Bromocriptine in Parkinsonism: long-term treatment, dose response, and comparison with levodopa. Thirty-seven patients with Parkinsonism were treated with bromocriptine 2.5-300 mg daily. Bromocriptine, alone or combined with levodopa, caused a 20-30% reduction in disability scores in 11 patients treated for one year. Tolerance did not develop during this period. Bromocriptine treatment was not of value in six patients who had previously not responded or who had lost their response to levodopa. However, in four of five patients with response swings on levodopa due to rapid changes in plasma dopa levels, the addition of bromocriptine caused a more stable response. Dose response curves to bromocriptine 12.5, 25, 50, and 100 mg and to levodopa 250, 500, 1000, and 2000 mg were studied in seven patients. Levodopa 2 g had a greater therapeutic effect and caused a greater rise in plasma growth hormone concentration than bromocriptine 100 mg. Levodopa caused emesis more commonly and hallucinations less commonly than bromocriptine. Bromocriptine appears to be a less potent stimulant than dopamine, and has both pre- and post-synaptic effects. Metoclopramide 60 mg oral was given 30 minutes before bromocriptine or levodopa to establish whether this caused dopamine-receptor blockade. Metoclopramide acted as a competitive antagonist to the anti-Parkinsonism and growth hormone effect of both drugs and in individual cases prevented emesis and hallucinations. The fall in blood pressure due to bromocriptine or levodopa was not antagonised by metoclopramide. Central and peripheral vascular dopamine receptors may be different in nature.


Sclerosing spinal pachymeningitis. A complication of intrathecal administration of Depo-Medrol for multiple sclerosis. Reported complications of intrathecal steroid therapy include aseptic meningitis, infectious meningitis, and arachnoiditis. We report a case of sclerosing spinal pachymeningitis complicating the attempted intrathecal administration of Depo-Medrol for multiple sclerosis. The lesion is characterised by concentric laminar proliferation of neomembranes within the subdural space of the entire spinal cord and cauda equina, resulting from repeated episodes of injury and repair to the spinal dura mater by Depo-Medrol. There is clinical and laboratory evidence that Depo-Medrol produces meningeal irritation and that the vehicle is the necrotising fraction.


New neonatal problems of blood coagulation and fibrinolysis. II. Thromboplastic effect of amniotic fluid and its relation to lung maturity. Pulmonary hyaline membrane disease in newborn infants is considered an abnormality in the alveolar lining layer. Quantitative analysis of this surfactant is necessary for the intrauterine diagnosis of lung maturity of the fetus. The presence of surfactant in amniotic fluid has been demonstrated by the shaking method [1]. But it is also well known that amniotic fluid has a thromboplastic effect [3,6]. In order to compare the correlation between the shaking method and the thromboplastic effect of the amniotic fluid, recalcification time and partial thromboplastin time were measured with and without amniotic fluid using an aggregation-meter. In each of 15 cases, a shortening of these times was recorded after the addition of amniotic fluid after the 30th week of pregnancy. In all cases the addition of amniotic fluid resulting in shortening these times. Surfactant seems to have enhancing effect on the coagulation. These results demonstrate the presence of surfactant in amniotic fluid in agreement with the results of the shaking method. Although these methods are of limited utility as quantitative assays for surfactant, they are of sufficient accuracy and of great value for clinical diagnosis.


Prenatal prediction of respiratory distress syndrome. Measurement of surface properties and Lecithin/Sphingomyelin ratio in human amniotic fluid. 118 samples of amniotic fluid were taken from 102 patients in the 25th to the 43th week of pregnancy by amniotomy or by transabdominal amniocentesis. 76 samples were obtained from patients with normal pregnancies without evidence for either induction or retardation of lung maturity; they served to establish normal values. In 37 cases samples were taken within 72 hours prior to delivery, the decisive period for the prediction of a respiratory distress syndrome. In seven cases a respiratory distress syndrome occured which was diagnosed by an independent pediatrician. The following tests were performed for all samples: 1. Surface tension was measured biomechanically using the Wilhelmy balance and a surface tension area diagram (Fig. 1) was made: A platimum plate is immersed into the liquid placed in the trough; the surface tension is measured via a transducer. The surface film of th liquid to be studied is compressed cyclically from an initial area of 100% to 20% by a moveable barrier and is expanded afterward. Platinum plate and barrier are connected to an X-Y recorder. The surface tension area diagrams are interpreted on the basis of the following criteria: see article 2. The determination of the L/S ratio (simultaneous comparison with the standard method): The method of GLUCK as modified by BORER(planimetric interpretation of the the spots) was employed. Both methods produced normal values. For the biomechanical measurements a classification into three groups was made (25th-30th, 31st-35th, 36th-43rd week of pregnancy) (Tab.I);the L/S ratio showed the usual steep increase from the 36th week of pregnancy onwards. In cases with RDS (Tab.II) surface tension-area-diagrams show high values for gamma max and a slight decrease in surface tension on compression (high gamma min values); the stability index is low, the hysteresis is reduced. Fig. 3. Up to the 34th week of pregnancy the 2:1L/S ratio assumed as the threshold for a sufficient surfactant concentration does not permit a clear interpretation; in subsequent weeks all cases fail to coincide with the normal pattern of distribution (Fig.2). Both the L/S ratio and the criteria of the surface tension area diagrams show significant differences in cases with and without RDS. The prognostic validity of both methods was tested for the probability of predicting occurrence of RDS, probability of RDS occurence and probability of non-occurrence of FDS. The prognostic value seems equal to the L/S Ratio.


Influence of molecular variations of ionophore and lipid on the selective ion permeability of membranes: I. Tetranactin and the methylation of nonactin-type carriers. The manner in which molecular structure of the carrier and the lipid composition of the membrane modulate the membrane selectivity among monovalent cations has been investigated for nonactin, trinactin, and tetranactin, which differ only in their degrees of methylation, and for membranes made of two lipids, phosphatidyl ethanolamine and glyceryl dioleate, in which "equilibrium" and "kinetic" aspects of permeation, respectively, are emphasized. Bilayer permeability ratios for Li, Na, K, Rb, Cs, Tl,and NH4 have been characterized and resolved into "equilibrium" and "kinetic" components using a model for carrier-mediated membrane transport which includes both a trapezoid energy barrier for translocation of the complex across the membrane interior and a potential-dependence of the loading and unloading of ions at the membrane-solution interfaces. The bilayer permeability properties due to tetranactin have been characterized in each of these lipids and found not only to be regular but to be systematically related to those of the less methylated homologues, trinactin and nonactin. This analysis has led to the following conclusions: (1) The change in lipid composition alters the relative contributions of "kinetic" vs. "equilibrium" components to the observed carrier-mediated selectivity. (2) Increased methylation of the carrier increases the contribution of the "kinetic" component to the selectivity relative to that of the "equilibrium" component and additionally alters the "equilibrium component sufficiently that an inversion of Cs--Na selectivity occurs between trinactin and tetranactin. (3) For all ions and carriers examined, the "reaction plane" for ion-carrier complexation and the width for the "diffusion barrier can be represented by the same two parameters, independent of the ion or carrier, so that in all cases the complexation reaction senses 10% of the applied potential and the plateau of the "diffusion barrier" extends across 70% of the membrane interior.


[Cytological changes in the csf caused by inthathecal administration of methotrexate. II. Studies on a case of neuroblastoma with cerebellar symptoms in a child]. A case of an olfactory neuroblastoma of a 5 years old child is reported. The tumour propagated into the intracranial space and produced cerebellar symptoms. Features of the neuroblastic cells, found in the cerebrospinal fluid and their alterations as an effect of the intrathecal therapy with Mathotrexat are analysed. Authors emphasize the differences of alterations of leukaemic and neuroblastic cells called into being by the Methotrexat therapy.


Relationship between experimental results in mammals and man. II. Cytogenetic analysis of bone-marrow cells after treatment of cytembena and cyclophosphamide- cytembena combination. Cytogenetic analysis and the micronucleus test of bone-marrow cells was used to study the possible extrapolation of results from experimental animals to man. Cytembena was given i.p. in doses of 5, 10, 20, 40 and 80 mg/kg body wt. to Wistar rats and in doses of 20, 40 and 80 mg/kg body wt. to ICR mice and to Chinese hamsters. Five patients with various types of malignancy, so far medically untreated, received 20 mg Cytembena/kg body wt i.v. A combination of Cytembena and cylophosphamide was applied i.p. in single equal doses 1 : 1 of 5,10, 20, and 40 mg/kg body wt to ICR mice, Chinese hamsters and Wistar rats. Patients were given i.v. 20 mg Cytembena and 20 mg cyclophosphamide/kg body wt. Bone-marrow cells were examined 24 h after the administration. The frequency of abnormal metaphases and chromosomal breaks after Cytembena treatment was low; nonetheless, the indicated dose-effect relationship was found in all the rodents used. The frequency of chromosomal breaks was 2--3 times higher in rodents in comparison with man, after treatment with a dose of 20 mg Cytembena/kg body wt. Highest frequencies of induced aberrations were found in mice. The rodents appeared to be 3--4 times more sensitive to the induction of chromosomal breaks and abnormal metaphases than man, after a dose of 20 mg Cytembena and 20 mg cyclophosphamide/kg body wt. The micronucleus test may be regarded as a screening method for assessing mutagenic activity of chemical compounds. Chromosomal analysis and the micronucleus test were about equally convincing in detecting mutagenic effects even with the lowest doses of drugs used. However, the dose-effect relationship was more pronounced in chromosomal aberrations than in the micronucleus test.


[The value of cytological screening for neoplasms in young women]. The question of the incidence of positive or suspect cervical cytology-tests in young women of 30 years or less of age out of a total of 54,604 cervical cytology-tests is discussed. The results of clinical, cytological, and histological follow-up are reported. According to our experiences that 158 smears of group Pap. III and 99 smears of group of Pap IV and V were found in young women of 30 years or less of age this group of patients should not be excluded from consecutive cervical cytology-tests or national health-screening programs.


[Adeno-epidermoid carcinoma of the cervix. An opinion on the so-called cervical adenocancroid]. The so-called adenocancroid of the cervix represents a relative rare type of tumors. The diverse morphological criterions are shown on hand of 10 personel observations and are distinguished between forms of combination and collision. The histological findings of these epithelial mixforms motify a closer occupation with the formal genesis of this cervical carcinoma. In the formal genesis of the cervical carcinoma. In the formal genesis of carcinoma of the cervix, a decisive role is being played by the proliferation of differentiated intermitotic cells (reserve cells) in the course of indirect metaplasia. Consequently the majority of carcinoma of the cervix, are not squamous-cell-carcinoma, but bipotent-cell-carcinoma. The bipotent qualities of these cells are also maintained in malignant degeneration and enable in rare cases a secondary differentiation running in two different directions. The confusing denotation "adenocancroid" should be replaced by the definition "adeno-epidermoid-carcinoma of the cervix".


Time lapse cinematographic demonstration of humoral and cell mediated immunity in squamous cell carcinoma of the lung. Out of 42 attempts in one case a cell line derived from biopsy material of a squamous cell carcinoma of the lung has been established. Tumor-associated-antigen could be demonstrated by indreict immunofluorescence. The effect of allogeneic cytotoxic antibodies, absorbed with normal human lung and sera, on the target cells is shown. Blood lymphocytes obtained from patients with squamous cell carcinoma of the lung proved to be cytotoxic against this cell line. The cell to cell interactions of this phenomenon and the effect of cytotoxic antibodies are shown by time lapse cinematography.


Serum cholesterol levels of Seventh-day Adventists. Serum cholesterol levels and dietary habits were surveyed in 27 male and 34 female Seventh-day Adventist. All subjects studied were lacto-ovo-vegetarians and a few consumed some meat products. Their serum cholesterol levels, significantly lower than those of the United States general population, showed no sex difference but increased with age and were higher in overweight males. Their levels, however, were much higher than those of true vegetarians which was most likely attributable to their consumption, even though to a limited acount, of dairy foods.


Effect of prolactin and the anit-prolactin bromocriptin on the testosterone uptake and metabolism in androgen-sensitive and insensitive canine organs. Prolactin promotes the growth and function of the prostate in low doses, whereas high doses or previous castration reduce this effect. The antiprolactin bromocriptin should reverse the prolactin action. In the castrated dog the highest accumulation of H3-testosterone given i.v. occurred in the prostate as compared with muscle, urethra, penis, liver and kidney. Prolactin pretreatment increased the radiosteroid uptake only in the liver. Converseley, bromocriptin suppressed the tracer incorporation into the liver, but increased prostatic accumulation. The highest testerone reduction occurred in the prostate of the untreated castrated dogs as compared with other organs. Prolactin suppressed 5 alpha -dihydrotestosterone formation but otherwise did not significantly influence testosterone turnover. Bromocriptin, however, stimulated dihydrotestosterone formation in the prostate and caused complete inhibition of hepatic testosterone reduction.


[Products of the interaction of ethazole with mustard oils]. Synthesized were nonsymmetrical N1N1--replaced products of thiocarbamide containing residual alkyl- and arylsinapic oils and the sulfonamide ethasole, in order to study their pharmacologic activity. The synthesis was performed through heating the components up to the point of weak boiling in an ethanol medium. The obtained nine new N1N1--thiocarbamide products were identified in terms of their melting point and sulfur analysis. Tentative microbiologic testing showed that the newly obtained compounds produce bacteriostatic and bactericidal effects.


[Determination of the concentration of copper, lead, cadmium and zinc in milk by atomic absorption spectrophotometry]. Developed was an atom-absorption method for determining microconcentrations of copper, lead, cadmium, and zink in milk originating from various regions of this country. The study was carried out by means of an atom-absorption spectrophotometer AA-5. Established were the optimal conditions for determining the trace elements reaching the following values of susceptibility: for copper--0.04; for lead--0.11; for cadmium--0.001; and for zinc--0.009 mg/cu.cm, with an allowance of 5%. The results obtained are discussed and statistically processed. Literature data are comparatively studied reflecting the amounts of these elements in milk as found in this country and abroad. Such data will be made use of in the elaboration of Bulgarian reference tables necessary for establishing various regimes and norms concerning the food products offered in children creches, hospitals, canteens, etc.


Production of Candida utilis on slop by-product of fermentation industries. The slop (vinas) liquor, a major by-product a alcohol fermentation industries, has been used as growth medium for production of the torula yeast, Candida utilis. Supplementation of the slop with 0.2% ammonium sulphate and 1% to 5% molasses improved the cell yield significantly. The crude slop gave better results than the diluted or centrifuged liquors. Under optimal conditions, more than 15 grams of yeast were obtained on dry weight basis. The application feasibility of these results is presented.


Effect of some pesticides on the efficiency of the inoculated Rhizobium associated with broad bean plants. The effect of some pesticides on the efficiency of the inoculated rhizobium in broad bean plants (Vicia faba) was studied in greenhouse experiments. Different pesticides were used in this work, including insecticides, herbicides, nematocides, and a molecide in different concentrations. The study revealed the following conclusions. Application of insecticides in different concentrations generally affected the formation of efficient nodules on the root system of broad bean plants. The inhibitory effect was also reflected to some extent on the dry weight of the plants and total nitrogen fixed by rhizobia in association with the mentioned plants. Birlane (insecticide) was found to be the most inhibitory insecticide on the inoculated rhizobium. Some of the insecticides, such as Temik and Dursban, at lower concentration were found to be a stimulant to symbiotic N-fixation, giving higher amounts of nitrogen fixed in the macrosymbiont.


Possible role of solar radiation on the viability of some air fungi in Egypt. The high occurrence of Alternaria humicola and the moderate occurrence of Stemphylium verruculosum, Rhizopus nigricans, and Epicoccum nigrum in the air of Egypt could be correlated to their apparent resistance to solar radiation. Cladosporium herbarum, Aspergillus niger, and Penicillium oxalicum, although highly occurring, were light-sensitive. The miniumum solar radiation in November, coupled with the highest total fungal catch, dominated by Cladosporium herbarum, reveals the importance of solar radiation as a factor with direct effect on the air fungal population.


Actinomycetes in the desert of Kuwait.

Actinomycetes in the desert of Kuwait. The distribution of actinomycetes in two desert localities in Kuwait was investigated. The genus Streptomyces was dominant in the two studied localities. Attempts to classify this genus in groups and species were made. Species producing straight or wavy spore chains were dominating in the two localities. Species producing oval spores and smooth spore surfaces were widely distributed. The most frequent is the cinereus series. Streptomyces aburaviensis and S. wedmorensis were more frequent in Cyperus locality, while S. calvus was the dominant one in Rhanterium locality. Each locality was characterized by different groups and species.


Simple method for carbon determination in microbiological experiments. A wet combustion method for the carbon determination was developed. It has been proved that the method can be successfully used for the determination of biochemical changes in microbe cultures, the soil, in composts, in farmyard manures etc. The samples are combusted in evacuated flasks by means of chromic sulphuric mixture, and the CO(2) evolved is determined interferometrically.


The effect of some organic substances on the mycelium of the fungus Ustilago nuda (Jens.) Rostr. Research was performed for studying the effect of some organic compounds, considered by many authors as the products ob barley seed metabolism generated after anaerobic seed treatment, on the mycelium of the fungus Ustilago nuda (Jens.) Rostr. The author examined the effectiveness of ethylacohol, acetaldehyde, acetic acid, succinic acid, lactic acid, and hydroquinone in concentrations from 1 M to 10(-6) M, and the effectiveness of extracts from disinfected seeds in doses from 10 g to 0.001 g/l. The effect of the mentioned solutions was examined as exerted on the growth of dicaryotic mycelium and on the growth of the haploid promycelium of the fungus. The dicaryotic mycelium of Ustilago nuda (Jens.) Rostr. was cultivated on potato agar with benzoic acid. The presence of the acid prevents mitosis, and the chlamydospores germinate on the nutritive medium with two fibres having binuclear cells. The haploid promycelium was cultivated  on potato agar; chlamydospores germinated with one four-cell fibre, and individual cells are mononuclear and haploid. Only later, a dicarytic mycelium is created in a complex process. In all the substances used, the concentration of 1 M was found to stop further growth of mycelium. The concentration of 10(-1) M of acetic acid and hydroquinone also stopped growth, the same concentration of acetaldehyde, lactic acid, succinic acid, ethylacohol stimulated mycelium growth in comparison with the control. The concentration of 10(-6) M stimulated mycelium growth in a majority of cases. Extracts from disinfected seeds did not influence mycelium growth significantly in all cases in comparison with the control. The results were similar in the two types of mycelium.


[Relations within genus Cryptococcus (Sanfelice) Vuillemin]. A collection of 49 Cryptococcus strains was studied by means of 62 tests, which emphasized morphological, physiological and biochemical properties. The experimental results were subjected to computer analysis using matching coefficient and taxanomic distance. Cluster analysis were carried out using average linkage method. Two clusters and one individual strain were formed, the first cluster represented the genus Cryptococcus, the second cluster and the individual strain did not belong to this genus. The cluster of the genus Cryptococcus was divided into five phenons: Laurentii Neoformans, Albidus, Terreus and Aerius. The belonging of strains to these phenons is discussed comparing the results with those of GC% content in DNA, of the production of coenzyme Q and many other. The quick identification phenons was suggested.


Effect of phosphate fertilization and seed inoculation with ""Okadin'' at high rate on yield of broadbean and lentil. The effect of phosphate fertilization and seed inoculation with ""Okadin'' preperation of rhizobia strains on the yield of broadbean and lentil was tested in field experiments during the seasons 1969 to 1972 in the farm of Faculty of Agriculture, Assiut University. Superphosphate was added at the rate of 0, 50, 100, or 200 kg/fa., and ""Okadin'' preparation, specific for the kind of legume planted, was applied to the seeds at 10 times the recommended rate. Application of superphosphate at any of the tested rates did not significantly affect total yield obtained, seeds yield, or the nitrogen content of seeds of lentil or braodbean. Seed inoculation with Okadin showed no significant effect on the yield of broadbean, but resulted in significant reduction in the yield of lentil seeds in the two seasons of the experiment.


The lack of detectable immune complexes in rat anaphylaxis. Attempts were made to detect soluble immune complexes (IC) in sera of rats submitted to anaphylactic shock 12 days following BPV plus antigen treatment, and their in vitro formation following the addition of specific antigens to sera or heparinized platelet rich plasma of sensitized rats. We failed to detect ICs or IC formation by studying Hageman factor activation and platelet aggregation or by using a very sensitive radio-assay of ICs. It is established that the anaphylactic activation of Hageman factor as well as the aggregation of platelets are not mediated by immune complexes, therefore, other explanations must be found.


Clinical significance of the house dust mite (Dermatophagoides pteronyssinus) in asthmatic children in Japan. Clinical studies were conducted to evaluate the role of the house dust mite. Dermatophagoides pteronyssinus, as an allergen in children's asthma in Japan. Skin testing and Prausnitz-Küstner type skin testing showed good correlations between the allergenicity of house dust and the mite. A positive Prausnitz-Küstner type skin reaction to house dust was neutralized by a mite extract. Radioallergosorbent test showed good correlation between house dust and the mite (r=0.687). The mite exhibited in vitro inhibition of radioallergosorbent test to house dust. The inhalation provocation test resulted in an acute respiratory attack in one of the patients. These results suggest that the house dust mite is an important allergen in asthmatic children in Japan.


Inheritance of asthma in families and its linkage to HLA haplotypes. Four families in which asthma occurred in more than three members, and in which there were at least three children, were studied in terms of clinical symptoms, serum IgE levels determined by RIST and RAST, and HLA haplotypes. No association between clinical asthma and serum IgE level was found, but a close association between asthma and a particular HLA haplotype in a family was demonstrated. It was therefore postulated that a disease susceptibility gene closely linked to an HLA gene complex may play a role in the development of asthma.


Why a meniscectomy fails.

Why a meniscectomy fails. The clinical and roentgenological data on 30 patients with unsatisfactory recovery or recurrent symptoms after meniscectomy were analysed. The meniscectomy was regarded as having been the wrong choice of therapy in four patients and as ineffective therapy in 11. In 10 patients other knee lesions dominated postoperatively, in three the recovery was delayed for no obvious reason but the symptoms slowly disappeared, and in the remaining two patients a degenerative osteoarthritis developing some time after the meniscectomy was regarded as the cause of the recurring symptoms. We conclude that with an optimal clinical and arthrographic analysis and with careful operative tecnique as many as 17 arthrotomies (out of 30 primary and 13 reoperations) in the material presented could have been avoided.


The place of total thyroidectomy in the management of 909 patients with thyroid disease. An analytic review of 909 total thyroidectomies reveals complications and sequelae comparable to those that follow subtotal operations for Graves' disease, nodular goiter, and chronic thyroiditis. It is suggested that when surgery is indicated for the management of these diseases, nothing less than total thyroidectomy should be performed because of the important additional advantages obtained with this operation.


Use of chestnut in the feeding of infants allergic to cow's milk or intolerant to lactose. The aminoacid contents of native chestnut and its powdered form were studied. It was found that it has low cystine and methionine contents but if it is supplemented accordingly, the chestnut pulp can well be used for infant feeding. More than 50 infants were fed with chestnuts, and only in two cases was there intolerance. The aminoacid content of supplemented chestnut formula was lower than that of cow's milk and soy bean, but equal to that of human milk and as its essential aminoacid ratio was high, the infant's development was normal. Chestnut pulp is recommended as an alternative to soybean in the treatment of lactose intolerance and cow's milk allergy.


[Influence of heated linseed oil on reproduction in the female rat and on the composition of hepatic lipids in young rats]. During gestation and lactation, six month old female Wistar rats were fed diets containing 10 p. 100 by weight of various vegetable oils; thermopolymerized linseed oil at 275 degrees C for 12 hours under nitrogen atmosphere (group T), oxidized linseed oil at 200 degrees C for 100 hours under air atmosphere (group O). The two oils contain respectively 11,5 and 1,1 p. 100 of cyclic monomers (18 C). Control groups were fed either fresh linseed oil or fresh peanut oil under the same conditions. In group T, most of the newborn rats die at birth or during the first three days of life; none of them survive 13 days after birth. In group O, mortality of youngs is not so high but is still significantly higher than in control groups. Moreover, dead young rats of group T have heavier livers and higher lipid content in the organ. Cyclic monomers were detected in liver fatty acids. In surviving young rats of group O,the body growth during lactation is significantly slower than in control animals. Young rats of group O were sacrificed at the age of 14 days. Liver weight and lipid content of the organ are increased and cyclic monomers were detected. The effects are however less pronounced than in group T. One can assume that among abnormal compounds formed during heating of linseed oil, cyclic monomers are responsible for the toxic effects observed in the present experiment since they have been transmitted to the litters either during gestation or lactation.


[Transference of cyclic monomeric acids into the milk of female rats eating thermopolymerised linseed oil]. Six month old female Wistar rats were fed a commercial diet until littering. Then they received a diet containing 10 p. 100 by weight of thermopolymerized linseed oil at 275 degrees C for 12 hours under nitrogen atmosphere. No mortality has been found among young rats during lactation but body growth is slower. In rats sacrificed at the age of 14 days stomach content (milk) and liver were analyzed for lipids. In milk and liver fatty acids respectively 2,7 and 3,0 p. 100 cyclic monomers (18 C) were detected. Consequently, the present study shows that these abnormal compounds formed during hearing of the oil are transmitted to the youngs before weaning through mother's milk.


[Local anesthesia after percutaneous administration. I]. Local anesthesia of the intact skin is difficult because of the skin barrier to epicutaneous penetration. Using solutions of local anesthetics in organic agents, which have the ability of penetrating the skin without causing irreversible damage and enhancing the percutaneous absorption of all materials dissolved therein, topical anesthesia seems to be attainable. A satisfactory method for determining pain threshold in uninjured skin of animals has been set up. Measurments of the pricking pain threshold have been made by exposing the skin of guinea-pigs to defined mechanical and electrical stimuli. A nociceptive muscle reflex (twitch) has been taken as the index of pain sensation. The suppression of this twitch has been used as an indicator of anesthetic potency. Two methods have been applied with varying parameters: stimulation at a fixed intensity until the pain threshold was reached (duration of anesthetic effect) and stimulation with increasing stimulus strenght until the cutaneous reflex was elicited (intensity or "depth" of anesthesia). The local anesthetic effects of lidocaine, fomocaine and procaine bases were studied, after dissolving them in dimethyl sulfoxide (DMSO), a wellknown carrier for transmembranal application. The duration of local anesthesia measured by electrical stimuli was longer than that obtained with mechanical ones. Differences are discussed. All results indicate that fomocaine (5%) has a greater local anesthetic potency than procaine (5%) but both are less active than lidocaine (5%). No effect could be seen after application of DMSO alone.


[Local anesthesia after percutaneous application. II]. Cyclohexane and hexadecane have been found to accelerate the penetration of local anesthetics (lidocaine, fomocaine, procaine) through the intact skin of guinea-pigs. Dissolved in cyclohexane, the potency of lidocaine is twice that of fomocaine, the latter being more active than procaine. When dissolved in hexadecane, the activity of the local anesthetics in markedly reduced. In combination with 2-butanone, (30% w/w), a solvent without any apparent effect on the permeability of skin, enhanced anesthetic effects are noted. The anesthetic bases, dissolved in dimethyl sulfoxide, produce a much deeper and longer local anesthetic effect than the solutions of their salts.


Effect of pre- and post-surgical active BCG immunotherapies on murien EAkR lymphosarcoma. A combined treatment modality incorporating surgery plus BCG immunotherapy was administered to (DBA/2 X C57B/6) F1 mice grafted with EAkR lymphosarcoma. 30% of mice survived free of disease when BCG was injected intravenously two days after operation consisting of tumorectomy plus excision of the regional lymph node performed on the 8th day after tumor inoculation. Similar results were obtained when BCG was injected subcutaneously 6 days before surgery. Pre-operative intravenous and post-operative subcutanous BCG administration failed to cure the animals just as BCG or surgery alone.


Effects of the removal of the regional lymph nodes on the survival of mice bearing B 16 melanoma or EAkR lymphosarcoma. This work presents data concerning the effect of tumor excision accompanied or not by the removal of the regional lymph node (RLN) on the survival time of mice bearing the EAkR lymphosarcoma or the B16 melanoma. The operations were performed at various times to study this effect in relation to tumor volume. Early tumorectomy, on day 6 for the EAkR lymphosarcoma, on day 10 for the B16 melanoma, prolonged significantly the survival time. The additional removal of the RLN abolished this beneficial effect. In the case of the EAkR lymphosarcoma, a beneficial effect on the survival time was in contrast observed after a total excision of the tumor accompanied by RLN removal performed on day 8. The two surgical procedures were ineffective in increasing the survival time when they were applied after the 8th day for the EAkR lymphosarcoma and after the 10th day for the B16 melanoma. These results suggest that the preservation of the RLN may be favorable for the host at least at an early stage of the tumor growth.


[Electric abdominal epidutaneous findings in the pathology of colonic motility]. Abdominal epicutaneous electrical activity has been studied in a group of 58 gastroenterically normal subjects or suffering form colon motor pathology. An evident similarity of behaviour was observed in the various groups: 17 out of 18 subjects with irritable colon and 6 out of 7 with subocclusion of the colon presented waves with characteristic amplitude and frequency. This type of electrical activity was present in only 1 normal subject out of 20; 11 patients with paralysis of the colon did not present waves of note; three patients with ulcerative colitis showed behaviour similar to the majority of the normal subjects. The technique illustrated would appear adequate for the study of colon pathology with motility alterations.


[Effect of prolonged hyperoxia on rabbit lung lipids and their fatty acid content (author's transl)]. The effect of a 36-hour hyperoxia (60 % oxygen) on rabbit lung lipids has been investigated. It has been established that hyperoxia leads to the increase of all lipid fractions in lung tissue and alveolar surfactant, phospholipid and cholesterol being most significantly affected. It has also been found that hyperoxia leads to the decrease of palmitic acid and to the increase of linoleic and arachidonic acids almost in all lipid fractions. Marked changes in the positional distribution of fatty acids in alveolar surfactant phosphatidylcholine have also been observed. The possible mechanisms of the effect of oxygen on lung lipid metabolism have been discussed, and the consequences ensuing from it which could affect the structural organization of membranes have been evaluated.


[Contribution to the study of Salmonella in Martinique. Evolution during 1972, 1973 and 1974]. In La Martinique a study of 7,861 coprocultures shows that the number of Salmonella carriers constantly increases; in 1974, it reaches 3-95 0/0. The main serotypes are: S. panama, S. saint-paul, S. typhi murium and S. anatum. Imported foodstuffs seem to be responsible for this dissemination.


[Blastomyces dermatitidis blastomycosis in Africa. First Algerian case]. A case of fatal generalized Blastomycosis is reported. It was the first case of that mycosis observed in Algeria. The parasitic yeast-like cells of the fungus were seen in pus and tissue sections and Blastomyces dermatitidis cultured from pathological specimens. Yeast-like form was obtained in vitro on Kurung's agar at 37 degrees C. Male hamsters infected with this strain failed to develop an experimental disease. The occurrence and distribution of Blastomycosis in Africa are discussed.


[Prevention of reintroduction of malaria in Reunion in 1972-1973]. On the island of the Reunion, malaria was eradicated; however the situation remains precarious because of the presence there of a very effective vector and also because of the frequent trips in neighbouring countries in particular Madagascar. The fight against the reintroduction of this formerly prevalent disease requires strict control of travellers as well as the detection and rapid treatment of imported cases. Ever on a small island with a strong sanitary organization; this vigilance can be difficult.


Allergy to ingredients of vehicles.

Allergy to ingredients of vehicles. Common ingredients of vehicles such as perfumes, antibacterial agents, emulsifiers and other surface active agents, propylene glycol, lanolin and wool alcohols were tested in eczema patients over a three-year period. Perfume allergy was detected in 3.6% of the cases, sensitivity to thiomersal in 2%, to sorbic acid in 0.8%, to parabens in only 0.3%, and to wool alcohols in 1.2%. Reactions to emulsifiers were seen over 1% of those tested.


Epidemiology of cutaneous leishmaniasis in Iran: B. Khorassan Part V: Report on a focus of zoonotic cutaneous leishmaniasis in Esferayen. During August and September 1975, an epidemiological investigation was carried out in another focus of cutaneous leishmaniasis in Khorassan province namely the Esferayen district located in the north western part of this province. The disease in Esferayen area is of zoonotic type having Rhombomys opimus as reservoir and P. papatasi as vector.


Venereal herpes-like molluscum contagiosum: treatment with tretinoin. Molluscum contagiosum spread by sexual contact may be mistaken for other venereal diseases. The occurrence of a penile lesion resembling herpes progenitalis, and successful therapy of genital mollusca with topical tretinoin (vitamin A acid) is described.


New topical agents for dermatophytosis.

New topical agents for dermatophytosis. Several new synthetic antifungal agents have recently become available for topical use. Reported experiences with haloprogin, miconazole and clotrimazole are reviewed. Topical preparations of these agents are nonirritating and effective in the treatment of superficial fungus infections. They are effective in the management of tinea versicolor and cutaneous candidiasis as well as dermatophytosis.


[An epidemic of trichinosis in Paris suburbs. (Preliminary note)]. A recent trichinosis epidemy involved around hundred patients in southern Paris suburbs; most frequent and marked clinical features were: facial and palpebral oedema, fever, bowel troubles (mostly constipation; diarrhea was seldom) and muscular tenderness. Most of the time eosinophiles cells and muscular enzymes were markedly raised. Trichinosis was proved by serological changes, with some delay. One muscular biopsy was found positive. Therapy consisted either in Thiabendazole (manufacturer's name: Mintezol) sometimes associated with prednisolone, or fluoromebendazole. There was no lethality.


Nongonococcal urethritis.

Nongonococcal urethritis. Nongonococcal urethritis may now account for most cases of symptomatic urethritis seen at VD clinics in the United States. Well-controlled etiologic studies in nongonococcal urethritis have implicated Chlamydia in over 40% of cases but the etiology of Chlamydia-negative cases remains uncertain. Tetracycline provides effective antimicrobial therapy, but tests for cure are often inadequate, and distinguishing relapse and reinfection is difficult. For tetracycline-allergic patients, erythromycin should be used. Control measures to decrease transmission of nongonococcal urethritis are not well established.


[Lipid and protein balance in diabetic Senegalese]. Lipids and protids in diabetic Senegalese show the following characteristics: 1. Lipids. The lipid content of the blood and all its component parts are increased in a significant manner in relation to the homologous values of healthy Senegalese which are lower than those of Europeans. Therefore diabetic Sengalese have the same lipidic values as those of healthy Europeans. 2. Protids. The protidic value is higher in diabetic Senegalese than in healthy Senegalese. Proteinograms show a particular distribution of the various protidic compounds. In effect, if the A/G ratio of healthy Senegalese is 0.8 (1.2 in healthy Europeans), the same ratio is equal to 0.4 in diabetic Senegalese.


[Human leptospirosis in Martinique].

[Human leptospirosis in Martinique]. Eco-geographic conditions are good for spread of Leptospiroses in Martinique. Leptospiroses are widespread in all parts of the Island. Many people have animals in inhabitation area. When they are sought, Leptospiroses can be diagnosed. During 3 years, we found many cases confirmed by biological diagnosis (immunological research of antibodies). Icterohaemorrhagiae is the first serogroup encountered and the most frequent. After follow Canicola, Ballum, Cynopteri and Javanica. Actually, Leptospiroses are a disease more frequent than is generally thought in Martinique. But only the severe cases are hospitalized, so diagnosed. Many cases of fever of unknown origin can be Leptospiroses.


Social class and morbidity in clinically treated alcoholics. The lifetime physical disease profiles of 122 lower and 724 middle class non-skid row alcoholics admitted to an inpatient treatment facility were compared to further clarify the significance of social class as a determinant of morbidity in alcoholics. The overall severity of physical disease and the frequency of all recorded lifetime illness diagnoses were greater in the lower than in the middle class. The former experienced more trauma, genitourinary disorders, venereal disease and malnutrition, as well as small excesses of respiratory and nervous system disorders. There were no class differences in the lifetime frequencies of liver and biliary tract, gastrointestinal, cardiovascular, endocrine and metabolic, integumentary, locomotor and haemopoietic disorders, or in the incidences of a number of disease entities including acute brain syndromes and chronic brain damage. The drinking patterns of the classes were similar, but the average duration of hazardous drinking was longer and the average current consumption was greater in the lower class. There were no class differences, however, in the average duration of hazardous drinking before the first occurrence of certain diseases. The referral sources of the classes were significantly different. Possible explanations for the differences between the findings of this and earlier studies are discussed.


[Wound myiasis caused by Lucilia sericata]. Report of a case of miyasis in Lucilia sericata infected wounds recently observed in Paris in a 67-year-old vagrant. The authors describe the role played by Lucilia sericata in therapy before the appearance of sulfanilamides and antibiotics.


[Epidemiological study on the incidence of chronic lymphocytic thyroiditis in childhood (author's transl)]. An epidemiological survey on the incidence of chronic lymphocytic thyroiditis in childhood was performed in 11,353 apparently healthy school children in Chiba prefecture, Japan. The present study included 9,416 school children (4,401 boys and 5,015 girls, ages 6--18 yrs) in Chiba City and 1,937 children (744 boys and 1,193 girls, ages 16-18 yrs) in Tateyama City. The first group was selected as a representative of urban area, and the second group was selected as that of seaside area. Children having goiter were selected for testing antihyroblobulin and antimicrosomal antibodies in sera. Final diagnosis of chronic lymphocytic thyroiditis was based on histological specimens obtained by needle biopsies on the antithyroid antibody positive subjects. The overall incidence of chronic lymphocytic thyroiditis in these children with 1.7 per 1,000 children. There was a considerable sex difference in the prevalence. None of the patients were boys. In girls the incidence increased with age: ages 6-12 0.9, ages 13-15 4.6 and ages 16-18 3.1-4.2 per 1,000, respectively. The incidence in the seaside area, 2.6 per 1,000 was not significantly higher than that in the urban area, 1.8 per 1,000. Histologically, all cases were classified as focal thyroiditis.


Immune deposit nephritis in infectious mononucleosis. A 22-year-old white male (L.V.) died of gram-negative septicemia complicating infectious mononucleosis (IM) that was associated with jaundice and oliguric renal failure. The kidney showed mesangial granular deposits of IgM and C3, mesangial electrondense deposits, and interstitial infiltrates of infiltrates of mononuclear cells, including atypical lymphocytes. Eluates obtained from kidney, spleen and liver contained Paul--Bunnell (PB) antibodies. Presence of PB antigens in these tissues was indicated by absorption of PB antibodies from IM sera, with the sediments resulting from tissue elutions. The IgM mesangial deposits were partially eluted with acid buffer at 56 degrees C and then reconstituted by incubation with IM sera or with immunoglobulins eluted from tissues of patient L.V. The presence in renal structures of PB antigens, IgM heterophile antibody, C3 and electron-dense deposits is consistent with the hypothesis that heterophile immune complexes were localized in the kidney and that they contribute in the pathogenisis of IM nephritis.


[Rift valley fever and rickettsial retinitis including fluorescein angiography (author's transl)]. Three cases of Rift Valley fever retinitis and one case of Tick Bite fever retinitis are presented. The clinical features are indistinguishable, manifesting as localised areas of retinal ischaemia and soft exudate formation. Fluorescein angiography shows that there is primary involvement of the retinal circulation without involvement of the choroidal circulation. Vascular occlusion is a feature of the retinal pathology. These patients were treated with steroids and immunosuppressives as their maculae were threatened and they all regained normal to near normal vision except in one case in whom old macula scarring from previous episodes of the disease prevented visual improvement.


[Study of mechanical work of the heart in patients with toxic goiter by means of electrokymography]. A study was made of the electrokymogram (EKG) of the left and the right ventricle of the heart in 54 patients suffering from toxic goiter chiefly with a marked clinical picture of the disease. Electrokymography permitted to detect enlargement of the ventricles. Excited pulsation of the ventricles with a rapid rise in systole and a sharp fall in diastole pointed to myocardial hyperfunction. Rapid and energetic contractions of the heart led to intensification of the oscillatory movements of the heart in the chest cavity, and to its rotation. A low-wave pulsation with small frequent waves of low amplitude pointed to a reduction of the contractile function of the myocardium; this was also indicated by the increase of the latent EKG time and the paradoxical movements at the beginning of systole. After the effective treatment the EKG of the ventricles showed almost no difference from the curves of healthy individuals. Changes in the character of the ventricular pulsation in toxic goiter were observed already at the early phase of the disease when some of the patients still displayed no changes in the ECG, and no X-ray data pointing to the affection of the heart were as yet evident. In the presence of phenomena of cardiac insufficiency the EKG objectively proved the presence of changes in the myocardium. The EKG data corresponded to the severity of the clinical picture of the disease. Electrokymography serves as a valuable method for analysis of the function of myocardium of the ventricles in toxic goiter.


Studies of an inhibitor of the thrombin-fibrinogen reaction localized in rat liver microsomes. Interference with the polymerization step. A heat-stable, macromolecular inhibitor of the thrombin-fibrinogen reaction localized in rat liver microsomes has been shown to interfere with the polymerization step in the fibrinogen-fibrin conversion. The inhibitor had no effect on thrombin activity as measured with the synthetic, chromogenic substrate BZ-Phe-Val-Arg-pNA. The amount of fibrin formed and the release of fibrinopeptide A were not affected by the inhibitor. Recording of turbidity at 350 nm and 600 nm indicated an inhibition of the lateral aggregation of the end-to-end fibrin polymers. The inhibitor was localized in both the luminal and membrane fractions of the microsomes. The inhibitor activity was not affected by warfarin treatment of the rats.


Effect of the root extract of Fagara zanthoxyloides on blood coagulation. The clot-promoting activity of the aqueous extract of Fagara-zanthoxyloides Lam plant is described for the first time. It significantly shortened the PTT (K) of normal and factor VIII deficient plasma while it manifested no such action on factor IX-deficient plasma. This activity could be demonstrated in the residue of the lyophilized aqueous extract after its successive extraction with ether, chloroform and methanol. It could not be attributed to the purified fractions: Zanthoxylol or its modified form 3, 4-dihydro-2,2-dimethyl-2H-1 benzopyran-6-butyric acid (DBA), hesperidin, Fagaramide or the ether soluble fraction of the aqueous extract.


The influence of ethanol feeding on the activities of factors II, VII, VIII, IX and X in rats. The effect of chronic administration of ethanol to rats in a controlled regimen upon the activities of the coagulation factors II, VII, VIII, IX and X has been studied. No significant differences were found for factor II, IX and X between the ethanol-treated rats and the control group given an isocaloric diet with carbohydrate replacing ethanol. Factor VII activity was somewhat higher and factor VIII activity decreased significantly in the experimental group when ethanol treatment was combined with an approximately two-fold increase in dietary polyunsaturated fatty acid.


Bleeding disorder with abnormal wound healing, acid-soluble clots and normal factor XIII. An unusual bleeding disorder clinically resembling factor XIII deficiency is presented. The only detectable coagulation abnormality was rapid clot dissolution in 1% monochloroacetic acid. This abnormality was ascribed to the sustained increase of  a pepsin-like plasma protease which is activated at low pH. Asystematic search for similar phenomena revealed that massive blood transfusion may also enhance plasma-clot solubility in acid, possibly by release of a red cell protease. We conclude that the acid clot solubility test is not a specific indicator of factor XIII deficiency, but this simple assay is recommended for further studies of acid plasma protease activity. The diagnostic relevance and pathophysiologic importance of increased pepsin-like activity in plasma remain to be elucidated.


Plasma factor XIII and platelet factor XIII in hyperlipaemia. Plasma factor XIII activity measured by a quantitative assay was found to be significantly higher in hypertriglyceridaemic patients (type IV and combined hyperlipoproteinaemia), as compared to normolipaemic controls. No such elevation in plasma factor XIII activity was found in patients with type Ha hyperlipaemia. Plasma pseudocholinesterase was found to parallel the elevated factor XIII activity in hypertriglyceridaemic subjects. In contrast, platelet factor XIII activity was not raised in hyperlipaemic subjects, and plasma factor XIII was found to be normal in a normolipaemic subjects with thrombocythaemia. It was concluded that there is no significant contribution from platelets to plasma factor XIII activity, and that the observed increase in plasma factor XIII in hypertriglyceridaemia results from enhanced hepatic synthesis of the enzyme.


Demonstration of reactivity to airborne and food allergens in cutaneous vasculitis by variations in fibrinopeptide A and other blood coagulation, fibrinolysis and complement parameters. In a 32-year-old woman and a 40-year-old man with cutaneous vasculitis, etiological allergic responses to foods and airborne allergens were found. During provocation tests, observations were made on blood levels of fibrinopeptide A(FPA) and coagulation factors, fibrinogen degradation products (FDP) and serum complement components. Skin biopsies were taken for microscopic and immunofluorescence analysis. In case 1, anaphylactoid allergy to milk and reaginic and anaphylactoid hypersensitivity to grass pollens were found. Dermal provocations with grass pollens gave arthralgia, hematomas, serum C3 fluctuation, factor VII reduction and fibrinolysis. During peroral milk challenge, transient increases in FPA and FDP levels were observed before symptoms appeared. In case 2, anaphylactoid hypersensitivity responses to bacteria, animal danders, foods and pollens were found. Two inhalations with sheep-wool extract resulted in a typical skin eruption. The first also gave an early reduction of C3 and then FPA liberation. Nasal birch-pollen test gave an increase of FPA in the latent period and then typical nodules. At least no low molecular weight FDP were detected during provocations. In patients with vasculitis reactions to exogenous allergens, FPA and FDP estimations after provocations may discriminate harmful from innocuous allergens and reveal individual response patterns in coagulation and fibrinolysis systems.


The effect of the fibrinogen concentration and the leukocyte count on intravascular fibrin deposition from soluble fibrin monomer complexes. Fibrin formation from fibrin monomer (FM) complexes was studied in experimental animals utilizing a previously described technique for quantitating fibrin deposition. A uniform thrombin infusion was used to produce FM, fibrinolysis being inhibited by EACA. In vivo complex formation between FM and 125I-fibrinogen was demonstrated chromatographically. A direct correlation was found between blood fibrinogen concentration and fibrin deposition in organs. By contrast, an inverse correlation between fibrinogen concentration and both enzymatic or non-enzymatic fibrin formation was found in vitro. The mechanism by which fibrinogen potentiates FM precipitation in vivo could not be explained by coprecipitation of fibrinogen in the complex which could not be demonstrated. The inhibitory effect of HN2 on fibrin deposition despite the associated hyperfibrinogemia induced by this drug is believed to underscore the importance of leukocytes in certain types of fibrin deposition. A correlation between the leukocyte count and fibrin formation from FM was also found. It was concluded that the risk of intravascular fibrin deposition is increased by a raised fibrinogen level especially when accompanied by leukocytosis.


Thrombin elaboration in endotoxin-induced intravascular fibrin deposition. A leukocyte dependent process distinct from systemic hypercoagulability. Intravascular coagulation was induced by two appropriately spaced doses of endotoxin and by infusion of thromboplastin. The resulting fibrin deposition was measured by a previously described quantitative technique. Evidence of thrombin elaboration was obtained indirectly by measurement of fibrin monomer (FM) and by the detection and isolation of a thrombin-induced anticlotting activity. Venous segments were isolated at intervals and examined for thrombus formation following 40 minutes of stasis. Endotoxin triggered thrombin elaboration was not detectable in the circulation for at least one hour and was not accompanied by any thrombosis in isolated venous segments. No thrombin elaboration was found in leukopenic rabbits given endotoxin. In the thromboplastin infused animals, the quantity of fibrin deposited in the organs was comparable to that found after endotoxin. However, thrombin was found in the blood immediately and was associated with thrombosis in the isolatet venous segments. Less thrombin-induced anticoagulant activity was found after thromboplastin than after endotoxin. The findings suggest that endotoxin-induced intravascular coagulation is probably not caused by a mechanism of systemic hypercoagulability due to the release of thromboplastic material into the blood stream. A focal process of thrombin elaboration involving leukocytes is postulated. The study is believed relevant to patients with disseminated intravascular coagulation in whom venous thromboembolism is rarely found despite evidence of extensive microvascular fibrin deposition.


Inhibitory effect of acetylsalicylic acid on human platelet function in normal volunteers and in women using a combined oral contraceptive regime. Six parameters related to the release reaction were measured simultaneously in 10 human volunteers prior to the intake of one single dose of 1 g acetylsalicylic acid and 1, 4, 5, 6 and 7 days alter: deltaE5 with diluted collagen, deltaE10 with Thrombofax and the serotonin-14C release by undiluted and diluted collagen, by Thrombofax and by bovine plasma. The duration of the inhibitory effect varied according to the test used. It was the most prolonged (through the 7th day) if serotonin-14C release by diluted collagen was measured. A systematic investigation of the platelet release reaction in women taking a combined oral contraceptive was also performed. There were no statistically significant differences from a control group. No difference in acetylsalicylic acid sensitivity, measured 24 hours after intake of 1 g of aspirin, could be demonstrated.


Effect of aspirin on platelet phospholipids. It was observed that the acetylsalicylic acid "in vitro" (final concentration 10(-4) M) as well as "in vivo" (1 g of aspirin) caused a platelet phospholipids variation which basically consisted of: 1. A diminution of the phospholipids/proteins rate of 22%. 2. A reduction of sphingomyelin "in vivo" of 27.66% and "in vitro" of 16.82%. 3. An increase in phosphatidyl choline "in vivo" of 12.24% and "in vitro" 10.28%. The possible effects that these changes might have on the platelet function are evaluated.


Impairment of ADP-induced platelet aggregation by hashish components. ADP-induced aggregation of washed human platelets is inhibited by the hashish components delta1-tetrahydrocannabinol (THC) and cannabidiol (CBD). The inhibition is counteracted by added ADP. When the cannabinoids are present at concentrations higher than 10(-5)M, the platelets aggregate non-reversibly, independently of an added inducer, apparently due to lysis and release of endogenous inducers. THC is clearly more potent than CBD in exhibiting the biphasic effect. Collagen- and thrombin-induced aggregation of washed platelets are hardly affected by the cannabinoids. THC and CBD also curtail ADP-induced reversible aggregation in platelet-rich plasma, while serotonin release and irreversible aggregation, caused by either ADP, collagen or thrombin, are not affected by the cannabinoids in platelet-rich plasma. The data point to associated sites for ADP and the cannabinoids on the platelet membrane.


[Immediate results of surgical treatment of thyrotoxic goiter]. The author presents an analysis of the results of operations performed for struma in 520 patients. There was one lethal issue (0.2%), intraoperative hemorrhage was noted in 2.1%, a damage of the n. recurrens -- in 0.9% of patients. The method of preoperative preparation and postoperative management in these patients is described.


[Relaparotomy in abdominal injuries in children]. An analysis of 18 relaparotomies in 12 children with injuries of the abdominal organs is presented. Inadequate measures against paresis immediately after laparotomy are felt to be the main cause of reoperations for an adhesive-dynamic form of the obstruction. While accomplishing relaparotomy, it is recommended not to resort to reconstructive operative procedures in cases where a palliative operation promptly liquidating complications would suffice.


Nature and properties of C3Hf natural antitumor cytotoxins directed against murine lymphosarcoma cells. The nature and some biological properties of the natural antitumor cytotoxins previously found in normal C3Hf serum, have been investigated. By immunoelectronmicroscopy study, employing rabbit hybrid antibodies with specificity for mouse Ig and ferritin, the C3Hf cytotoxins were shown to belong to immunoglobulins. By gel filtration, by inhibition experiments of the cytotoxic serum activity with monospecific anti-IgG and anti-IgM sera, and by 2-mercaptoethanol treatment of the C3Hf serum, the cytotoxic immunoglobulins were demonstrated to belong to the IgM class. They were not inactivated by heating until 60 degrees C and were able to activate guinea pig, rabbit, and human complement. The highest cytotoxic activity of the normal C3Hf serum was found when cells and serum were incubated at the low temperature, suggesting a low binding affinity of the cytotoxic IgM.


[Comparison of lung-mechanical and physico-chemical Parameters in view of the pulmonary surfactant system (author's transl)]. Evaluation of static pressure-volume-diagram of lungs and of surface-tension-area-diagram of lung-elutions measured on the Lamgmuir-balance is tested. Well known parameters are used to characterize alveolar surfactant activity in guinea pigs after perbronchial application of extracorporal surfactant Tacholiquin and detergent "Fit" 1% and after application of vagomimetics Acetylcholine 1% and Histamine 0.1%. Mean values of physico-chemical parameters show the most significant increase of the area of hysteresis (Benzer) during Tacholiquin and Acetylcholin application; the minimal surface-tension: gamma min, and the compressibility-index: gamma min/delta gamma (Kötter, Rüffer) decreased, the difference between maximal and minimal surface-tension: delta gamma and the stability-index: 2 delta gamma/(gamma max + gamma min) (Clements) increased. Tacholiquin and Acetylcholin both improve pulmonary surface-activity. The Tacholiquin-effect is documented in lung mechanics only by elevation of the inspiratory volume-rations: V10I/V20I (Clements) and V10I/Vmax (Kittelmann) referred to static pressure 10, 20 cm H2O and maximal pressure but not by elevation of the expiratory stability index V10E/Vmax (Gruenwald). The area of hysteresis is decreased indicating a preponderant inspiratory effect. The Acteylcholin-effect is covered by the well-known bronchial obstructive effect. Both inspiratory constants are decreased, and the area of hysteresis is increased. We did not find any significance of the expiratory stability index. Both inspiratory constants and the area of hysteresis are conditional surfactant parameters in view of bronchial obstruction.


[Lipolytic activity in some Candida strains (author's transl)]. The authors carried out an examination on the production of lipase in 300 Candida strains. The lipolytic activity was present in the majority of strains. In the 60 of the strains a more precise measurement of lipase production was performed qualitatively in a solid medium according to SIERRA (1957) and quantitatively in a liquid medium by titration with 0.1 N KOH. Furthermore, the correlation was determined between the production of lipase and the Candida growth. It was found that the qualitative proof of lipase in a solid medium according to SIERRA (1957) is a good informative method for determining lipolytic activity in Candidae. A much more sensitive method, however, is the quantitative method in a liquid medium; by this method the authors were successful in determining lipolytic activity even in some cases where the qualitative test was negative. On the whole, Candidae are lipolytically highly active. The mean values of lipase production in the Candida albicans cultures is 622 units in 1 ml of liquid medium; in other strains it is 798 units in 1 ml. There is a direct relation between the density of the culture and the amount of lipase produced.


The longest symbiotic bacterium as found in a membracid insect. An insect tumour cell, carrying germs, contains nuclei and also cellular debris as protoplasmic and nuclear degradation bodies. In histological sections the nucleus may be seen surrounded by such bodies, cut across, which then appear round in form. They have therefore been mistaken for yeast-like germs, called "Cicadomyces". But in smears the protoplasmic debris is stained blue and reveals bizarre shapes. T. assamensis is an exception and offers the key to properly interpret the bodies named Cicadomyces. Its symbiote is a long filamentous bacterium and persists in protoplasmic debris, the so-called Cicadomyces. Since Cicadomyces themselves cannot be infected by germs as long as themselves, the former can only represent cellular degradation bodies.


[Virus infestation of garden radish (Raphanus sativus L. var. sativus) (author's transl)]. In July 1974 a mosaic disease was stated in seed plants of garden radish near Aschersleben which spread more and more within some weeks and eventually infected over 40 per cent of the stand. Investigations in comparison with healthy seed plants demonstrated the following average losses induced by the disease: number of pods 51 per cent, seed weight 67 per cent, number of seeds per plant 53 per cent, weight of 1,000 seeds 33 per cent. Nearly unaffected were: number of seeds per pod, percentage of seed germination, and percentage of emerged seedlings. However, the seedlings were smaller when they derived from diseased mother plants. From diseased seed plants cauliflower mosaic virus was isolated. Seed transmission of this virus could not be stated with several hundreds of seedlings deriving from diseased garden radish. Back transmissions were successful with sap and with aphids. Only one strain which was cultivated in greenhouse for a long time gave no positive results. Three isolates of cabbage black ring virus from different plant species and the four beetle-transmissible viruses, namely turnip yellow mosaic, turnip crinkle, turnip rosette, and radish mosaic viruses induced no symptoms on garden radish seedlings. However, Erysimum latent virus, also belonging to the beetle-transmissible viruses, sometimes caused symptoms in garden radish. For the first time the investigations demonstrated in Europe, but probably also for the other continents, a spontaneous virus infection of Raphanus sativus var. sativus.


Evaluation of some biological tests as parameters for microbial activities in soils. I. Laboratory experiments. The experiments were confined to the effects of the addition of different sources of carbon (glucose, wheat straw, and sawdust) on the microbial activities in soils: loamy sand, loam and saline clay were used. The parameters used for this purpose were total bacterial counts, dehydrogenase test, CO2 evolution, and oxidation of organic carbon. Salinity of soils had deleterious effects on all the parameters used. Addition of organic matter resulted in marked increases in bacterial counts, formazan production, and CO2 evolution. Glucose showed the most rapid effect and highest levels. Wheat straw yielded the highest results and sawdust always showed the least effect.


Evaluation of some biological tests as parameters for microbial activities in soils. II. Field investigations. Investigations were designed to study the effect of certain factors on the microbial activities in soil. The parameters, used as an index of the microbial activities, were total bacterial counts, dehydrogenase activity, oxidation of organic carbon, and CO2 evolved/7 days. Bahteem Farm clay soil was examined for determining the effects of depth, type of fertilization, and crop rotation on the microbial activities. It appears that the microbial activities, as indicated by the tested parameters, were more pronounced in the surface 15 cm-layer than in the subsurface layer (15-30 cm). Results of all the parameters tested showed markedly higher increases with farmyard manure than with nitrogenous fertilizer and in the control, without significant differences between the latter two. Moreover, the time of sampling had no effect on the results obtained for all parameters. Different types of rotations did not exert significant variation in total bacterial counts, though more than one crop per year increased the organic carbon content of soil and mostly the dehydrogenase activity, whereas the evolution of CO2 tended to decrease. At Gabal el-Asfar Farm, the effect of irrigation with sewage effluent, for long periods, on the microbial activities of sandy soil was investigated. Sewage water stimulated the total bacteria, raised the dehydrogenase activity, the organic carbon, and the production of CO2. In North El Tahreer and Mariut Sectors, the effect of both the type and age of cultivation on the microbial activities in the calcareous soils were examined. Cultivation raised the figures of all the tested parameters progressively with time of cultivation. It was also noticed that crops exerted more beneficial effects on microbial activities than orchards, and the dehydrogenase test was the most reliable parameter to reveal this fact.


[Proof of soil sickness in growing apple plantations (author's transl)]. 1. Soils from five apple orchards of different age and from different sites were tested with respect to the occurrence of soil sickness. 2. Severe or very severe soil sickness could be proved in four of the sites. In one site weak soil sickness could be obtained. 3. These results confirm earlier observations on the occurrence of soil sickness within the regions of growing root systems of older trees. 4. The occurrence of soil sickness in growing plantations can be brought in good correspondence with the ascertainment that microorganisms associated with roots are to be considered as the cause of soil sickness. 5. The significance of the occurrence of soil sickness in growing plantations for development and yield of trees must be investigated in further experiments.


Biological activities during ripening of composts. Three investigations were carried out. The first determined the relationships between dehydrogenase acitivty throughout the course of composting wheat straw and the changes in both organic carbon and total nitrogen. The second investigation tested the validity of the first investigation results. The third dealt with the effect of the degree of ripening of a compost, expressed by age and C/N ratio, on its dehydrogenase activity, and production of CO2. The results revealed continual decreases in the organic carbon, coincident with increases in total N and dehydrogenase activity. Noticeable chemical and biological changes occurred in the first and third month. Levels of dehydrogenase were highest in rice straw and lowest in cotton stalk compost, while the wheat straw compost occupied an intermediate position. Aging of the compost resulted in increases in the dehydrogenase figures and decreases in the amounts of CO2 produced.


[The influence of choramphenicol and streptomycinsulphate on the growth of Pectobacterium carotovorum var. atrosepticum (van Hall) Dowson (author's transl)]. The influence of the antibiotics chloraphenicol (D-threo-form) and streptomycin sulphate against Pectobacterium carotovorum var. atrosepticum (syn. Erwinia carotovora) was investigated in vitro and on potato tubers. Chloramphenicol showed a greater effect as streptomycinsulphate in the applied concentrations. The success of the control of soft rot is determined by the period between the inoculation and the treatment of the tubers. 6 several strains of P. carotovorum var. atrosepticum showed a different sensibility to chloramphenicol and streptomycinsulphate.


New leaf diseases of barley in Egypt.

New leaf diseases of barley in Egypt. Leaf diseases of barley were observed also in Egypt. From leaves of barley were isolated: Helminthosporium teres, H. gramineum, Stemphylium vesicarium, Alternaria triticina, Vlocladium chartarum, Acnemonium kiliense, Stemphylium spec. accompanied with the Pleospora stage. Inoculations on both attached and detached leaves showed that all the tested fungi were pathogenic, except Acremonium kiliense and Ulocladium chartarum.


The formation of heteroagglutinins in rats "chemically" splenectomized by ethyl palmitate, in comparison to animals surgically splenectomized. In Wistar rats "chemically splenectomized" by an i.v. injection of ethyl palmitate the formation of heteroagglutinins against human O-erythrocytes has been followed. Ethyl palmitate applied 2 hrs before immunization induced on the 5th day a significant decrease of the antibody level. This temporary inhibition, however, was at a later stage replaced by a significant increase of antibody level with the peak of 8--14 days. Animals surgically splenectomized 24 hrs prior to immunization displayed a weak antibody response throughout the experiment. An injection of the ethyl palmitate on the 6th day after immunization induced a pronounced and persistent decrease of the antibody level. Surgical splenectomy performed within the same interval had a comparable effect. The experiments revealed that the inhibitory effect of ethyl palmitate on antibody production was temporary only, and at a later stage could be compensated by an enhanced antibody activity.


[Reactions of hereophilic agglutinins with L-cells and different toxicity of anti-A HP to fibroblasts and L-cells in vitro]. The carbohydrate binding glycoprotein Anti-AHP binds to the plasma membrane of the (transformed) L-cell both in agglutination reactions and by the immunofluorescence technique. On the surface of (normal) mouse embryo fibroblast cells Anti-AHP receptors were not detectable. Anti-AHP is suitable as another marker for L cells. The random distribution of the binding sites at 4 degrees C changes with elevated temperatures (clustering, capping of sites). Anti-AHP inhibits the growth of L cells much more than that of fibroblasts. It does not act as a mitogen for the investigated cells.


[Antitumor activity of carminomycin antibiotic used orally]. Antitumor activity of karminomycin used perorally was studied with respect to 3 strains of mouse transplantable tumors, i. e. one ascitic strain of lymphadenosis NK/LI and two solid strains of lymphosarcoma L10-1 and sarcoma 180. Karminomycin was shown to have a high antitumor activity against the above tumors on its oral administration. In the experiments with lymphadenosis NK/LI the efficiency of karminomycin was higher when it was used perorally as compared to its intravenous administration. It was found that karminomycin had practically the same inhibitory effect on growth of lymphosarcoma L10-1 and sarcoma 180 on its peroral and intravenous administration in doses equivalent by their toxicity.


[Preparation of dihydrocarminomycin and a comparison of its antitumor activity with the activity of carminomycin]. A dihydro derivative of karminomycin was prepared using chemical reduction with potassium boron hydride. When dihydrokarminomycin was administered intravenously to healthy albino mice in a single dose it practically showed the same toxicity as karminomycin. However, unlike the latter dihydrokarminomycin induced the death of the animals at later periods of time. Studies on mice with transplantable tumours showed high antitumor activity of dihydrokarminomycin against lymphosarcoma L10-1, sarcoma 180, Garding-Passy melanoma, lymphoid leukosis L-1210 and lymphocytal leukosis P-388. In treatment of the mice with leukosis L-1210 and Garding-Passy melanoma dihydrokapminomycin was much inferior by its efficiency than karminomycin.


[Extra-adrenal pheochromocytoma associated with bilateral diffuse-nodular hyperplasia of the adrenal cortex and micro-macrofollicular goiter]. At autopsy there was found extra-adrenal pheochromocytoma, bilateral diffuse-nodulous and adenomatous hyperplasia of the adrenal cortex in a female patient who had suffered for a long time from high arterial pressure. In the enlarged thyroid gland there was revealed micro-macrofollicular colloid goiter with basedowification. The morphological changes and results of an investigation of the liquor (drop in the content of potassium) justify the assumption that in this case there is a combination of extra-adrenal pheochromocytoma with hormonally active rearrangement of the adrenal cortex--primary hyperaldosteronism and basedowified goiter.


Incidence of intestinal parasites in children of different socio-economic population of Dacca city. Stool samples of 1500 children of different socio-economic status of Dacca city was examined for the presence of intestinal parasites. Samples were collected on voluntary basis which may be treated as randomised. Out of these 1500 children, 816 were male and 684 were female. The overall incidence of parasites was 65.80%, the male children slightly prepondering over the female children. Children of age group 6-10 years showed high incidence of almost all the parasites. Children of Basti area showed the highest incidence (about 90%) and most of them harboured multiple parasites. About 27.13% of infants under the age of one year (mostly from Basti area) harboured parasites. Intestinal parasites were observed that both housing and economic status played vital roles in the occurrence of intestinal parasitosis but the housing and environmental conditions were found to be in a stronger position than economic status.


Effects of tranquillising, antidepressant and central nervous system stimulant drugs on the gamma-aminobutyric acid (GABA) level of rat brain. The level of y-aminobutyric acid (GABA) was determined in the brain of rats 1 hr. after i.p. injection of chlorpromazine, prochlorperazine, diazepam, trimipramine, methamphetamine and nikethamide. Diazepam increased, and, trimipramine and amphetamine decreased the brain GABA level over wide dose ranges. Low doses of chlorpromazine and prochlorperazine increased but high doses of the drugs reduced the GABA level. Low doses of nikethamide reduced whereas high doses increased the level of GABA. The effects of the drugs have been discussed in relation to the brain GABA level.


Infective polyneuropathy (a report of 14 cases). Fourteen cases of infective polyneuropathy were admitted in the Institute of Postgraduate Medicine and Research, Dacca, during a period of one year. The clinical features and laboratory investigations of these patients have been recorded. The management was done as usual but particular stress was given to the use of a short course of corticosteriod to all patients. The results of treatment was satisfactory and uniform for majority of the cases.


Changes in the process of aging.

Changes in the process of aging. Anthropometric data, caloric intake and blood glucose, cholesterol, urea and bilirubin level were compared in a group of elderly persons (mean age, 55.72 years in males and 52.04 years in females) with a group of young persons (mean age, 27.80 years in males and 27.30 years in females) from similar socio-economic background. It was observed the elderly persons were slightly heavier than the young persons and consumed less calories. In the absence of active disease, the blood glucose, cholesterol, urea and bilirubin of the elderly persons were within normal limits and comparable to young persons.


Incidence and causes of blindness amongst the rural population. A survey of blindness was conducted in a few union councils of the districts of Chittagong, Comilla and Noakhali in a population of 1,14,624 and 1,085 cases of blindness (842 adults and 243 children) were detected. The most common cause of blindness in the adults was cataract whereas in the children it was corneal affection. Trauma constituted 26.7% of blindness in the children and 10.2% in the adults. Glaucoma was responsible for 16.3% of blindness in the adults.


Chronic diarrhoeal diseases in adults (a preliminary report). The relationship of chronic diarrhoeal diseases in adults on socio-economic condition, parasitic infestation and degree of anaemia have been investigated. The disease was more prevalent in poor socio-economic group of people. Most of the patients had mixed parasitic infestations. Anaemia was present in all the cases. Difference in the degree of anaemia was not significant amongst the patients having either Ascaris or hookworm infestation.


[ On the metabolism of ethyl-DL-trans-2-dimethylamino-1-phenyl-cyclohex-3-ene-trans-1-carboxylate-hydrochloride (Tilidine-HCl). 2nd Communication: Studies with 14C-labelled substance on rats and dogs]. Absorption, distribution, metabolism and excretion of the potent analgesic ethyl-DL-trans-2-timethylamino-1-phenyl-chclohex-3-ene-trans-1-carboxylate-hydrochloride (tilidine-HCl, Gö 1261 C, active ingredient of Vloron) were investigated in rats and dogs, using the radioactively labelled substance. Following oral administration, tilidine-HCl is rapidly and completely absorbed from the duodenum. During absorption, tilidine undergoes a marked first-pass effect. In plasma several metabolites are found, part of them occurring in higher concentrations than the unchanged substance. The metabolites are also formed rapidly after parenteral administration, unchanged tilidine being found in higher concentrations than any of the metabolites at all times measured. Following both routes of administration, the Met. I (nortilidine), also possessing a strong analgesic activity, reaches similar plasma levels. 14C distribution studies in rats showed a relatively high concentration of the radioactivity in the excretory organs, liver and kidneys. In brain, muscle tissue and blood much lower 14C concentrations are found. The concentrations measured in the foetal organs correspond to those in the muscle tissue of the mother animals and are, therefore, much lower than in most maternal organs. The radioactivity is eliminated from the foetal organs at the same rate as from the maternal organs. Tilidine is rapidly and completely eliminated with the excrements, nearly exclusively in the form of metabolic products. Rats eliminate 50% of the given radioactivity via the kidneys. The relatively high fecal elimination is based on the biliary metabolites. Following intraduodenal and intravenous administration to rats with an interrupted enterohepatic circulation, about 80% of the dose is eliminated with bile. The biliary metabolites are partly reabsorbed. In dogs, approx. 80% of the applied radioactivity is eliminated with urine.


Studies on the determination and induction of cholesterol 7alpha-hydroxylase. To determine the activity of cholesterol 7alpha-hydroxylase, different fractions from rat liver homogenates are incubated with glucose-6-phosphate, glucose-6-phosphate dehydrogenase and NADP as well as with cholesterol-4-14C. The 7alpha-hydroxycholesterol-4-14C formed is separated from the extract of the incubation preparation by means of thin-layer chromatography and its radioactivity is calculated as a percentage (conversion figure) of the total radioactivity on the plate. The highest conversion is found in the 18 000 X g supernatant. It is of the order of 1--4%. This activity decreases to about one-half when the homogenate or the cell fraction is stored, while cooling, for two days. It can be shown that repeated pretreatment of rats with phenobarbital increases the activity of hepatic cholesterol 7alpha-hydroxylase by more than three times over the control values. 1-(2'-Hydroxyphenyl-acetyl)-4-methyl-1,2,3,6-tetrahydropyridine (Bay a 4798) a choleretically active drug also increases the activity of this enzyme in the rat more than twofold. This effect is confirmed by reduced biliary excretion of radioactive cholesterol and increased biliary excretion of radioactive bile acids following i.v. administration of DL-mevalolactone-2-14C and continuous intraduodenal infusion of Bay a 4798.


[On the mode of action of difenoxin (R 15 403). Part 2: Studies on the perfused isolated colonic loop of the rat (author's transl)]. The effect of 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-isonipecotinic acid hydrochloride (difenoxin, R 15 403), a new antidiarrhoic agent, was studied in vivo in rats with an isolated colonic loop. Difenoxin had no effect on transport or absorption of fluid during perfusion experiments. When given i.p. it inhibited the motility of the coecum but not that of the colon. Difenoxin has apparently no effect on normal rat colon, although an effect may have been masked by the wide variation of parameters measured under identical conditions.


[Pharmacology of 2'-[2-hydroxy-3-(propylamino)-propoxy]-3-phenylpropiophenone (Propafenone, SA 79)-hydrochloride]. The pharmacologic actions of 2'-[2-hydroxy-3-(propylamino)-propoxy]-3-phenylpropiophenone (propafenone, SA 79) hydrochloride were investigated in animal experiments. The drug showed antiarrhythmic action in anesthetized dogs, cats and rabbits after i.v. (1 mg/kg) and oral (2-10 mg/kg) application. The model arrhythmias were induced by epinephrine infusion plus chloroform inhalation or by infusion of digoxin, calciumchloride or aconitine or by occlusion of the left coronary artery. Propafenon prolonged the refractory period in isolated atria of guinea pigs and elevated the electrical fluttering level of the ventricle in anesthetized guinea pigs or conscious rabbits. It showed local-anesthetic action on the cornea of the guinea pigs. In doses of 3-10 mg/kg i.v. it lowered blood pressure, inhibited contraction force of the heart ventricle and dilated coronary arteries. Heart rate was unchanged by anti-arrhythmic doses. With higher doses (more than 7 mg/kg i.v.) ECG was altered. The autonomic nervous system was unaffected but bronchial adrenergic beta-receptors appeared to be inhibited. The results show, that propafenon has a specific antiarrhythmic action on the heart. The doses to be used have no influences on other circulatory parameters. Propafenon acts after oral application too.


Gas chromatographic determination of dimethophrine in biological specimens of rabbit. A method to measure the alpha-sympathomimetic amine, 1-(3,5-dimethoxy-4-hydroxyphenyl)-2-monomethyl-amino-ethanol (dimethophrine, DMP), was developed and applied for the determination of the drug in biological specimens. The gas chromatographic degradation of the drug was investigated, and in order to avoid this process, DMP is converted to the trifluoroacetyl derivative and assayed by gas liquid chromatography on an OV 1' column. The minimum detectable amount is 25 pg per injection. Linearity (using hexachlorobenzene as internal standard for quantitation) was found up to mug amounts of the substance, without any interference with endogenous substrates. Values from plasma, red blood cells and urine in rabbits treated with a single dose of DMP (10 mg/kg) are also reported.


Drug absorption from the irradiated rat small intestine in situ. The absorption of acidic drugs phenobarbitone and sulphafurazole, basic drugs mecamylamine and quinidine, and a neutral drug isoniazid was studied in situ. Rats were irradiated 750 rad whole-body with 60Co and the absorption experiment was done three and six days thereafter using the cannulated small intestine of urethane-anaesthetized rats. Drug disappearance from the intestinal lumen and drug levels in the whole blood and intestinal wall were measured. In control rats phenobarbitone showed the most rapid absorption and mecamylamine the slowest. Irradiation retarded the disappearance of all drugs from the intestinal lumen on the third postirradiation day. Fluid absorption was also diminished. On the sixth postirradiation day the absorption of phenobarbitone, sulphafurazole and mecamylamine had returned to the control level, but the absorption of quinidine and isoniazid was still retarded. After i.v. administration of drugs they were not significantly excreted into the intestinal contents and irradiation did not modify excretion. The distribution of drugs between the intestinal fluid and the intestinal wall was complete in the first 10 min of experiment. Mecamylamine and quinidine were lowered in the whole blood by irradiation. Blood levels of drugs did not correlate well to the rate of disappearance of drugs from the intestinal lumen. The reversible changes in absorption induced by irradiation are probably secondary effects of irradiation on intestinal morphology, permeability and transport capacity, composition, and possibly blood flow.


[Suitability test of various food mixtures for breeding and rearing of beagle dogs. 2nd Communication: Methods and results of feeding experiments of the Mannheim team (author's transl)]. A comparison of 3 commercially available dog foods (Ssniff C, Altromin H, Altromin HW) with 2 newly formulated dog food mixtures was carried out with regard to breeding, rearing and maintenance of Beagle dogs. No significant differences were found between the individual feeding groups with regard to the fertility and breeding ability of the bitches. All the foods supplied the requirements for energy, nutrients and feed additives in the rearing and maintenance of the dogs. The parameters used for the assessment, such as body weight, daily gain, daily food consumption and feed efficiency, were satisfactory for all food groups and were partially reproduceable. If the consumption of food, energy and nutrients per kg body weight are calculated and are related to the rearing results obtained then inconsistencies occur which can only be explained by differences in digestibility of the individual food components, and these underline the need for digestibility tests in dogs. The 2 newly formulated foods compared favourably with the other food stuffs and fulfilled the requirements for better standardised food mixtures. Further experiments will investigate the effects on the morphological, haematological and clinico-chemical characteristics. A comparison of different age groups confirmed the data in the literature which indicates that younger animals have a higher requirement for energy and nutrients per kg body weight than older animals. Results that have not yet been explained are the findings that the consumption of food, and thus of energy and nutrients, per kg body weight in younger male animals is lower than that of the female animals of the same age to a highly significant degree.


Posthaemorrhagic iron deficiency. Clinical course, 59Fe whole-body iron losses, and oral iron supplementation. Clinical and laboratory data characterizing post-haemorrhagic anaemia with still normal iron stores and posthaemorrhagic iron deficiency in the manifest, latent or prelatent stage are presented. Initially, increased 59Fe whole-body iron losses (greater than 0.1-3.6%/day) returned to normal range (less than 0.1%/day) after haemostasis. Subsequently, slow increase of haemoglobin and repletion of iron stores occurred under normal diets. Manifest, latent, and prelatent iron deficiencies were corrected much more rapidly by total doses of 12.0, 10.5 and 8.0 g iron (Fe2+ sulfate), respectively, when 2 X 50 mg/day were given in quick-release capsules apart from meals.


The effect of colestipol on digitoxin plasma levels. The effect of colestipol (colestipol hydrochloride; U-26 597 A), a copolymer of tetraethylenepentamine and epichlorhydrine, on plasma digitoxin levels has been investigated. Recently, it has been stated that colestipol decreases the enterohepatic circulation and the plasma half-life of digitoxin. Colestipol was administered to 11 patients having a digitoxin plasma level which is generally accepted to be above the therapeutic range (greater than 40 ng/ml). The elimination rate of digitoxin measured by serial radioimmunoassay in these colestipol treated patients was compared with the elimination rate of digitoxin in 11 patients not treated with colestipol. The results of this study did not demonstrate a significant difference in the mean (+/- S.D.) digitoxin plasma half-life between the colestipol treated (6.3 +/- 1.3 days) and the non-colestipol treated patients (6.8 +/- 1.0 days).


The influence of cholic acid and dehydrocholic acid on the biliary excretion of unconjugated and conjugated sulfobromophthalein in rats. Urethane anesthetized Wistar rats with biliary fistulas were infused during 100 min with sulfobromophthalein (BSP), the glutathione conjugate of sulfobromophthalein (BSP-GSH), cholic acid (CA) and dehydrocholic acid (DCA). The dyes (594 nmol/100 g/min) and the bile acids (1200 nmol/100 g/min) were infused separately, and in combination as well. When BSP was infused, CA and DCA increased the maximal excretion of total BSP (conjugated plus unconjugated) from 1400 to 4100 and 3300 nmol/100 g/10 min. The bile flow observed with BSP plus CA was not significantly different from that with BSP plus DCA. The biliary excretion of total BSP was higher throughout with CA than with DCA because CA increased the biliary concentration of PSP while DCA did not. The bile flow attained with CA alone was significantly lower than that with BSP plus CA. The current data provide arguments for abandoning the view that choleresis per se is the crucial determinant for BSP excretion. When BSP-GSH was infused instead of BSP, the excretion rate of the dye was not altered by the additional infusion of CA whereas it was significantly reduced by DCA. The maximal biliary concentration of BSP-GSH fell from 25.9 nmol/mul to 15.3 and 9.4 nmol/mul with CA and DCA, respectively. Both CA and DCA impaired the hepatic uptake of BSP and BSP-GSH. During the infusion with CA, BSP plus CA and BSP-GSH plus CA the biliary excretion rates of bile acids did not differ significantly from each other. This favours the view that the transfer for CA from the liver to bile is different from that for BSP and BSP-GSH. A fraction of bile fluid "independent of choleretics" (viz. of bile salts, BSP and BSP-GSH) is estimated and discussed in view of the different types of infusion.


The synthesis of ethyl apovincaminate.

The synthesis of ethyl apovincaminate. Starting from (+) vincamine (I), simple derivatives of vincaminic acid (II), apovincaminic acid (V) and apovincaminol (VII) were synthetized. Out of these the synthesis of ethyl apovincaminate (Cavinton), as a representative, is described in detail. The water elimination and esterification of II can be carried out in one step.


General and cerebral haemodynamic activity of ethyl apovincaminate. Systemic and cerebral haemodynamic effects of ethyl apovincaminate (RGH-4405, Cavinton), a new compound, have been investigated in anaesthetized dogs. The compound was administered i.v. and produced an increase in cerebral blood flow accompanied by a decrease in cerebral vascular resistance which persisted for 15 min. The effective dose was 0.2-0.5 mg/kg. Mean arterial blood pressure, total peripheral resistance and cardiac work were decreased, heart rate and cardiac output were increased. Cerebral metabolic rate of oxygen was enhanced. It is assumed that the compound has a direct effect on cerebral metabolism. RGH-4405 has a weak antiarrhythmic and coronary dilating activity. Its effect on smooth muscle is more marked than that of papaverine. RGH-4405 appears to be a potent cerebral vasodilator enhancing cerebral metabolism.


Effect of oral pretreatment with ethyl apovincaminate on the cardiac output and nutritive blood flow of various organs in rats. Effect of ethyl apovincaminate (RGH-4405, Cavinton), administered repeatedly p.o. in doses of 0.5-1.5-4.5 mg/100 g body weight for 5 days, on cardiac output and organ fractions of cardiac output were studied in rats anaesthetized with sodium pentobarbital by Evans-blue dilution and isotope fractionation technique of Sapirstein. Cardiac output, cerebral, coronary, renal, intestinal and dermal blood flow was increased by 18-42% after 4.5 mg/100 g Cavinton, while blood pressure was unaltered. Total peripheral resistance, cerebral, coronary, dermal resistance and that of the carcass decreased significantly. Organ fractions of the cardiac output were not significantly altered after treatment.


Effect of ethyl apovincaminate on cerebral, cardiac and renal flow rate in dogs in the course of administration. Cerebral, myocardial and renal capillary flow rate was significantly increased by 10 to 20 mug/kg/min doses of ethyl apovincaminate (RGH-4405, Cavinton) injected in slow infusion to dogs. These effects were long-lasting. Since perfusion pressure and heart rate were not affected by the compound, it was concluded that increased flow rate was attributable to decrease of peripheral vascular resistance. Results indicate that Cavinton has a vasodilatory effect.


Protective activity of ethyl apovincaminate on ischaemic anoxia of the brain. Effects of ethyl apovincaminate (RGH-4405, Cavinton), a new cerebral metabolic and vasodilatory agent, on cerebral regulatory functions under ischaemic anoxia were studied on immobilized cats by EEG. Cortical resistance time increased and recovery time decreased for a long period after i.v. administration of the compound. Results point to the possibility of further enhancement of cerebral regulatory processes by specific drug effects. It is assumed that tolerance or adaptation to hypoxia might be increased by RGH-4405 if spontaneous regulatory processes are impaired.


Effect of ethyl apovincaminate on cerebral circulation of dogs under normal conditions and in arterial hypoxia. Effects of 1, 2 and 4 mg/kg i.v. doses of ethyl apovincaminate (RGH-4405, Cavinton) on cerebral blood flow, determined in the internal carotid and vertebral artery, were studied in anaesthetized dogs under 21, 16 and 11% O2 inhalation. Total cerebral blood flow was increased by 4 mg/kg Cavinton under normal O2 and between 100 to 200 mmHg perfusion pressures, while 2 mg/kg doses were effective under hypoxia. Similar phenomena were observed in the carotid and vertebral flow, separately. Arterial hypoxia seems to potentiate the effect of Cavinton on cerebral blood flow.