Validation of the in vivo somatic mutation method in the mouse as a prescreen for germinal point mutations.

The in-vivo somatic mutation method developed by us in an earlier X-ray experiment was tested for its usefulness in chemical mutagenesis work, specifically in the prescreening for germinal point mutations. In order to explore possible parallelisms, the 7 compounds chosen for study, as well as the genetic markers used, were those with which large-scale specific-locus mutation-rate experiments in germcells had been conducted in the past or were in progress. From 1--3 dose levels were tested for each compound. On day 10 1/4 after copulation of C57BL females with T males, a single injection of the test compound was administered, and about 2000 offspring altogether were subsequently scored for survival, morphology, and presence of spots of various types. In accordance with our earlier results we found 3 types of spots: white near midline ventral spots (WMVS) which probably result from killing of melanocyte precursor cells; spots resulting from misdifferentiation; and the remainder, which probably result from expression of the recessive by one of several mechanisms (RS). Induction of teratogenic effects, which were stage-specific rather than agent-specific, generally paralleled induction of WMVS's. Both are interpreted as resulting from cell killing. Induction of RS's did not always parallel induction of WMVS's, but roughly paralleled relative frequencies of specific-locus mutations induced in spermatogonia by the same compounds. Even though the in vivo somatic-mutation method probably detects genetic changes additional to point mutations, the results indicate that it may be a useful prescreen for germinal specific-locus mutations, provided care is taken to distinguish between the 3 types of spots, only one of which (RS) is indicative of expression of the recessive.


The induction of somatic mutations in mouse embryos by benzo(a)pyrene.

With the object of establishing a test for specific locus mutations in the somatic cells of mice, the effect of benzo(a)pyrene on the developing pigment cells of mouse embryos was investigated. Embryos were heterozygous for genes affecting coat-colour so that mutations could be scored as spots on the adult mouse. If the pregnant female was treated, with 2 mg/day orally, before day 7 or after day 10 of pregnancy no mutations were seen in the offspring. Treatment at any time from day 7 to day 10 was effective in producing mutations with no day giving a peak response. The effect of treatment on consecutive days appears to be additive. It is suggested that further chemicals be investigated lest differing rates of uptake and metabolism should alter the period in which treatment should be given in order to detect a mutagenic effect.


Hepatic vein thrombosis in mice ingesting chlorinated hydrocarbons.

Hepatic vein thrombosis, as well as hepatocellular carcinomas, was induced in inbred C3H male and female mice ingesting 10 ppm of dieldrin, aldrin, heptachlor, or heptachlor epoxide in the diet. Thrombosis was present in 5% of mice ingesting dieldrin or aldrin and in 10.5% of mice ingesting heptachlor or heptachlor epoxide. Occlusion of the hepatic vein often resulted in infarcts of the liver. Females ingesting heptachlor or heptachlor epoxide were slightly more susceptible than males. There was no difference between male and female mice ingesting dieldrin or aldrin. Hepatic vein thrombosis did not appear to be related to the development of carcinoma of the liver because it was present in livers without carcinomas as well. Thrombosis was usually seen only in the liver but also rarely was present in the atria of the heart.


Toluene concentrations in various tissues of rats after inhalation and oral administration.

The uptake, distribution, and elimination of 3H-toluene in  various tissues of rats were studied after inhalation or after gastric intubation. The maximum radioactivity was measured 2--3 h after gastric intubation in tissues, except in white adipose tissue, where the peak radioactivity was reached at 5 h. After inhalation exposure, the uptake to various tissues was very rapid. The maximum radioactivity in most tissues was reached in 15--30 min. The accumulation was slowest in white adipose tissue, where it took 1--2 h. The radioactivity in tissues decreased after inhalation exposure more rapidly than after gastric intubation. Brown adipose tissue and white adipose tissue were different from other tissues in their ability to retain toluene. Twenty-four hours after exposures, only 1% or less of the initial radioactivity was found in tissues other than white adipose tissue, in which the corresponding value was 3.5--5%. The results show a very rapid absorption and distribution of toluene after inhalation and a retention of radioactivity in white adipose tissue. After oral ingestion the distribution showed a similar but much slower pattern.


Pharmacokinetics of cyanide in poisoning of dogs, and the effect of 4-dimethylaminophenol or thiosulfate.

Cyanide in blood, plasma, and urine of dogs after administration of K14CN was determined with the isotope dilution technique. The addition of large amounts of inactive KCN as soon as possible to a sample to be analyzed inhibited the decrease of the original cyanide concentration. After administration of several lethal doses of cyanide into the stomach or by slow intravenous infusion a concentration of about 40 micron cyanide in plasma was found at the moment of respiratory arrest. Since 60% of the cyanide in plasma was bound to proteins the concentration of free cyanide which stopped respiration was about 16 micron. Quick formation of ferrihemoglobin by i.v. injection of 4-dimethylaminophenol after plasma cyanide had risen to or above 40 micron decreased the cyanide concentration in plasma and restored respiration, while  cyanide  was  accumulated in red cells by formation of ferrihemoglobin cyanide. Equilibrium constants calculated for the reaction between ferrihemoglobin and cyanide in vivo indicated that the reaction approached equilibrium in a few minutes. Up to 60% of the radioactive cyanide absorbed was found as non-cyanide radioactivity in the urine.


Hexachlorobenzene residues and effects on esterase activities in pre-weanling rats after a reciprocal transfer between HCB-treated and control dams.

Female Wistar rats were divided into two groups. One group was fed ad libitum powdered rat chow containing 80 ppm hexachlorobenzene (HCB) and the other was fed HCB-free diet 2 weeks before mating until the termination of the experiment. Immediately after parturition, the pups were randomly culled to 10 per litter and 5 pups were reciprocally transferred between HCB and control dams. All pups within same paired litters were sacrificed on the 16th to 17th day and on the 20th to 23rd day after birth. Liver esterase activity toward indophenyl, thiophenyl, and p-nitrophenyl acetates was determined. The liver to body weight ratio, liver esterase activity and HCB residues were significantly higher in pups nursed by HCB-fed dams than in those nursed by control dams. The HCB residue in the liver, kidney, spleen, heart and brain was analyzed by gas-liquid chromatography. At about the weaning time, the HCB residue levels in pups transferred after parturition from HCB fed to control dams were similar to those in pups which remained with the control dams. The results demonstrated that HCB in tissues at about weaning time was obtained largely through milk. In addition, transmission of HCB through milk had greater effects on esterase activities in suckling pups than placental transmission. The pups born to HCB-treated dams and nursed by the control dams were similar to the pups born and nursed by the same control dams.


The effect of selenium on the brain uptake of methylmercury.

Twenty-four h after the subcutaneous administration of 0.5 mumoles selenite labelled with 75Se to rats of 200 g body weight, the retention of selenium at the injection site was significantly increased by the presence of equimolar amounts of methylmercury in the injection solution. The retention of Me203HgCl was not affected by the presence of selenite. The most significant shift caused by interaction was a decrease in the blood content and an increase in the brain content of 203Hg. The brain content of 75Se was also increased to a lesser extent. The shift in the distribution--which was the same whether the two metals were injected at the same site or separately--continuously decreased from 6-48 h. The same interaction pattern was observed when methylmercury and selenite were administered by gastric gavage and differences in distribution increased when the dose was increased from 1.25 mumoles/kg to 2.5 mumoles/kg. The increase in the brain content of mercury caused by selenite was not restricted to simultaneous administration and occurred when selenite was given 2-7 days after methylmercury.


[Control of the intensive treatment of thallium intoxications (author's transl)].

A report is given on the control of the thallium level at poisoning during therapy with forced diuresis and extracorporeal hemodialysis. The success of these methods was controlled ty the determination of the thallium level in vomit, blood, urine and dialysate by flameless atomic absorption spectrophotometry. Since the results are obtained within a few minutes, thallium measurements may be helpful for the decision on the therapy to be applied.


Binding of mercury and selenium in subcellular fractions of rat liver and kidneys following separate and joint administration.

The distribution of mercury and selenium has been examined in subcellular fractions of rat liver and kidneys in prolonged exposure to HgCl2 and Na2SeO3 administered separately and simultaneously. The molar ratio of mercury and selenium concentrations in subcellular fractions of the organs examined varied considerably. Selenium displaced mercury from the soluble kidney fraction bound mainly with metallothionein to the nonhistone protein fraction of liver nuclei. The Hg-stimulated biosynthesis of metallothionein has been eliminated under the influence of selenium.


Trichloroethylene and 1,1,1-trichloroethane: effects on brain and liver after five days intermittent inhalation.

The inhalation exposure of adult male rats to 7.9 mumol/l (200 ppm) of trichloroethylene for 4 days 6 h each day led to an accumulation of the solvent in the perirenal fat 17 h after the last exposure. Exposures to 20 mumol/l (500 ppm) of 1,1,1-trichloroethane caused similar accumulation. The latter rats presented no changes in their behaviour in an open-field test whereas the motor behaviour of the animals exposed to trichloroethylene was more active in comparison to controls 1 h after the exposure on the 4th day. Trace effects of trichloroethylene on emotional behaviour of the same rats could be seen 17 h after the last exposure. Further exposures on the 5th day increased brain, liver, lung and blood contents of trichlorethylene and 1,1,1-trichloroethane. A slight decrease in brain RNA content was found in the 1,1,1-trichloroethane exposed rats while RNA decreased significantly after the fifth day of trichloroethylene inhalation. The exposure to 1,1,1-trichloroethane on the 5th day depressed also the microsomal cytochrome P-450 content in liver of rats whereas trichloroethylene increased the hemochrome content slightly at the same time.


[Submicroscopic changes in the hepatocytes of guinea pigs under the effect of heterologous mitochondrial antibodies].

The electron microscopic examination of livers of guinea pigs treated with heterologous mitochondrial antibody showed that under these circumstances pathological changes developed in hepatocytes entailing various disorders of cell metabolism. These changes consisted in marked disturbance of the circulation of intracellular fluids leading to the general or partial edema of the cell and disorientation of organoids, in different rearrangements of mitochondria with loss of calcium phosphate salts, in degranulation and formation of numerous large cavities of granular endoplasmic reticulum, reduction of the Golgi complex, decrease in the amount or complete lack of glycogen in hepatocytes. The experimental evidence attests to the damaging effect of heterologous mitochondrial antibody on numerous cellular and subcellular structures causing the disorders in the water-salt, protein, and carbohydrate metabolism.


Experimental study of sacculotomy in endolymphatic hydrops.

Thirty-nine guinea pigs were used for four groups of experiments: 1. sacculotomy only, 2. sacculotomy and simultaneous obliteration of the endolymphatic duct, 3. sacculotomy followed by obliteration of the endolymphatic duct, and 4. obliteration of the endolymphatic duct followed by sacculotomy. Sacculotomy alone caused only minimal cochlear pathology, whereas sacculotomy on hydropic ears produced severe atrophy of the organ of Corti and cochlear neurons as well as connective cells of the limbus. There was histological evidence that Reissner's membrane in hydropic ears was ruptured by the sacculotomy procedure. The primary cause for the severe atrophic changes is thought to be the toxic effect of intermixing perilymph with a large volume of endolymph. The surgically induced saccular tears appeared to be healed in all ears, and the procedure had no significant effect on the course of endolymphatic hydrops. Although two out of eleven specimens in which sacculotomy was performed on hydropic ears showed tears and collapse of Reissner's membrane, since others with similar tears showed extensive hydrops, the possibility of artifact could not be ruled out. In one specimen with simultaneous sacculotomy and obliteration of the duct, persisting fistulae were noted at the sites of accidental fracture of the osseous spiral lamina; this ear is the only one which failed to develop hydrops following obliteration of the duct. The results of this experiment, namely sacculotomy on hydropic guinea pig ears, suggest that sacculotomy is not a rational procedure for the control of endolymphatic hydrops in Ménière's disease for the following reasons: 1. surgically induced tears in the saccular wall are followed by rapid healing and 2. intermixing of perilymph and a large volume of endolymph causes toxic atrophy of the limbus, organ of Corti and cochlear neurons.


The influence of intravenous injection of lidocaine on optokinetic nystagmus in rabbits.

The effects of lidocaine in doses of 2.0--6.0 mg/kg with intravenous injection on optokinetic nystagmus were observed in 21 rabbits. No effect of lidocaine was obtained on the frequency of OKN. On the other hand, the amplitude of OKN in lidocaine groups decreased after the injection. The mode and place of the action of lidocaine on OKN were discussed.


[Concerning the morphology of the supraglottic submucosa and its relation to the growth of cancer (author's transl)].

The histological structure of the supraglottic submucosa consists of a wide-mesh connective net, which builds compartments where glands are included. Somewhere, the walls of compartments are so thick that they may be considered as true ligaments. Some of them are located at the limit between glottis and supraglottis; therefore one may argue that the so-called "biological vallum", which hinders the downward propagation of supraglottic cancers is not only due to the interruption of lymph ways between vestibulum and vocal chords but also to the presence of this thick connective barrier. Two gaps interrupt the continuity of the barrier, the first one at the anterior commissure, the second at the posterior extremity of the ventricle. The situation of the gaps corresponds to the main directions of propagation of the supraglottic cancers, when they spread inferiorly.


[Pharmacokinetical, histological, and histochemical investigation on the ototoxicity of gentamicin, tobramycin, and amikacin (author's transl)].

The pharmacokinetics of gentamicin, tobramycin, and amikacin in the inner ear fluids and serum of the guinea pig were studied. The concentrations of these antibiotics were determined by a microbiological method and could be confirmed by the use of 14C-labeled gentamicin. Retention was clearly demonstrated in perilymph and endolymph, whereas there was no retention in the cerebrospinal fluid and the compartments of the eye. A linear relation between concentrations in the perilymph and dosage of gentamicin was ascertained. There was no difference between the concentration of drug in endolymph and that in perilymph. The concentrations of these antibiotics in the perilymph were symmetrical and many times higher than those in the brain. Long-term treatment did not influence the pharmacokinetics of the three antibiotics in the inner ear. However, increased levels of drug in the inner ears in animals with uremia and in some animals with otitis media explained the increased ototoxicity that was observed in histological investigations of these two conditions. Cisternal puncture and diuretics did not change the concentrations of aminoglycoside antibiotics in the inner ear. In large experimental series the hair cell degeneration pattern of the new aminoglycoside antibiotics was determined by the surface preparation technique as well as the influence of the different factors upon this pattern. A prophylactic effect on the ototoxicity of the aminoglycoside antibiotics could not be found in the 2,3-dimercaptopropanol, but by dividing the daily dosage administered. Young guinea pigs were generally not very sensitive to gentamicin, in some cases however much more. Late ototoxicity could not be found after administration of gentamicin. The pharmacokinetical and especially the histological investigations allowed an evaluation of the ototoxicity of the new aminoglycoside antibiotics. By histochemical investigations no influence of the new aminoglycoside antibiotics upon the amount of unspecific esterases and alkaline phosphatase in the inner ear could be detected, but an increase of the amount of acid phosphatase in slightly damaged outer hair cells.


[Incus, controlled deepfrozen or in cialit conserved, after allogenetic implantation. An animal-experimental study with comparing histology (author's transl)].

The histological reactions to the implantation of allogenetic incus after conservation in Cialit or after controlled deepfreezing are described. After 5 months the incusses of both conservation technics show the same good tendency of revitalisation. Therefore the controlled deep-freezing technic does not offer an advantage compared to the Cialit conservation method at least for the present state of knowledge.


Sacculus laryngis.

100 preparations of the larynx from 104 autopsies were examined with reference to the condition of the laryngeal saccule. In 54% of the cases the saccule could not be demonstrated. The examination showed a clear sex difference regarding the existence and size of the laryngeal saccule. In 6% the laryngeal saccules were pathologically enlarged as interne laryngoceles, in all cases in males. The laryngeal saccule must regarded as an atavistic structure.


[Three cases of giant cell fibroma of the vocal cord (author's transl)].

Three cases of giant cell fibroma of the vocal cord are reported. The histological and cytological features of the extirpated tissue confirm the benigne character of these tumors.


The nystagmus and the therapeutic effects on early-diagnosed cases of sudden deafness.

We investigated the hearing prognoses of early diagnosed cases of sudden deafness. We tried to find the most reliable factor to determine the prognosis of hearing loss. Of various possibilities that affect the prognosis; the period of onset to first examination, therapeutic manner and vestibular test findings, the findings of caloric test and spontaneous nystagmus showed much better correlation with the hearing prognosis than others. Thus, we presume the vestibular dysfunction in cases of sudden deafness may reflect the extension and severity of inner ear involvement.


Tympanoplasty in Korea (ossiculoplasty).

Three hundred and ninety three cases of ossicular reconstruction are presented. In the most favourable cases with both malleus handle and stapes present, this presents a closure of the air-bone gap to within 20 dB better than 80%. With connective tissue, underlay and fixation technique and staging are all important aspects of ossicular chain repair. Preservation of the function of the sound conduction mechanism in most favourable cases (malleus handle and stapes arch present) were improved by the employment of a sculptured, fitted incus prosthesis between the handle of the malleus and the head of the stapes.


[Auditory thresholds in guinea-pig and mouse by the pinna-reflex of Preyer (author's transl)].

Auditory thresholds were obtained by controlling Preyer's pinna-reflex for sound pressure levels quantitatively and selectively for single frequencies. Under the reported test conditions the auditory thresholds are very well reproducible and quickly done.


[Acidosis and clinical condition in asphyctic calves].

In depressed calves (modified APGAR score 4-6) there is at birth an evident combined respiratory-metabolic acidosis (pH = 7.082 +/- 0.175; pCO2 = 73.3 +/- 26.8 mm Hg; BE = -10.6 +/- 7.2 mmol/l). The metabolic adaptation is completed after 6 hours, the respiratory acidosis is present up to 24 hours after delivery. In comparison to normal calves there are significant deviations in pH-values, base excess standard bicarbonate and actual bicarbonate during the whole investigation time. The carbon dioxide tensions of the depressed calves are at birth similar to those of normal calves, but in the following hours they are significantly higher. A definite relationship can be demonstrated between the 1 minute APGAR score and pH-value, base excess, standard bicarbonate and actual bicarbonate. Oxygen tension, oxygen saturation and carbon dioxide do not correlate with the clinical condition.


[Effect of a benzopyrone compound on embryonic tissue and cell cultures (author's transl)].

Embryonic tissues and cells of the chicken were treated with a coumarin-rutin derivative preparation (Venalot). A total of 3000 cultures from embryonic epithelia, skeletal muscle tissue, and connective tissues were tested. At high dosages, never administered in the therapy, the preparation inhibited the cell proliferation strongly. With the diminution to therapeutical concentrations no longer inhibitory but stimulatory effects, viz. to mitosis, were revealed. High cell partition rates in the connective tissue (fibroblasts), in the epithelial cells and in the bony tissue of the embryonic os frontale (osteoblasts) are an indication of the mechanism of the known wound-healing accelerating action of the preparation. The effect of stimulating the proteolytic action in mesenchymal cells, observed on isolated peritoneal macrophages has been confirmed for the mesenchymal cell of the embryonic chicken.


Synthesis of some indole acrylamides. Short communication.

The synthesis of some indole acrylamides via the acid chloride is reported. Disubstituted indole acrylamides are successfully prepared by the application of Vilsmeier reaction.


Biological properties and clinical application of propolis. IV. The action of ethanol extract of propolis (EEP) on cells cultured in vitro.

An increase of total cell number was shown in the cell culture in vitro under the influence of ethanol extract of propolis (EEP). Addition of EEP to the nutrient medium of the cells caused a strong activation of mitoses. Besides, distinctly intensified metabolism of these cells expressed by a strong activation of NADH2-reductase was also observed.


Chemistry and pharmacology of arginine pyroglutamate. Analysis of its effects on the CNS.

By studying the influence of the arginine pyroglutamate on the CNS its variations were evidenced which are clearly identifiable through the analysis of the interaction with molecules having either a depressive or excitatory action. In the case of pentobarbital the antagonistic effect of the compound on the general anaesthesia is very intense and is equally present even when medazepam and flurazepam are associated. Equally obvious is the  antagonism with barbiturate in the case of spontaneous motility but much less so with the two benzodiazepines. As far as the specialized behaviour is concerned, arginine pyroglutamate does not alter the sound discrimination capacity (responses in Sdelta punished) at fixed intervals (F.I.) nor does it influence the learning of a sound discrimination (responses in Sdelta punished) at varied intervals (V.I.). The process of learning is instead moderately accelerated in the case of a temporal discrimination and of a conditioned avoidance response (CAR) in the shuttle-box. No effect was found when the same amino acids were introduced alone or in random association. The hypothesis is proposed that the phenomena described depend on the different pharmacokinetics of arginine pyroglutamate that ensures brain concentrations sufficient to block the activity of depressive compounds but is not capable of influencing in a significant way the spontaneous and specialized behaviour of normal animals.


Action of phenylisopropyl-adenosine (PIA) on the synthesis of corticosterone in rats.

The effects of the stereoisomers of phenylisopropyl-adenosine (l- and d-PIA) were studied on the synthesis of corticosterone in rats in vivo and in rat adrenal slices in vitro. In vivo l- and d-PIA elevated plasma corticosterone level in normal but not in dexamethasone-pretreated rats. l-PIA was at least 20 times more active than d-PIA. The ACTH-stimulated steroidogenesis was modified by pretreatment with l-PIA neither in normal nor in dexamethasone-treated rats. Adrenal slices prepared from the l-PIA-pretreated rats were less sensitive in vitro to the stimulatory action of ACTH or N6,2'-O-dibutyryl-3',5'-adenosine monophosphate (DBA) than those from control animals. In vitro l- and d-PIA slightly increased the basal steroidogenesis. On the other hand, both the ACTH- and DBA-stimulated synthesis of corticosterone was inhibited by l- and d-PIA to approximately the same degree. The type of inhibition proved to be competitive in ACTH-stimulated and non-competitive in DBA-stimulated steroidogenesis. l- and d-PIA did not disturb the release process of corticosterone from the adrenal tissue into the incubation medium.


Influence of hypercapnia on the cerebrovascular activities of some drugs used in the treatment of cerebral ischemia.

The effects of twelve substances on local cerebral blood flow (LCBF) were studied in the normocapnic and hypercapnic conscious rabbit. In normocapnia, an increase in LCBF was observed after naftidrofuryl (NAF), cinnarizine (CI), viquidil (VI) and heptaminol acefyllinate (HA). The LCBF was only slightly increased or unchanged after hydrogenated ergot alkaloids (HEA), cyclandelate (CY), hexobendine (HE), ifenprodil (IF), piridoxilate (PI), vincamine (VC) and xantinol niacate (XN). It was reduced by theophylline (TH). In hypercapnia, a more pronounced increase in LCBF than in normocapnia was seen with CY, HE, NAF, and VI and a decrease or lesser effect with HA, IF, VC and XN. The decrease in LCBF with TH was enhanced by hypercapnia. The effects of CI, HEA and PI were not modified. The therapeutic implication of these modifications of drug effects by hypercapnia, is discussed.


Effects of metformin on glucose metabolism of isolated perfused rat skeletal muscle.

It was investigated whether N,N-dimethylbiguanide hydrochloride (metformin) lowers blood glucose levels by stimulating glucose uptake of skeletal muscle using the isolated perfused rat hindquarter. Osborne-Mendel rats were subjected to a special feeding regimen (food intake only 2 h daily) and were treated orally by metformin (125 mg/kg body weight twice daily) or placebo, respectively. The hypoglycemic effect of metformin could be demonstrated. Thereafter, control rats were perfused in the absence, and metformin-treated rats in the presence of added metformin (0.67 microgram/ml perfusate). Neither the basal nor the insulin-stimulated glucose uptake of skeletal muscle was increased by metformin. Lactate and alanine release, O2 uptake as well as the tissue metabolite levels of glucose, lactate, pyruvate, ATP and creatine-P remained unaffected. On the other hand, metformin caused a significant decline of lactate oxidation as well as an elevated glycogen content of skeletal muscle. It is proposed that the inhibition of lactate oxidation may under certain conditions be instrumental in the development of lactic acidosis associated with biguanide therapy.


Differences in the response to pentobarbital sodium of Roman high- and low-avoidance rats.

Wistar-derived, Roman high- and low-avoidance rats (RHA and RLA) have been bred solely for divergent patterns of performance in a behavioral test. In the present study, single and multiple injections were used to investigate the acute and chronic effects of pentobarbital sodium in these 2 strains. The median lethal dose was found to be significantly higher for the male RHA rats than for the RLA males. RHA males also had proportionally larger livers, kidneys and hearts, and lower erythrocyte counts, hematocrits and hemoglobin levels than had RLA males.


Evaluation of a 4% gelatin solution in the treatment of canine haemorrhagic shock.

The effects of volume replacement with 4% gelatin containing 1% glycine at pH 5.8 and 6.4 on the changes in mean arterial blood pressure (MABP) and blood levels of glucose, lactate and urea following acute haemorrhage in dogs were studied. Comparison was made with dogs given homologous blood. Dogs bled 30% of blood volume, maintained in shock for 30 min, and infused with gelatin solutions, showed values of MABP, blood glucose, lactate and urea nitrogen insignificantly different from dogs similarly bled and infused with homologous blood. The responses obtained in dogs infused with gelatin at pH 5.8 were better than at pH 6.4.


Comparison of the biological effectiveness of injected testosterone propionate and testosterone released from silastic capsules.

The in vitro release and biological effectiveness of silicone rubber implants containing testosterone in orchidectomized male rats was investigated over a period of 20 weeks. A marked reduction in release in 0.9% saline solution could be observed in vitro relative to the incubation time in the medium. The reduction in release was greatest during the first few weeks of the experiment. Rat seminal vesicles and prostates, which were greatly stimulated at the start of the experiment, lost weight corresponding to the release rate in vitro. The implants containing testosterone used here were 4 to 26 times more effective than testosterone propionate injected s.c.


Alcohols-histones metabolic interactions in intact human erythrocytes.

Alcohols have a stimulating effect on the intracellular peroxidatic reactions of intact human erythrocytes. This effect depends directly on the molecular weight of alcohol and the H2O2 concentration. The human leukocyte nuclear histones, flavin-adenine-dinucleotide (FAD) and nicotinamide-adenine-dinucleotide (NAD) inhibit the peroxidatic reactions during the metabolism of alcohols in intact human erythrocytes. The participation of erythrocyte catalase, the possible metabolic pathway and the inhibitory effect of human leukocyte nuclear histones, FAD and NAD on the intracellular metabolism of alcohols is discussed.


[Quantitative determination of pemoline in serum and urine after ingestion of therapeutic doses (author's transl)].

Serum and urine 5-phenyl-2-imino-4-oxazolidone (pemoline, Tradon) levels have been determined in normal subjects after therapeutic doses (40 mg). Peak levels in serum were reached within 4-6 h (1.1-1.5 mg/1). The half-life was 16-18 h. After the oral administration of 40 mg of pemoline 35-50% of the dose was excreted in urine within 32 h.


[Iron absorption after oral application of a combination of Fe2+-succinate and multivitamins (author's transl)].

The rate of iron absorption of Fe2+-succinate orally applied with multivitamins, was measured by means of whole-body counter in 45 subjects. The dosage was 330 mg ferrous succinate (115 mg Fe2+). Absorption was generally 4.5% (5.2 mg) in normal subjects, 8.6% (9.9 mg) in subjects with latent iron deficiency, and 29.6% (34 mg) in subjects with manifest iron deficiency. In women taking oral contraceptives and not suffering from iron deficiency, no significant increase in the iron absorption rate was measured.


[On the pharmacokinetics of phenazone in man (author's transl)].

Studies were carried out on the pharmacokinetic behaviour of 5-oxo-2,3-dimethyl-1-phenyl-3-pyrazoline (phenazone) by means of intraindividual comparison following oral and rectal administration in man. A one-compartment model served to describe the course of blood levels, in which the twin peaks of following rectal administration are quite remarkable. The influence of variation in the pharmaceutical dosage form on the pharmacokinetic behaviour patterns of phenazone were studied and intraindividual differences not inconsiderable are obvious.


[Electromyographic studies on the effect of the cinnamamide derivative LCB-29 in spastic syndromes (author's transl)].

In ten patients with para- or tetraspastic syndromes of various etiology 5 different spastic phenomena demonstrating pathologically raised excitability of muscle regulation functions were registered electromyographically before and 1 h after i.v. administration of N-(hydroxy-2-ethyl)-cinnamamide (LCB-29). In the majority of cases a marked decrease of spasticity was registered. The rapid onset of this effect of LCB-29 allowed constant test conditions and therefore eliminated other influences on spasticity. The decrease of raised polysynaptic excitability at spinal level led, at least in part, to the assumption of a spinal site of action of LCB-29. The absence of a sedative effect with oral medication makes a strong central effect seem less probable.


[Modification-possibility of the enterohepatic circulation of digitoxin in man].

Tritiated digitoxin (0.25 mg) was i.v. administered to a control group of 5 patients as well as to 5 patients with a T-tube quantitatively draining the bile fluid. During the initial 24 h after injection, 10% of the dose administered, on the second and third days 5 and 3,5%, respectively, were biliarily excreted. The amount biliarily excreted did not influence the course of the blood level as compared to the controls. Also charcoal given perorally in a sufficient amount (50 g) did not affect the blood level of radioactive digitoxin and/or its metabolites. As obtained from in vitro experiments the absorptive potency of cholestipole and cholestyramine for digitoxin and its metabolites in human bile fluid is similar to that of charcoal.


Spironolactone metabolism in normal subjects and in patients with liver cirrhosis.

The dynamic excretion of aldadiene, the principal metabolite of spironolactone with biological activity, was studied in normal subjects and patients with liver cirrhosis following administration of spironolactone. Aldadiene appeared in the three-days urine collection in around 3% of the dose. There was no significant difference in the biological half-life, calculated from the urinary pattern, and in the rate of excretion in patients with hepatopathy and hospitalized controls. Healthy volunteers without hospitalization exhibited the most rapid elimination of the metabolite. An increase of spironolactone dose enhanced the per cent rate of aldadiene excretion, while the biological half-life did not change. Spironolactone decreased the rate of dehydroepiandrosterone and androsterone excretion even after a single dose. Determination of total 17-ketosteroids is of no value on evaluation of adrenal function during spironolactone therapy, due to a Zimmermann-positivity of spironolactone metabolites.


The fate of intravenously infused gelatin.

The fate of i.v. infused gelatin was studied by measuring the rise in the level of total hydroxyproline (HP) in some organs of the rat following the infusion of a 5% autoclaved gelatin solution (1 ml/100 g body weight). The results obtained showed that HP levels were consequently increased in all of the organs studied, then the levels were generally normalised during the 3rd day post infusion. Small concentrations of HP were still retained by the kidneys and blood plasma, at the end of the first week after infusion. The rat ratio HP/creatinine (HP/C index), which increased from 0.33 to 3.78 during the first 24 h post infusion, declined gradually to the base-line level after 4 weeks, during which time 94% of the HP infused could be accounted for in the urine. Most of the HP was excreted in the bound form.


[Structure-activity relationships of etozolin, a novel diuretic (author's transl)].

Selection of a structurally confined group of diuretics out of 2-methylenethiazolidones-(4), a new class of compounds, and related heterocycles with partly choleretic properties is described. The physico-chemical parameters of ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (3; etozolin, Gö 687, Elkapin), which has been selected for therapeutic use, are discussed with respect to its close structural relation to the choleretic piprozoline (2). Both the spectroscopic results and the anomalous thermodynamic data of 2, 3 and the homologous compounds 4 and 5 demonstrate a structural specificity of 3 unknown up to now with diuretics.


[On the pharmacology of Etozolin (author's transl)].

Ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin, Gö 687, Elkapin) is a diuretic with a new chemical structure. Animal experiments with etozolin showed low toxicity, potent diuretic and saluretic properties with a mild onset of action. A marked antihypertensive effect was found in long-term experiments in hypertensive rats. In investigations concerning general pharmacology etozolin showed no effects which stand against its use as a diuretic.


Effect of Etozolin on whole kidney function and fluid and electrolyte reabsorption in rat proximal convoluted tubules and loops of Henle.

The effects of ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (etozolin, Elkapin) on whole kidney function and on fluid, sodium and potassium reabsorption in proximal convoluted tubules and loops of Henle of superficial nephrons were studied in rats using clearance and micropuncture techniques. Etozolin (50 mg/kg i.v. initial dose; 50 mg/kg per hour i.v.) markedly increased urinary fluid and sodium excretion and decreased glomerular filtration rate. Fractional tubular sodium reabsorption fell by 8.7%. Fluid and electrolyte reabsorption in the proximal convolution was not significantly influenced by etozolin. The substance significantly increased flow rate, sodium and potassium concentration and decreased tubular fluid/plasma inulin ratio of the early distal tubular, indicating an inhibitory effect on fluid and electrolyte reabsorption in the loop of Henle. Although etozolin is chemically different its site of diuretic action is the same as that of furosemide and ethacrynic acid.


[Toxicological studies on Etozolin (author's transl)].

The tolerance of ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin, Gö 687, Elkapin) has been investigated over 18 months after oral administration in rats and over 1i months after intragastric application in dogs. Further the influence of the compound on pregnant animals and their fetuses after intragastric application has been investigated in rats and rabbits. The investigation of the influence on fertility and breeding capacity as well as on the peri- and postnatal development was carried out in rats after peroral administration. In the course of the chronic experiments a dose related increase of the excretion of fluid and electrolytes was observed. Side-effects, which mainly occurred during the last weeks of the experiment in the highest dosage group, were most probably due to the exhaustion of the fluid and especially of the electrolyte reserves of the animals. The experiments in rats and rabbits did not yield any findings indicating teratogenic properties. Fertility and breeding capacity were likewise not influenced by etozolin. An influence on the peri- and postnatal development could be demonstrated only in the toxic dose range.


[Metabolism of Etozolin in rat, dog and man].

Investigations on the metabolism of the new diuretic ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (Gö 687, etozolin, Elkapin) were carried out with urine of rat, dog and man as well as rat bile after enteral administration of the 14C-labelled substance. Seven metabolites were isolated with either the aid of high-pressure liquid chromatography (HPLC) or extraction and thin-layer chromatography. Mass spectroscopy was applied to determine the structures of the metabolites, partly by use of authentic reference substances. Because of the instability of most of the metabolites, some of them showing strong polarity, the described investigations on the metabolic profiles and the enrichment and purification of some metabolites could only be carried out with the HPLC-radioactivity detector system, which requires no clean-up for the samples. The metabolisation process of etozolin is qualitatively equal in rat, dog and man; it is characterized by 3 steps: 1. enzymatic cleavage of the ester group, which leads to the also diuretically active main metabolite (metabolite I) in the plasma of all 3 species; 2. glucuronidation of the resulting metabolite I, leading to metabolites II and III, which are diastereoisomeric esters of the two enantiomeric forms of metabolite I with beta-D-glucuronic acid. 50--60% of the urinary radioactivity can be described with these two metabolisation steps in all 3 species; 3. Oxidation of the piperidine moiety to metabolites IV--VII.


The distribution of radioactivity in pregnant rats after repeated oral doses of the diuretic agent Etozolin.

1. The distribution of radioactivity has been studied by whole-body autoradiography after administration of daily oral doses of (2-14C)-ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin, Gö 687, Elkapin) at a dose level of 100mg/kg to pregnant rats during the 10th to the 17th day of gestation. 2. After the last dose, most of the radioactivity was excreted rapidly and was mainly assoicated with the gastrointestinal and urinary tracts and kidneys of the mothers. 3. Maximal distribution in the mothers occurred at 3--6 h after the last dose, and radioactivity at these times was detectable also in the lungs, muscle mass, fat, mammary and uterine tissue, the reticuloendothelial system, placentae, some ducted and endocrine glands, and in blood, but not in brain or spinal cord. At 4 days, traces of radioactivity had persisted in kidneys, liver, lungs, thyroid and placentae. 4. Radioactivity was present in low and uniform concentrations in most foetal tissues such as the heart, lungs and lens and in even lower concentrations in the brains of the foetuses during 3--6 h after dosing, but was not detected in foetal tissues at 2 days. Concentrations of radioactivity in maternal tissues were at all times much higher compared with those in foetal tissues at corresponding times after dosing.


[Effect of the diuretic Etozolin (Gö 687) on renal elimination of water and solutes in subjects with normal renal function (author's transl)].

The novel diuretic ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin, Gö 687, Elkapin) has been investigated on 10 volunteers with intact renal function. Administration of 800 mg of the compound caused a significant increase of the renal elimination of water, sodium, chloride magnesium as well as of the sum of the osmotic constituents while an influence on the creatinine-clearance could not be demonstrated. Potassium elimination was also raised, however, at the same time the sodium-potassium ration increased strongly. Due to its long-lasting action etozolin seems particularly indicated for the treatment of cardiac and renal edema as well as for the treatment of hypertension.


[Effect of the diuretic Etozolin in patients with normal and impaired renal function (author's transl)].

The effect of the novel diuretic ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (etozolin, Gö 687, Elkapin) on renal function and especially on the elimination of solutes has been investigated under clearance conditions on 25 hydrated patients with different glomerular filtration rates (GFR). On normal persons the compound caused a decrease of GFR and of urea elimination while the absolute and the fractional elimination of sodium and chloride as well as the fractional potassium clearance increased significantly. In patients with chronic renal insufficiency (GFR less than 20 ml/min) these values could not be influenced. A significant correlation between initial GFR and decrease of GFR as well as between initial GFR and increase of renal elimination of sodium and chloride could be demonstrated: the lower the initial GFR the weaker the elimination of electrolytes and the decrease of the filtration rate, the latter being neglible at an initial GFR of 80 ml/min or less.


[Comparative studies on the diuretic activities of Etozolin and a reference compound in normal volunteers (author's transl)].

The novel diuretic (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)-acetic acid ethylester (Etozolin; Elkapin) has been investigated against a benzothiazide (Vs) and placebo on 8 volunteers. Etozolin and Vs show a dose dependent diuretic effect: 400 mg etozolin being equipotent to 75 mg Vs and 1200 mg etozolin being 2.8 times more effective than 75 mg Vs. Both substances show maximum effect 2 to 4 h after application, no differences from placebo being demonstrable 10 h after administration. There were no significant differences in potassium excretion between etozolin, Vs and placebo, etozolin and Vs causing, however, a significant excretion of sodium and chloride in contrast to placebo. Etozolin seems to act like a diuretic of the sulfonamide-type in respect to the profile of daily urinary output whereas resembling the loop-diuretic type in respect to urinary volume elimination.


The intrinsic structural asymmetry of highly curved phospholipid bilayer membranes.

Phosphorus-31 NMR studies of solutions of small L-alpha-dipalmitoyl phosphatidylcholine bilayer vesicles containing sodium dimethyl phosphate uniformly distributed between the continuous external and the intravesicular aqueous spaces, with the paramagnetic shift reagent Pr3+ present only in the external space, are reported. These studies give the distribution both of dipalmitoyl phosphatidylcholine in the vesicle inner and outer monolayers and of dimethyl phosphate in the aqueous spaces. With the third necessary parameter obtained from the vesicle sedimentation coefficient, the very different packing parameters of dipalmitoyl phosphatidylcholine in inner and outer monolayers can be determined. The vesicle outer radius is 109 A. Although the total bilayer thickness is virtually identical to that of planar bilayers, the outer monolayer is thicker (20 A) and the inner monolayer thinner (15 A). The area per head group at the inner surface, 68 A2, is like the planar value, but the tails are much more folded, so as to decrease the radial lengths and increase the tangential spreat (to 94A2). The reverse is true in the outer layer: the surface per head group is 76 A2, tapering to 51 A2 in the tail region, so that outer layer tails are relatively extended. The difference is equivalent to a shift of about two 2g1 kinks from outer to inner layers; the uneven packing certainly affects fluidity, and may have important biological consequences.


Lateral phase separations in binary mixtures of phospholipids having different charges and different crystalline structures.

Synthetic dipalmitoyl phosphatidylserine exhibits a sharp chain-melting transition temperature at 51 degrees C as judged by partitioning of the spin label 2,2,6,6-tetramethylpiperidine-1-oxyl. Phase diagrams representing lateral phase separations in binary mixtures of dipalmitoyl phosphatidylserine with dipalmitoyl phosphatidylcholine as well as with dimyristoyl phosphatidylcholine are derived from paramagnetic resonance determinations of 2,2,6,6,-tetramethylpiperidine-1-oxyl partitioning, freeze-fracture electron microscopic studies and theoretical arguments that limit the general form of acceptable phase diagrams. The reported phase diagrams are the first to describe binary mixtures in which one lipid is charged and the second lipid uncharged. These phase diagrams also are the first to include the problem of solid phases with different crystalline conformations as it relates to the occurrence of a pretransition in phosphatidylcholines and its absence in phosphatidylserines. In addition to the phase diagrams reported here for these two binary mixtures, a brief theoretical discussion is given of other possible phase diagrams that may be appropriate to other lipid mixtures with particular consideration given to the problem of crystalline phases of different structures and the possible occurrence of second-order phase transitions in these mixtures.


Oxygen consumption of the newborn rabbit treated with pulmonary surfactant.

A method is described for measuring oxygen consumption of small animals. It was used for 151 newborn rabbits delivered on the 27th, 28th, 29th, and 30th day of gestation. Half of the neonates were given a pharyngeal deposition of a concentrated surfactant (SA) suspension prior to their first breath. The remaining neonates served as controls. The survival rate among the immature rabbits treated with SA was significantly higher. The treatment did not affect oxygen consumption in any age-group. With increasing maturity, the neonates consumed more oxygen, and the controls delivered on the 30th day of gestation consumed 29.6 +/- SEM 4.2 ml oxygen per kilogram and minute.


[Lead content of evaporated milk].

In order to determine the concentration of lead in evaporated type of commercially available milks, a study was carried out in 40 cans. Out of them, 20 were of the "vitamin" brand and the other 20 were of "protein" quality. The lead content in either type of milk was not significantly different; "protein" milk showed 38.4 mug/100 ml, while the figure for the "vitamin" grade was 35.0 mug/100 ml. Considering the use of evapored milks in infant feeding, it was deemed wise to carry out an estimation of the amount of lead ingested in case the volume consumed reached from 500 to 1000 ml. As a result of this study, it is stated that somewhat between 150 to 200 mug of lead are ingested daily in the consumption of evapored milk at normal dilution. Based on the tolerance levels, the findings are discussed.


[Changes in the surface-active substance in the lungs of rabbits during endotracheal fluothane anesthesia].

Endotracheal phthorothan anesthesia without any surgical intervention in rabbits for 3.5 hours diminished the surface active properties of the surfactant by increasing the surface tension of the lung washings measured on the Wilhelmy scales. A study of phospholipid fractions in the lung washings by means of the thin-layer chromatography on silicagel showed a decrease of one of the major structures of the surfactant lipoprotein, phosphatidylcholine, with a simultaneous increase of the lysophosphatidylcholine. Determination of the free fatty acid content in the lung washings after the action of phthorothan anesthesia showed their significant increase as compared with control. A possible mechanism of the damaging effect of phthorothan anesthesia on the lung surfactant is discussed.


[Change in the state of surfactant in experimental pneumonia].

The state of pulmonary surfactant in rabbits at different periods (3 to 60 days) of experimental pneumonia was compared with the changes of the redox enzymes in the alveolar epithelium and the cells of the inflammatory infiltrate. At the initial stage (3 to 7 days) of the cellular metabolism activation there occurred a transitory intensification of the synthesis of surfactant lipids with a relative suppression of phospholipid synthesis. Later the progress of dystrophic processes and parenchymal sclerosis was accompanied by reduction of the synthesis of all the surfactant components. Surfactant surface activity became stable at a low level. This is possibly connected with the specific regulation of the surfactant synthesis determined by functional peculiarities of the organ.


Severe disseminated lung disease and bronchiectasis probably due to Mycoplasma pneumoniae.

Severe disseminated lung disease causing acute respiratory failure developed in a previously healthy 6 1/2-year-old boy. Mycoplasma pneumoniae was implicated and a complement-fixing antibody titre of 1:1024 against this organism was detected. At autopsy bronchiectasis was found, affecting chiefly the right middle and lower lobes. The unusual radiologic and pathologic findings are discussed.


[Effect of valinomycin on the phase state and passive permeability for calcium ions of membranes from artificial phospholipids].

Effect of valinomycin on passive permeability for calcium ions of liposomes from artificial phospholipids of dimiristoillecithin and dipalmitoillecithin under the conditions of thermotropic structural transitions which were controlled by means of fluorescent probe of 3-metoxibenzantron. It was found that the incorporating of valinomycin into the membrane depends on the density of phospholipid packing. The change of the physical state of phospholipids under the effect of antibiotic was correlated with the change of passive permeability of liposomes for calcium ions.


Familial occurrence of colon and uterine carcinoma and of lymphoproliferative malignancies: clinical description.

Carcinoma of the colon occurred in four generations of a family, including two of three siblings of one generation and eight of 19 members of the next generation. In addition, uterine cancer or lymphoproliferative malignancies were found in two family members. Of 41 members of the fourth generation, two were found to have colon cancer and one had malignant lymphoma. Clinical features were similar to those patients with "cancer family syndrome." Although a precise genetic mechanism is uncertain, it appeared to be transmitted as an autosomal dominant character.


The value of Gastrografin in the differential diagnosis of paralytic ileus versus mechanical intestinal obstruction: a critical review and report of two cases.

Two cases in which serious intra-abdominal complications were masked by results of the contrast examination using Gastrografin were encountered. This caused the authors to review critically the use of Gastrografin in the differential diagnosis of paralytic ileus versus mechanical intestinal obstruction. In a series of 41 cases in which the diagnostic problem was not solved initially by means of physical examination and plain abdominal roentgenograms, the Gastrografin examination proved reliable in 28 (68 per cent). The reliability of the examination was defined as the relative number of cases in which a correct decision could be made for or against surgical operation. It is concluded that Gastrografin is a valuable diagnostic aid in controversial cases of ileus. A "negative" result of the examination, however, would never be allowed to damp the surgeon's awareness of possible serious intra-abdominal conditions, which the contrast examination has failed to disclose and which require immediate surgical intervention.


[CNS complications and their prevention in malignant non-Hodgkin's lymphoma (author's transl)].

Among 334 patients (aged 15-57 years) with malignant non-Hodgkin's lymphoma there were 14 who developed CNS complications, none in 144 with lymphoma of low malignancy. Lymphoblastic lymphoma predominated amoung those with CNS involvement. In adults with this form treatment should therefore be undertaken to prevent such complications. The study confirms the need for histological subclassification in malignant non-Hodgkins's lymphoma.


Lactose malabsorption among the Pima indians of Arizona.

Lactose loading tests and other means were used to determine the pattern of primary "adult" lactose malabsorption (LM) and milk use among 171 subjects, including 122 children and 49 adults, almost all of them Pima Indians of Arizona. LM develops at quite young ages in full-blooded Pima children: already in the 3- to 4-year age group, 40% had LM. Of 62 full-blooded Indians (greater than or equal to 4 years of age), 59 (95%) had LM. Of 41 Indians (greater than or equal to 4 years) who were of mixed Indian-northern European ancestry, however, only 25 (61%) had LM, and, among them, prevalence of LM correlated with degree of northern European admixture. Whereas only 21% of Pima lactose absorbers reported symptoms after the loading test, 72% of malabsorbers did so, with older malabsorbers more likely to experience symptoms. In their everyday lives, only 23% of malabsorbers recognized symptoms brought on by milk consumption, but the percentage of malabsorbers making such an association increased with age. Nevertheless the Pima, adults as well as children, continue to drink reasonable quantities of milk. Family pedigrees are consistent with the hypothesis that adult lactose absorption is inherited as an autosomal dominant trait. Over-all results of this study, moreover, support the geographic hypothesis advanced to explain ethnic or racial differences in prevalence of LM, rather than the induction hypothesis.


[Therapeutic effects on disorders of spermatogenesis in hyperprolactinemia without pituitary adenoma].

As in patients with high pituitary prolactin secretion disturbances of the spermatogenesis are observed, we picked out from our patients with low sperm count those showing hyperprolactinemia without pituitary adenoma. They were treated for 50 days with 2-brom-alpha-ergocryptin (Pravidel, Sandoz AG, Nürnberg), which selectively inhibits prolactin release. Following treatment, in 7 cases an increase in sperm count was observed, while in 2 cases a decrease occurred. 4 cases with azoospermia showed no alteration. No explanation for the possible stimulation of spermatogenesis can be given today.


Examination of the aqueous humor as a diagnostic aid in anterior uveitis.

The aqueous humor of 20 cats and 17 dogs was examined to determine its importance as a diagnostic aid in anterior uveitis. Aqueous humor cytology and protein concentration differed in acute and chronic anterior uveitis but was not specific enough to be an aid in the diagnosis of feline infectious peritonitis. Cytologic examination of the aqueous humor was of benefit in determining the cause of anterior uveitis in 2 of 7 cases of lymphosarcoma. Cultures of aqueous humor proved negative in uveitis of more than 3 weeks' duration. Pseudomonas sp was cultured from the aqueous humor of a dog with anterior uveitis secondary to a perforating corneal injury.


Alkaline phosphatase activity in the preimplantation mouse embryo.

Alkaline phosphatase (AP) activity has been assayed in frozen sections of preimplantation mouse embryos by an azo-dye cytochemical method. The results indicate that during preimplantation mouse development AP activity is first expressed between the 8- and 16-cell stages and develops in all cells by the late morula stage. During blastocyst formation AP activity is lost or greatly reduced in trophoblast cells while activity is maintained in the inner cell mass.


The ultrastructure of a porcine hereditary lymphoma with some observations on cell cultures and enzyme cytochemistry.

Ultrastructural studies have been made on affected tissues and cell cultures established from an hereditary lymphosarcoma of Large White pigs. Certain hydrolytic and lysosomal enzymes have been investigated at light microscope level in tumour cells and in cells established in culture. Morphological, behavioural and enzymatic characteristics indicate that two types of surface-adherent cells persist in primary cultures established from the marrow of affected pigs, namely macrophages and myeloid cells. The latter show an initial tendency to colonial growth which disappears in subsequent passages. In nearly all cases the tumour is considered to be a poorly differentiated lymphocytic lymphosarcoma. There is, however, considerable variation in cellular components and tumour-cell differentiation, and on purely morphological grounds one case might be considered to be an histiocytic i.e. macrophage lymphoma. Intra-nuclear bodies were observed in one case and occasional cytoplasmic virus-like particles were seen in both fresh tissues and cultured cells. In older pigs tumorous lymph nodes often show a cellular depletion associated with an increase of fibroreticular stroma.


The effect of exogenous nucleosides on postimplantation development of mouse embryos.

Exogenous nucleosides, either singly or in combination, do not enhance postimplantation development of mouse embryos in vitro, and adenosine, guanosine and thymidine are toxic to the embryos at high concentrations.


A comparison of D.O. and M.D. student performance.

The performances of students from two medical colleges, one allopathic (M.D.) and one osteopathic (D.O.), at Michigan State University in a first course in psychiatry are compared. Although the M.D. students had scored significantly higher on the Medical College Admission Test, there was no difference in examination performance in the psychiatry course, which included measures of both basic information and of skill in diagnostic clinical application.


Supplemented fasting as a large-scale outpatient program.

Although supplemented fasting is now established as an efficient means of achieving substantial weight reduction in massively obese persons, widespread application of this treatment is contingent on its successful adaptation to a large-scale outpatient regimen. Of 519 patients treated as outpatients, 78% lost a minimum of 18.2 kg during the course of treatment. The overall rate of weight loss was 1.5 kg/wk, with females averaging 1.3 kg/wk and males, 2.1 kg/wk. The majority of patients tolerated the regimen well and were able to continue normal daily activities without experiencing any serious side effects.


Cystic fibrosis. An expanding challenge for internal medicine.

The number of adults with cystic fibrosis (CF) receiving care from the US Cystic Fibrosis Centers has been increasing at an average rate of about 200 patients each year. A model based on the continuation of this rate of increase predicts that almost 4,000 adults will be receiving care at the centers by the end of 1985. Four other models developed are based on continuation of a steady state with two variations: a 50% reduction in mortality and universal newborn screening. These models show the boundaries of an equilibrium population to be between 24,000 and 64,000 patients, with 7,000 to 18,000 adults.


Upper airway obstruction in euthyroid goiter.

Although it is recognized that an enlarged thyroid may occasionally cause tracheal compression, the incidence in euthyroid goiter is unknown. Twenty patients with nontoxic goiter were investigated for upper airway obstruction. Although none of them had dyspnea as a chief complaint, on direct questioning 9/20 had a history of shortness of breath on exertion and choking sensation. Upper airway obstruction was detected in 7/20 (35%) by roentgenography, 12/20 (60%) by flow volume loop (FVL), and in 16/20 (80%) by combined roentgenography and FVL. After therapy for goiter, there was a reduction in the size of the goiter and an improvement in FVL in the whole group. The statistically significant change occurred in peak expiratory flow (P less than .01) and peak inspiratory flow (P less than .05). These findings and the change in configuration of the curve suggested less upper airway compression. We conclude that goiter often causes unsuspected upper airway obstruction, usually slow in onset and not noticed by the patient.


Tricyclic plasma levels. Effect of age, race, sex, and smoking.

Steady-state plasma tricyclic antidepressant levels were determined in 65 patients undergoing treatment for depression with either amitriptyline hydrochloride or nortriptyline hydrochloride to determine if common factors such as age, race, sex, or smoking status were predictors of steady-state drug levels that have been shown to vary up to 36-fold. Evaluation of these factors did not disclose differences in the rate of demethylation of amitriptyline to nortriptyline, or steady-state tricyclic levels in the amitriptyline-treated patients. No differences were found in the nortriptyline-treated patients except regarding race. Black patients had significantly higher (50%) nortriptyline plasma levels than did white patients, which may explain the more rapid response to tricyclic treatment demonstrated in blacks. Decreased rates of nortriptyline metabolism in blacks can result in increased side effects and treatment failure if the therapeutic plasma range is exceeded.


Unusual cause of acute abdomen. Sickle cell trait and nonhypoxic splenic infarction.

Splenic infarction under hypoxic conditions is a well-known complication of sickle cell trait (Hgb AS). However, this case illustrates that it may occur without any clinical conditions of circumstances associated with decreased Pao2. In addition, sickle cell trait should be included in the differential diagnoses of splenic infarction even if the patient is not of African ancestry.


Triamcinolone aerosol. Treatment of aspirin-hypersensitive asthmatic patients.

The efficacy of triamcinolone acetonide aerosol in the management of asthma in six patients with aspirin hypersensitivity was evaluated during a one-year trial. Five patients were previously chronically dependent on systemic corticosteroids and had undergone unsuccessful trials with cromolyn sodium therapy. Substantial reduction in corticosteroid requirements was observed; in two patients, oral prednisone therapy was completely eliminated. Forced expiratory volume and flow were maintained at levels better than those recorded before triamcinolone therapy throughout the year of follow-up. No substantial side effects due to triamcinolone were observed.


Corticosteroid treatment in systemic lupus erythematosus. Survival studies.

Survival rates of two groups of corticosteroid-treated patients with systemic lupus erythematosus (SLE) have been compared using life-table analysis. Group 1 consists of 209 SLE patients studied in New York City between 1957 and 1968; group 2 consists of 156 SLE patients studied in Connecticut between 1968 and 1976. A similar percentage of patients in each group was followed up closely by one of us. The five-year survival rate for group 1 was 70%, compared with 93% for group 2. The improved survival could not be explained by differences in racial composition, incidence of CNS manifestations, or incidence of severe renal disease. The markedly improved survival may be due to several factors, including a generally better understanding of the disease and the recent use of newer antibiotics. The management of the two groups was similar, except that group 2 patient's conditions were managed not only on the basis of clinical evidence of disease activity but also on the basis of the serum complement (C3) level and on the basis of the level of antibody to native DNA. The data suggest that the use of such serologic values may lead to improved survival.


Combination chemotherapy (CISCA) for advanced urinary tract carcinoma. A preliminary report.

Twelve patients with metastatic transitional cell carcinoma from the urinary bladder were treated with a combination chemotherapy program consisting of cisplatinum, cyclophosphamide, and doxorubicin hydrochloride (CISCA). Ten patients had conditions for which a response to therapy could be determined, and nine achieved an objective response (one complete response, eight partial responses). Two additional patients with metastatic transitional cell carcinoma from the renal pelvis were also treated, and one achieved a partial response. In our experience, CISCA combination chemotherapy has given the highest response rate of any protocol thus far tested in advanced, metastatic urinary tract carcinoma.


Reversal of central anticholinergic syndrome by galanthamine.

Ten volunteers were given 2 mg scopolamine intravenously (IV) to produce substantial drowsiness and sleepiness. Galanthamine, 0.5 mg/kg IV, effectively reversed the central anticholinergic syndrome produced by scopolamine. Electroencephalographic monitoring of two subjects matched the observed changes of consciousness: scopolamine replaced the dominant awake alpha rhythm with a disorganized, slow, 4- to 6-Hz activity. Galanthamine promptly returned to EEG pattern to the control, awake state. Galanthamine produces effective, safe, and long-lasting reversal of the central anticholinergic syndrome in man.


Familial lupus erythematosus.

The child of a woman with discoid lupus erythematosus (DLE) had lesions of DLE develop at the age of 2 months. The original lesions persisted and new lesions continued to develop to date; the child is now 28 months old. In a second child, now 11 months old, a probable lupus erythematosus rash developed at 1 week of age.


Epidemic faintness and syncope in a school marching band.

On Sept 21, 1973, during and following a football game at which they had participated, 57 members of an Alabama high school marching band (and one accompanying adult) experienced an illness characterized by headache, nausea, weakness, or dizziness. Six girls fainted. Thirty-six students were treated at a hospital emergency room. Those who had played wind instruments and had worn heavier uniforms including an impermeable plastic jacket overlay were affected earlier and more frequently than the others. Several organic causes were examined in an epidemiologic investigation and considered unlikely to explain the epidemic. Female preponderance, a bimodal epidemic curve, hyperventilation, relapses, and clinical features characterized by subjective complaints in the absence of physical findings suggested a syncopal reaction to heat exacerbated and propagated by mass hysteria.


Participants' reaction to amniocentesis and prenatal genetic studies.

Little is known about the effect of amniocentesis and prenatal diagnosis of genetic disease on couples undergoing such studies. A questionnaire was composed to evaluate, among other things, the reason for referral, attitudes and concerns of the pregnant woman and her husband toward prenatal study, and suggestions for improving the experience. Of 315 women referred to this unit for this purpose, 196 have had time to complete their pregnancy and were mailed the questionnaire; 157 (80%) of the latter responded. The majority of the women found the experience reassuring, would recommend it to others, and would seek it again themselves with a subsequent pregnancy.


Severe degenerative joint disease. Mild and moderately severe hemophilia A.

Severe degenerative joint disease developed in three adults with mild to moderately severe hemophilia A, as judged by the clinical course and by levels of factor VIII coagulant. Bilateral total hip arthroplasty was required in one patient, unilateral hip arthroplasty in the second, and a recommendation for bilateral knee replacement in the third. The pathogenesis of the arthropathy may be multifactorial and the result of repeated joint hemorrhage that remains unrecognized and inadequately treated. These observations suggest the need for more careful monitoring of patients who have relatively mild hemophilia.


Cooperative study of hospital frequency and character of transient ischemic attacks. V. Symptom analysis.

All patients (1,328) suspected of having transient ischemic attacks (TIA) who came to six institutions during a 21-month period were identified. Symptoms and symptom complexes were related to the clinical diagnoses by cross-tabulation, factor analysis, and discriminant analysis. The diagnoses obtained by the discriminant analysis program were comparable to those of reviewing clinical neurologists. Symptoms of importance in the vertebral-basilar system (VBS) were bilateral visual blurring, diplopia, ataxia, and dizziness; In either carotid system (CAS), ipsilateral monocular visual disturbance anc contralateral weakness or sensory complaints; in the left CAS, language disturbances; and in those whose ultimate diagnosis was not TIA, loss of consciousness, confusion, and bilateral leg weakness. Patients with VBS TIAs have symptoms common to conditions that are not TIA and have a greater variety of symptoms and more combinations of symptoms than CAS TIA.


Microcytic polycythemia. Frequency of nonthalassemic causes.

A high RBC count combined with a low mean volume generally is attributed to thalassemia minor, either alpha or beta, or to polycythemia vera with iron deficiency. Among 330 patients with a mean corpuscular volume (MCV) less than 70 cumu, 35 had increased RBC counts. Of these, 26 had thalassemia minor and four had polycythemia vera. Five had secondary polycythemia (four from hypoxia, one from hypernephroma) with incidental iron deficiency. In the four of these patients given iron, the RBC count remained above normal and the MCV rose to normal. The RBC size distribution curves reliably distinguished between thalassemia minor and polycythemia with iron deficiency.


Giant cell tumor in the ischium. A therapeutic dilemma.

A patient with low back pain was found to have giant cell tumor of the ischium. After initial local radiation therapy, a hemipelvectomy was performed because of tumor progression.


Rheumatoid pericarditis. Rapid deterioration with evidence of local vasculitis.

In a patient with classical rheumatoid arthritis and pericardial involvement, accelerated restriction of cardiac filling resulting from pericardial constriction developed. Pericardiectomy was necessary to relieve this condition. Examination of the synovial and pericardial fluid showed noteworthy decreases in total hemolytic complement (CH50) and C3 levels, while these were normal in the serum. Immunofluorescence staining of the pericardium showed plasma cell infiltration and immune deposit staining of pericardial vessels with IgG, IgM, IgA, or C3. These findings suggest that immune complexes deposition plays an important role in the pathogenesis of this condition.


Prognostic implications of the e antigen of hepatitis B virus.

The e antigen HBeAg and its antibody anti-HB, have been said to be predictive of chronicity and resolution, respectively, in viral hepatitis. We found, as have others, a specific association with hepatitis B virus-induced disease. In addition, detectability of HBeAg in the acute phase of type B hepatitis was followed by a sixfold higher incidence of chronic hepatitis. Unfortunately, the prediction was erroneous in 65% of positive cases and 6% of negative cases. In chronic hepatitis, HBeAg did not necessarily disappear in advance of resolution, and its disappearance did not necessarily indicate resolution. Two patients with acute hepatitis progressing to chronicity were anti-HBe-positive in both phases, as were seven (5%) with chronic hepatitis. For individual patients, therefore, HBeAg and anti HBe are not prognostically useful indexes.


A survey of the effects of oral contraceptive patient information.

A nationwide survey of 1,720 current and 949 former oral contraceptive (OC) users gathered information about receipt, readership, knowledge, opinions, and reported behavioral changes induced by two forms of patient-oriented OC information. A substantial majority of women said they received and read the patient insert dispensed with the drug. However, only about one third of pill users said that they received the longer informational brochure supplied by physicians on patient request. Directions for use and side effects were the most often recalled information. Physician-patient contact patterns were reported as generally unaffected by written patient information. Respondents preferred the longer informational brochure to the insert. Survey results have implications for recently proposed changes in required OC patient information and for the development of patient information on additional prescription drugs.


Syncope in patients with pulmonary embolism.

A review of 132 consecutive cases of acute pulmonary embolism (PE) documented by pulmonary angiography indicated that syncope was the initial or predominant clinical feature in 17 (13%). When massive PE causes syncope in a nonhospitalized patient, the diagnosis of PE is frequently overlooked. Hypotension after PE may resolve spontaneously after a short interval. In this circumstance, the syncopal episode might easily be attributed to another cause. The appropriate diagnosis can be established only if other clues, suggestive of PE, are sought. Both arterial blood gas determinations and pulmonary scintigraphy are helpful in making this diagnosis.


Cooperative study of hospital frequency and character of transient ischemic attacks. VI. Patients examined during an attack.

Examination during an episode of transient ischemic attack (TIA) was performed on 121 of 1,307 patients suspected of having a single type of TIA. This examination supported the diagnosis of TIA in 79 patients and contributed to the establishment of a diagnosis other than TIA in 42. Although the examination increased diagnostic reliability, it did not always result in a definite diagnosis. The most common neurologic findings during a TIA were weakness of an arm or side of the face. Important findings not suggested by history included visual defects and blood pressure fluctuation. Also unexpected were the absence of findings such as sensory deficits in the presence of sensory complaints, retinal emboli, and cardiac abnormalities. Severe arteriosclerotic disease was less evident, the attacks were longer and more severe, and monocular blindness was rare.


Primary type V hyperlipoproteinemia in childhood.

Metabolic studies of a 9-year-old girl with primary type V hyperlipoproteinemia demonstrated normal glucose tolerance, plasma insulin and glucagon responses to stimuli, and serum uric acid level. Fasting plasma triglyceride levels rapidly increased when the patient received a diet containing 40% of the total calories as fat and rapidly decreased on a 10% fat diet. Hepatic and nonhepatic lipase activities in postheparin plasma were normal, thus excluding type I hyperlipoproteinemia. Because of the potential complication of acute pancreatitis in this disorder, early diagnosis and prompt institution of diet therapy is important.


Successful renal revascularization after prolonged nonfunction.

Surgical teaching has suggested that renal nonfunction of more than a few days' duration usually precludes success of revascularization procedures. The efficacy of delayed renal revascularization in selected cases has been reported. In this case, the intravenous pyelogram, renal scan, and ureteral catheterization verified nonfunction 30 days before surgical correction of essentially complete atheromatous occlusion of the renal artery. Postoperative studies conducted six weeks and 18 months postoperatively showed normal bilateral renal function. Current temporal limitations on attempts to preserve renal tissue may be too stringent. Revascularization of kidneys may be successful after prolonged periods of ischemia.


Leptospirosis in New England.

Although rarely reported in humans in New England, leptospirosis is enzootic in western and central Massachusetts. Recently there were three cases of Leptospira interrogans, serotype var pomona, in Easthampton, Mass. Our study and others indicate a potential for waterborne epidemics in humans.


Cooperative study of hospital frequency and character of transient ischemic attacks. IV. The reliability of diagnosis.

All patients (1,328) suspected of having transient ischemic attacks (TIA) who came to six institutions over a 21-months period were identified. Each case was reviewed by a neurological investigator, and a definite diagnosis of TIA was supported in 39% and ruled out in 30%. The reliability of the neurologist's review diagnosis was assessed by three methods, and close agreement (84% to 93%) was obtained. Factors demonstrated to effect the diagnosis were historical information, neurological training of the examiners, type of symptom complex, presence of carotid artery bruits, and examination during an attack.


Child abuse and hemoglobinuria.

Hemoglobinuria occurred in two children following severe beating. The development of transient oliguria in one child and acute renal failure in the other emphasizes the importance of early recognition of these unusual complications in the syndrome of child abuse. Appropriate therapy should be given to prevent or lessen the severity of acute renal failure in this clinical situation.


Computerized tomography, diagnostic ultrasound, and radionuclide scanning. Comparison of efficacy in diagnosis of pancreatic carcinoma.

Forty-six patients, including 33 with proved pancreatic carcinoma, were studied with computerized tomography (CT), ultrasound (US), and radionuclide (RN) scanning. The results of each scanning procedure were compared with the surgical and clinical findings. The detection rate was 82% for CT, and 92% with US. A mass is the most important finding in the diagnosis of pancreatic carcinoma. Measurements of the pancreas with CT and US were similar, with visualization of all parts of the pancreas routinely better with CT scans. Radionuclide scans were abnormal in 96% of the patients with pancreatic carcinoma as well as in 75% of patients without pancreatic disease. A rational approach to examination of a patient with suspected pancreatic carcinoma should begin with US scan with available, because the detection rate with this method is equal to that with CT and its cost per procedure and for equipment is substantially less.


Examining the homosexual male for sexually transmitted diseases.

Homosexual men may be deterred from seeking an examination for sexually transmitted diseases because it would require an open admission of sexual preference. For these diseases to be controlled, gay men must be motivated to be examined for sexually transmitted diseases. If a medical or health professional feels unable to respond to a gay patient's needs, he should refer the patient to someone who deals well with gay patients. Health care services must be offered in a way that minimizes the anxiety many homosexuals associate with examination and treatment for sexually transmitted diseases.


Boerhaave's syndrome. Spontaneous formation of an esophageal-bronchial fistula.

Although Boerhaave's syndrome is usually a surgical emergency, we recently observed a 57-year-old man with a chronic Boerhaave's syndrome. Initially, he responded to conservative management. However, the spontaneous formation of an esophageal-bronchial fistula complicated his course. Pulmonary symptoms and weight loss prompted surgical intervention. We speculate that the patient's six-week clinical course before surgery was tolerated because the contamination of the mediastinum following the initial esophageal tear was well contained and allowed sufficient time for the spontaneous formation of an esophageal-bronchial fistula.


'Burning hands' in football spinal cord injuries.

Central spinal cord injury in two high school football players caused only complaints of burning paresthesias and dysesthesias in the hands at the time of injury. Strength was affected only in the upper extremities where it was slightly reduced. Failure to recognize the relationship of "burning hands" as a symptom of cord injury can result in injudicious management of unstable cervical fracture dislocations with disastrous consequences.


Electron-dense deposits in the follicular basal lamina of obese strain chickens with spontaneous hereditary autoimmune thyroiditis. An electron microscopic study.

Thyroid glands of 36 chickens of the obese strain with hereditary spontaneous autoimmune thyroiditis were examined by electron microscopy at 1, 3, 5, 7, 10, and 14 weeks of age with particular emphasis on basal lamina changes. All chickens were of the B1B1 genotype. The electron microscopic results were compared with six normal White Leghorn chickens of the same age. The major abnormality observed in obese strain chickens was the persistent presence of electron-dense deposits along the follicular basal lamina in the thyroid beginning with 7-week-old chickens. The deposits morphologically comparable to immune complexes were noted either between the basal plasma membrane and the follicular basal lamina or below the follicular basal lamina. In 14-week-old chickens, the electron-dense deposits were observed within abnormally thickened basal lamina. The deposits were not present in the vascular basal lamina adjacent to the thyroid follicles and were not observed in the thyroids of 1- to 5-week old chickens and were also not encountered in normal White Leghorn chickens. Indirect morphologic evidence suggests that these may be antigen-antibody complexes, but characterization of these deposits and their role remain to be determined.


Experimental hydrocephalus of the rat, produced by cisternal injection of kaolin-solution (author's transl).

Experimental hydrocephalus was produced in rats in high percentage, by direct injection of kaolin-solution into the cisterna magna under a operating microscope. Rats with hydrocephalus showed retarded development of the body. The skull enlarged round and became so thin, that the cortical vessels were observed through the skull. The brain showed marked internal hydrocephalus, retaining cerebrospinal fluid passage in the ventricular system, but there was an obstruction at the ambient cistern and the basal cistern. Review of the literature dealing with the methods to produce acquired hydrocephalus showed that this is the first report of experimental hydrocephalus of the rat produced by injecting kaolin-solution.


PaO2 levels and retrolental fibroplasia: a report of the cooperative study.

The relation between PaO2 and retrolental fibroplasia (RLF) was studied prospectively in 719 premature infants born in or treated in the intensive care units of a group of university hospitals. Blood gas studies were performed on 589 of these infants, 66 of whom had a diagnosis of RLF; in 27 of these 66, some grade of mostly nonblinding cicatricial disease developed. The frequency of RLF was highest among infants of lowest birth weight. A multivariate statistical method was used to analyze simultaneously the effect of possible etiologic factors associated with RLF. The occurrence of RLF was found to be unrelated to PaO2, as determined by the limited information available from intermittent sampling. RLF is associated with concentration of oxygen administered in the lightest birth weight group, but the strongest association, aside from birth weight, was with time in oxygen. None of the other variables involving blood chemical values appeared to be associated with RLF. The severity of cicatricial RLF is clearly greater in infants weighing less than 1,200 g at birth. Conservative administration of oxygen may have been responsible for failure to demonstrate quantitative association between PaO2 levels and disease. Agreement between the observed and predicted numbers of infants with RLF demonstrate the strength of the multivariate technique employed in making the statistical analyses.


[The influence of Halothane on surfactant activity of the lung (author's transl)].

Halothane, momentarily the most popular inhalation anaesthetic, was examined in respect of its surfactant irritating properties in 13 rabbits. After five hours IPPB-anaesthesia with this compound there was a highly significant fall of the compliance quotient (CQ), at the moment the most reliable criterion for the surfactant activity "in situ", from 3.34 to 2.76. Lung histology revealed patchy atelectasis, dystelectasis and interstitial edema. In contrast to this remarkable mechanical and structural deterioration, blood gas analyses showed a surprising stability of gas exchange, hinting a tremendous functional reserve. Postnarcotic examination of lung extracts in the Wilhelmy balance exhibited no persistent damage of the specific alveolar lining layer. On the basis of these experimental findings we recommend that halothane should not be used in patients with preexisting impairment of pulmonary surfactant system.


The pharmacological activity of tribenoside.

Ethyl-3,5,6-tri-O-benzyl-D-glucofuranoside (RBGF) the active substance of Glyvenol displays a unique spectrum of activities. It possesses anti-inflammatory, mild analgesic, antitoxic, wound-healing, fibrinolysis-promoting, anti-arthrotic, amine-release-inhibitory, membrane-stabilizing and venotropic properties. Unlike corticosteroids or nonsteroidal anti-inflammatory agents, TBGF dose not exert untoward effects on the gastrointestinal system, the connective tissue or the body's defence systems. In addition, TBGF does not affect the prostaglandin-synthetase system. TBGF thus seems to share the positive pharmacological properties ascribed to glucocorticoids and non-steroidal anti-inflammatory agents, yet is free from the undesirable effects of both.


[Improvement of resolution of positron annihilation radiation energy spectrum measurement by data analysis (author's transl)].

Recently much attention is being paid to positron annihilation radiation energy spectrum measurement as a simple method that gives information about the momentum distribution of an annihilating pair. However, this method has a disadvantage that it is sensitive to drifts of the measuring system and the resolution is still insufficient. We have succeeded to reduce the influence of the drifts to a negligibly small degree by using, in addition to the necessary procedure for a temperature control and stabilizing of AC power lines, a compensation technique in data analysis. We have further attempted to improve the resolution by deconvolution processing. By these procedures, we have been able to separate a narrow component which has not otherwise been resolved directly from the spectrum. The resolution attained by this way is 0.43 keV (FWHM), and is two- or three-fold superior to those ever reported.


[Radiochemical purity of 123I for medical use (author's transl)].

123I for use in clinical diagnostic procedures has been produced by bombarding antimony with 40 MeV 3He particles. The purity of 123I was measured with a Ge(Li)spectrometer and a low energy Ge(Li) detector. The 123I-product was followed for 1.5 months with a well-type NaI scintillation counter to establish the half-life and confirm the identity of the nuclides. In order to minimize the yield of 121I the optimum cooling time and chemical procedures are presented. After 20 h cooling, the 121I, 124I and 125I contaminants were about 1.8, 4.3 and 0.04% respectively. These values were in agreement with those calculated from the thick-target yield curves. The calculated absorbed dose to the thyroid by the 123I and by-product nuclides were only 4.3 and 7.3% of 131I. 123I could be measured at the window of 99mTc of a NaI scintillation camera and a curie-meter with an error of 10%.


[Absorption, distribution, excretion and metabolism of SC-11800EE, a combined steroid preparation of SC-11800 (ethynodiol diacetate) and ethinyl estradiol in rats and mice (author's transl)].

Absorption, distribution, excretion and metabolism of SC-11800EE, a combined steroid preparation consisting of SC-11800(ethynodiol diacetate)as gestagen and ethinyl estradiol (EE)as estrogen in 20:1 (w:w), were studied with the use of 14C-SC-11800 and 3H-EE by radiometry in female rats and by the whole body autoradiography in female normal and pregnant mice. The gestagen orally given with EE was rapidly absorbed from digestive tracts and distributed in tissues in various levels. Gestagen levels in liver and kidney exceeded that in plasma. About 75% of dosed radioactivity was excreted in feces largely via bile and more than 20% in urine within 72 hr after administration. The gestagen was metabolized extensively to more polar products and their conjugates. The pharmacokinetic behavior of the gestagen given with EE did not alter after repeated administrations for 7 days, but was slightly different from that without EE, possibly due to the estrogen effect. The pharmacokinetic behavior of the estrogen was independent from the gestagen given simultaneously. The distribution of the gestagen given with EE revealed by the whole body autoradiography in normal mice were essentially consistent with the radiometric results in rats and that in the pregnant mice showed that the gestagen in fetus was virtually nil under the present conditions.


[Clinical effects of monocomponent insulin and commercial insulin preparations on insulin requiring diabetics (author's transl)].

Diurnal variation of blood sugar, C-peptide immunoreactivity (CPR), free insulin and total insulin were measured in 10 insulin requiring diabetics after obtaining adequate control of diabetes with commercial lente insulin treatment. Following these tests, insulin treatment were changed to monocomponent insulin (MC-insulin) from commercial lente insulin treatment in all subjects and the same tests were performed at 7th day of MC-insulin treatment. Diurnal variations of blood sugar in both groups were not changed significantly. Also changes in CPR of both groups were nearly same magnitude and endogenous insulin secretion in these insulin treated diabetics were suggested except a case of juvenile diabetic subject. However personal variation were great in diabetics with high antibody titer, diurnal variations of total extractable insulin in both groups were quite comparable. And mean diurnal changes in free insulin were resemble to that of CPR. All of these data suggested that clinical effects of MC-insulin and commercial insulin treatment on insulin requiring diabetics were comparable except insulin antibody or proinsulinspecific antibody production.


[Simultaneous analyses of gaseeous and particulate sulfur in the atmosphere by X-ray fluorescence spectrometry--results of observation and discussion-- (author's transl)].

Concentrations of gaseous and particulate sulfur in the atmosphere were simultaneously measured for 24 hours at a time interval of one hour by the use of the method described in the previous report (this journal, 24, 312 (1975)). Such measurements were made sixteen times in the period from April to September, 1975. As the result of the measurements, it was found that the method used can be applied to practical observation with sufficient reliability. The concentration of gaseous sulfur showed always a larger variation coefficient than that of particulate sulfur. Both the concentrations of gaseous and particulate sulfur were found strongly dependent on the wind direction and velocity and other meteorological conditions. After hot and fine days continued, the concentration of particulate sulfur rose considerably reaching 20 microgramS/m3.


[Simultaneous analyses of gaseous and particulate sulfur in the atmosphere by X-ray fluorescence spectrometry--discussion on the results of observation and presentation of the problems involved in the methods of sampling and analysis (author's transl)].

Following the previous article, the results of observation are discussed in relation to meteorological conditions. The frequency distribution of gaseous sulfur concentrations (1 hr mean values) was bimodal as the result of the alternation of land and sea winds. The frequency distribution of particulate sulfur concentrations was also bimodal, but this can be rather ascribed to the variation of weather. The correlation between the concentrations of gaseous and particulate sulfur was not so great as was expected. Autocorrelations of the concentrations of gaseous and particulate sulfur were respectively investigated, and it was found that the variation of gaseous sulfur concentration showed daily cycle, and, against this, the variation of particulate sulfur concentration did not show appreciable daily cycle, but had weather correlation. Some discussions are presented concerning the selection of sampling points suitable for clarifying the behavior of sulfur in the atmosphere as well as the improvement of the methods of sampling and analysis.


[The investigation of the absorption of 99mTc gamma-rays by bone and soft tissue (author's transl)].

Recently, the scintigram with 99mTc-labeled compounds has been routine procedure, because of it's ideal physical characteristics. The short physical half life of six hours, the absence of beta emission, and the gamma rays of 140 keV permit the administration of large amount of radioactivity. For scintigram of deep or large organ, the absorption of 99mTc gamma-rays by bone and soft tissue should not be negligible. For example, bone scintigram with 99mTc-phosphorous compounds shows different pictures depending upon the anterior and the posterior views, because of it's rather lower energy. Therefore, the linear attenuation coefficient and the half value layer of bone and soft tissue were measured with 99mTc gamma-rays and others (197Hg, 203Hg, 131I, 198Au, 85Sr). 1) The linear attenuation coefficient of 99mTc gamma-rays was: bone -0.240 cm-1, acrylite -0.173 cm-1, Mix D -0.155 cm-1. 2) The half value layer of 99mTc gamma-rays was: bone -2.89 cm, acrylite -3.98 cm, Mix D -4.47 cm. It was concluded that the lower photon energy of 99mTc was influenced by bone and soft tissue, but it appeared to be most suitable for the present imaging devices. Therefore, pictures of multiple views are necessary in case of the scintigram was 99mTc-labeled compounds.


Activation analysis of mercury in urine samples of electrolysis cell workers.

The activation method of determination of trace amounts of Hg in human urine has been studied by introducing a simple amalgam deposition method. Human urine samples were obtained from the alkali chloride, electrolysis plant equipped with Hg cells. The capacity of Cu powder for Hg quantity, the pH conditions, and the shaking time were described. The results showed that the Hg contents in workers' urine samples varied from 33 ppb to 60 ppb depending on working conditions.