Potentially thrombogenic materials in factor IX concentrates. Factor XI concentrates manufactured from human plasma and intended for therapeutic infsuion in man have been suspected for some time of being potentially thrombogenic. In the current studies, assays were carried out in vitro and in vivo for potentially thrombognic materials. It was possible to rank the various materials tested according to the amount of thromboninic material detected. For concentrates not containing heparin, there was substantial agreement between the in vivo and in vitro assays, with a coefficient of correlation of 0.77. There was no correlation between the assays for thrombogenicity and the antithrombin III content. We conclude that many presently availabel concentrates of Factor IX contain substantial amounts of potentially thrombogenic enzymes, and that this fact must be considered in arriving at the decision whether or not to use them therapeutically.


[Prevention of Teat Injuries in Dairy Cattle by Remodelling of Tying Stalls (author's transl)]. The effects of longer standings and affording adequate freedom of movement by the use of cow trainers were studied on sixteen commercial farms with short standing tying stalls. Comparison with the results obtained in previous studies showed that the incidence of severe teat injuries had decreased by 41.5 per cent. This was also apparent from the reduced average period required for healing of the injuries. Observations were continued on five farms when the cows were turned out to pasture in the summer. The period required for healing as well as the sites and types of teat injury observed in the remodelled tying stalls and during the grazing period were found to be very similar. The incidence of severe teat injuries was 43.5 per cent lower on the pastures than it was in the remodelled tying stalls.


[Distribution of Rifamycin SV in de Bovine Tissues Following Intramammary Administration of Rifamastene (author's transl)]. Depending on the physiological activity of the udder, from 4 to 95 per cent of the rifamycin SV administered by intrammary injection are absorbed from the udder and approximately 95 per cent of the absorbed rifamycin SV are excreted through the liver. The rifamycin SV eliminated in the faeces will lose its microbiological activity more or less rapidly, depending on the temperature and oxygen tension. Accumulation of rifamycin SV in the meat and organs will not occur on intramammary administration of this antibiotic. A balance between absorption and excretion is attained within sixty minutes after intramammary administration of Rifamastene in cattle. The maximum rifamycin SV concentrations determined in the serum, bile and urine were 0.12, 18.2 and 0.32 mug/ml respectively. Van Schothorst's S. lutea kidney test which is required by law in the Netherlands, was negative in every case.


[Psychosedatives in Veterinary Medicine (author's transl)]. In this paper the psychosedatives are reviewed which have found application in veterinary medicine. To reduce to the utmost the negative effects, combinations are used of sedative agents from different groups. Where possible, neuroleptic and narcotic analgetics are therefore combined.


[Iron Dextran Administered to Horses (author's transl)]. A description is given of three cases in which horses died very shortly after being given an intramuscular injection of iron dextran. The use of iron dextran in the case of horses is inadvisable.


[What is your diagnosis].

[What is your diagnosis]. A case of craniomandibular osteopathy with a rather successful therapy is reported.


[Results obtained in the surgical treatment of right-sided abomasal displacement and torsion of the abomasum in cattle (author's transl)]. The results obtained by a modified method of surgical treatment in right-sided abomasal displacement and torsion of the abomasum in cattle are discussed. The usual surgical procedure is extended by pyloromyotomy, the technique of which is described. In addition, postoperative drug therapy is discussed and the importance of examination of the blood at regular intervals is stressed. Sixty-five animals took part in these studies pyloromyotomy being performed in twenty-five cases. The results show that pyloromyotomy has a beneficial effect on the prognosis of surgery. Moreover, the present study showed that the use of fixation of the abomasum by omentopexy is open to doubt in these cases.


[Parturient hypocalcaemia prevention in parturient cows prone to milk fever by dietary measures (author's transl)]. Dietary measures designed to prevent low postparturient plasma calcium concentrations were tested in dry dairy cows in Hoorn during a number of weeks before and after calving for a period of five years (1967-1972). Approximately 170 cows prone to milk fever took part in these trials. The effects of various concentration of calcium and phosphorus in the rations, a day's fasting, feeding below energy and protein requirements as well as those of intravenous and intramuscular infusion of EDTA (ethylenediamine-tetra-acetate) on the calcium, phosphorus and magnesium plasma levels and on the haematocrit value of the blood were studied in these trials. Dietary measures by which the postparturient plasma calcium levels were kept within normal limits in a trial with forty-five calving cows prone to milk fever, were based on the results obtained. These forty-five cows were fed a diet low in calcium (33.1-43.9 g. of calcium daily) during the dry period. After calving, they were given a diet high in calcium (148.3-196.3 g. of calcium daily). The diet was adequate as regards energy, protein, phosphorus, magnesium and vitamin D requirements. Milk fever did not occur in these cows and only four animals showed a decrease in plasma calcium to less than 7.5 mg/100 ml.  The following dietary measures are recommended to prevent parturient hypocalcaemia. (1) During the dry period, cows should be fed rations containing the lowest possible concentrations of calcium (for instance, smaller than 0.50 per cent of calcium in the dry matter of the total ration). Phosphorus and vitamin D intakes should be adequate. (2) The intestinal calcium intake should be increased immediately after calving. This may be achieved by administration of 250 g. of calcium carbonate in the form of an aqueous suspension which is fed orally by bottle. The concentration of calcium in the rations should also be increased (greater than 1.0 per cent of calcium in the dry matter). Phosphorus and vitamin D intakes should again be adequate. (3) Additional administration of 30 g. of magnesium daily before and after calving is advisable to prevent not only low plasma magnesium levels but also grass-tetany-like symptoms after calving.


[Chronic hepatitis in lambs (author's transl)]. When deaths and symptoms of chronic emaciation not due to any apparent cause occurred in weaned lambs, the morphological changes observed suggested that the liver probably was the main organ, the function of which was impaired. This was believed to be so because of the homogenity of the changes in this organ and the disseminated character of the lesions of the liver. These were termed chronic as secondary perilobular reactions occurred in addition to primary degenerative changes of the parenchyma, in which septa appeared in addition to lymphocytic infiltration in the portal triad. In view of the epidemiological findings, this heaptitis was believed to be infectious rather than toxic.


[Prevention of retained placenta and endometritis on cattle farms by hygienic procedures (author's transl)]. Animals showing retained placenta or endometritis are present on a large number of farms. This has become a serious problem, particularly when the animals are housed in cubicles. Effective hygienic procedures at the time of parturition will considerably reduce the incidence of retained placenta or leucorrhoea. Preventive insertion of after-birth capsules into the uterus is inadvisable.


[New Castle disease in imported birds. Cases observed and experimental vaccination (author's transl)]. An acute, highly virulent form of Newcastle disease is frequently observed in imported birds. Particularly parrots and, in some cases, pheasants are a potential source of danger. Diseased birds are imported from Asia as well as from South America. Outbreaks among birds imported from Africa have not so far been observed. The number of shipments in which Newcastle disease was found to be present in the birds is reviewed. Moreover, experimental vaccination is discussed.


[[Mycoplasma synoviae and Infectious Sinusitis in Turkeys (author's transl)]. Studies on two flocks of table turkeys affected with chronic respiratory distress and sinusitis showed that M. gallisepticum infection could be ruled out, whereas it was apparent from serological tests as well as examination by culture that M. synoviae infection was present in these cases.


[Preliminary studies on the incidence of Filaziae in equidae in the Netherlands (author's transl)]. Biopsies of the skin of the umbilical area were taken from ninety-nine horses and one donkey, all reared in the Netherlands. The biopsy specimens were examined for the presence of microfilariae by a recovery procedure. Microfilariae were identified in eight horses. These were microfilariae of the species Onchocerca cervicalis in each case.


[Myocardial fibrosis. A case of falling disease (author's transl)]. A case of chronic progressive heart failure in a bull, resulting from myocardial fibrosis, is reported. In view of the low concentration of copper in the liver, this condition is believed to be similar to that termed falling disease.


On the localization of the Gb locus within the MHS region of chromosome No. 6. Further data on the Gb - HL-A linkage relationship are presented. All three GBG informative recombinants investigated are Gb - first HL-A recombinants; therefore Gb must be situated on the second HL-A side of the first HL-A locus. Ninety additional apparently Gb - HL-A non-recombinant offspring from 23 matings indicate that the Gb locus is situated in clsoe proximity to the second HL-A locus.


W4(4a) and W6(4b) in diverse human populations. Demonstration of their genetic identity in population and segregation studies. The status of the W4, W6 system as related to the HL-A system was re-evaluated by means of segregation and mating studies in 200 Dutch families with 755 children. Inclusion analyses were performed on the Fifth Workshop human populations and related to a reference analysis on the main file in Leiden. The results of the mating and segregation analyses showed a good fit for W4 and W6 as a genetic system. The inclusion analyses showed a high degree of concordance. Based on those results, and other cited evidence, it was suggested that W4 and W6 may represent the basic substance of the HL-A antigens in the FOUR series.


Second, third locus and 4a/4b antigen associations in Negroids and Caucasoids. In Caucasoids the third locus antigen Hu (FJH or T-2) shows a 91% association with W27 and W10. Less than 10% of the Hu positive cells had an unknown antigen at the second locus. In a Negroid population from Zambia studied with 1972 Workshop data W27 was absent and W10 present in low frequency. Hu in contrast was present with twice the frequency seen in Caucasoids. Eighty-six % of positive cells had an unknown antigen at the second locus. Data from the use of platelet complement fixing sera suggests that this unknown allele was Da(6), an antigen present in very low frequency in Caucasoids. Recombination between second and third locus alleles has been proposed as an explanation for these associations. Associations of HL-A12 and Hu with 4a, W5 with 4b in Caucasoids and vice versa in the Negroids was demonstrated, and the possibility that this finding may be an indication of recombination between a separate 4a/4b locus and the second and third loci was discussed.


HL-A8: a genetic link with thyrotoxicosis. The incidence of HL-A8 was significantly increased in 64 Caucasian patients with thyrotoxicosis compared with 700 Australian blood donors (42% versus 24%). No significant correlation was observed between HL-A8 and autoantibodies to thyroid components in thyrotoxic patients; thus the association of HL-A8 must be either with the disease itself, or possibly with immune responses not tested for this study.


Anti-HL-A7 lymphocyte-dependent antibody. Target cell specificity of a human cytotoxic lymphocyte-dependent antiserum correlated with the presence of HL-A7 on target cells. Target cells from 10 of 11 HL-A7-positive donors were damaged in vitro by this antiserum together with lymphocytes from normal donors. Target cells from six donors lacking HL-A7 were not damaged. Cytotoxic activity was removed by adsorption of the antiserum with lymphocytes from any one of four HL-A7-positive donors. Adsorption with lymphocytes from any one of three HL-A7-negative donors failed to eliminate cytotoxic activity.


The HL-A7 histocompatibility antigen in sarcoidosis in relation to tuberculin sensitivity. Eighty cases of sarcoidosis have been investigated. In all except eight patients a histological verification of the diagnosis was obtained by mediastinoscopy or liver biopsy. The HL-A7 antigen was not increased in the entire group. However, in the group of patients with a negative sensitivity to tuberculin after the appearance of the disease there was a significant increase compared with controls. In the patients with a positive reaction, there was a complete absence of HL-A7. The HL-A system therefore does not seem to influence the liability to contract sarcoidosis, but once this condition has developed HL-A7 positives are more likely to lose cellular immunity to tuberculin and to reveal symptoms.


Histochemical studies of pancreatic calculi. Fourteen pancreatic calculi from the corresponding number of pancreatic lithiasis patients were examined mineralogically and histochemically. The following results were obtained. The main components of calculi were calcium carbonate in 13 of the 14 cases, and calcium phosphate in the remaining one. Calcium carbonate calculi were all so-called intraductal calculi, with acidic glycoprotein apparently enwrapping the component particles. Acidic glycoproteins acted to bridge calcium carbonate particles, as in the cases of gallstone and urinary stone. The calcium phosphate calculus had a histochemical feature of pathologic calcification with degenerated collagen fibrils as the matrix, suggesting the calcification of the fibrotic pancreatic parenchyma after pancreatitis.


Viral hepatitis B and aplastic anemia.

Viral hepatitis B and aplastic anemia. Although many cases of hepatitis associated with aplastic anemia have been described, the nature of hepatitis is not fully understood. There has been so far no report of hepatitis-B-antigen-positive case. A case of acute viral hepatitis B developing aplastic anemia is presented.


Effects of diagnostic ultrasound irradiated during fetal stage on development of orienting behavior and reflex ontogeny in rats. The physical growth, the development of orienting behavior and neuromotor reflexes of offspring of rats that received an irradiation of a diagnostic level of ultrasound on the 9th day of gestation were estimated and compared with those of two control groups (untreated control and sham-irradiated or immobilized control). Results showed no significant group differences in terms of either physical development or development of orienting behavior. In the reflexological tests, however, a number of those reflexes that developed after 6 days of postnatal life of the offspring of irradiated rats showed significant delays in maturation when compared with those of the untreated control rats, but showed no difference from those of the sham-irradiated group. From these findings it is suggested that under certain circumstances such as in stress, the prenatally irradiated ultrasound of even a low-intensity may affect the development of the brain of offspring.


Inhibition of serum alkaline phosphatase activity by phenylalanine and cholic acid. Serum alkaline phosphatase activity was found to increase more markedly in patients with liver cirrhosis than in patients with peptic ulcer and this increase was found to be influenced by blood types. After testing several amino acids and bile acids, phenylalanine and cholic acid were chosen and their inhibitory effects upon serum alkaline phosphatase activity were studied in 66 patients with various liver diseases. It was found that the combination of both agents demonstrates different patterns of inhibition between the patients with liver cirrhosis and obstructive jaundice. This inhibitory effects were also variable among cases of different blood types. Basing upon the present observation, the possible source of the elevated alkaline phosphatase activity in liver cirrhosis was discussed.


Recovery of catalase activity after inhibition with aminotriazole in acatalasemia mice. The kinetics of catalase synthesis and degradation were determined in acatalasemia and normal mouse livers during recovery of catalase activity after inhibition with aminotriazole. Catalase turned over with a half life of 10.0 hr in acatalasemia mice and of 19.2 hr in normal mice. The rate of catalase synthesis (Ks) was 0.168 (PU/mg protein/hr) in acatalasemia mice and 0.271 in normal mice. The rate of catalase degradation (KD) was 0.069 and 0.036 per hour in acatalasemia and normal mice, respectively.


Thickened cellular envelope of the horny cells in cow snout epidermis. The cow snout epidermis consists of two different parts. The one has the granular cell layers, and the other not. Electron-microscopically, the generation of the lamellated granules and the thickened cellular envelope of a horny cell were noted in both regions. In the horny cell layer the remnant of the lamellated granules were observed locating in the intercellular space, that is, outside of the thickened cellular envelope. The thickened cellular envelope was generated by the precipitation of electron dense material along the inner leaflet of the plasma membrane, but neither by the attachment of small keratohyalin granules to the plasma membrane nor by the coating of the plasma membrane with the content of lamellated granules.


Inhibition of PHA-induced lymphocyte stimulation by factors in maternal serum during late pregnancy. Immunosuppressive effect of pregnant serum obtained in the second and third trimesters was demonstrated in the PHA-induced homologous lymphocyte stimulation system, where 3H-thymidine incorporation into DNA was measured. Such an inhibitory factor was not present in the first trimester serum. The immunosuppressive principle detected in the second trimester serum was characterized by a potent inhibitory activity even at an increased concentration of PHA up to 75 micrograms, whereas the inhibitory activity found in the third trimester serum at optimum PHA concentration (15 micrograms) was not detectable when the PHA concentration was raised to 75 micrograms. Thus, the second and third trimester sera must contain different immunosuppressive principles.


Determination of hydroxyproline content in human heart muscle. Hydroxyproline content was chemically determined on 45 human hearts obtained at autopsy in order to study whether hydroxyproline contents vary in proportion to heart weight or not. There were no significant differences in the mean hydroxyproline content between the epicardium and the endocardium, between the left ventricle and the right ventricle, or among cardiovascular and renal disease group, malignant disease group and miscellaneous disease group. Total hydroxyproline content per mg dry weight of the left ventricle increased proportionally with heart weight. Hydroxyproline content in neutral salt soluble fraction increased more proportionally than that in acid soluble fraction. This tendency was more evident in the endocardium than in the epicardium of the left ventricle. These results seem to be well consistent with those of histometrical estimation of scar tissue in human heart muscle. Hydroxyproline content in acid soluble fraction of the right ventricle was increased proportionally with heart weight.


Diagnostic discrimination between organic and functional impotence by radioisotope penogram with 99mTcO4. Since the half-life of 99mTc is only 6.04 hr, its massive dosing for an elevation of diagnostic accuracy is possible with reduced radiation exposure to the body. On 11 impotent cases, radioisotope penogram was performed with 99mTcO4. The results indicate that the penogram curves obtained are satisfactorily favorable for diagnostic discrimination between organic impotence and functional impotence.


Glucagon-induced insulin secretion in normal diabetic subjects. Eight normal subjects and ten diabetic patients were studied to compare the response of plasma insulin to glucagon with that to glucose and tolbutamide. Oral glucose tolerance test, glucagon test and tolbutamide-glucagon test were performed at intervals of several days. In glucose tolerance test, insulin response was reduced in the patients with severe diabetes. Plasma insulin increased and reached the peak 3 min after glucagon injection (glucagon I) in the normal controls, while plasma insulin response was reduced in diabetic patients, especially in the severe diabetics. In the normal controls plasma insulin rose and reached the peak 6 min after the tolbutamide injection and thereafter fell to the initial level. Glucagon injection following tolbutamide (glucagon II) caused the rise in insulin in the control subjects. In diabetics insulin response to either tolbutamide or glucagon I was reduced. Tolbutamide or glucagon II caused a significant difference in plasma insulin response in all the diabetic groups compared with the normal subjects, while glucose or glucagon I showed a significant increment of plasma insulin between the normal subjects and the severe diabetics. These results suggest that injection of tolbutamide as well as glucagon II provides a definite discrimination of insulin response in diabetics from the normal controls. The usefulness of the tolbutamide-glucagon test in the diagnosis of diabetes mellitus was discussed. -- glucose tolerance test; glucagon test; tolbutamide-glucagon test; plasma insulin.


Maturation and interrelationship of mouse mononuclear phagocytes in bone marrow, peripheral blood and peritoneal cavity in terms of erythrophagocytic activity. Ingestion by mononuclear cells in bone marrow, peripheral blood and the peritoneal cavity of red cells treated with antibodies and various chemicals was studied in an attempt to characterize these cell lines during development and to clarify the interrelationship among them. Bone marrow mononuclear phagocytes became intensively phagocytic during the second day of culture, indicating that the maturation time from progenitor cells to macrophages was about 48 hr. Blood monocytes exhibited very active erythrophagocytic activity after 24 to 48 hr cell culture. Uptake of sensitized red cells by both the cell lines was markedly inhibited by IgG irrespective of time periods of cell culture. Majority of peritoneal lymphocyte-like cells (LLC) separated from other forms of mononuclear cells were shown to become capable of erythrophagocytosis with maturation time to macrophages between 24 to 48 hrs. Under non-stimulated steady state, uptake of sensitized red cells by peritoneal macrophages was far less sensitive to IgG inhibition than that by bone marrow mononuclear phagocytes and blood monocytes, suggesting that IgG receptor does not play main role for the erythrophagocytosis by peritoneal macrophages. Peritoneal cells collected under inflammatory stimulus exhibited a character similar to bone marrow mononuclear phagocytes and blood monocytes with regard to IgG receptor. It was suggested that under steady state peritoneal macrophages arise and mature from local proliferative pool with some different phagocytic mechanism from that of bone marrow mononuclear phagocytes.


Glutathione reductase activity in serum and liver tissue of human and rat with hepatic damage. Glutathione reductase activity of both serum and liver tissue homogenates was measured in normal controls and in cases of hepatic parenchymatous diseases, and the results were compared with those from animal experiments in which hepatic damage was produced by CCl4 injection. Glutathione reductase showed a different attitude from those of transaminases and alkaline phosphatases under these clinical and experimental conditions. Glutathione reductase activity increased in both serum and liver in patients with hepatic damage, and this increase occurred earlier than the changes in alkaline phosphatase activity.


Plasma renin activity in patients with renovascular hypertension. Plasma renin activity (PRA) in peripheral and renal vein blood was determined in 25 patients with renovascular hypertension. Significant elevation of resting peripheral vein PRA was observed in only 9 (36%) of them. 11 (61%) out of 18 patients whose conditions were improved by surgery had shown normal levels of resting peripheral vein PRA preoperatively. Provocation test for renin secretion was done in 20 patients. 10 patients showed a hyper-response. 7 out of 15 patients who benefited from surgery had shown no response in PRA on the stimulation. Renal vein PRA was determined in 23 patients. In 16 significantly higher renal vein PRA was found on the affected side. However, measurement of renal vein PRA failed to predict the surgical results in one-third of the patients. Postoperative PRA and blood pressure were followed serially in 10 patients. PRA became normal within 3 days postoperatively in 9 patients. While the normalization of blood pressure following operation was more rapid in 3 revascularized patients than in 7 nephrectomized, the normalization of PRA was quicker in the latter patients than in the former. These data indicate that measurement of PRA in peripheral and renal vein is not an infallible mean to determine the functional significance of renal arterial lesions.


Biochemical study of fibrosis in the rat liver in biliary obstruction. In an attempt to study the collagen formation in the liver occurring in association with obstructive jaundice, the authors carried out an experiment with liver slices from common bile duct-ligated rats. Hepatic collagen was fractionated into the neutral soluble, acid soluble and insoluble fractions, and the hydroxyproline synthesis rate of each fraction was measured using 14C-proline. Determination was also made for hexosamine content in the same liver tissue. The hydroxyproline content of hepatic collagen increased as biliary obstruction was prolonged, particularly from the 4th week, which is the transitional period of liver histology into biliary cirrhosis. The hexosamine content of hepatic collagen showed a similar tendency. The neutral soluble, acid soluble and insoluble collagen fractions all increased as biliary obstruction was prolonged. The collagenosynthetic activity of the neutral soluble fraction, attained a peak in 1 to 2 weeks of biliary obstruction, which indicates that collagen fibers are formed actively in the early stage of jaundice, although there is only a slight increase in the absolute amount of fibers developed then. Serum monoamine oxidase level tended to be parallel to collagenosynthetic activity but not to collagen content.


Diagnostic value of secretin provocation test. Plasma gastrin response to the intravenously administered secretin was investigated in various clinical entities. The marked increase of plasma gastrin was found in response to secretin in a case of suspected Zollinger-Ellison syndrome in contrast to various degrees of plasma gastrin decrease seen in patients with ordinary or postoperative recurrent peptic ulcer. The diagnostic value of secretin provocation test was stressed especially in relation to differentiation between Zollinger-Ellison syndrome and recurrent ulcer due to retained pyloric antrum kept away from the food-passing route, both of which are characterized by hypergastrinemia and acid hypersecretion.


Conformational studies of hepatitis B surface antigen (HBsAg) by amino acid analysis. The amino acid composition of hepatitis B surface antigen (HBsAg) purified from plasma of asymptomatic carriers was examined for further structural analyses. The protein of HBsAg sperical particles was characterized by the high contents of cystine, proline and tryptophan residues. A high a-helical content of HBsAg was discussed on amino acid composition.


Successful subclavian-left coronary artery anastomosis for anomalous origin of left coronary artery in infancy. Left subclavian artery-left coronary artery end-to-end anastomosis was successfully performed on a six-month-old female infant with anomalous origin of the left coronary artery from the pulmonary artery and severe mitral regurgitation. A piece of pulmonary arterial wall including the opening of the anomalous left coronary artery (ALCA) was isolated and was used for anastomosis instead of utilizing the left coronary arterial wall itself. Her postoperative course was uneventful and mitral regurgitation disappeared 6 months after surgery. This improved technique seems to be applicable for this anomaly, regardless of the age of patient or size of the left coronary artery.


Uptake ratio of (19-1311) cholesterol by adrenal glands as observed by a scintigraphic method. The adrenal scintigram was performed after administration of [19-131I] cholesterol. A high/low ratio of both adrenal glands was calculated to evaluate whether there is a difference between the left and right sides in adrenal diseases. During scanning, information was stored in a 64 X 64 matrix and then punched out on a computer compatible paper tape. This paper tape was processed with a small digital computer. The areas of interest were selected over adrenal glands. The computer decided mean counts per unit area. After subtraction of background counts, a high/low ratio of adrenal gland was calculated. In five patients with Cushing's syndrome due to bilateral hyperplasia, a high/low ratio ranged from 1.0 to 2.0. In four patients with primary aldosteronism due to adenoma, a high/low ratio ranged from 1.33 to 4.0. This method may be useful to differentiate bilateral hyperplasia from unilateral adrenocortical adenoma.


FSH, LH and testosterone levels in human seminal plasma. Testosterone levels in the seminal plasma of 5 normal males, and 30 male sterility patients were measured by radioimmunoassay. In 9 random cases, seminal plasma levels of FSH and LH were determined by radioimmunoassay. The average level of seminal plasma testosterone for the normal males was 72 +/- ng/100 ml, higher than that of the patients: 52 +/- 41 ng/100 ml. The average levels of FSH and LH in the seminal plasma of the 9 random cases were 4.4 +/- 2.0 mIU/ml and 35.4 +/- 5.4 mlU/ml, respectively.


Separation and determination of carnitine and its esters in human serum. A colorimetric method for the determination of carnitine and its derivatives is described. Free carnitine, acetylcarnitine and palmitoylcarnitine were extracted with chloroform-methanol. After evaporation, the residue was dissolved in n-butanol and water; palmitoylcarnitine in the organic phase, and free carnitine and acetylcarnitine by passing the aqueous phase through a column of Amberlite CG-120 (H+). Separated carnitine derivatives were hydrolyzed to free carnitine which was followed by the Amberlite column chromatography. After eluting with 2N NH4OH solution, the samples were esterified and determined colorimetrically.


Residue analysis of DDT, malathion and kelthane on pears. Malthion, DDT, kelthane and their mixture (3 : 10 : 5) were applied to pear fruits at the rate recommended by the Ministry of Agriculture. The rate of disappearance of their residues on pear fruits was investigated under refrigerated conditions (2 +/- 1 degree and 47% relative humidity (RH)). The same insecticides were tested in higher concentrations (1.5 and 2 times) to determine the effect of insecticides on the black spots usually found on pears after storage. No relation was found between the tested insecticides and the appearance of the black spots. Residue-disappearance curves of the three tested concentrations of these insecticides and their mixture were drawn on semi-log paper. The residues of each material found on pear fruits after one hour, 1, 8, 15, 30 and 45 days' storage in a refrigerator, estimated biologically by C. pipiens larvae and D. magna were recorded. The highest concentrations of the mixture and of the individual insecticides left higher residues on pears than the lower ones of all the insecticides either as a mixture or alone. Stored pears, refrigerated under the above conditions immediately after treatment with the mixture of insecticides recommended for the pest control of pears, cannot be consumed fresh after 45 days.


Toxicological effects of intravenous administration of pyridine in anaesthetized dogs. In 17 anaesthetized dogs effects on blood pressure, respiration and biochemical changes in blood, i.e. serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase (Alk.Pase), and urea, after intravenous administration of pyridine at various dose levels of 88 to 880 mg/kg body weight (LD5 to LD50) are reported. Commonly observed toxicity signs and symptoms are due to action of pyridine on the nervous system. There is no direct evidence of lowering of blood pressure. Lowering of blood pressure is noticed only at lethal doses and is accompanied by marked tachycardia. Death is due to respiratory failure. The significant biochemical changes are increase in SGOT and blood urea (p less than 0.01) and decrease in serum Alk,Pase (p less than 0.01).


Uptake, elimination, and biotransformation of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) by larvae of the aquatic midge Chironomus tentans. Accumulation of [14C]3-trifluoromethyl-4-nitrophenol ([14C]TFM) by chironomid larvae from sublethal aqueous concentrations is rapid and dependent on hardness of exposure water. TFM is readily biotransformed to at least two more polar derivatives, including sulfated TFM and TFM-glucuronide or galacturonide. Some TFM is also reduced to the phenol amine. Chironomids can quickly eliminate all TFM derivatives as well as the parent [14C]TFM.


Bromide pharmocokinetics: a model for residue accumulation in animals. Using data obtained from pharmacokinetic experiments with bromide, illustrations are given of the application of pharmacokinetics to toxicological studies. Analog computers may be helpful, though not indispensable. The significance of ancillary pharmacokinetic investigations in the evaluation of toxicity studies is discussed.


Contaminants in food: analytical problems and achievements. In evaluating the toxicological significance of such contaminants as trace metals, polynuclear aromatic hydrocarbons, mycotoxins, pesticides and nitrosamines, analytical chemistry plays an important role. The detection and identification of these in various foods at the mg/kg or mug/kg levels has posed some difficult analytical problems. Considerable progress has been made in this field in the past decade, however, an opportunity is taken to review the achievements in terms of specificity and sensitivity for each class of contaminant.


Biochemical studies on phthalic esters I. Elimination, distribution and metabolism of di-(2-ethylhexyl)phthalate in rats. Elimination, distribution and metabolism of di-(2-ethylhexyl)phthalate (DEHP) were studied in the rat by the tracer technique. About 80% of the dose was excreted in the urine and faeces in 5 to 7 days following intravenous or oral administration. Excretion in the urine was generally slightly greater than that in the faeces. After intravenous administration of [14C] DEHP the radioactivity was preferentially localized in the liver for a short period. Delayed excretion of DEHP was observed in particular in adipose tissue. After oral dosing no significant retention was found in organs and tissues. Radioactivity measurements showed that affinity was lowest for testicles and brain regardless of whether [14C] DEHP was administered orally or intravenously. Orally ingested DEHP was excreted unchanged in the faeces and four major metabolites were detected in the urine.


Toxicologic and hygienic investigation of potatoes irradiated with a beam of fast electrons and gamma-rays to control sprouting. Potatoes exposed either to gamma-rays at a dose of 20 krad, or irradiated with a beam of fast electrons at a dose of 30 krad to inhibit the sprouting of tubers, were studied for mutagenic effects. Toxic action and influence on the fertility were also investigated. Extracts of irradiated potatoes (10 krad gamma-rays), stored and then boiled, were also studied for their mutagenic effects. The induction of dominant lethal mutations (DLM) was used as indicator of mutagenic action of potatoes in male rats, that of the extracts of potatoes in male mice. Experimental animals (white rats) were fed with irradiated potatoes. Neither a toxic, nor a mutagenic action was found. Oral treatment of male mice with extracts of irradiated potatoes also did not increase the frequency of DLM in male mice.


Testing of cigarette smoke inhalation for teratogenicity in rats. The effect of cigarette smoke inhalation on the developing rat embryo was studied. Female rats were exposed to smoke prior to and after mating at miximal tolerated doses. Male rats were ezposed to smoke to prior to mating to investigate the influence upon sperm. On the 21st day of gestation pregnant females of all groups were killed and implantations, litter sizes, foetal resorptions and abortion, foetal weight and length recorded: no significant differences were observed for these parameters between smoke-exposed and control animals. Total maternal wight gain during gestation was lower for smoke-exposed animals than for non-smoke-exposed animals. Examination of foetuses stained according to the method of Frohberg and Oettle resulted in normal variation in the skeletal development in smoke-exposed and control groups as well as in placebo groups. No skeletal malformations could be found.


Coumarin and 4-methylcoumarin induced changes in the hepatic endoplasmic reticulum studied by quantitiative sterelogy. Coumarin and 4-methylcoumarin constitue chemicals widely available in foodstuffs and coumarin-induced hepatotoxicity has been characterized in laboratory animals. The present studies were undertaken to analyze the effects of these compounds on the structure of endoplasmic reticulum membranes. The liver of rats treated for seven days with 1 mmole/kg of either coumarin or 4-methylcoumarin were subjected to quantitative sterologic analysis and various morphometric parameters were determined. Coumarin induced cytoplasmic enlargement while 4-methylcoumarin produced changes in the endoplasmic reticulum and Golgi aratus (GOL) without altering cell size. Both compounds caused a significant overall reduction of smooth-surfaced (SER) membranes. Since 4-methylcoumarin stimulates drug metabolism, this indicates that conformational changes must have taken place in the membrane arrangement. On the other hand, the reduction of membranes by coumarin is accompanied by reduced enzyme activity and phospholipid metabolism, suggesting an impairment of membrane synthesis mircosopical examinations provides a useful and sensitive tool to study the effects of foreign compounds in the liver.


Chronic toxicity study of cyclamate: saccharin (10: 1) in rats. Chronic rat feeding studies were conducted on a 10: 1 cyclamate/saccharin (C/S) mixture to supplement previous investigations which had established the safety of the individual components. The test mixture was fed at dietary levels designed to furnish 500, 1120, and 2500 mg/kg body weight to groups of 35 male and 45 female rats. The protocol included observations of physical condition, growth response, food efficiency, blood, urine, and postmortem pathology. Reproduction and lactation performance was examined through 2 litters. Teratology was also investigated. Since conversion to cyclohexylamine (CHA) was found to occur in many of the rats, particularly in the higher dosage groups, it was included as an added insult in the diets of about half the animals during the last quarter of the 2-year test period. The only positive finding in these studies which proved to have crucial significance was the occurrence of papillary carcinomas in the bladders of 12 of the 70 rats fed the maximum dietary level of the mixture (equivalent to about 2500 mg/kg body weight) for periods ranging from 78 to 105 weeks (except for one earlier death). This finding was the principal reason for the removal of cyclamates from the "generally recognized as safe" (GRAS) group of non-nutritive sweeteners by the U.S. Department of Health, Education and Welfare. In the opinion of the authors, the sequelae following this precipitate ban on cyclamates, prompted by a verbal report of the preliminary findings, warrant placing the study on record for the information of toxicologists and regulatory agencies throughout the world.


Investigations in bitro and in vivo, of the effects of disulfiram (Antabuse) on human lymphocyte chromosomes. Pilinskaya showed that the fungicide ziram induced chrocosome aberrations in the lymphocytes of exposed industrial workers and also in lymphocyte cultures treated in vitro. Ziram is chemically similar to the drug Antabuse (disulfirm) which is used in the treatment of alcoholics. To establish whether disulfirm can also cause chromosome aberrations, we have examined the chrocosomes of lymphocytes from treated and untreated alcoholics and normal controls, and also the chromosomes of lymphocytes treated in vitro. Our results show that disulfirm is 800 times less toxic than ziram and suggest that it is at least 10 000 times less active as an inducer of chromosome aberrations. We found no significant increase in aberrations in vitro or in vivo with disulfiram and conclude taht if it is an inducer of aberrations in lymphoctes then they must be induced with a very low frequency indeed.


[Effect of anisole, anethole, butylhydroxyanisole and safrole on intestinal absorption in the rat (author's transl)]. Using an in situ method of perfusion for rat intestine, we have studied the effect of anisole, anethole, butylhydroxyanisole (BHA) and safrole on the absorption of three metabolites: glucose, butyric acid and  methionine. At a concentration of 2 mg/ml of perfusion medium, safrole, and particularly BHA, reduce the absorption of glucose and methionine but have no effect on that of butyric acid. These results could be explained by variations in intestinal water absorption induced by methoxybenzene compounds, or by changes in the digestive mucosa seen in histological studies.


Toxicity of Jatropha cucurcas for goats. Eleven Nubian goats were fed with Jatropha curcas seeds at doses ranging from 0.25 g to 10g/kg/day. All dose levels were found to be toxic with fatal conswquences within 2 to 21 days. Liver biopsy samples taken 2 days after the start of feeding and subsequent biopsies showed congestion, varying degrees of fatty change, considerable reduction in glycogen content and necrosis of the hepatocytes. Lack of appetite, reduced water consumption, diarrhoea, dehydration, sunken eyes and a steadily deteriorating condition were important clinical signs of Jatropha intoxication goats. In all animals there was a decrease in the level of glucose and a marked rise in the concentration of arginase and glutamate oxaloacetate transminase (GOT) in the serum. Post-mortem examination revealed haemorrhage in the rumen, reticulum, kidney, spleen and heart, catarrhal or haemorrhagic abomasitis and enteritis, congestion and oedema of the lung and excessive fluid in serous cavities.


Dieldrin toxicity and in vivo incorporation of DL-(1-14 C)leucine. The in vivo effect of a single oral dose (30mg/kg body weight) of dieldrin on proteolipid and phosphatidopeptide content of liver and brain and on total protein of liver, brain, plasma, muscle and kidney of rat was studied. Incorporation of (14C)leucine into total protein of liver was increased whereas labelling of total protein of muscle was decreased. Labelling of total protein of other tissues was unchanged. Incorporation into liver phosphatidopeptides was increased and this was consistent with an involvement of group. Proteolipid protein content of brain was increased and that of liver unchanged. There was, however, no change in the labelling of brain or liver proteolipids.


Inhalation experiments with 14C-labelled cigarette smoke. I. Determination of the effectiveness of two different smoking systems with labelled cigarettes. Two different smoking systems were tested by exposing Syrian golden hamsters to the smoke of cigarettes labelled with (14C)dotriacontane-16, 17 (DOT). In 3 experiments, the activity of mainstream and sidestream Total Oarticulate Matter (TPM) and of butts and ash was determined. Comparing the results, the system involving individual exposure was shown to provide the animals with higher amounts of mainstream TPM than the system using simultaneous exposure of numerous animals.


Inhalation experiments with 14C-labelled cigarette smoke. II. The distribution of cigarette smoke particles in the hamster respiratory tract after exposure in two different smoking systems. Male and female Syrian golden hamsters were exposed to the smoke of [14C]dotriacontane-16,17 ([14C]DOT)-labelled cigarettes in 2 different exposure systems. These 2 systems differed in terms of the smoke concentration drawn into the exposure chamber. To compare the effectiveness of the exposure systems, the inhaled dose of 14C-labelled cigarette smoke was determined in the different parts of the hamster respiratory tract by liquid scintillation counting. About 6 times more smoke particles were deposited in the respiratory tract after exposure to high smoke concentration with intermittent puffs of fresh air (closed system) than after exposure to smoke diluted with air (open system). About 80% of the diluted smoke reached the bronchi and lung compared to approximately 60% of the concentrated smoke. The remainder of the dose was trapped in the upper respiratory tract, mainly by the nose and larynx. Additionally, in the open system the total dose of inhaled smoke was dependent upon the position in the exposure chamber. The results are discussed with respect to the use of the exposure systems for chronic cigarette smoke inhalation studies in experimental respiratory tract carcinogenesis.


[Approach-related dosage calculation in the surroundings of enclosed radium preparations and its combination with dosage calculation]. This study contains discussions about different possibilities of dose calculation with an electronic computer in the environment of radium applicators. First of all, it is demonstrated that no time can be saved in the exact calculation, even if varying mathematical methods are chosen. Therefore, possibilities are discussed in order to save calculation time by approximation procedures; methods are quoted - one less and one more complicated - for realising such a procedure. Furthermore, the reasons are mentioned that are contrary to an immediate inclusion of this calculation into the physical irradiation planning. Possibilities to overcome these difficulties are cited.


[Improvement of focal dose determination in the small pelvis]. An easily applicable auxiliary method in order to register exactly the topographic relations on horizontal sections in the small pelvis is indicated. Only the body contour, pelvis pictures on two planes, diapositives with the corresponding pictures of the cross-section and a photographic enlarger are needed. A sagittal tomogram in the median plane, and for radium therapy the localization pictures on two planes are other helps.


[Therapy verification film for field control during cobalt-60 radiotherapy]. The therapy-verification-film RP/V X-omat, which the Society Kodak produces, is a gamma ray sensible film, which because of its relative non-sensibility by irradiation of about 25-150 r, presents a density of S =0,7 to S = 3,9 and is good exploitable. Therefore, it is appropriated to the field controls during the radiotherapy especially for the mantel field technique. It represents a good complement of the gamma ray sensible film RPTL.


Treatment of oedematous extremity in cancer patients with Jobst pneumatic sleeve. The results of pneumatic pressure treatment of 45 cancer patients with swelling of an extremity after operation and irradiation are presented. The treatment of the oedema was carried out with a Jobst pneumatic pressure device. 37 patients obtained relief according to evaluation made immediately after treatment, and 17 patients maintained a favourable result for more than 12 months. The treatment had no effect in 8  cases. As an oedematous extremity is the main debilitating factor in patients with cured breast carcinomas, pneumatic pressure treatment is highly recommended.


[A proposal to improve radioactive waste disposal following metabolic radio-iodine therapy]. After metabolic radio-iodine treatments of carcinomas of the thyroid, increased activities of I 131 are secreted from the patient's body by the renal route. The highly radioactive urine represents a serious danger of contamination for the nursing staff and third persons. The ideal conditions for the isolation of treated patients in a department disposing of a sewage disposal system of its own are not fulfilled at our hospital. Collection of radioactive urine of the patients for the purpose of annihilating radioactivity over several half-lifes of I 131 is extremely intricate. For this reason, we developed a filter system by means of which we were able to free the radioactive urine of the first five female patients treated from more than 99% of radioactivity. The contaminated locked filter patterns can be stored as "closed radio-sources" essentially more securely and space saving. The advantages of this system and their practical possibilities of use are discussed.


[Radiation-induced changes of skin enzyme activity. II. Acid phosphatase, alkaline phosphatase]. After application of solf X-rays with 100, 500 and 1000 R, the activity change of the acid and alcaline phosphatase in the skin of mice has been studied. The studies happened immediatly after the irradiation and at the 1st, 2nd, 4th, 8th and 16th day. The measurment of the enzyme activity washable out of the skin and remianing in the skin after the washing and the total activity of the skin have been taken up. With the acid phosphatase it would be determined that the quantity washable out of the skin is unusually low; the acitity values of the wash solution increase at the 2nd day after the irradiation in dependence on the applicated dose;at the moment 0 after an irradiation with 1000 R, a significative activity increase in the wash solution appears; the homogenate activity at the 2nd day only gets a significative activity increase after the irradiation with 500 R. The alcaline phosphatase was measurable in the wash solution at no moment of the measurement. However, the alcaline phosphatase has been decreased in the homogenate with few exceptions.


Studies on steroid conjugates: IX. Urinary excretion of sulfate conjugated metabolites of cortisol in man. Following i.v. administration of [4-14C]cortisol, various sulfate conjugated metabolites of cortisol in urine were identified and their respective excretion rates measured. The results obtained demonstrated the following: 1) sulfate conjugates as a group are excreted considerably slower than glucuronide conjugates; 2) sulfate conjugates of steroids with non-reduced ring-A (C-21 sulfates) are excreted (and presumably formed) much faster than steroid-3-sulfates, which require reduction of the ring-A prior to the conjugation; 3) the excretion of C-3 sulfates of ring-A reduced steroids with glycerol side-chain (cortols and cortolones) is significantly faster than those of the corresponding steroids with dihydroxyacetone side-chain (THF, THE and their 5alpha-isomers); 4) the relative concentrations of C-21 sulfates of steroids with ring-A intact (FK, EK, ER, epiER and 6beta-hydroxycortisol) are much higher than the concentrations of C-21 glucuronides of these steroids.


Gas chromatographic differentiation of 4-desmethyl-, 4-monomethyl- and 4,4-dimethyl-sterols. Part III: differentiation of sterols based on deltaROxo-values on four stationary phases. The deltaROxo-values, i.e., ratios of retention data for 3-oxo derivatives to those for the corresponding free sterols have been determined for fourteen 4-desmethylsterols, six 4-monomethylsterols and twenty-one 4,4-dimethylsterols on SE-30, OV-17, QF-1 and HiEFF-8B stationary phases. The QF-1 phase is found superior to the others in affording the values which are the most effective for differentiation between the three sterol groups. Within the same sterol group, the values for individual sterol members on any of the stationary phases differ to some extent due to minor variations in their skeletal structure. 4-Desmethyl-delta-5-sterols have strikingly large deltaROxo-values and are distinguishable definitely from other members of the 4-desmethylsterol group. The relative deltaROxo-values, i.e., ratios of deltaROxo-values of individual sterols to the deltaROxo-values of beta-sitosterol, also have been calculated from the deltaROxo-values of individual sterols.


Sterols from a species of Pichia, a n-alkane-utilizing yeast. The component sterols in the lipid from a yeast, a species of Picia, grown on n-alkanes have been studied. Ergosterol and zymosterol in the 4-desmethylsterol fraction, 4alpha-methylzymosterol in the 4-monomethylsterol fraction and lanosterol in the 4,4-dimethylsterol fraction are present as the major components in the respective fractions. Among the minor components, the presence of 24-methylene-lanostenol, in addition to fecosterol and 4alpha-methylfecosterol, is indicated.


Serum testosterone and dihydrotestosterone changes with age in rat. Serum testosterone (T) and 5alpha-dihydrotestosterone (DHT) were measured in young, adult and old Albino Wistar male rats using a sensitive and reliable radioimmunoassay, after separating T from DHT by thin layer chromatography. The mean plus or minus S.E.M. for T in young, adult and old rats were 62 plus or minus 11, 250 plus or minus 27 and 125 plus or minus 25 (ng/100 ml) respectively. Serum T was increased in adults (P less than 0.001) and decreased in old rats (P less than 0.01). The mean plus or minus S.E.M. for serum DHT was 8 plus or minus 2, 19 plus or minus 2 and 17 plus or minus 1 (ng/100 ml) for young, adult and old rats respectively. DHT was increased in adults (P less than 0.001), but did not change in old rats.


Sex dependence of clearance rates of aldosterone and its metabolites from plasma of intact rats. Following I.V. injection of 3H-aldosterone, the rates of clearance of plasma 3H-radioactivity was demonstrated to be sex-dependent in intact rats. Even though the percentages of CH2Cl2-extractable plasma radioactivity are greater in female than in male rats, the quantities of CH2Cl2-extractable label are similar until 60 min post-injection. However, the quantities of non-extractable, polar metabolites of aldosterone (NEPD) are markedly greater in the plasma of males and rapidly reach peak levels 10 min post-injection of aldosterone. In females, these polar metabolites (NEPD) are rapidly cleared from the blood. After bile-duct cannulation, the rate of excretion of aldosterone radiometabolites was demonstrated to be rapid and sex-dependent. Within 1 hr., female rats excreted via the bile 82% of the injected dose of 3H-aldosterone, compared to 49% in male rats. In both sexes, greater than 95% of the total radioactivity excreted in the bile are non-extractable polar metabolites of aldosterone (NEPD). The sex hormones appear to influence not only the nature of metabolism of aldosterone in the liver, but also the rates of clearance of aldosterone and its metabolites from the plasma into the bile.


Radioimmunoassay of unconjugated plasma ethynylestradiol in women given a single oral dose of ethynylestradiol or mestranol. A method for the radioimmunoassay of ethynylestradiol in plasma is described. The sensitivity is 18 pg/ml, recovery 86.5%, and precision 10.9% (coefficient of variation). Normal women, five at each dose level, were given 50 or 80 mug ethynylestradiol or 50, 80, or 100 mug mestranol of uniform bioavailability. Peak plasma levels were consistently obtained in the 1-hour plasma sample with the former compound. With mestranol, the peak levels of ethynylestradiol were lower than with the same quantity of ethynylestradiol and the time-curve of plasma levels much more variable. With this procedure, it is now possible to study certain aspects of the pharmacokinetics of these clinically important compounds.


Steroids and related products. XLI. (1) the synthesis of 11-oxa steroids. III. (2) 17-acetoxy-11-oxaprogesterone (3). The synthesis of 17-acetoxy-11-oxaprogesterone, the 11-oxa analogue of the orally active progestational and anti-fertility agent 17-acetoxyprogesterone, is described. An intermediate in the synthesis of 11-oxaprogesterone, 11-oxa-5alpha-pregnane-3,20-dione, available from hecogenin, was used as starting material and the 17-hydroxy function was introduced by a modified Barton oxidation. The new hormone analogue shows only extremely weak progestational activity in the oral Clauberg assay.


Participation of cytochrome P-450 in the steroid 17alpha-hydroxylase of testis microsomes. The effect of metyrapone on the activity of the steroid 17alpha-hydroxylase from rat testis was evaluated. A competitive pattern of inhibition was observed after analysis of data using a least mean squares computer analysis. The substrate for the hydroxylase induced a Type I difference spectrum in an active suspension of Triton treated microsomes. The magnitude of this spectral change was dependent on steroid concentration and was diminished by metyrapone. The effect of metyrapone was abolished at infinite steroid concentration. These results confirm the participation of cytochrome P-450 as a reactant in the 17alpha-hydroxylase reaction.


Mass spectrometry in structural and stereochemical problems CCXLV. [1] The electron impact induced fragmentation reactions of 17-oxygenated progesterones. The mass spectral fragmentation of a number of 17alpha-hydroxy-, 17alpha-acetoxy-, and 17alpha-methoxyprogesterones have been examined. Unlike other steroidal delta4-3-ketones, fragmentation reactions associated with the alpha,beta-unsaturated ketonic function are not particularly significant; rather, abundant ions are formed by decomposition processes occurring in and around ring D. Reactions of diagnostic significance include complete or partial loss of ring D, and elimination of the C-17 side chain (CH3CO), followed by loss of the C-17 oxygen function together with a hydrogen atom (H2O, CH3COOH, CH3OH).


An improved synthesis of 2- and 4-bromoestradiols. Bromination of estradiol-17beta by 2,4,4,6-tetrabromocyclohexa-2,5-dienone gives 2- and 4-bromoestradiols in good yields.


Metabolic fate of ethynodiol diacetate in the baboon. The enterohepatic circulation and metabolism of ethynodiol diacetate (3beta,17beta-diacetoxy-17alpha-ethynyl-estr-4-ene) in baboons were studied following the intravenous injection of this contraceptive steroid labeled with 14C (4-position) and with 3H (in either the 3- or 17-acetoxy moieties). Bile and urine from four baboons with biliary fistulas and urine from four intact baboons were collected for 7 hours. On the average, 40% and 44% of the injected dose were excreted in the bile and urine, respectively. Only 48% was recovered in the urine of intact baboons. Analysis of these excretion rates indicates an insignificant enterohepatic circulation of this compound. The steroid was excreted mostly (over 80%) as a glucosiduronate in urine and bile. Very little excretion of the 3-acetoxy compound was detected in the urine or bile at any time interval. 17-Monoacetoxy compounds, however, were detected both in urine and bile, suggesting a difference in the rate of in vivo hydrolysis of the 17beta- vs. the 3beta-acetate.


Regional cerebral blood flow estimated by 133-xenon inhalation. A method is described for estimating the clearance rate and fractional blood flow of the fast (gray matter) compartment of the brain from the first ten minutes of 122 XE clearance curves, following a one-minute inhalation. Computer-simulated data were used to test the adequacy of the two-compartmental model employed, and to evaluate the stability of the parameters in the presence of random noise. A comparison was made between this approach and the previously reported three-compartmental analysis. Regional cerbral blood flow data were obtained on 48 young control subjects and 20 elderly demented patients. Hemispheral, regional, and test-retest variations were determined, as well as differences between the groups.


Constriction of pial arterioles produced by prostaglandin F2alpha. Prostaglandin F2alpha constricted pial arterioles when locally applied to the cerebral surface. Norepinephrine and serotonin each elicted similar contractile effects. The constriction produced by F2alpha in combination with either biogenic amine was greater than the constriction elicited by F2alpha or amine acting alone. The effect of one agent on the other was additive rather than potentiating. Since F2alpha norepinephrine and serotonin are all naturally occurring agents, it is possible that their combined effect is important under pathological circumstances and this combined effect should not be overlooked in the search for single spasmogens of great potency. Before ascribing a pathologically important effect of F2alpha, either alone or in combination, evidence is required showing that doses effective in experiments are similar to the concentrations occurring during disease states and/or that vessels may become hypersensitive to F2alpha during such states.


Carotid compression tonography. Correlation with bilateral carotid arteriography in the diagnosis of extracranial carotid occlusive disease. One hundred twenty two patients ahd carotid compression tonography (CCT) followed by bilateral carotid arteriogaraphy. Inthe group (82 patients) which was felt to have significant occlusive disease of internal carotid at the level of carotid bifurcation (smaller than 50 percent stenosis), the CCT showed a 92 per cent correlation with arteriography. Of the group (48 patients) that underwent endarterectomy, there was a 94 per cent correlation with CCT testing. In  40 patients, with normal arteriogram or with less than 50 percent stenotic lesions on arteriography, there was a larger number (25% of patients with a CCT test which appeared to indicate decreased flow. Various reasons for this are discussed. The high correlation of the CCT test and carotid arteriography in the patients with surgically amenable lesions would suggest that the CCT test is a good noninvasive screening technique for the detection of significant occlusive disease of the extracranialcarotid vascular system.


Lipid composition of cerebral vessels in American Negroes, Caucasians and Nigerian Africans: a comparative study. The lipid content of cerebral vessels from American Negroes, Caucasians and Nigerian Africans living in urban areas was chemically quantitated. There are significant differences between the total and free cholesterol content of the vessels among the three population groups. The american Negroes have the greatest amount of cerebral vascular cholesterol compared with American Caucasians and Nigerians. This confirms previous morphological observations that the severity and extent of cerebral atherosclerosis are greater in American Negros than in American Caucasians and aftricans. However, there is no significant difference in the phospholipid content of the cerebral vessels except among the female Negro groups. Chemical quantitation of lipids in vessels may be utilized for assessment of degree of atherosclerosis and may prove to be an acceptable and reliable alternative methodology for epidemiological studies.


Serum lipids and uric acid relationship in ischemic thrombotic cerebrovascular disease. Serum lipids and serum uric acid have been studied in 50 patients with ischemic thrombotic cerebrovascular disease. Patients having diseases known to predispose to hyperuricemia were excluded. Abnormalities of large vessels were present in 14 or 30 cases (46.6%) as a whole, and in 9 of 16 cases (56.5%) below 40 years of age. Thirty percent of the cases showed hyperuricemia. A statistically significant rise in serum triglycerides, pre-beta lipoproteins and serum uric acid was found in all 50 patients and in patients below 40 years of age. In patients above 40 years of age, only the rise in serum triglycerides and pre-beta lipoproteins was found to be statistically significant. A statistically significant rise in serum triglycerides, pre-beta lipoproteins, cholesterols and uric acid was found in patients with abnormal angiograms. A statistically significant correlation was observed between serum uric acid and serum triglycerides in all the groups, between serum uric acid and pre-beta lipoprotein in patients below 40 years of age, and between serum uric acid and serum phospholipids in patients with abnormal angiograms. These factors may be playing a role in the causation of ischemic thrombotic cerebrovascular disease in general and especially in patients below 40 years of age.


Detailed description of a cranial window technique for acute and chronic experiments. Methods for implatation of cranial windows for the direct observations of the pial microcirculation in experimental animals are described in detail. These techniques are suitable for both acute experiments in anesthetized animals and chronic implantation permitting several months of observation in awake animals. Experience over several years shows that these techniques have an acceptably low rate of failure, are low in cost and can easily be mastered in most laboratories. They make possible observation of the microcirculation and accurate measurement of the diameter of pial vessels, and permit study of the effects on the microcirculation of a variety of maneuvers and vasoactive agents which can be studied by direct application as well as by intravascular administration. Because they preserve the intergrity of the skull, the techniques permit study of the cerebral microcirculation under conditions closely approximating the normal environment of these vessels.


Stoke in the young: a four-year study, 1968 to 1972. Twenty-six patients under 20 years of age having cerebrovascular disease were studied from 1968 to 1972. Common risk factors such as hypertension, diabetes mellitus, hyperlipidemia and heart disease were not present. Angiographical study showed a variety of abnormalities. No consistent defect was present. There was a high incidence of pyrexia and convulsions in the early stages of stroke and it appears possible that some form of arteritis might have been important in the production of the cerebral infarction.


Characteristics and survival of patients with brain stem infarction. A retrospective study of 141 patients whith ischemic brain stem infarction admitted to the Department of Neurology, University of Helsinki, during 1966 to 1973 was performed. The patients were contacted by mail in January and February, 1974; in case of death, the death certificates were procured. The follow-up period was from 4 to 99 months (median 46.5 months), during which a total of 39 patients had died. A life table analysis gave a 50% probability of a seven-year survival after the stroke. Survival was similar for men and women, and age appeared to have little influence on the prognosis with only a slightly higher case fatality in old age. Soft palate paralysis, disturbed sensorium, need of special treatment measures (feeding by gastric tube intravenous infusions, etc.) during the acute phase, abnormalities in the ECG (T-wave negativity, S-T segment depression), fasting blood glucose 100 mg/100 ml or higher, and an abnormal eeg (slowing down of alpha rythm alone or in association with paroxysmal and/or focal disturbances) were all associated with high case fatality. Preceding TIAs, blood pressure level, serum cholesterol and triglyceride values, and aortic arch angiogram findings, on the other hand, had no effect upon the prognosis. The effects of body build on prognosis remained obscure.


Carotid arterial supply of the feline brain. Applications to the study of regional cerebral ischemia. A study of the supply to the feline brain by the carotid-middle cerebral arteries was conducted using in vivo transcardiac injection with a mixture of micropaque and carbon black. Modifications in the filling pattern of the arterial vessels were visualized following short-term occlusion of a middle cerebral artery. A modified surgical method to induce occlusion of the M-l segment of the middle cerebral artery is also described.


Immediate effects of cerebral ischemia: evolution and resolution of neurological deficits after experimental occlusion of one middle cerebral artery in conscious cats. Acute occlusion of the left middle cerebral artery (MCA) was accomplished without anesthesia and inside an intact cranium containing cerebrospinal fluid (CSF) in ten cats five to nine days after implantation of an occlusive device through the orbit. Immediate neurological deficits included forced ambuxlation, circling, and tonic deviation of the head and neck toward the side of the occluded artery; weakness of the opposite limbs; and an apathetic or akinetic state. Two cats died within 24 hours. The other eight cats improved but secondary deficits developed in two, causing death. In two of the remaining six cats no deficits were apparent seven days later. The cerbral infarcts regularly involved the basal ganglia, internal capsule, and cortical regions, and were larger and less variable than those produced by MCA occlusion through and open optic foramen or craniectomy with cranial decompression by drainage of CSF. This model of acute focal cerebral ischemia may be of value for studies of physiological and biochemical factors uninfluenced by sedatives, anesthesia, or recent surgical procedures.


Some experimental errors in calculating regional cerebral blood flow from the intracarotid 133Xe clearance curve. A quantitative evaluation employing a digital model. A digital model study has been developed for quantitative assessment of experimental errors in the analysis of 133Xe clearance curve from the brain. A small computer synthesized a model of the clearance curve, varying combinations of fast and slow components. The curves were convoluted with Poisson random digits to simulate statistical fluctuations. Identical curves were overlapped with varying intervals to study the influence of remaining activity. The height over area method to ten minutes was confirmed to overestimate CBF by 10% to 15% with a slow component of 20 ml/100 gm per minute, and the overstimation was increased with a lower slow flow component. The initial slope value was shown to have a close relationship with the fast flow component when the latter was less than 100 ml/100 gm per minute. Errors due to statistical fluctuations were determined only by the initial height (Ho cps), as the percent standard deviation was deltaHo/Ho in the height over area method and 2 deltaHo/HologHo in the initial slope method, where deltaHo equals square rootHo. Remaining activity caused errors of 1% to 3% in the initial slope method with an injection interval of 15 minutes. The influence of remaining activity can be eliminated with an injection interval of more than 25 to 30 minutes in the initial slope method and more than 40 minutes in the height over area method.


Regional cerebral blood flow measured by the gamma camera after direct injection of 133Xe into the distal stump of the occluded middle cerebral artery. Regional cerebral blood flow (rCBF) was measured after intracarotid injection of 133Xe concurrently with measurements of local cerebral blood flow (LCBF) after injection of 133Xe directly into the distal stump of the occluded middle cerebral artery (MCA) by the use of the gamma camera after producing experimental ischemia in baboons by occluding the MCA. Regional MCA stump pressure (rMCAP) was also measured. Regions of ischemia assessed by intracarotid injection of 133Xe correlated well with the territory of infarct defined by injection of 133Xe into the distal MCA stump. Flow values in ischemic regions obtained by direct injection of 133Xe into the MCA were 15% to 20% lower than those obtained by intracarotid injection of 133Xe. Possible explanations for these differences are discussed. During induced hypertension autoregulation in ischemic areas was abolished and paradoxical responses of LCBF and rMCAP to changes in arterial carbon dioxide tension (PaCO2) were confirmed.


Endothelial cell ischemic injury: protective effect of heparin or aspirin assessed by scanning electron microscopy. Scanning electron microscopic observations of the luminal surface of the rabbit common carotid artery subjected to occlusion for 30 minutes or two hours revealed crater-like and balloon-like defects in the endothelial surface. The frequency of occurrence of these abnormalities was significantly decreased by pretreatment with heparin or aspirin in doses considered to have antiplatelet aggregating activity.


Cardiac arrhythmias and sudden death in subarachnoid hemorrhage. Life-threatening cardiac arrhythmias can occur in patients with subarachnoid hemorrhage secondary to rupture of intracranial aneurysms. The arrhythmias are secondary to acute dysfunction of the central nervous system and possibly to sudden increase in intracranial pressure. The autonomic nervous system is the mediator in the production of these disorders. The clinical significance of these rhythm disorders is discussed, particularly in regard to the sudden, unexpected death seen in this type of patient. The possible mechanisms of production are analyzed and their therapeutic implications are stressed.


Atheromatous emboli to the lumbosacral spinal cord. The lumbosacral spinal cords of 28 patients with atheromatous emboli to abdominal viscera and/or grafts to the abdominal aorta were examined by serial sections. In 12 patients, atheromatous emboli were found in spinal arteries, most commonly in the sacral cord, and most frequently in the anterior spinal artery. The general absence of spinal cord infarctions was attributed to the nature of the emboli, apparent good collateral circulation, and the absence of diffuse atherosclerosis. However, 38% of the patients had arteriosclerosis; this was generally focal and not associated with significant luminal narrowing. Only one patient had infarction, which was limited primarily to the gray matter. It would appear that hypoperfusion must exist in conjunction with atheromatous emboli in order for infarction to develop. Organized atheromatous emboli also caused focal ischemic atrophy of neurons. It is postulated that this change may be the morphological basis for some of the atypical lower motor neuron diseases found in the elderly.


Macrophage arming factor release by allografted mouse lymphocytes stimulated by phytohermgglutinin. Spleen cells from a C57BL/6 mouse allografted with DBA/2 skin may release a macrophage arming factor when stimulated with phytohemagglutinin. This in vitro nonspecific release is observed only when the recipient cells are collected during a limited period preceding or coinciding with graft rejection. The phenomenon disappears if the skin allograft has been removed before cell collection. It appears if an i.v. injection of donor cells is given to the recipient after graft removal, on the day preceding cell collection. These data suggest that this in vitro apparently nonspecific macrophage arming factor release by phytohemagglutinin-stimulated recipient cells may in fact disclose a previous specific in vivo immune cell triggering by graft antigens.


Global ischemia in dogs: cerebrovascular CO2 reactivity and autoregulation. One hypothesis on the pathogenesis of post-ischemic-anoxic encephalopathy is impaired cerebral perfusion or the no-reflow phenomenon. Therapies aimed at preventing the development of this phenomenon are increased cerebral perfusion pressure (CPP) and hyperventilation or hypercapnia. Using a dog model in which we have described the progressive development of post-ischemic (PI) cerebral hypoperfusion after 15 minutes of global ischemia induced by aortic and vena cavae clamping, our aims in this study were to determine during the PI cerebral hypoperfusion period: (1) cerebrovascular reactivity to CO2, and (2) cerebral blood (CBF) autoregulation. Post-ischemic cerebral hypoperfusion to about 50% of normal was not accompanied by raised intracranial pressure (ICP) but cerebrovascular CO2 reactivity was markedly attenuated while maintaining some kind of autoregulatory phenomenon. Cerebral uptake of oxygen was not significantly affected by changing PACO2 from 20 to 60 torr at constant CPP or by changing CPP from 64 to 104 torr at constant PaCO2. These results suggest that increasing both CPP and hypocapnia/hypercapnia would not significantly attenuate PI neurological deficit after global cerebral ischemia. However, in two dogs inadvertently hemodiluted in the PI period, increasing CPP from 50 to 200 torr increased CBF by 200%, suggesting that hemodilution plus increased CPP may be effective therapy for amelioration of post-ischemic-anoxic encephalopathy. The significance of our findings on cerebrovascular CO2 reactivity and autoregulation with respect to the mechanism of the no-reflow phenomenon is discussed.


[Cytochemical study of the elimination chromatin in silkworm meiosis]. The elimination chromatin separating from chromosomes during the first maturation division of female sex cells of lepidoptera insects was studied cytochemically on paraffin sections of eggs of Bombyx mori L. Ocytes at the metaphase-telophase stage of the first meiotic division were stained for RNA by metyl green-pyronin and gallocyanin with negative results. These data differ from earlier positive results for Solenobia triquetrella reported by Ris and Kleinfeld, 1952.


Carotid arterial elastic hyperplasia in a newborn. Cerebrovascular insufficiency in infancy and childhood is well documented and has a diverse and often unknown etiology. Reported here is a polycythemic, microciphalic infant girl of 43 week's gestation with bilateral cerebral infarction occurring in the perinatal period. Infarction was the result of bilateral carotid artery stenosis produced by massive reduplication of the internal elastic lamina. Review of the literature failed to reveal any reports of similar arterial lesions. The angiographical picture was also unique. The etiology of this unusual defect is not known, but we believe the problem was congenital perhaps due to an intrauterine infectious process.


[Differentiation of oocytes and trophocytes in insect ovaries with different ovariole structures]. Early stages of differentiation of the oocytes and nurse cells are comparatively studied in the polytrophic ovarioles in larvae, pupae and imago of the butterfly Laspeyresia pomonella and in the telotrophic ovarioles in larvae and imago of the bug Eurigaster integriceps. In L. pomonella, the oocytes and trophocytes, being the descendants of one oogonial cell, pass synchroniously through early stages of meiotic prophase up to the pachyten. After the pachyten chromosomes of the future trophocytes transform into diakinetic bivalents, whereas in the oocyte nucleus chromosomes retain their pachyten stage appearance. In the fifth instar larva of E. integriceps, two zones may be seen in the germarium of the telotrophic ovariole: the apical trophocyte zone and the distal oocyte zone. The oocytes develop up to the zygotene("bouquet") stage. As to the future trophocytes, they miss zygotene and reach directly diakinesis. Thus,the earlier divergence in the development ways of oocytes and trophocytes is observed in the telotrophic ovarioles, since the trophocyeres pass themeiotic stages more quickly then oocytes. The supposition is advanced that the quicker development of the nurse cells in the bug's ovarioles takes place due to missing the synaptonemal complex formation. The patterns of similarity and distinction between the telotrophic ovarioles in Coleoptera, on the one hand, and the polytrophic ovarioles of the butterfly L. pomonella and telotrophic ovarioles of the bug E. integricept, on the other hand, are discussed.


A paradoxical cerebral hemodynamic effect of hydralazine. Hydralazine is shown to have a very complex cerebral hemodynamic effect. It raises the intracranial pressure which, together with its effect upon systemic blood pressure, reduces the cerebral perfusion pressure. In spite of this and a concomitantly induced hyperventilation by hydralazine, CBF increases with some delay. The conclusion is that hydralazine is a cerebral vasodilator acting immediately upon cerebral capacitance vessels but later upon the resistance vessels as well.


[Comparative ultrastructural study of the protonephridium of Eteone longa and the metanephridium of Lumbricus terrestris]. In the initial part of the protonephridium of E. longa specialized cells, cyrtocytes, are observed in addition to cells of the protonephridial duct among which dark and light cells are distinguished. The metanephridial duct of L. terrestirs is characterised by a comples differentiation and subdivision into several parts whose cells deffer in their morphology. The functional role of the two excretory organs is discussed.


[Electron microscopic characteristics of neurosecretory cells in the preoptic nucleus of sturgeon fry]. In the sturgeon fry nucleus preopticus (Npo), light and weakly differentiated neurosecretory cells (NSC) as well as differentiated (i-cells) were revealed. Among these types of cells, there were the transitional forms. No "picnomorphic" cells were found in any Npo zone. NSC contained different amounts of elementary secretory granules 110-270 nm in diameter. The distribution of organelles was evaluated statistically, their number increasing from i-cells to the NSC. These data suggest that growth and differentiation of the NSC take place during this stage of ontogeny. The results are discussed in terms of specific functioning and maturity of the NSC.


[Processes determining changes in the shape of a cell following detachment from a substrate]. In contrast to living cells, glycerin extracted mouse embryo fibroblasts do not round up after detachment from the substrate. The addition of ATP makes these fibroblasts round up. Thus, the rounding of the detached cell occurs in result of active, ATP-requiring contractile forces rather than due to the action of elastic forces or of surface tension. The ATP-induced contraction of the glycerinated cell is accompanied with the loss of the parallel orientation of 50-70 A microfilaments. The loss is suggested to result from the attachment of different microfilaments of the same bundle to different points of the cell surface. Microtubules are not essential for the contraction: the rounding of living or glycerin-treated cells is not colcemide affected. Living cells treated with cytochalasine B (CH) reversibly lose their ability to round up after detachment. ATP is able to induce no contraction of glycerin-extracted cells treated with CH before extraction. In contrast, the addition of CH to the ATP-containing solution does not inhibit the contraction of glycerin-extracter normal cells. These results give reason to suggest that CH may inactivate contractile structures of the cell. It may be thought that some unknown additional factors, available in the living cell and not available in the glycerin-extracted one, are essential for this inactivation.


[Aggregation of normal and transformed cells attached to a substrate]. On the surface of the nirtocellulose membrane filter (pore size 0.3--0.5 mem), normal mouse or hamster embryo fibroblasts formed discrete cell aggregates. Behaviour of transformed fibroblast-like cells of 9 different lines was compared with that of normal cells. Cells of 3 transformed lines grew on this substratum as a uniform monolayer displaying no tendency to aggregation. The following 3 cell lines exposed a slightly "patchy" cell distribution on the 3rd--4th day of cultivation but were unable to form discrete aggregates. The remaining 3 lines did form aggregates but the dynamics of aggregation and the final aggregation pattern for two of them were abnormal. Only one of the 9 investigated transformed lines had the normal aggregation behaviour. Hence, in the course of the neoplastic evolution, cells lose their ability fo form aggregates on the filter surface. Mechanisms of cell aggregation and possible reasons of differencies in the aggregation behaviour between normal and transformed cells, are discussed.


[Morphology of hemolymph cells in cabbage butterfly catterpillars]. Using morphological and cytochemical methods, a comparative analysis of the haemocytes isolated from 5-aged caterpillars of cabbage butterfly was made. The following groups of haemocytes were found in haemolymph: proleucocytes--7%, macronucleocytes--25, micronucleocytes--48, enocytoides--5, phagocytes--15%, and single eosinophil-like cells. The number of haemocytes in each group is closely related to their functional activity. Micronucleocytes, phagocytes and macronucleocytes are most numerous in 5-aged larvae before their pupation. This phenomenon is in connection with pinocytotic activity of micronucleocytes, and with phagocytotic function of phagocytes and macronucleocytes. The liquid media of haemolymph is rich in proteins and polysaccharides.


[Basic factors in the polyploidization of cerebellar Purkinfe cells in chick embryogenesis. III. Kinetics of RNA and DNA in Purkinje cell nuclei]. The content and concentration of RNA and DNA in the nuclei of the Purkinje cells of cerebellum of chick embryos (10-21 day-old) were determined by cytospectrophotometry. The RNA concentration shows a dayly rhythm, its content significantly increasing. The periods of the increase of RNA synthesis coincide with the periodicity of protein synthesis, the morphogenesis of the Purkinje cells and with the embryo's development as a whole. The DNA concentration remaining constant, its content increases sharply with the onset of the specific functional activity of cells and of the intensive growth of axons and dendrites. The variability of the mean values of this growth increases which is conditioned by the appearance of cells with hyperdiploid, tetraploid and hypertetraploid DNA contents in their nuclei. The Purkinje cells do not divide, their increased DNA content may be regarded as the expression of polyploidization or polytenization (which are functionaly equivalent) of a part of the nuclei. It is not excluded that in this case a differential gene amplification may take place. The increase of DNA content is associated with the onset of morphofunctional maturity of cells and may be due to a continuously increasing intensity of protein synthesis secured by the matrix material.


[Effect of actinomycin D on cell proliferation induced by phytohemagglutinin in human lymphocytes]. Actinomycin D at a dose inhibiting the synthesis of ribosomal RNA (0.15 MUG/ML) BLOCKS THE TRANSITION OF CELLS INTO ACTIVE PROLIFERATION DURING THE FIRST 6 HOURS AFTER PHYTOHAEMAGGLUTININ TREATMENT. The effect of actinomycin D becomes weaker as the cells proceed through the prereplicative period. 1 mug/ml actinomycin D blocks the synthesis of all RNSs. It has been found that actinomycin D at this concentration blocks the transition of cells into the proliferation during the entire prereplicative period.


[Analysis of the kinetics of cell transition to DNA synthesis in systems with stimulated proliferation. I. Properties of a mathematical model of cell kinetics]. Some features of the mathematical model of cell kinetics in the systems stimulated or induced to proliferate are under consideration in this work. The proposed model serves as a basis of the kinetics analysis of the transition of cells to the DNA synthesis.


[Inequality of numbers of cells passing daily from S phase into G2 and from G2 into mitosis for a population of young mouse hepatocytes]. The formulas are proposed which allow to verify the equality of the diurnal streams of cells from one to another phase of mitotic cycle for systems with the diurnal rythm of mitotic index. The unequality of the diurnal stream of cells from S into G2 phase and the diurnal streams from G2 into M phase for hepatocytes of 3-weeks old mice is assumed to be caused by the passage of about 75 percent of cells from G2 phase directly to the resting phase R1. Part of these cells may then return from R1 to G1 phase.


[Stimulation by insulin of DNA synthesis in cultured mouse fibroblasts]. With the aid of autoradiography, the effect of insulin on entering S- from G1-period of the mitotic cycle and on the rate of DNA synthesis of the mouse fibroblasts (L), was studied,--in the cells incubated for 24 hr in serum-free medium. In these conditions the cells were temporarily blocked in G1-period. Insulin (100 mcU/ml) increased by 1.5-fold the amount of cells in S-period as well as caused a marked stimulation of DNA synthesis.


[Study of localization of H3-pentagastrin in the fundal gland area of the rat gastric mucosa by means of light and electron autoradiography]. The most frequent localization of H-3-pentagasrine was found in the gastric mucosa of rats, a weak incorporation was observed in the cells of duodenum; liver and skeletal muscles showed no incorporation. In the acid-secreting region of gastric mucosa, the labeled pentagastrine was accumulated selectively in the main and endocrin cells, which allowed to suppose the presence of gastrine receptors in these cells. These data, together with the absence of the label over the oxyntic cells, amy evidence for the participation of endocrine histamine-containing cells in the control of hydrochloric acid secretion in the rat stomach.


[Binding of acridine orange by chromatin in human lymphocytes with different capabilities for adhesion]. A population of morphologically homogenous peripheral blood lymphocytes separated on a column with glass beads was studied microfluorimetrically. It was found that high adhesive lymphocytes bound acridine orange in a greater extent than did low adhesive cells.


Evaluation of ultrasonic bubble detectors in vitro using calibrated microbubbles at selected velocities. Two standard Doppler ultrasonic devices, currently used for detecting bubbles in vivo, have been evaluated and compared in vitro using carefully calibrated uniform micro-bubbles rising at terminal velocity through a static aqueous medium. Two unexpected findings were observed: (a) the focal length of the transducer apparently decreases for smaller bubble sizes, and (b) a significant horizontal convection current was produced by one of the instruments. When the medium was in motion, it was found that the sensitivity varied markedly with bubble velocity, varying from a minimum detectable diameter of 40 mum at 55 cm/sec to 170 mum at 20 cm/sec. These findings are discussed with regard to the limitations of the Doppler technique for monitoring gas emboli in vivo and as an early warning for decompression sickness in divers.


Reproducibility of human eye length measurement by ultrasound in vivo. This article deals with the reproducibility of the ultrasound pulse echo method for the measurement of intra-ocular distances. It analyses individual kinds of errors and evaluates the minimum size of an intra-ocular pathological formation which still could be traced by the pulse-echo method.


Renal vein renin: value and limitations in the prediction of operative results. Renal vein renin determinations, in contrast to isolated peripheral venous renin determinations, provide great help in the selection of patients who can benefit from an operation for renal hypertension. Patients with essential hypertension usually have renal vein renin ratios, larger/smaller, close to unity, but the available cumulative data show that, statistically, ratios as large as 2.0 may occur in this group (95 per cent confidence limits). In patients with unilateral stenosis of a main renal artery, large renal vein renin ratios (stenotic/normal) have been followed by operative success in more than 90 per cent of patients. However, many operative successes have also been achieved in patients without a large renal vein renin ratio. This may be explained by inaccurate renal vein catheterization, inactive renin secretion, nonsimultaneous sampling, assay variability, and problems related to bilateral or segmental lesions. Recent refinements in the interpretation of renal vein renin data (contralateral suppression, ipsilateral hypersecretion in absolute terms, and a combination analysis scoring system) appear to increase the accuracy of the test. Detailed anatomic information, provided by arteriography, is essential for proper interpretation of renal vein renin data.


Ureteral catheterization studies.

Ureteral catheterization studies. It is apparent that the split function study and renal vein renin determination are complementary and afford valuable information for selecting patients with potentially curable renovascular hypertension. The split function study, when interpreted with the recently defined split function ratio, offers the clinician a highly accurate means of diagnosing significant renal ischemia. Because the split function ratio shows the disparity between the ischemic and contralateral kidney to a greater degree, the chance of misdiagnosis due to laboratory or physician error is minimized. The split function study, however, is of limited value in patients with pyelonephritis since the water- and salt-losing characteristics of the pyelonephritic kidney may mask significant renal ischemia. In these patients, as well as those with a nonfunctioning kidney or hydronephrosis, the renal vein renin determination is the test of choice. In addition, the added morbidity of the split function study is not warranted in a patient with an elevated peripheral renin which, for interpretation, requires an accurate 24 hour urine for sodium, a renal vein renin ratio outside the range of patients with essential hypertension (renal vein renin ratio greater than 1.7) and evidence of suppression of renin secretion from the contralateral kidney. If, however, the renin determination does not afford convincing evidence of significant renal ischemia in a patient with radiographic evidence of renal arterial stenosis, a split function ratio definitely should be determined to more completely define the pathology. The attendant morbidity of a carefully performed split renal function study does not approach the morbidity and mortality associated with unnecessary surgery or inadequately treated hypertension.


[Therapy of the carcinoma of the prostate and case control (III) (Author's transl)]. In a third information of our long-term study with now 304 cases we report on 54 cases with monotherapy-only orchiectomy, only hormones and combination of boths. With it the rectal palpable results have coincided significantly with the histological findings in all 3 therapeutic forms. As for the therapeutic result no difference is to be seen either histological or clinical after a 3 years' observation period. We cannot tell anything now about optimal methods of treatment with regard to the histological starting material. In all 3 therapeutic forms we observed regressions to stage O. The smallest plasma-testosteron concentration was found after orchiectomy, where no increase was recorded during the whole observation period.


[Coagulation disorders in prostatic carcinoma (author's transl)]. 70 nonselcted patients with prostatic carcinoma underwent coagulation analysis. Sxi had typical evidence of diffuse intravascular coagulation and in 8 cases such a disorder was highly probable. In 3 patients coagulation alterations appeared only after estrogen treatment, 17 patients (24.3%) thus showed evidence of intravascular coagulation. The hemostatic distrubance was silent in all but 3 cases where bleeding occurred. Coagulation disorders were found mainly in advanced stages and poorly differentiated carcinomas. There was a much higher content of thromboplastic activity in prostatic carcinoma than in normal prostatic tissue. Heparin plays a predominant role in the treatment of the coagulation disorder. In addition to therapy of clinically maifest consuption coagulopathy heparin can be used in prophylaxis against bleeding and thrombosis in cases with clinically silent intravascular coagulation and also in estrogen treatment.


[Inhibition of platelet aggregation under estrogen-treatment in patients with carcinoma of the prostate (author's transl)]. In patients with carcinoma of the prostate treated with estrogens platelet aggregation is increased. Patients with increased platelet aggregation have a high incidence of cardio-vascular and thrombo-embolic diseases. Platelet aggregation was measured by the platelet-aggregation test (PAT). Platelet aggregation was inhibited by administration of acetyl-salicylic acid (ASS) 2 times 500 mg daily. An aggregation inhibiting effect was found in all 38 patients. To reduce the cardio-vascular complications of estrogens in treating carcinoma of the prostate acetyl-salicylic acid as an adjunct therapy is recommended. A long-term study has been started.


[Obstructions of the lower ureteral segment caused by vascular anomalies (author's transl)]. On four cases we show the clinical symptomatology of the lower ureteral segment by restricting and aberrant vessels. At the same time we pay attention to the right vena ovarica syndrome as an etiological factor of pyelonephritis of pregnancy and to the other vascular anomalies, which cause unilateral ureteral obstructions. Therapy of choice is an operation.


[Trocar-catheter for suprapubic cystostomy (author's transl)]. The Balloon-Trokar-Catheter can be recommended as a simple and quick method for a suprapubic urinary diversion (cystostomy). The instrument and its application are described.