic evaluation of renovascular hypertension. Presented herein are initial experiences with the RP/ED renogram, a unique radioisotope differential split function study, which can be performed with a minimum of discomfort to the patient. This test should totally supplant the existing renogram and, with additional experience, may replace the use of split function studies in the evaluation of renovascular hypertension.


Renal functional abnormalities in post-unilateral ureteral obstruction in man: a comparison of these defects to post-obstructive diuresis. The failure of fluid and electrolyte conservation in post-obstructive diuresis has not been demonstrated after release of unilateral ureteral obstruction. Despite this, balance and renal function studies in patients with this disorder indicate similar renal defects. The clinical difference is caused by a markedly low glomerular filtration rate in unilateral problems that prevents the excessive losses found with total obstruction.


Iliac artery aneurysm: a common cause of ureteral obstruction. Iliac artery aneurysms may cause ureteral obstruction. Six cases are reported. The major symptom is renal colic but a palpable aneurysm and a bruit may be found preoperatively and urinalysis may reveal microhematuria. On x-ray the ureter may be deviated medially, anteriorly or laterally. The ureter is bound down in a dense, desmoplastic reaction. All of our patients were treated by ureterolysis, with resection and grafting of the aneurysm in 4 of the 6.


The isolated sigmoid segment: its value in temporary urinary diversion and reconstruction. Two patients with severe bladder disease have undergone temporary urinary diversion with a sigmoid conduit as part of planned reconstruction of the lower urinary tract. Their lower urinary tracts have been reconstituted successfully by means of sigmoid cystoplasties. Experimental data further support use of the sigmoid conduit vis-a-vis use of the traditional ileal conduit for long-term diversion and reconstruction. A main advantage of the sigmoid segment is the ability to create an antirefluxing ureterointestinal anastomosis. We have demonstrated that ureteral reflux from ileal conduits produces histologic evidence of pyelonephritis. Colonic conduits, by preventing reflux, reduce the frequency of pyelonephritis and function in an equivalent manner to ileal segments when used either for cutaneous diversion or ureteral substitution in reconstruction.


Family study of vesicoureteral reflux.

Family study of vesicoureteral reflux. A retrospective analysis of 242 families revealed that the incidence of reflux among siblings of children with reflux was 2.2 per cent. In a prospective study of 24 families, 8 of 50 siblings (16 per cent) had reflux. Although the incidence of reflux in the prospective study is surprisingly high infections was absent in all affected siblings in whom cultures were obtained and in only 2 siblings (4 per cent) was surgical correction necessary.


Diagnostic value of the penile pulse and blood pressure: a Doppler study of impotence in diabetics. Penile pulses were palpated and brachial, penile and popliteal pressures were measured with the Doppler technique in 29 normal subjects and in 15 impotent diabetics. The pulses were palpable in all normal subjects but not in 6 diabetics. The penile blood pressure was obtainable in all the normal subjects but not in 2 diabetics. Using the penile pulse data and a comparison of the penile with the brachial systolic pressures, 2 or possibly 3 grades of penile ischemia are definable, providing a measure of pelvic vascular insufficiency.


Varicocelectomy as therapy in male infertility: a study of 504 cases. During a 10-year period 504 selected subfertile men underwent surgical correction of varicocele and had a followup of at least 1 year. Improved semen quality was reported in 71 per cent of the men and 55 per cent of the wives became pregnant. Statistically, results were better in terms of semen quality improvement and pregnancy in patients who had preoperative sperm counts greater than 10 million per cc (88 per cent improved, 68 per cent pregnant) compared to patients who had preoperative sperm counts of less than 10 million per cc (33 per cent improved, 23 per cent pregnant). The impiric use of postoperative human chorionic gonadotropin therapy in the latter group of patients improves results significantly (56 per cent improved, 44 per cent pregnant).


Transurethral prostatic resection in patients with prosthetic cardiac valves. Twenty-one patients with prosthetic cardiac valves successfully underwent transurethral prostatic resection at the Mayo Clinic. Temperature elevation in 4 patients was the only postoperative complication; in particular, neither congestive heart failure nor thromboembolic complications developed and there were no operative deaths. Preoperative evaluation and clinical management of potential complications are based on the recognition of the complications that are peculiar to these patients. Particularly important is the proper use of antibiotics and anticoagulants and avoidance of overloading the circulation with fluid from open prostatic venous sinuses.


Non-urologic flank pain: a diagnostic approach. Pain typical of that from the diseased reno-ureteral unit can emanate from any adjacent organ or any organ with the same innervation. It may also be the result of, or be exacerbated by, mental illness. Case examples of herniated thoracic disk, T12 neuralgia and short leg syndrome, costovertebral joint arthritis, metastatic carcinoma, myofascial syndrome and pancreatitis demonstrated the need for an orderly approach to the problem. Currently, patient screening with the Cornell medical index and the urology questionnaire allows direction of the physical examination, special radiographic and laboratory studies and psychiatric evaluations. An orderly evaluation of flank pain will prove rewarding and may prevent unnecessary urologic operations.


Direct and indirect radionuclide cystography. Direct radionuclide cystography, using short half-life radiopharmaceuticals, is considered to be more reliable for detecting vesicoureteral reflux than conventional roentgenographic techniques. In addition to the detection of vesicoureteral reflux, other parameters determined include the bladder volume when reflux occurs, calculation of volume of fluid that has refluxed, accurate calculation of residual urine volume, estimation of reflux drainage time, and the visualization and diagnosis of gross anatomic abnormalities. Currently, a major disadvantage is poor resolution, prohibiting analysis of small bladder defects and urethral abnormalities. The major advantage of nuclear cystography is the small radiation dose delivered with its use. It is estimated that at least 100 radionuclide studies can be performed for the same radiation expense as a single roentgenographic study.


Embryonal rhabdomyosarcoma of the bladder and prostate in childhood. Of 30 children treated for embryonal rhabdomyosarcoma the primary site of tumor was the bladder in 14 cases (9 boys and 5 girls) and the prostate in 16 cases. The mean age at diagnosis was 3 years in patients with bladder sarcoma and 6.5 years in patients with sarcoma of the prostate. Over-all survival rate has been 23 per cent--5 children with rhabdomyosarcoma of the bladder and 2 with rhadbomyosarcoma of the porstate are alive from 1 1/2 to 23 years postoperatively. Aggressive coordinated treatment with surgery, radiotherapy and cyclic combination chemotherapy is recommended.


The genital aspects of exstrophy.

The genital aspects of exstrophy. Genital anomalies associated with exstrophic deformities are mainly caused by the wedge effect of the cloacal membrane. The more primitive the exstrophy the more severe are the genital defects. With exstrophy of the cloaca genital tract invariable. The main practical problem relates to the male subject with epispadias alone or in association with bladder exstrophy. Correction of the penile deformity requires release of the chordee by freeing the short urethra from the corpora cavernosa and lengthening the organ by partial separation of the crura from the bony rami. The possession of an adequate phallus is generally the prime consideration of the patient and his parents, and surgical reconstruction should aim to provide maximal correction of the anomalies at an early age.


Study of an intravenous fat tolerance test with Intralipid. II. The relation between K2 and PHLA with special reference to clinical data in human subjects. The relation between K2 and PHLA was studied in human subjects with special reference to clinical data determined by routine laboratory and physical examinations. The results obtained by Multiple Regression Analysis indicated that those factors which may contribute to K2 variation were fasting triglyceride level and age. There was an inverse partial correlation between K2 and fasting triglyceride level and between K2 and age. The first and second principal components calculated by Principal Component Analysis indicated that K2 is closely related to obesity and hyperlipidemia, especially hypertriglyceridemia, while PHLA related to albumin. These two components also suggested that K2 fibes different clinical information from that obtained by PHLA measurement. There was no partial correlation between K2 and PHLA. The various lipoprotein paper electrophoretic patterns, type IIa, type IIb, type IV and normal patterns, were clearly characterized by such factors as K2, plasma triglyceride and degree of obesity which has high coefficients in the first principal component.


Comparison of measurements of left ventricle by echography and cineangiography. A comparison of echocardiography with cineangiocardiography in estimating left ventricular dimensions and volumes was undertaken in 43 patients classified into four groups according to the pathophysiology of the left ventricle. There were high correlations between echographic and angiographic ventricular minor axis dimensions, however, when minor axis dimensions were more than 5.0 cm, there were underestimations of minor axis dimensions by echography. From the mean value of long-to-short axis ratio of the left ventricle at end-diastole and end-systole, the following equations were derived for calculating left ventribular volumes from echo dimensions alone: EDV equals 0.837 Dd-3, ESV equals 0.994 Ds-3. That these equations allowed relatively accurate prediction of volumes over a wide range of ventricular sizes was confirmed by comparison with Pombo's formula and Fortuin's formula for calculating left ventricular volume by echo dimensions alone. A comparison of echographic and cineangiographic ejection fraction (EF), relative changes in shortening of internal diameter (delta S), and the mean velocity of circumferential fiber shortening (mean Vcf) was made i; 33 patients with sinus rhythm. There were significant correlations between EF and mean Vcf by echocardiography, except one discordant patient with aortic insufficiency who showed decreased mean Vcg in the face of normal EF, all these results were confirmed by cineangiography. This discrepancy between EF and mean Vcf was ascribed to the prolonged ejection time which characterizes aortic insufficiency.


A comparative study on the electrical and mechanical properties of human and guinea pig atrial muscles in vitro. The transmembrane action potential and contractile force of isolated human atrial muscles which were obtained during cardiac surgery by using cardio-pulmonary by-pass technique here studied, compared with those of guinea pig left atrium. Force-requency curves showed a characteristic triphasic pattern, just as other mammalian atria. When extracellular calcium concentration was raised, percent change in contractile force was strengthened at high frequency of stimulation. When extracellular potassium concentration was reduced, contractile force became stronger and showed a monophasic pattern in response to increased frequency of stimulation. In a solution of lower ouabain concentration, action potential leaved unchanged or showed larger amplitude and longer durati-n. In a solution of higher or "therapeutic" concentration of ouabain, the duration of action potential was shortended, and in its "toxic" concentration, marked decreases in amplitude and duration were induced. The positive inotropic effect of ouabain was attributable to an increase in intensity of active state, because the rate of development of tension was increased without any significant change in the time to peak tension. When extracellular potassium concentration was reduced, contractile force became maximum at louer conce,tration of ouabain, and further increase of concentration induced ectopic impulse formation. In other words, atrail muscles cecame more sensitive to ouabain in a solution with decreased extracellular potassium concentration.


Congenital heart disease in forty years of age and over. Prevalence, relative incidence and clinical features. The number of patients of C.H.D. over 40 years old was 40 (male 26, female 14) among 43285 (male 30320, female 12965). Its item: ASD 24, VSD 6, PDA 3, PS 3, ECD 2, Coarctation of the Aorta 1, Eisenmenger whose shunt site was unclear 1. The total prevalence rate was 0.92 per 1000 and female showed slightly higher rate than male (male 0.86 per 1000, female 1.08 per 1000). When it was compared with rheumatic valvular diseases, the ratio of both male and female was about 1/3. C.H.D. is assumed to decrease to about 1/3 or less between the period of school age and the middle age, but the prevalence rate over 60 years old was never lower than the overall prevalence investigated. C.H.D. in the middle and old aged should be kept in mind while examination.


Vectorcardiograms of electrocardiographic incomplete left bundle branch block. Vectorcardiographic and pathologic studies were made on 21 cases with electrocardiographic incomplete left bundle branch block. Marked left ventricular hypertrophy, severe coronary sclerosis and myocardial infarction were more frequently observed in the presence of incomplete left bundle branch block than in the control group. A figure-of-eight pattern of the QRS loop in the horizontal plane, a classical pattern of incomplete left bundle branch block hitherto described, was observed only in 9 of 21 cases, although the normal initial deflection of the QRS loop directed to the right and anteriorly was absent in all the cases. The configuration of the QRS loop in the horizontal plane was very helpful for the diagnosis of associated myocardial infarction and marked left ventricular hypertrophy. A smooth figure-of-eight QRS loop in the horizontal plane was observed in the cases with marked left ventricular hypertrophy, while a bizarre distorted QRS loop with a figure-of-eight pattern was observed in the cases with extensive myocardial infarction. A T loop directed to the right and posteriorly was also considered to be a suggestive sign of myocardial infarction. The present observations clearly indicate the usefulness of vectorcardiograms for clinical diagnosis in the presence of electrocardiographic incomplete left bundle branch block. The results also suggest that it seems to be unlikely that one common mechanism is responsible for the development of electrocardiographic encomplete left bundle branch block.


Vascular lesions in the various substrains of spontaneously hypertensive rats and the effects of chronic salt ingestion. Among different races, countries and districts there are definite differences in incidence of hypertensive vascular diseases, for example cerebral bleeding. Hereditary and dietary factors presumably play significant roles. Experimental studies under controlled conditions and utilizint suitable animals are indispensable for analysis of the related factors. For confirmation, hypertensive vascular changes in the spontaneously hypertensive rats were histopathologically studied and related to the difference of substrains. Dietary effects of sodium chloride on these vascular changes were investigated by providing the animals with 1% saline for drinking.


[Studies on P waves of mitral valvular diseases by the high-speed and magnified electrocardiograms]. Atrial waves of the electrocardiograms (ECG) of 50 cases of normal subjects and 113 cases of mitral valvular diseases (76 cases of mitral stenosis, 20 cases of mitral insufficiency and 17 cases of mitral steno-insufficiency) were studied by means of the high-speed and magnified electrocardiography. Leads II and V1 and three scalar leads of Frank system (X, Y and Z leads) were recorded by this method. Morphologic observations as well as the quantitative measurements of the amplitudes and the durations of P waves were carried out. Correlations among the various parameters of the P waves and hemodynamic data were examined. and the electrocardiographic criteria for the diagnosis of the left atrial overloading were investigated. The results obtained were as follows: 1) More detailed informations regarding to P waves were obtained by means of the high-speed and magnified ECG. 2) On statistical comparisons of the mean values of the P waves among the normal and the three groups of mitral valvular diseases, the amplitude, the duration and the peak time in lead II were larger in the latter, and the amplitude of positive and negative phases, the duration of negative phase of the diphasic P waves in lead V1 were learger in the latter, while the duration of positive phase was larger in the former. In leads X and Z of Frank system the findings were similar to those in leads II and V1 respectively. 3) The mean values of the instantaneous amplitudes of each 10 msec interval of P waves of scalar ECG of Frank system were compared among the normal and the three groups of the mitral valvular diseases..


[Studies on the absorption and excretion of doxycycline for intravenous use (author's transl)]. The absorption and excretion of a new doxycycline solution for intravenous use (DOTC iv) were studied with the following results. 1. Serum levels following one shot intravenous injection of DOTC iv in glucose solution showed a good dose-response comparable with that of the same dose injection of pyrrolidinomethyltetracycline (PRM-TC). The urinary excretion was also examined. In 200 mg injection, nausea, general warm feeling, odor in mouth and tongue numbness were complained. 2. When DOTC iv was injected intramuscularly, the serum level did not reach the peak value and low level continued for a long time. Moderate local pain was complained at the site of injection. 3. The serum level following drip infection of DOTC dry fill showed a dose-response as well. The local vein tolerated well. 4. No abnormalities were found in clinical and laboratory examinations in all volunteers.


Effects of gentamicin on the thyroid function of rats. The effect of gentamicin (GM) on the thyroid function was investigated in relation with its stimulating action to the growth of rats at a very small dose level. The results may be summarized as follows: (1) Changes in 131-I-uptake of the thyroid after administration of GM were unremarkable. The change in wet weight of the thyroid was also unremarkable. Therefore, GM may not affect the thyroid itself. (2) GM-treated rats clearly showed a decrease in 131-I-triiodothyronine resine sponge uptake (trisorb test) as compared with the control animals, viz.,GM-treated rats indicated hypofunction of the thyroid. (3) Thyroxin (t4) levels in theserum, determined by 125-I-T4 resine sponge uptake (tetrasorb test), were apparentlylower in the GM-treated rats than in the control. (4) The thyroid function test for synthesis of the hormones revealed an increase in diiodotyrosine (DIT) value and decreases in 3, 5, 3'-triiodothyronine (T3) and T4 values in the GM-treated groups as compared with the values in the control. (5) In view of the above results iit was obvious that GM does not cause abnormalities on iodine-uptake, iodine oxidation, organic conversion to iodinated tyrosines, deiodination and thyroglobulin. In contrast, GM may induce abnormality on coupling reaction from DIT to T3 and T4 because the increase in DIT value and decreases in T3 and T4 values are seen following administration of GM. The whole of these facts seems to play an important role in stimulation to growth of rats after administration of the drug.


Deep hypothermia and its effect on the 24-hour clock of rats and hamsters. Intensive hypothermia in rats and hamsters whose breathing and heartbeat had stopped for 1-4 hours was used as a setting in which to study the 24-hour biological clock. Pre- and post-hypothermia analyses depended on behavior wherein spontaneous running activity in revolving drums was used as a "hand" of the biological clock. Hypothermia had various effects. In some cases the clock was temporaily stopped, i.e., reset. In others it was simply slowed. Some clocks were both reset and slowed. Others ran without interruption even though breathing and heartbeat had stopped for 3-4 hours.