Inhibition of injury induced thromboatherosclerotic lesions by anti-platelet serum in rabbits. We have previously shown that repeated or continuous intimal injury caused by an indwelling aortic catheter causes a variety of lesions in rabbits maintained on a diet unsupplemented by lipid. These include fatty streaks, lipid-free fibrous plaques and lipid-rich raised thromboatherosclerotic plaques. Whether lipid-rich raised lesions are a result of injury or co-existing thrombosis or both is not clear. The present experiment was designed to answer this question. Anti-platelet serum (APS) to washed sonicated rabbit platelets was raised in sheep. PE 60 polyethylene catheters were placed in the aortas of 35 rabbits by way of a femoral artery. The animals were randomly divided into 2 groups. The experimental group (17 rabbits) received an intravascular injection of 1.0 ml of APS followed 8 hours later by a subcutaneous injection of 0.5 ml. Thereafter, 0.5 ml APS was given subcutaneously each day for 13 additional days. The control group (18 rabbits) received no APS. Platelet counts were done prior to surgery, at 5 minutes following surgery, at 4 days, 8 days and just prior to killing. Extent of lesions was estimated by photographing the opened aortas, projecting the photographs on cardboard, cutting out the areas occupied by the different lesions and weighing the cardboard. The mean weight of raised lesions in the control group was 6 to 7 times greater than in the experimental groups. Statistical analysis of this difference based on Welsh's "t" test for unequal variances was highly significant (P less than 0.001). Platelet counts in the experimental groups varied from 0 to 20,000 at 14 days. In animals with platelet counts less than or equal to 1,000 mm3 raised lesions were completely prevented. In a second experiment the effect of APS was compared with normal sheep serum (NSS). A similarly significant inhibition of raised lesions occurred in the APS group. The extent of lesions in the NSS control was similar to that in the No-APS group of the first experiment. These findings indicate that thrombosis is more important than injury in the development of lipid-rich raised lesions.


Isolation of preliminary characterization of a vitamin K dependent peptide from human prothrombin. A peptide containing the vitamin K dependent Ca2+ binding region of human prothrombin has been isolated by adsorption of the tryptic digest of the native protein on barium citrate. Its aminoacid composition has been determined. The N- and C-terminal residues have been characterized. The obtained results are showing some slight differences with the corresponding bovine peptide. Since they were not strictly identical for two different preparations, the eventuality of a molecular heterogeneity is discussed.


Biological control of factor VII.

Biological control of factor VII. The tissue factor pathway is initiated by factor VII in the presence of tissue factor. The first proteolytic reaction involves cleavage of factor X by factor VII. Activated factor X, the product of this reaction, can activate factor VII by cleavage of a specific bond. The apparent coagulant activity of factor VII then rises about 60-fold. Activated factor X can also inactivate factor VII by catalyzing the cleavage of a second bond which results in a three chain molecule. Fragments of Hageman factor and perhaps kallikrein can also activate factor VII. Hageman factor, however, does not catalyze the inactivating cleavage of factor VII at a significant rate. Recent data showing that the tissue factor pathway can activate the intrinsic system are discussed. We have shown that activated factor X, which can be generated by the tissue factor pathway, can feed back and activate factor IX in a calcium and phospholipid requiring reaction.


[Determination of the initial stage of fat auto-oxidation in dry dairy products by ultraviolet spectrophotometry]. Studied were the values of the conjugated dienes using ultraviolet spectrophotometry of fats contained in the dry dairy products produced in this country, such as powdered milk for children, Vitalakt 1, Bébé 1, and Biolakton in the first months of storage. It was found that the extinction maximum values characteristic of the conjugated dienes for the fats of all studied dry milk products were at 227 nm. The juxtaposition of changes taking place with conjugated dienes and peroxide numbers of the fats during storage revealed the greater stability of conjugated dienes in comparison with the hydroperoxides.


[Inhibitory action of the residues of some new disinfecting agents on the microflora of Bulgarian milk]. Studied were the amounts of residues of disinfection solutions such as antigerm 0.3 per cent, bradophen 0.2 per cent, abosanit 0.35 per cent, trosilin 0.5 per cent, and oxania 2 per cent which could produce inhibitory effects of the microflora of the Bulgarian sour milk. It was established that the presence of more than 25 ml/1 of a given disinfection solution in the milk of the above-mentioned ones at the concentrations cited (with the exception of trosilin) exert a strong inhibitory action on milk microflora and the enzyme processes. As a result no curdling sets in. The use of Bac. stearothermophilus as a test organism can detect but the presence of 150 mg/1 antigerm in the milk.


[Assessment and treatment of intractable pain: six months' experience in the relief of pain at the ludwig Boltzmann Institute of Clinical Oncology (author's transl)]. A preliminary report is presented on the results achieved in the assessment and treatment of patients with intractable pain during the first six months experience gained following the appointment of a pain consultant at the Ludwig Boltzmann Institute of Clinical Oncology. Nerve blockade was carried out 106 times in 45 patients suffering from primary or secondary malignant disease and 71 times in 18 patients with other conditions; intrathecal instillation of 96% alcohol was performed once and 2 chordotomies were also performed. One patient needed antidepressive therapy. Major questions relating to this problem are discussed. Gratifyingly satisfactory results were observed in more than two thirds of the patients. These objective findings and the subjective impressions obtained from patients, their relatives and our personnel prompted us to continue with this type of treatment for pain and to increase our efforts in this direction.


[The estimation of surface actitity of the lungs in dependence from duration of pregnancy (author's transl)]. The surface tension of amniotic fluid was measured in a Langmuir balance in 98 persons with normal pregnancy between 23 and 42 weeks of gestation. An increase of surface activity in dependence of gestational ages was found. It is possible to use the surface tension of amniotic fluid as an indicator of fetal pulmonary maturity in high risk pregnancy.


[The appearance of surface-active phospholipids of the surfactant-system of the lung during ontogenetic development of humans (author's transl)]. In order to characterize the pulmonary maturity during ontogenetic development the following parameters were determined in the lungs of 30 fetuses respectively newborns with a weight between 15 and 4450 g: Water content (WC), total phospholipid content (TPC), lecithin concentration (LC), sphingomyelin concentration (SPC) and surface activity (SA) of the extracts. The water content decreases with increasing gestation age. The total phospholipid content and the lecithin concentration increase during the ontogenetic development. The sphingomyelin concentration remains approximately constant during lung development. No significant correlation exists between phospholipid content and surface activity. A relatively high TPC and a high SA was found in a 43 g-fetus (about 14th week of gestation). This result suggests, that the surfactant-system of the lung is produced earlier than supposed till now. Lungs of infants who developed respiratory distress syndrome (RDS) have a low concentration of TPC. The lecithin/sphingomyelin-ratio rises as gestation progresses. Lungs of RDS-children have - similarly in amniotic fluid - a low lecithin/sphingomyelin-ratio.


[Morphological demonstration of phospholipids in the lung (author's transl)]. A short review of the different methods for light microscopic demonstration of phospholipids in the lung tissue is given. As shown in own experiments, the phosphomolybdic-acid-stannous-chloride reaction (Landing et al., 1952) appears as a successful method for rapid demonstration of phospholipids.


[Acute poisoning with L-triiodothyroinine, L-thyroxine and phendimetrazine bitartrate with suicidal intention]. It is reported on an acute intoxication after application of 8 mg L-thyroxin, 2 mg L-triiodotyronine (200 tablets Thyreotom) and 4.5 g hendimetrazine bitartrate (100 tablets Sedafamem). The clinical picture is described. An endangering of the vital function of the organism was not observed. The symptoms disappeared after 4 days. The pharmacological aspects of the intoxication after application of the hormone of the thyroid gland, its significance for the pathogenesis of the thyreotoxic crisis and its therapy are discussed


[In vivo and in vitro investigations of the effect of decortilen (16-methylenprednisolone) on lecithin synthesis in the fetal lung (author's transl)]. Lecithin synthesis in fetal lungs of the rat over three-fold methylation and over choline and CDP-choline was quantitatively determined via the incorporation rate of marked metabolites. The ability of decortilen to influence both modes of synthesis was investigated. In vivo and in vitro, the glucocorticoid stimulates lecithin formation, which can be as high as 200%, only over choline and CDP-choline.


[Experimental investigations in regard to the optimal stimulation of lecithin synthesis in the fetal lung via glucocorticoids (author's transl)]. On the basis of curves illustrating the effects of dosage on experimental animals, it was shown that glucocorticoids inhibit as well as stimulate lecithin synthesis in the fetal lung. Equivalent doses of corticoids produce comparable results. It was established that the concentration necessary to produce an optimal stimulation of lecithin synthesis was 0.5 to 2.0 mg/kg body weight.


[Surfactants in amniotic fluids: a comparision between biomechanical and biochemical analyses (author's transl)]. 44 specimens of amniotic fluid from the 25 week's gestation onwards were tested in a modified Wilhelmy-Langmuir surface balance. In addition percentage of lecithin in total phospholipids, total phospholipd phosphorus concentration and fatty acid composition of lecithin was determined. Lecithin, total phospholipid-phosphorus and palmitic acid show significant rises in concentration with gestational progress. The results of the surface tension measurements are significantly correlated with the biochemical analysis. Therefore, fetal lung maturity seems to be well estimated by the biomechanical method.


Determination of lead and cadmium in milk with modern analytical methods. Methods to determine lead and cadmium at the low mug/kg-level in milk were investigated. Methods tested were differential-pulse anodic-stripping voltammetry (DPASV) and flameless atomic-absorption spectrophotometry (FAAS). Under the circumstances in which these methods were used, the analytical procedure based on DPASV was the most sensitive, with an estimated detection limit of about 0.2 mug/1 for lead and cadmium in liquid milk. The pretreatment of the milk samples before the DPASV-analysis included: freeze-drying, ashing in a muffle furnance at 550 degree C and finally dissolution of the ash in 0.1 M-hydrochloric acid. The recoveries of known amounts of lead and cadmium added to milk were 95 and 59%, respectively. A survey of the contents of lead and cadmium in the Swedish manket milk was performed. This investigation showed that the average lead content in Swedish market milk was 2.0 mug/1, with a standard deviation of 0.5 mug/1. The cadmium content was below 0.2 mug/1 in all samples analyzed.


T4 and T3 release from the perfused canine thyroid isolated in situ. A method for once-through perfusion of the canine thyroid isolated in situ is described. The perfusion medium was a modified Krebs Ringer buffer with 4% dextran added. In 4 control experiments of the T4 and T3 concentratios in effluent were stable or slightly falling during 3 h perfusion. There were no significant alterations in the T4/T3 ratio in the effluent during these experiments. A 10-min infusion of bovine TSH (1 mU/ml) caused an increase in the release of T4 and T3 after 15-25 min. The T4/T3 ration in the effluent was significantly reduced after TSH stimulation. However, the ratio returned to pre-stimulation values while the hormone release was still very high. T4 and T3 content of the contralateral thyroid was determatio in the homogenate was twice as high as the T4(3 ratio in the effluent during control perfusion. Thus there was a preferential secretion of T3 from the perfused canine thyroid and this was increased after TSH stimulation.


Oocytic meiosis in cultured rat follicles during inhibition of steroidogenesis. Steroid release by cultured Graafian follicles explanted from rat ovaries on the morning of pro-oestrus was measured by radioimmunoaso the medium reduced the basal level of steroid secretion (progesterone, androstenedione and oestradiol-17beta) and abolished the steroidogenic effect of luteinizing hormone (LH; 5mug/ml) and prostaglandin E2 (PGE2; 10 mug/ml). However, the induction of oocyte maturation by either LH or PGE2 was not impaired by total suppression of the steroidogenic response of the follicles to these hormones by cyanoketone or aminoglutethimide. It is concluded that the meiosis-inducing action of LH on the mammalian egg is not mediated by the effect of the hormone on the rate and pattern of follicular steroidogenesis.


A case of male pseudohermaphroditism associated with elevated LH, normal FSH and low testosterone possibly due to the secretion of an abnormal LH molecule. A 27 year old female is described who had 46,XY chromosome complement, ambiguous external genitalia with elevated LH, slightly above normal FSH and low testosterone. Her plasma testosterone level increased 15-20 fold after HCG stimulation (5000 IU X 3). then returned to prestimulation level 3 months later. This was possibly due to the secretion of an abnormal LH molecule which is immunoreactive but biologically inactive in the human.


The effect of 2-bromo-alpha-ergocryptine (CB154) administration of the hormone levels, organ weights, prostatic morphology and zinc concentrations in the male rat. 2-Bromo-alpha-ergocryptine (CB154) administration to male rats produced a significant decrease in plasma prolactin levels without changing the LH and testosterone concentrations. The weights of the accessory sex tissues, testes, adrenals and kidney were unaltered by the treatment. Zinc concentration and distribution in the cell organelles of the prostatic tissue was markedly changed by CB154 treatment. No changes in the uptake of testosterone in vivo occurred in the treated animals. Prolactin did not consistently influence the prostatic adenyl cyclase activity in vitro and only at high concentrations was the testosterone uptake in vitro with cultures of prostatic tissue increased.


Triiodothyronine binding to lymphocytes from euthyroid subjects and a patient with peripheral resistance to thyroid hormone. Triiodothyronine (T3) binding to Ficoll-Isopaque purified human lymphocytes was studied. During incubation of lymphocytes with [125I]T3 in a calcium-free medium at 37 degrees C, maximal uptake of T3 in nuclei occurrred after 2 h and declined after prolonged incubationd incubation . Incubation of lymphocytes with T3 concentrations ranging from 1 X 10(-11) TO 1 X 10(-9) mol/l and subsequent treatment with Triton X-100 to strip off [125I]T3 bound with low affinity was used for the estimation of affinity and capacity of nuclear T3 binding sites. The mean equilibrium affinity constant (Ka) estimated with the Scatchard method in 11 euthyroid healthy subjects was 4.5 X 10(9) l/mol, and the mean maximal binding capacity 25 X 10(-5) mol/100 mug DNA. In a female patient with peripheral resistance to thyroid hormone action, the estimated Ka was 3.5 X 10(9) l/mol and the number of T3 binding sites 37 X 10(-15) mol/100 mug DNA. Although not statistically different from the mean value in euthyroid subjects, this Ka value was outside the range of control values observed and was considered presumptive evidence that the nuclear T3 receptors in this patient have abnormally low affinity for its ligand. The nuclear T3 binding capacity in this patient was significantly increased.


Medullary carcinoma of the thyroid in Norway. Clinical course and endocrinological aspects. A study of the clinical, biochemical and histological findings of 57 patients with medullary thyroid carcinoma (MCT) in Norway, is presented. The diagnosis was established by light and electron microscopy and by measurements of immunoreactive calcitonin (iCT) in serum. The major factor influencing the prognosis was the extension of the disease at presentation. None of the 24 patients with tumour confined to the thyroid gland have died of the disease, and serum iCT was normal in 15 patients. Of 19 patients with regional lymph node metastes only 11 are alive 1 to 14 years after treatment, and of these 9 had increased serum iCt. 14 patients technically inoperable and/or with distant metastases, 12 have died of MCT, 1 are alive with elevated serum iCT. Of 14 patients with raised serum iCT, 8 have no clinical recurrence of the disease from 1 to 15 years after the operation. MCT-associated diseases were found in 8 patients, chronic thyroiditis in 10. Serum iCT was measured in 249 relatives of 42 patients, and abnormal elevations were found in 11 members of 6 families.


An evaluation of lithium as an adjunct to carbimazole treatment in acute thyrotoxicosis. The rate of control of thyrotoxicosis during the first 2 weeks of treatment was documented in 63 patients. Twenty-three patients received carbimazole 40 mg plus lithium carbonate 750 mg daily and a comparable group of 20 patients were given carbimazole 40 mg plus potassium iodide 120 mg daily. In the lithium treated patients the mean percentage fall of serum T4 after 2 weeks treatment was 49% and the fall in serum T3 57%. The results were similar in the iodide treated patients; the mean falls in serum T4 and T3 being 47% and 64%, respectively. Serum lithium values varied between 0.1-1.25 mEq./l; lithium side effects were minor. In a companion study 20 patients were treated with carbimazole alone. The responses in this group were less impressive; the mean falls in serum T4 and T3 at 2 weeks being 18% and 36%, respectively. It is concluded that lithium is a safe adjunct to conventional antithyroid drug therapy in the initial treatment of acute thyrotoxicosis.


Influence of low dose oestrogen on circulating prolactin. LH and FSH levels in post-menopausal women. The effect on serum prolactin, LH and FSH levels of 25 mug ethinyloestradiol administered daily per os during 27 consecutive days was investigated in 5 post-menopausal women aged 52-78. Blood samples were collected before, during and after treatment. The hormones were assayed in serum by radioimmunological methods. Both LH and FSH decreased progressively and significantly from 120 and 115 mIU/ml before treatment to 52 and 51 mIU/ml, respectively after three weeks of oestrogen administration. Two weeks after interruption of treatment, LH (90mIU/ml) and FSH (112 mIU/ml) were significantly higher than during the last week of treatment. Mean prolactin level increased from 127 muU/ml before treatment to 237 muU/ml after 10 days of oestrogen administration (P less than 0.001). This increase was significant after 4 to 8 days and the levels remained about twice as high as the control values for the rest of the treatment period. Two weeks after interruption of treatment, serum prolactin had fallen (136 muU/ml) to the pre-treatment levels. Such results raise the question of possible effects of elevated levels of this hormone during long term oestrogen medication in post-menopausal women on the development of breast cancer.


Normal values in clinical electrooculography. II. Analysis of potential and time parameters and their relation to other variables. The following EOG potential and time parameters from 72 normal subjects were analysed: base value B, dark trough D, light peak L, light induced potential rise L-D, interval between beginning of dark adaptation and occurrence of dark through d and interval between dark trough and light peak l. Their relations to sex, age pupillary diameter, degree of iris pigmentation, refractive error, axial length, corneal curvature and diameter, ocular protrusion and interpupillary distance were assessed. Right eye and left eye samples of the EOG parameters were congruent, although individual differences were sometimes appreciable. The levels of B and D were higher in the female half of the sample. A positive correlation existed between age and D level. L-D was negatively correlated to the degree of refractive error and positively correlated to the ocular protrusion. A positive correlation was found between d and the four potential parameters, and there was a positive correlation between age and l. Practical consequences of the statistical analysis relating to the interpretation of such EOG data are discussed.


A case of late pseudomonas ocular infection following scleral buckling. Two and half years after a circling buckle operation in which two Supra-mid sutures and a solid silicone explant were employed, a Pseudomonas infection developed around the explant and progressed to the inner eye. Removal of all implanted foreign material and treatment with Rifamicin saved the eye. The relevant literature on infection following sclero-plastic procedures is reviewed, and the pathogenesis of the late infections is discussed.


Scleral buckling with Bioplast fibrin in retinal detachment. The study includes a series of 38 patients with retinal detachment of different aetiology. Scleral reduction combined with the intrascleral implantation of absorbable Bioplast fibrin scleral buckling rods was performed and reattachment achieved in 31 cases. The implant material is biocompatible and is eliminated from the eye in the course of a few weeks.


Effect of orally administered hydrocortisone on the ocular tension in primary open-angle glaucoma subjects. Preliminary report. We studied the possible influence on the pattern of diurnal ocular tension curve by peroral hydrocortisone in 16 eyes of 16 subjects with primary open-angle glaucoma. The baseline diurnal curve was determined by Schiotz tonometry six times daily starting at 10 a.m. and repeated every four hours. The baseline curve showed a significant rise in the daytime with a fall during the night. On another day, 20 mg hydrocortisone was given perorally at 5 p.m., for a repeat 24-h measurement period. A significant rise in ocular tension over the baseline resulted in the following night-time tonometric readings, i.e. at 10 p.m. (P less than 0.01) and 2 a.m. (P less than 0.001). The results seem to strongly indicate that plasma cortico-steroid levels dictate the pattern of diurnal variation of ocular tension.


A simple relationship between the probability distribution of visual acuity and the density of retinal output channels. Throughout the retina, the parameters of the probability distribution of visual acuity for monochromatic interference fringes are closely proportional to the number of retinal ganglion cells per degree of visual angle. There are no simple relationships to receptor spatial frequencies. These findings suggest that neuro-retinal acuity is determined principally by the spatial frequency of neural output channels.


The cyclopentolate provocative test in suspected or untreated open-angle glaucoma. I. Effect on intraocular pressure. The mydriasis provocative test with 1% cyclopentolate (CPT) was performed on 218 patients with suspected or untreated open-angle glaucoma, on 431 eyes in all. Gonioscopy was performed before and during the test to ensure that te chamber angles were open throughout. The effect of cyclopentolate on intraocular pressure (10P) in these eyes is reported in the present paper. The mean change in IOP (+/-SD) During CPT was +2.5 +/- 3.1 mmHg in the glaucoma group (196 eyes), +0.4 +/- 2.5 mmHg in the group with suspicion of open-angle glaucoma (235 eyes), and +1.4 +/- 2.9 mmHg in the total series. The difference in IOP change between the groups with glaucoma and suspected glaucoma is statistically highly significant. The incidence of positive responses (IOP rise larger than or equal to 8 mmHg) in the glaucoma group (8.7%: 17 eyes) was significantly higher than in the suspicion group (1.7%: 4 eyes). Significant IOP elevations in the total series were demonstrated in 21 eyes of 18 patients (4.9%). Including the borderline cases, IOP elevations larger than or equal to 5 mmHg were also significantly more frequent in eyes with glaucoma (24.0%: 47 eyes) than in eyes with suspected glaucoma (11.9%: 28 eyes). The occurrence and magnitude of positive responses were not dependent on the initial IOP level. Further analysis of the responder group and clinical studies of the mechanism of IOP elevation on the same patients are presented in parts II and III.


The cyclopentolate provocative test in suspected or untreated open-angle glaucoma. II. Clinical studies on the mechanism of intraocular pressure elevations. The mydriasis provocative test with 1% cyclopentolate (CPT) was performed on 218 patients with suspected or untreated open-angle glaucoma, on 431 eyes in all. Significant IOP elevations (larger than or equal to 8 mmHg) were demonstrated in 21 eyes of 18 patients. The present paper analyses the responder group and presents some other investigation results and clinical findings to throw additional light on the mechanism of IOP elevation in responders. The responders did not differ from the other patients of the material in age or sex. Patients with capsular glaucoma constituted the biggest group among the responders. 48% of the significant IOP elevations during CPT were encountered in eyes with pseudoexfoliation (PE) and open-angle glaucoma. A positive response during CPT was statistically significantly more common in PE eyes than in eyes without PE. Capsular glaucoma was diagnosed immediately or later in all PE eyes which displayed a larger than or equal to 5 mmHg IOP elevation during the CPT. In addition to the importance of pigment in PE eyes, PE material may play a certain role in the elevation of IOP . The mechanism of this role is not known. No correlation was established between the results of the water drinking test and the CPT. The mechanism that causes the elevation of IOP must be quite different in these two tests. Nor was a statistically significant difference observed in the incidence of cataract, the maximal variation of IOP in the 48-h tension curve, the occurrence of cupping of the optic disc or visual field defects between the responder and non-responder eyes in the glaucomatous group.


Episcleral venous pressure and flow dynamics. Episcleral venous pressure was measured by means of an air jet at different levels of occlusion of the measured vessel. This was repeated at different points in one branching venous plexus system. The results indicate that the most reliable estimate of the pressure is obtained at the pressure level at which the blood column becomes somewhat paler. Occlusion of the vessel causes a rise in venous pressure which may be considerable, especially in large veins.


Readaptation time after photo stress. Readaptation time as a function of oxygen concentration. Optokinetic nystagmus (OKN) is used to study the eye's ReAdaptation Time (RAT) after a brief exposure to a light flash. The effects on RAT of breathing different concentrations of O2 are examined. Significant changes in RAT have been registered, showing that inhalation of 100% O2 as compared with room air, results in a shortened RAT (i.e. improvement), while inhalation of 9% O2 leads to an increased RAT (i.e. impairment). The physiology of RAT and the possible mechanisms behind the changes caused by different O2 concentrations are discussed. The findings of this group are compared with those of other studies.


Intrathecal prednisolone therapy in postoperative arachnoiditis following operation of herniated disc. Fourteen patients with severe, chronic sciatica operated on repeatedly but without lasting success were treated by two intrathecal injections of methyl prednisolone (40 mg and 80 mg) at an interval of a few days. Significant improvement was obtained with regard to pain in many cases, but as there was no control series it is difficult to assess the results.


Intrathecal pharmacotherapy in coma.

Intrathecal pharmacotherapy in coma. A study was made of intrathecal infusion as a route for administration of drugs for the CNS. We recognize the presence of blood brain and CSF brain barriers. CDP-choline was used as the brain activator, and the effect of the intrathecally infused drug was investigated clinically. Fifteen patients with disturbances of consciousness due to primary cerebral lesions received a total of 39 intrathecal infusions of CDP-choline, and were examined neurologically and electroencephalographically before and after treatment.


A few tips in treating venereal disease. Venereal disease is a subject which has been exhaustively covered in the literature. Unfortunately, there are practical problems of diagnosis and treatment which are still not well described.


Prosthetic valve endocarditis: clinicopathologic analysis of 22 necropsy patients with comparison observations in 74 necropsy patients with active infective endocarditis involving natural left-sided cardiac valves. Clinical and morphologic features are described in 22 necropsy patients with endocarditis involving rigid-framed prosthetic valves: aortic in 15 patients and mitral in 7. The interval from valve replacement to onset of symptoms of prosthetic valve endocarditis was less than 2 months in 8 patients and longer than 2 months in 14 patients. The most frequent infecting organism was the Staphylococcus (13 patients). In each of the 22 patients the infection was located behind the site of attachment of the prosthesis to the valve ring, and the infection spread to adjacent structures in 13 patients, 11 of whom had aortic prostheses. Prosthetic detachment causing severe regurgitation occurred in 12 of the 15 patients with an infected aortic valve prosthesis, and in 2 of the 7 with an infected mitral valve prosthesis. Prosthetic obstruction by vegetative material occurred in 5 of 7 patients with prosthetic mitral infection and in only 1 of 15 with prosthetic aortic infection. High degrees of conduction defects developed in seven patients with aortic prosthetic valve endocarditis: complete heart block in five, and complete left bundle branch block in two. Comparison of observations in the 22 patients with prosthetic valve endocarditis with those in 74 patients with active infective endocarditis involving natural left-sided cardiac valves revealed significant (P less than 0.05) differences in the percent with ring abscess, hemodynamic consequences of the endocarditis (valve stenosis), frequency of Staphylococcus as the causative organism and percent with complete heart block or left bundle branch block. No significant differences were observed between the two groups when comparing age, sex, type of underlying valve disease or frequency of organ infarcts of splenomegaly.


Cutaneous microabscess formation from Alernaria alternata. A 69-year-old farmer with acute lymphocytic lymphoma developed multiple ulcerated hemorrhagic cutaneous lesions. Alternaria alternata was cultured from the lesions and hyphae were seen in biopsies of the lesions. The potential role of Alternaria as a human pathogen is discussed.


Antibody against the hepatitis type B core antigen. A new tool for epidemiologic studies. Four random samples representing populations at low (volunteer blood donors), intermediate, (VD clinic patients), high (family contacts of chronic antigen carriers) and very high (male homosexuals) risk of exposure to HBV were surveyed. Among HBsAg and anti-HBs negative individuals an average of 3.3% were found to be anti-HBc positive, and among those with anti-HBs, 19.4% were anti-HBc positive. Anti-HBc, with concurrent anti-HBs and without, was detected more frequently in the high risk samples than in the low risk. Individuals was a past history of acute viral hepatitis were more frequently anti-HBc positive than those without such a history, and anti-HBc positivity was frequently accompanied by serum transaminase elevation. Anti-HBc may persist for many years after an episode of acute hepatitis. In households of carriers, the highest frequency of anti-HBc was observed among spouses, which would argue for the possibility of sexual transmission. A significant excess of females with both types of antibody was observed in families of carriers. Anti-HBc determinations in conjunction with other HBV markers, provide a useful new tool for epidemiologic studies.


Aneurysm of the sinus of Valsalva. Clinical considerations and surgical treatment of five patients. Five patients underwent operative repair of an aneurysm of the sinus of Valsalva. Four of the aneurysms were considered as congenital and one as mycotic. There were four males and one female. One patient with VSD and characteristics of Marfan's syndrome die on the first postoperative day of a recurrence of fistulae. The follow-up time is over one year for all but one of the surviving patients. There are no late deaths, and all patients are doing well. Aneurysms and fistulae of the sinus of Valsalva, which are perhaps not as rare as was previously thought, present a challenging surgical problem. Ruptured aneurysms and fistulae, even if asymptomatic, should be treated operatively, preferably by a transaortic approach.


Failure of hypothermia as treatment for asphyxiated newborn rabbits. Cooling is known to prolong survival in newborn animals when used before the onset of asphyxia. It has therefore been advocated as a treatment for birth asphyxia in humans. Since it is not possible to cool a human baby before the onset of birth asphyxia, experiments were designed to test the effect of cooling after asphyxia had already started. Newborn rabbits were asphyxiated in 100% nitrogen and were cooled either quickly (drop of 1 degree C in 45 s) or slowly (drop of 1 degree C in 2 min) at varying intervals after asphyxia had started. When compared with controls, there was an increase in survival only when fast cooling was used early in asphyxia. This fast rate of cooling is impossible to obtain in a human baby weighing from 30 to 60 times more than a newborn rabbit. Further litters of rabbits were asphyxiated in utero. After deliver they were placed in environmental temperatures of either 37 degrees C, 20 degrees C, or 0 degrees C and observed for spontaneous recovery. The animals who were cooled survived less often than those kept at 37 degrees C. The results of these experiments suggest that hypothermia has little to offer in the treatment of birth asphyxia in humans.


[On the circadian changes of concentration of free amino acids in pregnancy (author's transl)]. Concentrations of 17 free amino acids were measured in the serum of 15 healthy pregnant women at the end of pregnancy in intervals of 4--5 h. A circadian rhythm with its concentration peak at 5 p.m. could be observed for Ser, Val, Met, Ile, Leu, His, Lys and Arg. Exogenic and endogenic synchronizators are being discussed as possible causes for these fluctuations during the day. The rhythm of the free amino acids makes it necessary that only fasting blood is examined and that the time of day is always registered when the blood specimen is taken.


Experimental studies on the positive feedback effect of progesterone, 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone on the pituitary release of LH and FSH in the human female. The estrogen priming of the progesterone feedback on pituitary gonadotropins in the eugonadal woman. Administration of progesterone eugonadal women during the midfollicular phase of the menstrual cycle failed to induce a positive feedback effect on the serum concentrations of LH and FSH. The levels of estradiol in serum decreased following the injection of progesterone without a parallel change in LH and FSH concentrations indicating a direct ovarian effect of the exogenous progesterone. In the late follicular phase of the cycle, when preovulatory levels of estradiol were present in serum, or under a ethinyl estradiol treatment progesterone was able to induce an LH discharge indicating the requirement of an estradiol priming of the positive feedback of progesterone in eugonadal women. In order to establish the time required for a sufficient estrogen priming with preovulatory levels of estradiol in serum 3 mg of estradiol-benzoate were administered i.m. 1, 12 and 24 h prior to the administration of 30 mg of microcristalline progesterone in the midfollicular phase of the menstrual cycle, when progesterone alone did not cause an LH surge. Only when estradiol-benzoate was injected 24 h prior to the progesterone administration an LH surge reproducible in time course and magnitude occurred. Administration of estradiol-benzoate alone under these conditions did not cause an LH surge within the elapse of time after the injection when the progesterone induced LH surge occurred. Thus, these experiments demonstrate that a defined estrogen priming is required for the positive feedback effect of progesterone on the gonadotropin release in eugonadal women. Furthermore, progesterone levels in serum of about only 1--2 ng/ml were required for the induction of an LH surge indicating that under physiological conditions progesterone may have an supplementory effect on the primarily estradiol induced LH midcycle peak. 17-hydroxyprogesterone administered during the mid follicular phase of the menstrual cycle and under pretreatment with ethinyl estradiol failed to induce a positive feedback effect on the serum concentrations of LH and FSH, indicating that this steroid does not play a regulatory role on the midcycle LH release in women. 20alpha-dihydroprogesterone administered under the same experimental conditions as 17-hydroxyprogesterone seems to be able to induce an LH surge in serum provided there is an adequate estrogen priming.


Leiomyoma of the Fallopian tube. A case report and review of the literature. A relatively rare benign tumor of the fallopian tube is presented, i.e. an intramural leiomyoma, which was incidentally found during histologic examination of the tubal isthmus excised for sterilization. The literature is briefly reviewed.


Low molecular weight peptides with anti-thrombin and anti-urokinase activity isolated from human maternal and cord blood serum and amniotic fluid. Peptides with antithrombin and anti-urokinase activity were isolated from maternal and cord blood serum and amniotic fluid from pregnant women at term. Chromatography data, fingerprinting and activity of peptide inhibitors revealed active peptides, which were similar to those recently isolated from human placenta. They are distinctly different from protein inhibitors previously isolated from human placenta.


The re-epithelization of endometrium after menstrual desquamation. Human uteri were removed by vaginal hysterectomy on the first, second and sixth day of the menstrual cycle. Washing, pinning, fixation in glutaraldehyde 2.5%, dehydration in ascending concentration of ethanol, critical point drying with carbon dioxide, sputter coating with gold. The re-epithelization of the endometrium starts immediatley after the onset of menstrual bleeding due to desquamation of the premenstrual endometrium. The remaining stumps of endometrial glands after the endometrial break-down, proliferate rapidly, forming marginal collars. Up to the sixth day the proliferative process has produced a continuous layer of fusiform cuboideal epithelial cells, which cover the entire endometrial surface of the uterine cavity. The dynamics of epithelial growth can be "seen" in following three subsequent stages of the process and in analyzing the arrangement of the cells around the openings of the endometrial glands. Accordingly ciliogenesis occurs in some surface endometrial cells. The paper gives an inconographic survey of the early proliferative phase, illustrating changes from glandular epithelium to the lining epithelial layer and ciliogenesis in the latter. The new formation of ciliae in endometrial epithelial cells is an unique phenomenon, being influenced by the cyclic endocrine regulation of the endometrial function in human reproduction.


[Effect of oral contraceptives on plasma insulin and blood glucose levels after long term use (author's transl)]. Blood glucose and plasma insulin were measured during an intravenous glucose tolerance test (0.33 g/kg body weight) performed on 75 subjects. Various types of oral contraceptives were taken for an average period of 6.5 yrs. The cases were divided into several groups in order to examine the effect of combination-type drugs (group A; n= 40) and sequential-type drugs (group B; n = 23) separately. A third group had used both types of drugs (group C; n = 13). Fifteen women who have never taken hormone drugs served as control group. It was found that plasma insulin levels, blood glucose and k-values were not significantly elevated in the drug treated groups. The duration of treatment does not seem to have an effect on glucose tolerance and insulin secretion. In this study the patient's age is the most important associated data, and not overweight, family history of diabetes or past obstetric history. No statistical change in insulin levels, reaction areas of glucose and insulin after IVGTT was seen in any drug treated group.


Altered carbohydrate metabolism in breast cancer and benign breast affections. Breast diseases in 792 women were studied by biopsy and histological evaluation. In all subjects glucose tolerance was examined by OGTT (100 g glucose). The diabetes frequency of 22% in 326 women with breast cancer was compared with the frequency in women with fibroadenoma (n = 101), papilloma (n = 80), fibrocystic disease (n = 107), lipoma, granuloma, fibrosis (n = 88), papilloma with proliferation (n = 32), mastopathy with proliferation (n = 33) and carcinoma in situ lobulare (n = 11). The statistical evaluation was done with an electronic data processing system. We used matched pairs according to age, height and weight. Diabetogenic factors like age and overweight were thus allowed for. These comparative statistics showed a frequency of diabetes twice or three times higher in women with breast cancer. This result cannot be regarded as a consequence of age, overweight and menopause. In groups with fibroadenoma, fibrocystic disease and lipoma, we found glucose tolerance in 1-3%, whereas the group with proliferation (including carcinoma in situ) showed an incidence of 7%. The remarkably high incidence rate of 14% in women with papilloma can be explained by the higher age and the more frequent obesity in this collective.


Early experimental myocardial infarction. Evaluation of histologic criteria and comparison with biochemical and electrocardiographic measurements. Light microscopical criteria of early experimental myocardial infarction were compared with biochemical changes in glycogen content and the tissue K+/Na+ ratio in 19 mongrel dogs. Five sham-operated dogs served as controls, and seven of the 14 dogs with experimentally induced infarcts received infusions of glucose, insulin, and potassium (GIK). Infarcts were diagnosed by a scoring system based on edema formation, congestion, waviness of myofibers, myofibrillar degeneration, polymorphonucleosis, glycogen depletion, and fuchsinorrhagia. Significant histologic scores were associated with tissue K+/Na+ ratios of less than 1.2, with 30% depletion of biochemical glycogen, and with epicardial ST-segment elevation. Progression of the infarction zone to involve the surrounding border zone was prevented by GIK infusions. Routine light microscopy used in conjunction with tissue K+/Na+ ratios enabled early infarction to be diagnosed with a high degree of accuracy.


Experimentally produced hypertension and aortic acid esterase. The effect of hypertension, which is known to enhance atherosclerosis, on acid esterase activity of rat aortic wall was studied histochemically. The purpose was to test our notion that atherogenesis depends on the balance between supply of lipids to the arterial smooth muscle cells and the lysosomal esterase activities. Hypertension was produced in rats by unilateral nephrectomy and administration of desoxycorticosterone acetate and sodium chloride. The animals reacted with varying degrees of hypertension. In rats with hypertension of a sufficiently high degree and of long duration, inhibition of aortic acid esterase activities occurred. No inhibition of these enzymes occurred in the other organs examined.


Vascular alterations in delayed radiation necrosis of the brain. An electron microscopical study. A 51-year-old woman who had been given cobalt therapy for nasopharyngeal carcinoma was seen three years later with a mass in the left frontotemporal region of the brain. Biopsy specimen of the lesion showed the classic features of delayed radiation necrosis on light microscopy. In addition, several blood vessels showed endothelial cell proliferation. Transmission electron microscopical study demonstrated numerous alterations of the endothelial cell, such as intraluminal infoldings of the plasma membrane, an increased amount of cytoplasmic organelles, and the frequent occurrence of tubular bodies in addition to degenerative and reactive changes in the neuropil.


A diffuse form of pulmonary silicosis in foundry workers. Pulmonary silicosis usually is characterized by typical hyalinized, concentric nodules as seen under the microscope and in the corresponding roentgenogram. In the case of three foundry workers, lung biopsy specimens contained no nodules. The chest roentgenograms were not suggestive of silicosis. Examination of the biopsy tissue by scanning electron microscopy and energy dispersive x-ray analysis (EDXA) revealed significant (P less than .05) amounts of silicon in the thickened fibrous tissues of septa, pleura, and around blood vessels, enough to permit the diagnosis of silicosis. All three patients had severe functional impairment. It is not clear at this time what factors were responsible for a diffuse distribution of silicon in these cases.


Secular trends in prevalence and concentration of pulmonary asbestos bodies--1940 to 1972. A necropsy study. This study was designed to inquire into changes in the prevalence and concentration of asbestos bodies in the lungs of the necropsy population in Sinai Hospital of Baltimore during a 33-year period, 1940 to 1972. A tissue digestion technique was used to extract and quantitate asbestos bodies not only in fresh samples of pulmonary tissue but also in older fixed and blocked samples. A significant increase in the proportion of lungs containing asbestos bodies was found in the later years, as well as an increase in the concentration of asbestos bodies in lungs of the older age groups. Currently, 91.1%of this necropsy population in Baltimore harbor asbestos bodies in their lungs. The biologic importance of this increase is uncertain and speculative.


Perivascular xanthogranulomatosis in the lungs of diabetic patients. A total of 339 histologic lung samples obtained on autopsy from diabetic patients were re-examined to investigate the frequency of perivascular deposits of xanthoma cells in the lungs. Lung samples from 156 nondiabetic patients were used as controls. Xanthogranulomas were noted in 20 diabetic cases/5.9%). In the control group, three cases (1.9%) of xanthomatous deposits were detected, a frequency notably lower than in the diabetics. It seems possible that xanthogranulomas were due to some dysfunction in the transportation of lipids through the vascular wall.


Perforating pseudoxanthoma elasticum. Its distinction from elastosis perforans serpiginosa. It is not generally appreciated that pseudoxanthoma elasticum (PXE) can be associated with epidermal perforation by elastic fibers. We report an example of this phenomenon. The term "perforating PXE" is suggested and a distinction is made from elastosis perforans serpiginosa (EPS). We believe that most reported cases of coexistence of PXE and EPS are perforating PXE and that the coexistence of EPS has not been clearly demonstrated.


Brown fat retention in sudden infant death syndrome. This study was undertaken to confirm the findings of Naeye with regard to the pathological retention of the so-called brown fat cells in the periadrenal adipose tissue of infants who die of the sudden infant death syndrome. The percent of multilocular fat cells was determined in histological sections of periadrenal adipose tissue obtained from a series of 289 autopsies. In general, our morphological observations confirm his. However, our results indicate that the percent of periadrenal multilocular cells cannot be used as a diagnostic criterion in any single case. Futhermore, we consider that the mechanism for this delay in transformation remains unclear.


Peroxidase-antiperoxidase complex. Binding by Mallory bodies in unfixed tissue. An antigen-antibody complex of horseradish peroxidase, peroxidase-antiperoxidase (PAP), was found to selectively bind to Mallory bodies (MBs). Specific PAP binding to MBs was consistently demonstrated in liver sections from 14 patients with alcoholic cirrhosis and from one patient with hepatoma. Mallory bodies in isolated fractions also bound PAP. No structures stained with PAP in six control sections. The PAP-binding method is useful in the identification of MBs in situ and in isolated fractions. The nature of the affinity of MBs for PAP is not known, but it is postulated that nonspecific protein-immunoglobulin binding is involved.


Morphological features and healing of stress ulcers induced by alcohol and restraint. Gastric mucosal damage was produced in 130 mice by forced ingestion of alcohol, followed by restraint in the cold. Animals were killed at intervals from six hours to 27 days following the stress. Linear hemorrhagic erosions and diffuse hemorrhagic patches were found grossly, predominantly in the glandular portion of the stomach, in about 75% of the animals 6 to 24 hours after stress. At later time intervals, the linear mucosal depressions persisted; these became progressively less prominent with time but substantial numbers were still readily discernible three weeks after injury. Microscopical examination of the fresh lesions showed a variable amount of mucosal necrosis and acute inflammation. Epithelial regeneration became prominent after three days and persisted for several weeks. The first regenerating epithelial cells were primitive, cuboidal elements followed by mucous cells, parietal cells, and zymogen cells, in that order. The morphological features and evolution of the lesions were similar to that described in human stress ulcers.


Glomerulocystic kidney. Report of a case. We describe a rare type of congenital renal cystic disease involving the Bowman capsule and adjacent abnormal tubules. The patient had a moderate degree of proteinuria, but otherwise normal renal function. Two subcapsular hepatic cysts manifested the only other visceral involvement. This case is morphologically similar to one previously reported. A purely descriptive morphologic term is suggested for this distinctive lesion, viz, glomerulocystic kidney.


Regression of injury-induced atheromatous lesions in rabbits. For four consecutive weeks, 61 rabbits received weekly injections of lymphocytotoxic-positive human serum into the left carotid artery and of autologous serum into the right carotid artery as a control. Serum cholesterol and serum triglyceride levels were measured before the study, in the second and fourth weeks of the study, and weekly thereafter. The results show that repeated intimal injury caused raised, lipid-containing thromboatherosclerotic lesions and that there was a consistent regression to lipid-free fibromusculoelastic plaques from the first week after completion of the injection regimen to the fourth week. Apparently, regeneration of an intact covering cell layer resulted in the elimination of lipid deposits from raised lesions, resulting in lipid-free fibromusculoelastic plaques. In addition, fatty streaks were observed to occur during regression. A statistically significant rise in serum cholesterol level during the phase of progression of lesions and a subsequent fall during regression were observed.


Histomorphologic features of ultrasonic renal injury. Fifteen-second exposure of rabbit kidneys to 2 MHz focused ultrasound with approximately 900 w/sq cm acoustic power consistently produced localized parenchymal destruction. Evolution of the lesions was followed histologically over a one-year period. The lesions were sharply delineated from outlying renal tissue and had a concentric multizonal structure. Resorption of the damaged tissue with scarring was completed in 6 to 12 months following intermediate phases characterized by cellular infiltration. The lesions are compared to other models of renal injury, particularly with respect to cellular infiltration. A combination of mechanical, thermal, and ischemic factors seem to be responsible for development of ultrasonic lesions. The sharply circumscribed nature and ultimate complete scarring of the lesions suggest the feasibility of ultrasound in achieving selective complete destruction of renal parenchyma.


Alterations of liver and spleen following intravenous infusion of fluorocarbon emulsions. Mice were injected via tail vein with emulsions of fluorocarbon (FC), an oxygen-carrying compound that has great potential as a blood substitute. Different types of FCs were used. All produced vacuolar changes in hepatocytes, and in reticuloendothelial cells throughout the body. In the liver, occasional inflammatory foci were also observed, but fibrosis was never seen. The vacuolated cells, presumably containing FC, were found as late as one year following a single infusion. However, such cells might also disappear from the liver and spleen. The numbers of affected cells and their rate of disappearance depended on the type of FC, the amount of FC infused, the length of time between infusion and killing. Fluorodecalins, especially PP-5, produced the least amount of change and the most readily reversible change of all FCs tested. The morphologic observations suggest that PP-5 would be more suitable as a blood substitute than the other FCs tested. However, other studies have shown that apparently healthy long-term survival is obtainable even when the infused FC is one that produces extreme vacuolar change in the liver and spleen.


Palmitic acid-1-14C incorporation and turnover in lung phospholipids of rats treated with chlorphentermine, RMI 10.393 and Ro 4-4318. The effects of 3 lipidosis-inducing drugs on the incorporation and turnover of palmitic acid-1-14C in lung phospholipids was studied. In rats treated with 1 dose of chlorphentermine or RMI 10.393, the incorporation of palmitate-1-14C into most lung phospholipid fractions was moderately decreased, but markedly lowered after 1 dose of Ro 4-4318. Eight doses of chlorphentermine and RMI 10.393 strongly inhibited the incorporation of palmitate-1-14C into lung phospholipids, whereas with 8 doses of Ro 4-4318 the incorporation was highly increased. Thirty hours after the last of 3 injections of the labeled palmitic acid the turnover of most lung phospholipids was considerably lower in chlorphentermine- and RMI 10.393-treated rats than in controls. Ro 4-4318, however, induced a highly increased turnover of most phospholipids. After 54 h, this effect had practically disappeared. Our studies showed that phospholipid storage after treatment with chlorphentermine and RMI 10.393 is mainly due to decreased degradation of phospholipids, whereas increased synthesis accounts for the effect of Ro 4-4318.


Inhibition of salicylate and lithium absorption in the human intestine by copper sulfate. Copper sulfate, given orally in an emetic dose, decreased the absorption of therapeutic doses of acetylsalicylic acid or lithium carbonate, more than was expected judging from the recovery of salicylic acid in the vomit. Ten volunteers participated.


Effect of phenobarbital pretreatment on in vitro enzyme kinetics and in vivo biotransformation of benzene in the rat. Phenobarbital pretreatment (50 mg/kg/day for 3 days orally) of male Wistar rats increased Vmax of benzene in vitro hepatic microsomal biotransformation about 6-fold without changing Km. However, benzene blood levels after oral, intraperitoneal, or subcutaneous benzene administration (3-3.5 mmoles/kg) were not influenced by phenobarbital pretreatment. The phenol blood levels after oral or intraperitoneal benzene were increased by phenobarbital pretreatment, but less than expected from in vitro data and only 3 h after benzene administration. Phenol elimination in urine after subcutaneous benzene was not affected by phenobarbital. After oral or intraperitoneal benzene administration, phenol urine excretion closely followed the levels of phenol in blood, i.e., rate of phenol urine excretion was significantly, but shortly increased, and the cumulative urine excretion of phenol increased very little or remained unchanged. Differences between the in vitro and in vivo observations of the effect of phenolbarbital on benzene biotransformation may partly be explained by distribution of benzene, which apparently limited benzene availability for biotransformation (Vd = 5.5) and caused rapid decrease of benzene concentrations in blood. Conditions for enzyme activity may have been substantially different in vitro vs. in vivo: in vitro concentrations of benzene were at least by an order of magnitude higher than phenol concentrations, while in vivo, an opposite relation prevailed making a competition for microsomal monooxygenase possible. Cofactor availability may be another rate-limiting step or factor of in vivo benzene biotransformation, as benzene ring hydroxylation requires high energy. The rate of in vitro hepatic microsomal benzene biotransformation proved to be of limited value when predicting benzene quantitative biotransformation in vivo in contradistinction to various substrates where the in vitro and in vivo biotransformation data are in good agreement.


[Extracorporeal hemoperfusion in acute carbon tetrachloride intoxication]. A case of severe carbon tetrachloride intoxication and its successful treatment by extracorporeal hemoperfusion with activated charcoal is reported. The therapeutic effect of this treatment is confirmed by investigation of in vitro clearance studies. Results are discussed together with literature.


[Investigations of the decomposition and detection of morazone by thin-layer- and gas-liquid-chromatography]. Three decomposition products of Morazone (ingredient of the pharmaceutical preparation Rosimon-Neu) were observed following heat treatment in acid medium (hydrochloric or tartaric acid). These products were isolated by TLC and identified as bis-antipyryl-methane, phenmetrazine and 4-hydroxymethyl-antipyrine by mass spectrometry and IR-spectroscopy and 1H-nuclear magnetic resonance. Morazone and the metabolite phenmetrazine may be extracted from alkaline urine using chloroform, however acid hydrolysis (pH 1) of the urine before alkaline extraction will improve the sensitivity of detection of morazone by producing the metabolite phenmetrazine in addition to bis-antipyrylmethane. The metabolite 4-hydroxymethyl-antipyrine is barely detectable by TLC from alkaline extraction of urine.


Effects of drugs on mushroom poisoning induced in the rat by Cortinarius speciosissimus. The effect of phenobarbital and phenylbutazone treatment on the renal damage induced by the toxic mushroom Cortinarius speciosissimus was studied in female rats. Phenobarbital sodium was given in drinking water (0.05% solution) for 11 days prior to the administration of mushroom. Phenylbutazone was given s.c. in doses of 50 and 100 mg/kg 1 h before the mushroom administration. Homogenized mushroom was given orally by stomach tube at a dose of 250 mg dried mushroom/kg body weight. It was found that the phenobarbital treatment strongly increased the damage induced by C. speciosissimus in the tubules of the kidney cortex but had no effect on the inflammation in the renal outer medullary zone induced by this toxic mushroom. Phenylbutazone treatment had no effect on the renal damage induced by C. speciosissimus.


Relationship between lead concentration in blood and biological response for porphyrin metabolism in workers occupationally exposed to lead. The biological responses of the heme biosynthesis pathway in male workers moderately exposed to lead are discussed in relation to the concentration of lead in the blood. The level of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) activity in the group of lead-exposed workers was remarkably reduced while the level of erythrocyte protoporphyrin (Proto) in them was strikingly increased, compared to normal levels. On the other hand, the amounts of hemoglobin (Hb) and urinary delta-aminolevulinic acid (ALA) in the group of lead-exposed workers kept the normal levels. In the workers moderately exposed to lead, the log of erythrocyte Proto level was closely correlated to the blood lead level and the sensitivity of the Proto test was almost equal to that of erythrocyte ALA-D test. It was observed that the erythrocyte Proto was remarkably increased even in lead-exposed workers whose ALA excretion into the urine was in the range of normal level.


Dopamine-sensitive adenylate cyclase in homogenates of rat striata during ethanol and barbiturate withdrawal. Repeated administrations of ethanol and of phenobarbital to rats led to characteristic withdrawal symptoms when the drug had been stopped. Since both drugs affect brain dopamine metabolism, the postjunctional sensitivity to dopamine in the corpora striata was tested during ethanol or phenobarbital withdrawal. This was done by studying the dopamine-sensitive adenylate cyclase in homogenates of the copora striata of ethanol- or phenobarbital-dependent rats. The results demonstrated a slight postjunctional subsensitivity to dopamine in withdrawal from both ethanol and phenobarbital. Both drugs, when added in vitro, did not affect the postjunctionsl sensitivity to dopamine. The results do not support the hypothesis, at least not in the case of dopamine, that a postjunctional supersensitivity to neurotransmitters is important for withdrawal symptoms after chronic administration of drugs inducing physical dependence.


The effect of tricyclic antidepressant drugs on the heart. The effects on the heart rate and ECG of anaesthetised guines-pigs of amitriptyline, doxepin, imipramine and nortiptyline infused at 1.0 mg/kg/min until death were observed. In addition an in vitro study on guinea-pig atria was performed on the chronotropic and inotropic effects of these drugs and of desmethylimipramine and protriptyline at a concentration of 10(-5) M. The effect of sodium bicarbonate (3 mEq/kg i.v.) and propranolol (0.01--0.2 mg/kg i.v.) on amitriptyline and doxepin induced ECG changes was also assessed. A difference in the cardiac effects of the in vivo and in vitro model was observed. Guinea-pigs infused with doxepin survived significantly longer than those infused with amitriptyline, imipramine or nortriptyline. No statistically significant difference was found between the tricyclic drugs with respect to onset of widening of the QRS complex, increased PR and QT intervals. In the spontaneously beating atrial preparation doxepin was the most potent cardio-depressant. Sodium bicarbonate had no effect on arrhythmias induced by tricyclics, while propranolol, apart from the bradycardia induced, was without beneficial effect on the ECG. The guinea-pig provides a good model for studying the arrhythmogenic actions of tricyclic antidepressants.


Dichlorvos -- a 2-year inhalation carcinogenesis study in rats. To determine the effects of dichlorvos vapour on the tumour incidence in rats, 5 week old Carworth Farm E strain rats weighing between 94 and 150 g were exposed to 0, 0.05, 0.5 and 5.0 mg/m3 in a 2-year inhalation study. The growth rate of all treated rats was depressed, particularly in the males. There was increased survival of the rats exposed to 5 mg/m3. There were no consistent differences in food intakes, organ weights, haematological or blood chemistry estimations, except in cholinesterase activites, amongst the various groups of rats. No compound-related differences were seen in acetylcholine and choline estimations carried out on a small number of female rats' brain tissues after two years' exposure. There were no gross or microscopical compound-related changes in the rats' tissues. Ultrastructural examination of the respiratory tissues of the rats from the control and 5 mg/m3 group showed no changes attributable to dichlorvos. The results of a relative risk analysis of the tumour data showed that no dose-related increase in tumour risk was established for rats of either sex. These data confirm the results of earlier st.udies supporting the safety of insecticidal uses of dichlorvos.


Role of iron deficiency in inducing susceptibility to manganese toxicity. Daily intraperitoneal administration of manganese chloride (15 mg/kg) to rats, maintained on an irondeficient diet, produced marked alterations in the activity of succinic dehydrogenase, monoamine oxidase, and in the morphology of the liver. Manganese accumulation was also significantly increased in such rats than after similar treatment to normally fed rats. Iron deficiency leads to increased absorption of manganese which is responsible for increased susceptibility to manganese toxicity in these animals.


[Trichlorethylene-, carbon tetrachloride- and gasoline-intoxication in connection with arterio- and coronary sclerosis (author's transl)]. On the occasion of autopsies of 4 toxicomaniac adolescents sniffing and occasionally drinking trichlorethylene, carbon tetrachloride and gasoline severe arteriosclerotic damage of the coronary vessels was encountered. Experimental intoxication of 12 rabbits with these solvents over a period of 10 weeks, each time until a prenarcotic stage, provoked pathological changes in accordance with well known findings but no arteriosclerosis. Ergometrical examination with simultaneous recording of the E.C.G. of 6 adolescents with solvent-sniffing history and of 1 man, working for years under trichlorethylene exposure conditions and showing symptoms of chronic intoxication, revealed no signs of coronary-artery insufficiency. These findings are not inconsistent with the assumption -- though not substantiating it -- of a causal relationship between the intoxication with trichlorethylene, carbon terachloride and gasoline and the development of arteriosclerosis, as the coronary sclerosis may be of the elstic type with a very high degree of adaptability and the probands proved unable to reach the limit of maximum stress. In addition to the main purpose the occurrence of epileptic seizures following chronic trichlorethylene sniffing in one case and the manifestation of pulmonary obstruction following i.v. application of Methyl-Phenidat (Ritalin) in two cases are reported.


[Bilateral cerebral mycotic aneurysm in a child. Report of a case and review of the literature]. The case of a 6 year-old boy, who was hospitalized with the diagnosis of purlent meningits is reported. The CSF examination disclosed pleocytosis and the antibioticotherapy was instituded. The bilateral carotid angiography demonstrated an arterial aneurysm of the frontal ascendent artery with hematoma in the left side and another in the posterior temporal artery, in the right side. The patient was operated on because of the hematoma, in the left side. The condition of the patient in the post-operatory period deteriorated and the death ocurred. The post-mortem examination disclosed a sub-arachnoidal hemorrhage, fronto-temporal hematoma in the left side and a para-capsular hematoma in the right side. The histological examination of the central part of the right side. The histological examination of the central part of the hematoma revealed a dilated arterial walls with a supurative inflammatory process.


Hereditary deafness in the dalmatian dog. The temporal bones from 18 deaf Dalmatian dogs were examined with the light microscope, and the cochleo-saccular degeneration process studied. End organ degeneration is already advanced by the age of 4 weeks, whilst loss of neurons in the spiral ganglion was found only in adult animals. Both processes are first evident in the central portion of the cochlea, and increase in extent with advancing age, The implications of these findings for the management of non-conductive hearing loss in man are discussed.


[Acoustically evoked potentials (aep) in children (author's transl)]. The differences between amplitudes and latencies of acoustically evoked potentials (AEP) in children, aged between 3 and 7 years, were tested using random distributed stimuli with mean interstimulus intervals (ISI) of 1.45 sec, 2.1 sec, and 4.1 sec and periodic stimuli with the same ISI. We applied three different intensities, 30, 50, and 70 dB SPL and a frequency of 1000 c/s. We determined the peak to peak amplitudes P2N2 and N2P3 and the latencies of P2, N2, and P3 for our calculation because of the typical AEP pattern in children. There were no significant differences between the mean amplitudes and mean latencies, using an error probability of 1% comparing the AEP determined by the two different ways of stimulation. The increase of the ISI from 1.45 to 4.1 sec didn't yield to a significant improvement of the AEP in both stimulation patterns. In the tested group of children the used stimulation pattern, as we already stated in adults, is without greater importance.


Input-output function and adaptation behaviour of the five early potentials registered with the earlobe-vertex pick-up. At twenty-three 20-30-year-old normal-hearing subjects the characteristic curves of amplitudes and latencies of the five early potentials, appearing within the first 8 ms after stimulus onset, were obtained. The potentials were registered with the earlobe-vertex pick-up, as described by Sohmer and with click stumulus rates of 5/sec, 10/sec and 100/sec; It could be seen: All five potentials depend in amplitude and latency on intensity; all potentials show with increasing click rate an adaptation and a delayed latency, when increasing the click rate from 10/sec to 50/sec; the adaptation phenomenon of the 1st, 2nd, 3rd and 4th potential is the most prominent, the 4th potential shows the smallest adaptation effect; the characteristic curve at 10/sec of the 1st and 3rd potential demonstrates a break at 70 dB SPL; the latencies of the five potentials begin to increase at click rates higher than 10/sec; the 4th potential seems to be the most suitable one for measuring the acoustical threshold; only the fifth potential diminishes in amplitude and increases in latency after administration of an anaesthetic, but an additional relaxant does not alter it any more.


[Histological examinations about possible heat lesions of bone and cartilage during boring and grinding (author's transl)]. In skull bone and septum cartilage holes were bored with rose trepans and diamond cutters of various sizes (2-20) and at different revolutions (5,000-42,0000 rev/min) with and without the use of cooling fluid. The specimens were examined histologically. Borings with rose trepans without cooling fluid cause sometimes considerable heat lesions up to a depth of 30 mu. Bone shows the more severe lesions. The use of cooling fluid reduces the damage quite considerably (burns zone up to a maximum depth of 12 mu). In the normal range of up to 10,000 rev/min practically no heat lesions occur. In the high range above 20,000 rev/min the lesions are often only plaque-shaped. Water jet or spray cooling is superior to droplet cooling. Diamond cutters cause more severe lesions. Boring and grinding in the highest range (up to 300,000 rev/min) without cooling fluid cause very deep burns (up to 56 mu),


[Experimental research of resistance to air currents in laryngeal-tracheal specimens (author's transl)]. Flow resistance to air currents was experimentally determined in 69 human laryngeal-tracheal specimens. Vocal cords were held bilaterally in the paramedium position, simulating bilateral recurrent nerve paralysis, and in five other positions following certain surgical interventions. It was found that under simulated physiological conditions (inspiratory position) as well as in the presence of a simulated recurrent nerve paralysis, the laryngeal flow resistance depended on individual factors, i.e., form and size of each specimen. Different degrees of improvement occurred with various surgical methods. Based on the discussion of the experimental results, clinical conclusions are offered.


[Chronic laryngitis and carcinoma (author's transl)]. 35 cases of continuous series of 841 laryngeal cancers were studied separately. Those patients had already been suffering from hoarseness for more than 2 years, in the average for 9 years. Many of these patients had been examined and treated by inhalations, and biopsies were taken because of a chronic laryngitis. Clinically in half of the cases a big carcinoma could be found. In 10 cases a chronic laryngitis had been diagnosed; in spite of the preceeding examination by microlaryngoscopy in 4 cases, however, the carcinoma could only be proved by histologic examination. The histologic examinations of the specimens regularly displayed an extended field of epidermisation of the laryngeal mucosa following chronic laryngitis, In these fields of epidermisation the carcinoma developed multicentrically and--in the early stages--mostly showed a covering-like, minutely infiltrating growth. Disseminated dot-like cancer-focuses in the epidermisation field and cancer buds arising from the basal layers of an intact covering of the hypertrophic epithelium could be observed several times. Chronic-hypertrophic laryngitis seems to favour the development of cancer within some patients (promoting factor), it even might accelerate it. As in about 6% of all the vocal cord cancers a preexistent chronic laryngitis is proved by history and clinical findings each patient with a chronic hypertrophic laryngitis must be examined by microlaryngoscopy as well as histological examinations and must be constantly observed.


Nystagmographic Analysis of the Fistula Symptom. An electronystagmographic examination of the fistula symptom was carried out to ascertain the relation to pressure, the temporal pattern and the reversability of the nystagmus. The relation of nystagmus-intensity to pressure is not constant, often this relation is expressed by an s-curve. The nystagmus does not increase significantly above intensities of 70 degrees/s. The nystagmus-intensity has a typical temporal pattern: it starts immediately after application of pressure and for several seconds to minutes it practically remains on this level. Subsequently it slowly decreases. When, with a constant pressure, the nystagmus had faded out entirely, then, under relief of pressure, a nystagmus with reverse direction but equal intensity appears. After obtaining a fistula symptom there is a relative refractory time, which sometimes lasts for minutes. Only the change of pressure (which may have an effect of up to several minutes) and not the pressure by itself is decisive for the release of fistula symptom.


[Comparative studies of lactate concentration in the perilymph, blood and cerebrospinal fluid of normal and sound exposed guinea pigs (author's transl)]. The paper deals with comparative studies of lactate concentration in the perilymph (PL) of scala tympani and of scala vestibuli, arterial and venous blood, serum and cerebrospinal fluid (CSF) of normal and sound exposed guinea pigs, special consideration having been given to possible sources of error in the methods employed. Lactate was determined enzymatically using a micromodification of the Boehringer UV-test combination adapted to 1 mul PL. The lactate concentrations in the PL of scala tympani and scala vestibuli did not differ significantly. The mean values amounted to 4.5-5.2 mM/l in the case of the opened and of the unopened subarachnoid space (Table 1). The lactate concentrations in the PL of both cochlea scales were significantly higher already ten minutes post-mortem. In the exposure experiments the animals were unilaterally exposed to sound for 1 h in an acoustically isolated system using a wide-band noise at an intensity of 120 dB SPL for one series and 2-kHz pure-tone at intensities of 112 and 122 dB SPL for two other series. We did not detect any changes in the lactate concentrations neither in the PL nor in the blood and in the CSF, following sound exposure (Table 2 and 3). The lactate concentrations of arterial and venous blood and CSF did not differ significantly. The mean values amounted to 1.4-1.8 mM/l (Table 2). However, if blood was not deproteinized or centrifuged immediately after being taken, the lactate concentration increased markedly. A comparison of the present results has shown that the lactate concentration in the PL is about three times as high as in blood and in CSF. This difference in concentration suggests that the PL lactate is of intracochlear origin and that glycolytic processes take place in the inner ear also under normal conditions. Systematic studies of additional metabolic parameters must be conducted before a definitive physiological interpretation of the present analytical results can be given.


[Sturcture and function of the mononuclear phagocytic system (MPS) in chronic rhinosinusitis. A light and electron microscopic investigation (author's transl)]. Neither the concept of the Reticulo-Endothelial-System (RES) Aschoff's (1924) nor that of the Reticulo-Histiocyte-System (RHS) provides a satisfactory framework into which the present knowledge of the phagocytic mononuclear cells can be fitted. Current knowledge concerning morphology, histochemistry (peroxydase and esterase activity), immunology (specific surface antigens, receptors on the cell membranes), function (immune phagocytosis, pinocytosis), kinetics (3H-thymidine labelling) and culture makes it possible to place all highly phagocytic mononuclear cells and their precursors in one system, which is called the Mononuclear-Phagocytic-System (MPS) (Langevoort, Cohn, Hirsch, Humphrey, Spector, van Furth, 1969). Kinetic studies with labelled cells have shown, that mononuclear phagocytes originate from precursor cells in the bone marrow (stem cell leads to monoblasts leads to promonocytes), than are circulating in the peripheral blood as monocytes and are transformed to tissue macrophages entering tissues. The MPS comprises following cells in following organs: connective tissue (histiocytes resp. macrophages); liver (Kupffer-cells); lung (alveolar macrophages); lymph nodes (free and fixed macrophages); bone marrow (macrophages); serous cavities (pleural and peritoneal macrophages); bone tissue (osteoclasts?); nervous system (microglial cells) (SEE Table 1). The reticular cells, endothelial cells and fibroblasts (fibrocytes) can therefore not be included in the MPS. Besides differences in morphology, histochemistry and function, they derive from mesenchymal cells and not from the bone marrow as the MPS. The present investigation demonstrates the structure and significance of the MPS in various kinds of chronic-specific and non-specific rhinosinusitis. On semithin sections two kinds of macrophages can be distinguished light-microscopically: 1. Larger macrophages with many phagosomes (storage cells) (Fig. 1A), which can exhibit sometimes a ring-shape on sections embracing greater parts of the interstitium (Fig. 1B). Such forms are mainly found in chronic (maxillary) sinusitis and are interpretated as "scavenger" macrophages. 2. The second type consists of smaller macrophages with extremely ruffling of the cell surface, which is interpretated as an expression of highly (specific?) stimulated states. These later macrophages can be seen mainly in edematous nasal polyps, which might be caused by allergic reactions of the anaphylactic type. The fine structure of the phagocytes is to some extent dependent on the actual development and functional state: there are "immature" macrophages, which are practically indistinguishable from blood monocytes (Fig. 2A); some of them can be stimulated and can therefore show many surface foldings and projections (Fig. 2B). The "mature" macrophage shows a well developed Golgi-area and many secondary lysosomes (Fig. 3). The storage type of the macrophages, which can predominate in some cases of chronic maxillary sinusitis, is characterized by many electron-lucent vacuoles (Fig. 4)...


[Otitis media and cochlea. Morphological and biochemical studies in guinea pigs (author's transl)]. The paper deals with: 1. the protein concentration in the perilymph (PL), the serum and the cerebrospinal fluid (CSF), 2. the protein pattern in the PL and 3. histological findings in the middle and inner ear in unilaterally ear-infected guinea pigs. The studies were performed 6 h to 21 days post infectionem (Fig. 1). The pathological changes in the middle ear, which, in most cases, were limited to the infected ear, were initially evaluated under the operating microscope and divided into 4 stages. The analytical and histological results were presented as functions of these stages. As the inflammation intensity increased, the protein concentration in the PL of the infected ears increased to a level exceeding that of the normal value more than ten times (Fig. 2). However, in the serum and in the CSF this concentration remained unchanged. Likewise, no significant protein increase in the PL of the contralateral ears was detectable in most cases. As the inflammation intensity increased, the number of the precipitation lines detectable immunoelectrophoretically increased in the PL of the infected ears (Fig. 3). An increase in the alpha1- and gamma-globulins and a decrease in Albumin was found by electrophoresis on cellulose acetate strips (Tab. 3). The histological findings correlated with initially established inflammatory stages of the middle ear mucous membrane (Tab. 4). As the inflammation intensity increased, the round window, too, was changed pathologically, so that in some cases of purulent otitis media middle ear secretion could enter the cochlea. The protein increase in the PL immediately after the infection is probably due to an increase in the blood vessel permeability in the inner ear.


[Ultrastructural changes of the stria vaseularis and the spiral ligament in chronic uremic rats (author's transl)]. Looking for the morphological correlation of uremic inner ear damage a 5/6 resection of kidney parenchyma in rats was performed. A biochemically proven chronic uremia was so created. The ultrastructural examination of the stria vascularis showed a marked swelling of the intermediate cells, compressing occasionally stria vessels. The stria was enlarged and the mitochondria of the dark and light cells swollen. In the spiral ligament connective tissue cells were moderately swollen and blood vessels partially obstructed by swelling of the endothelium. These changes are proved not to be dependent on the urea. The pathophysiological significance for uremic inner ear damage can only be determined after further examination of cochlear tissue.


[The influence of various acoustic stimuli upon the cumulative action potential (SAP) of the auditory nerves in guinea pigs (author's transl)]. The impact of various acoustic stimuli upon the cumulative action potential of the auditory nerves in guinea pigs is investigated by means of the averaging method. It was found that the potential amplitude within the measuring range increases with the logarithm of the rising sonic pressure velocity. Unlike the evoked response audiometry (ERA), this potential seems unsuitable for furnishing information of the frequency-dependent threshold course.


[A contribution to the identification of the oral antidiabetic agent tolbutamide. 1st communication]. An identification reaction for tolbutamide given in several pharmacopoeias involves the reaction of n-butylamine, formed by acid hydrolysis of tolbutamide, with diazotised p-nitroaniline to yield a characteristic red colour of unknown structure(s). It is demonstrated that, by using TLC methods, this red colour can be separated into 8 red or yellow coloured components. The structures of these isolated compounds were determined by spectroscopical methods and, in six cases, confirmed by unequivocal synthesis. These coloured components include one pentazdiene, five triazenes and two nitro compounds.


[Synthetic low-molecular weight interferon inducers: derivatives of diaminofluoren-9-one, diaminobenzophenones and diamino biphenyls]. Among the aminoacyl derivatives of 2,7-diaminofluoren-9-one a few compounds were found capable of inducing interferon in the mouse when administered perorally. One of them, 2,7-bis[(diethylamino)acetylamino]fluoren-9-one exhibited an inducing activity comparable to that of 2,7-bis-(2-diethylaminoethoxy)-fluoren-9-one (tilorone). The synthesis of derivatives of fluorene, fluorenol, fluorenone, diaminobenzophenone, diaminiodiphenylmethane and benzidine, all of them with corresponding side chains, allowed to establish structural requirements for interferon inducing capability.


[Absorption studies with purines. Part 1: In vitro experiments with the Sartorius Absorption Model according to Stricker]. Various purines were investigated with the absorption model, according to Stricker, their kD-values calculated and compared with one another. The diffusion speed constants showed to be dependent upon the lipoid solubility and the polarity of the drugs. The experimental methods recommended by Stricker were analyzed.


A simple electronic circuit for simulation of pharmacokinetic processes. A simple electronic circuit is constructed for simulation of the theoretical curves associated with single and multiple dosing kinetics. The output is an analog device which generates plasma concentration curves versus time, consistent with the assumption in a one-compartment open model with rapid intravenous injection or first-order absorption. Potentiometer settings offer variations in dosing schedules, distribution volumes as well as in absorption and elimination rate constants. All details are made from standard electronic components. The device can be used in teaching of the elements of pharmacokinetics.


[Effect of halothane on catecholamine metabolism in the brain stem of rats]. In an experimental study we tried to find out whether halothane, in addition to its effects on vegetative efferents, has also an influence on catecholamine metabolism of the corresponding brain sections. We studied the effects of halothane in the brain stem of rats on dopamine and norepinephrine contents and on the transformation of L-dopa into dopamine and L-norepinephrine. Anaesthesia with 2 vol% halothane reduced dopamine content by 41.4%, norepinephrine content by 17.8%. These findings could be observed even 3 h after narcosis. Electrophysiological studies show that the central nervous sympathetic activity at rest and after central excitation is clearly reduced during anaesthesia with 2 vol% halothane; 70 min after narcosis it returned to normal. Administration of L-dopa led to an increase of dopamine by 43.5% within 45 min. This transformation of L-dopa into dopamine is not affected by concurrent halothane anaesthesia. There is no increase in norepinephrine after administration of L-dopa. Thus, the effect of halothane on catecholamine metabolism in the brain stem affects the precursors of L-dopa. Halothane is said to inhibit transport of the L-dopa precursor L-tyrosine from plasma to brain tissue. Along with such an inhibition goes the depression of the sympathetic activity. In this respect and obviously on the basis of its position within the catecholamine metabolism, dopamine is more important than norepinephrine.


Visually evoked potentials in cortical and subcortical brain structures of conscious rabbits with chronically implanted electrodes. Standardized normal values and the influence of some psychopharmacological agents on them. By means of a modified and simplified surgical and implantation technique, standardized values for visually evoked potentials (EP) from 7 brain structures (caudate nucleus, posterior hypothalamus, mesencephalic reticular formation, intra-laminar thalamic nuclei, amygdala, dorsal hippocampus and visual cortex) are obtained. The importance of a careful selection of the animal material, constant test conditions and the selection of test parameters as a prerequisite for the assessment of psychotropic drugs is emphasized and discussed. As an example of the specific influence on visually evoked potentials in the above named brain structures, the effects of haloperidol and amytriptyline on latencies and amplitudes of the individual parameters of EPs are described. It is assumed that the method described can be of great assistance for investigation and classification of newly developed substances.


[Electroencephalographic study on experimental brain edema induced by triethyltinsulfate (author's transl)]. The electroencephalographic effects of several doses of a brain edema inducing agent, triethyltinsulfate (TET), was studied by implanted epidural electrodes in cats. The effect of TET on the central nervous system was found to have two phases: 1. a six hours' acute toxic phase following TET administration, 2. An edematic phase developing on the 2nd  to the 4th day. Similarly to our earlier observations brain edema induced by TET was found to be dose-dependent, as shown by EEG-s, and their analysis performed by computation.


Some aspects in the pharmacology of diclonium bromide (2-(3,4-dicholoroanilino)quinolizinium bromide). Part II: Gastric acid-antisecretory and antiulcerogenic actions. Diconium bromide, 2-(3,4-dichloroanilino)-quinolizinium bromide, a potent antispasmodic in the lower bowel of the dog, was found in the present study to exert gastric acid-antisecretory and antiulcerogenic activities in the rat stomach. These effects were demonstrated by means of short- and long-term pyloric ligation, acetylsalicylic acid (ASA)-induced ulcerogenesis, and cold-and-restraint stress studies. A reduction of gastric acid concentration by the drug was probably responsible for the decrease in the degree of ulceration and hemorrhagic lesion formation. The drug's inhibition of stress hemorrhagic lesions may be related to an effect both on gastric HCl secretion and on the vasculature in the glabdular mucosa. The delay of gastric emptying by diclonium bromide results from its known antispasmodic or smooth-muscle depressant action. The toxicity of diclonium bromide, perorally, was low in rats and overt signs of drug effect were not evident until toxic doses were administered. It is concluded that diclonium bromide may represent a useful non-anticholinergic drug effective in treating both peptic ulcers and spasticity of the colon (irritable-colon syndrome) in man.


[Disaccharidases of the intestinal mucosa of the rat after cytostatic combined therapy with vincristin sulphate and ifosfamide (author's transl)]. Vincristin sulphate or 3-(2-chloroethyl)-2-(2-chloroethyl-amino)-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide (ifosfamide)--given alone--may reduce intestinal disaccharidase activities in the rat. However, combined administration of both the drugs, as used as a therapeutic means, results in a much more drastic decrease in enzyme activities. Consequently, also in man maldigestion of disaccharides might occur due to that polychemotherapy.


Antitussive activity and other related pharmacological properties of d-3-methyl-N-methylmorphinan (AT-17). Antitussive activity and some other related pharmacological properties of d-3-methyl-N-methylmorphinan were studied. Toxic symptoms in mice and dogs were due to the CNS excitation. Acute toxicity of (AT-17) in mice was slightly (s.c.) or far (p.o.) weaker than that of codeine, but it was three times as toxic as codeine in dogs (i.v.). Antitussive efficacy was about 40% of that of codeine in dogs, whereas 77% as potent as codeine in cats. It showed no relaxing effect on the bronchial muscle of guinea pigs in either normal tone or histamine-induced spasms. It had analgesic effect 1/3 as potent as codeine in mice but it was not antagonized by levallorphan. The prolongation of hexobarbital sleeping time by AT-17 was similar extent to that by codeine. Anti-electroshock effect was half as potent as that of phenobarbital. The inhibitory effect on the transportation of intestinal contents in mice was far weaker than that of codeine. Effect on the respiratory and circulatory systems were also investigated.


On the sites of antitussive action of d-3-methyl-N-methylmorphinan (AT-17). The sites of antitussive action of d-3-methyl-N-methylmorphinan (AT-17) were studied. It was assumed from the following results that AT-17 acts on the cough centre per se. a) When AT-17 was given by the routes leading to the brain stem such as the cerebello-medullar cistern, far smaller doses were sufficient to obtain the same effect as that by i.v. administration. b) It showed neither effect on the afferent pathway for cough reflex nor influence on pulmonary stretch receptors. c) Decerebration exerted no influence on the antitussive efficacy. d) It definitely depressed the potentials of both the recurrent and internal intercostal nerves evoked by the superior laryngeal nerve stimulation. e) Micro-injection of AT-17 into the bilateral solitary nuclei or their adjacent regions inhibited coughs induced by peripheral stimulation. f) In deafferentated and decerebrate cats, AT-17 increased the spontaneous discharges of the phrenic nerve, whereas codeine decreased them.


[Adaptational behaviour of peripheral and central acoustic responses in guinea pigs under the influence of various fractions of an extract from Gingko biloba (author's transl)]. Experimental studies on 114 guinea pigs proved definitely the influence of an extract from Ginkgo biloba batch no. 02 on the acoustic system. Experiments with animals ensured that the adaptation of excitation of the organ of Corti is significantly influenced. This result is shown by registrations of the acoustic nerve potentials in the adapted and nonadapted state. The relation of excitation to adaptation is significantly changed. Under adaptation of excitation an influence on the metabolism of involution is probable. The slow evoked potentials of the acoustic cortex showed no additional influence on the central auditory pathways. With the Ginkgo biloba extract it is probably possible to diminish sound damages caused by white noise. Further experiments on animals are necessary to ensure the application of this pharmaceutical preparation for clinical use.


[On the influence of oral antidiabetics on protein biosynthesis in vitro (author's transl)]. Inhibition of protein synthesis is one of the few side effects of sulfonylureas and biguanides. Regarding our results obtained with hepatic polyribosomes from diabetic and from control animals, with ribosomes directed by polyuridylic acid as a synthetic messenger, and by centrifugation of the ribosomes through sucrose gradients there is evidence of a direct inhibiting effect of tolbutamide on liver ribosomes. The effect of butyl-biguanide depends on the system used for in vitro protein synthesis. While it is inhibiting protein synthesis of normal liver ribosomes regardless of the attached messenger, it stimulates the incorporation of amino acids by ribosomes from diabetic rats directed by endogenous or by synthetic messengers. The specific pattern of ribosomal distribution in sucrose gradients is unchanged by the administration of tolbutamide to the animal prior to its decapitation. However, butyl-biguanide leads to reduction of the polyribosomal portion of liver ribosomes from normal animals while it is without any furhter effect on the amount of polyribosomes already reduced in diabetes mellitus.


Renal effects of gentamicin and cephaloridine. Evaluation by renal enzyme excretion studies in rats and comparison with other antibiotics. The renal effects of gentamicin and cephaloridine were investigated by determining the changes in renal enzyme excretion. Both drugs provoked significant elevations or urinary AP-, LAP-, or LDH-activities. This result permits the conclusion that both drugs take influence on the kidney. The exact pathomechanism leading to this increased renal enzyme excretion was not elucidated. The fact that gentamicin in the applied dosage (about 30% of LD50) provoked more pronounced changes than cephaloridine (about 20% of LD50) could be explained by an in-vitro interference of cephaloridine with the enzymatic activities investigated in this study. In the discussion, the changes elicited in the same model by other antibacterial compounds were compared with the data obtained with gentamicin and cephaloridine. In closing, implications, restrictions, and validity of renal enzyme excretion studies in rats for screening nephrotoxic properties of a drug for human use are briefly discussed.


[Influence of diazepam and phenytoin on penicillin-induced cerebral convulsions (author's transl)]. The effects of diazepam and phenytoin on penicillin-induced EEG changes and convulsions were studied in 32 rabbits. EEG changes and convulsions were elicited by 2.4 g/kg benzylpenicillin i.v. over 50 min. The dosages of the anticonvulsants were 1, 5 and 10 mg of diazepam and 10, 20 and 30 mg/kg of phenytoin. The qualitative and semiquantitative evaluation of the electroencephalograms revealed no reduction of spike frequency or spike amplitude for either of the two drugs. However, in contrast to phenytoin, diazepam was highly effective in preventing the development of generalized convulsions. None of the 12 diazepam-treated animals developed a convulsion, whereas in most of the phenytoin treated animals and in most of the controls generalized convulsions appeared. The results suggest that diazepam should be used in the treatment of penicillin-encephalopathy.