Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat. To evaluate the effect of starvation, oral and i.v. nutriments, and hypothyroidism on the peripheral conversion of thyroxine (T4) to 3,3', 5-triiodothyronine (T3) in the rat and mouse, an in vitro system for assessing T4 conversion to T3 by fresh liver homogenates was used. A 2-day starvation in the rat reduced hepatic T3 generation from T4 by 47% +/- 3.5% (mean +/- SE) in six separate experiments and also impaired the metabolism of 125I-r-T3. Administration of carbohydrate (CHO) and amino acids (P), but not lipid (L), significantly increased T3 generation above values observed in the starved rat. The mean serum glucose concentration was similar in all nutriment-infused groups, but serum insulin was significantly greater in the CHO- and P-infused as compared to the L-infused rats. These findings suggest that CHO and P, but not L, are important modulators of hepatic outer ring thyronine deiodination in the rat, perhaps due to increased intracellular glucose. Hypothyroidism in the rat induced by thyroidectomy and congenital secondary hypothyroidism in the dwarf mouse resulted in a striking decrease in hepatic conversion of T4 to T3. This decrease was restored to normal by the daily s.c. administration of physiologic doses of T4 (1.5 microgram/100 g) or T3 (0.5 microgram/100 g) for 14 days, and was increased above normal following treatment of normal rate with greater than physiologic doses of T4 (3microgram/100 g) or T3 (1 microgram/100g). In vitro hepatic conversion of T4 to T3 is, therefore, dependent upon thyroid function. Since 2-days starvation in the rat was associated with decreased serum concentrations of T4, T3, and TSH, and hypothyroidism resulted in decreased conversion of T4 to T3, the effect of a constant 2-day infusion of physiologic doses of T4 or T3 in the starved rat on the in vitro deiodination of T4 was assessed. Thyroid hormone replacement did not enhance the conversion of T4 to T3 in the starved rat. These observations suggest that the starvation-induced decrease in hepatic generation of T3 from T4 is not due to hypothyroidism and that the mechanism(s) of the decreased T3 production observed in starvation and hypothyroidism is different.


[Mechanism of the oxidation of divalent iron and manganese by iron bacteria developing in a neutral acidic medium]. The paper confirms the existence of a peroxide mechanism involved in oxidation of iron and manganeses by the most typical iron bacteria growing at neutral acidity of the medium. Oxidation of bivalent iron and manganese is accomplished by the simultaneous action of catalase and hydrogen peroxide produced in the respiratory chain in the course of oxidation of organic substances. Catalase performs the peroxidase function in these processes. The possibility of these biological reactions to occur and the necessary conditions have been studied in vitro. Possible variants of iron and manganese oxidation by iron bacteria are discussed, including the conditions for "symbiotic" oxidation of manganese by mixed cultures of microorganisms.


[Effect of the redox potential on the growth of aerobic microorganisms]. The effect of redox potential was studied on the growth of the following aerobic microorganisms: Candida utilis, Bacillus megaterium, Pseudomonas fluorescens. The action of oxidizing agents (K3Fe(CN)6, KIO3, K2Cr207 and KMnO4) and reducing agents (ascorbic acid, sodium thioglycolate, K4Fe (CN)6 and Na2S2O3) on the growth rate was investigated. K3Fe(CN)6, ascorbic acid, sodium thioglycolate and K4Fe(CN)6 were found to be suitable for buffering the Eh of the medium. The potential could be shifted by 50--200 mV by adding various reducing and oxidizing agents. The rate of growth of C. utilis, Bac. megaterium and Ps. fluorescens did not depend on the potential value.


[Alcohol dehydrogenase activity of the subcellular fractions of Torulopsis candida yeasts grown on glucose and hexadecane]. The activity of alcohol dehydrogenase was compared in subcellular fractions of Torulopsis candida grown on glucose ("glucose cells") and on hexadecane ("hexadecane cells"). Two groups of alcohol dehydrogenases (ADH) were found to be present in the cells: (1) soluble ADH located in the cytosol and (2) ADH bound to the membrane structures and located in the mitochondria and other cell structures. Soluble ADH of "glucose cells" actively dehydrated all alcohols tested from C2 to C16. Ln "hexadecane cells", the activity was low or absent. ADH bound to the cell structures dehydrated mainly C5--C16 alcohols; the activity of these ADH was almost by an order of magnitude higher in the "hexadecane cells" as compared to the "glucose cells" (in contrast to soluble ADH). The character of changes in the activity of ADH toward various alcohols in the course of physiological adaptation of the yeast to oxidation of glucose and hexadecane suggests that both soluble and bound ADH contain at least two ADH, one of which is specific to lower alcohols and the other to higher alcohols.


[A field study with the combination of Pindolol and Clopamid in antihpertensive therapy (author's transl)]. In a field study comprising 678 patients with arterial hypertension efficacy and tolerance of the stable combination VKB 105 consisting of 10 mg Pindolol (Visken) and 5 mg Clopamid (Brinaldix) were investigated. Treatment with 1--2 tablets of VKB per day resulted in a successful therapy in 94% of all patients corresponding on the average to a reduction in blood pressure to 145/85 mm Hg within 14 days. In mean arterial pressures ranging between 120 and 170 mm Hg a positive linear relationship between the individual initial value and the hypotensive effect of the combination could be observed. A controlled omission trial disclosed qualitatively the respective contribution to the effect of the two components Pindolol and Clopamid. With a systematic case control of the serum potassium under the combined therapy with VKB 105 and during a monotherapy with Clopamid and antihypokalaemic effect of Pindolol could be demonstrated diminishing the tendency for potassium loss. The result revealed a far-reaching potassium neutrality of diuresis-depending stimulation of renin by the beta-receptor blocker. In 61 patients altogether subjective side-effects could be recorded, such as vertigo (5%), palpitations (2.8%), fatigue (2%), insomina (1.9%), nausea (1.7%) and vomiting (0.8%). Laboratory controls gave no indication for clinically relevant changes.


Mapping of the locus involved in the catabolic oxidation of D-amino acids in Pseudomonas aeruginosa PAO. Mutants of Pseudomonas aeruginosa PAO deficient in their utilization of DL-valine have been found to have lost their capacity to utilize DL-alanine and L-proline. Use of conjugal and transductional mediated gene transfers have established the chromosomal location of this gene and also its pleotropic function in the induction of the D-amino acid oxidase, involved in the oxidative utilization of DL-valine, DL-alanine and L-proline. These point mutations are clustered in a single locus designated as Val D and mapped around the 19th minute on the chromosome.


[Fenfluramin (ponderax) intoxications in children (author's transl)]. 4 cases of accidental fenfluramine poisoning in children are reported. Excitation, coma, convulsions, tachycardia, mydriasis, nystagmus, and rubeosis of the face were the most important signs. They appeared 30--60 min after ingestion, and some of them lasted for several days. 2 children had severe trismus and therefore had to be given muscle relaxants before intubation and gastric lavage became possible. These observations agree well with  informations collected in our poisoning control center and with previously published data. Less than 5 mg/kg of body weight are toxic, 5--10 mg/kg may produce coma and convulsions, and the smallest lethal doses were 28,7 and 33,3 mg/kg. Early gastric lavage, good monitoring of the vital functions and, if necessary, administration of anticonvulsive drugs, beta-blocking agents, lidocaine, chlorpromazine, and artificial ventilation and cardiac defibrillation are the most important therapeutical measures.


[Therapy with beta-blocking-agents (author's transl)]. Within the last 10 years the indications for a therapeutic regimen with beta-blocking-agents have been differentiated: coronary heart disease with angina pectoris (interval regimen), essential hypertension, especially in younger persons; hyperkinetic heart syndrome; thyreotoxikosis, symptomatic therapy; heart rhythm disorders, extrasystolic or tachysystolic; neurologic-psychiatric diseases. The development of the newer beta-blocking-agents has effected different kinetic data (f.i. long acting effects of Tenormin) and a increased cardioselectivity. The recommendations for the therapeutic regimen have to be outlined to the underlying diseases. The sensitivity against the drugs depends on remarkable individual differences, with the consequence of a careful and low dosage in the beginning in each case. The side-effects of beta-blocking-agents are presumably: bradycardia, bronchospasm, fatigue, adynamia, myocardial insufficiency, gastrointestinal symptoms, hypoglycemia, hypotension.


Lymphocytic bronchitis associated with graft-versus-host disease in recipients of bone-marrow transplants. Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus.


Steroid-induced meiotic division in Xenopus laevis oocytes: surface and calcium. Progesterone reinitiates meiotic maturation in Xenopus oocytes. Evidence is reported which indicates that the steroid acts at the level of the cell surface and suggests that an induced change of Ca2+ distribution triggers in turn a cascade of cytoplasmic events including protein synthesis and germinal vesicle (nucleus) breakdown. These novel features of steroid hormone action in amphibian oocytes are discussed in relation to presently accepted views of the mechanism of action of steroid hormones in somatic cells.


Benzodiazepines and central inhibitory mechanisms. The effect of diazepam was evaluated on spontaneous activity and drug- and electrically-elicited inhibitions of neuronal activity. Doses of diazepam which did not change spontaneous firing rates markedly enhanced GABA-mediated inhibitions in rat cerebellum in situ and in tissue cultures of rat hypothalamus. The effects of diazepam were readily reversible, and could be antagonized by picrotoxin; no effect on glycine or norepinephrine-induced inhibition was seen. It is concluded that actions of diazepam are mediated, at least in part, by a specific increase in GABA-mediated inhibition in the central nervous system.


Bohr effect induced by CO2 and fixed acid at various levels of O2 saturation in duck blood. The Bohr factor, phi = delta log Po2/deltapH, was determined at various levels of hemoglobin O2 saturation (SO2) in fresh whole blood of the duck. Plasma pH was varied by either changing PCO2 of the blood at constant base excess (CO2 Bohr factor, phiCO2) or by addition of NaHCO3 and HCl at constant PCO2 (fixed acid BOHR factor, phiAH). No differences were found between phiCO2 and phiAH at SO2 levels between 20 and 85%, and there was no saturation dependence of the Bohr factor, its average value being -0.44. It is concluded that in whole blood of this bird species CO2 exerts no direct effect on the O2 affinity of hemoglobin.


Carbon dioxide and acid base balance in the isolated rat diaphragm. A method for measuring the net acid base exchange in an isolated rat diaphragm preparation is described. Particular attention is paid to monitoring the functional status and maintaining optimal diffusion conditions. A steady net acid efflux of the order of 250 n mole/g-min is found in the resting state. This increases following a series of isometric contractions. In the resting state the total measured lactate + pyruvate efflux was found to be less than the net acid efflux. The net acid efflux increases following a sudden decrease in pCO2 and decreases or reverses following a sudden increase in pCO2 or a decrease in external bicarbonate. The net base loss during a period of 1 h following the exposure to high (20%) CO2 represents a large fraction of the predicted total bicarbonate generated within the fibres by non-bicarbonate buffers. This indicates that the effects of intracellular non-bicarbonate buffers can be transmitted to the external solution following a change in pCO2. The most plausible explanation is that passive bicarbonate ion movements are responsible. Values of the 'apparent PHCO3' have been calculated and vary under different conditions from a value of 1.3 X 10(-7) to 1.9 X 10(-6) cm-s-1.


Modification of DNA by aflatoxin B1 creates alkali-labile lesions in DNA at positions of guanine and adenine. The damage to DNA by the hepatocarcinogen aflatoxin B1 was investigated. A DNA fragment of known sequence of the lactose promoter-operator region was used as a substrate for modification by aflatoxin B1. The DNA was incubated with aflatoxin B1 in crude mammalian liver extracts or with purified microsomes. Treatment of the DNA incubated in the complete system with either 1 M piperidine or 0.1 M NaOH at 90 degrees revealed alkali-labile lesions in the DNA. The exact location of the cleavage site was determined by comparison of the length of the cleavage products with the known sequence on polyacrylamide gels. The lengths of the cleavage products were the same as those produced by alkali-induced breakage of the same sequence of DNA that had been modified with dimethyl sulfate. The major cleavage products of the aflatoxin B1-modified DNA were at positions of guanine and the minor cleavage products were at positions of adenine. These studies show that modification of DNA by aflatoxin B1 creates alkali-labile sites at positions of guanine and, to a lesser extent, adenine.


Functional lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli: temperature and pH dependence of dansyl-galactoside binding. 6'-(N-Dansyl)aminohexyl-1-thio-beta-D-galactopyranoside binds specifically to the lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli. Binding can be induced by substrate oxidation (generation of an electrochemical gradient of protons), by potassium efflux in the presence of valinomycin (generation of a potassium diffusion potential), and by passive, carrier-mediated lactose efflux. We show that in all three cases the number of binding sites is temperature dependent. Binding is maximal and constant above 20 degrees ; it decreases between 20 degrees and 10 degrees . Oxidation of substrate (D-lactate) leads to the development of an electrochemical gradient of protons across the membrane (interior negative and alkaline), which is composed of interconvertible electrical and chemical gradients. We show that both the electrical potential across the membrane and the chemical difference in proton concentrations across the membrane are independent of temperature between 5 degrees and 25 degrees . We show that the number of binding sites induced by D-lactate oxidation depends on pH. At both 25 degrees and 5 degrees , the number of binding sites increases from pH 5 to pH 6.5, remains constant between pH 6.5 and 7, and decreases from pH 7 to pH 8. In contrast, the number of binding sites induced by passive, carrier-mediated lactose efflux is independent of pH between pH 5.5 and pH 8. From these findings, we conclude that the pH- and temperature-dependent effects on the number of 6'-(N-dansyl)aminohexyl-1-beta-thio-D-galactopyranoside binding sites have different origins. The pH dependence of binding is energy linked and reflects in part the pH dependence of the electrochemical gradient of protons across the membrane generated by substrate oxidation. The temperature dependence is not an energy-linked phenomenon. The decrease of the number of binding sites at low temperature probably reflects the aggregation of the lac carrier protein with other membrane proteins. This aggregation takes place as a consequence of the conformational disorder-to-order transition of the membrane lipids and the concomitant preferential segregation of the lac carrier protein in the membrane domains containing the disordered lipids.


A macromolecular transducer as illustrated by trout hemoglobin IV. Oxygen binding by trout Hb IV has been investigated as a function of pH up to 10 atmospheres (1 MPa) of pure O2. The results bring out an extreme proton-oxygen linkage, which gives rise to a Root effect. They are discussed in relation to the function of the hemoglobin as an oxygen pump. The system is of special interest as providing a prototype of a macromolecule acting as a transducer by coupling two allosterically linked reactions.


[Multicomponent system of specific estrogen-binding liver proteins. Some properties of a rapidly dissociating estrogen-binding liver protein from guinea pigs]. A study was made of some binding and physico-chemical properties of a special estrogen-binding protein of liver cytozol in sexually mature female and male guinea pigs following its partial purification by means of ammonium sulfate sedimentation, gelfiltration and ion-exchange chromatography. The given protein proved to bind estradiol (E2) with Ka of the 10(7) M-1 order and possessed a rather marked hormonal affinity specificity. Under unbalanced conditions its complexes with E2 were capable of rapid dissociation. Characteristics of the size of protein molecules were: molecular weight--about 60000, Stokes' radius--3.2 nm, sedimentation coefficient--4.6, friction coefficient ratio--1.18. Protein E2-binding activity was reversibly depressed in the presence of high salt concentrations, decreased in the presence of dithioerythritol and on heating at the temperature of over 50 degree C. The optimum E2 binding was observed at pH 7.3--7.7. There were no significant differences in the properties of protein from the liver of males and females. A conclusion was drawn on a close similarity between the given protein of guinea pigs and of a special estrogen-binding protein of the liver in male rats detected by the authors earlier.


Coated vesicles: characterization, selective dissociation, and reassembly. Sodium dodecyl sulfate/polyacrylamide gels of coated vesicles from porcine brain (mean 76% coated vesicles) show three major proteins (180,000, 125,000, and 55,000 daltons) that account for 73% of the total protein. Preparations consisting predominantly of coats (65%) have less of the 55,000-dalton protein. Clathrin (180,000 daltons) comprises 40% of the protein of a coated vesicle. Conditions of 2 M urea, 0.25 M MgCl2, or pH 7.5 disrupt the coat and solubilize clathrin. Solubilized clathrin reforms coat structures after dilution of urea or MgCl2. High-pH-solubilized clathrin reassembles after dialysis against buffer at pH 6.5 containing dithiothreitol (5 mM). Reassembled coats are predominantly clathrin.


Nerve growth factor-mediated induction of tyrosine hydroxylase in a clonal pheochromocytoma cell line. We have established a clonal cell line, PC-G2, from an experimentally induced rat pheochromocytoma. Administration of nerve growth factor to PC-G2 causes a 4- to 8-fold induction in the specific activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase(3-hydroxylating); EC 1.14.16.2]. The response is elicited in a dose-dependent fashion, at concentrations above 0.1 microgram/ml. Antiserum to nerve growth factor inhibited the induction of tyrosine hydroxylase. Dexamethasone enhances the nerve growth factor-mediated elevation of tyrosine hydroxylase. After 3--4 days of exposure to nerve growth factor the maximal induction of tyrosine hydroxylase is seen, although a significant increase can be observed after 24 hr. In contrast to the PC-12 cell line (derived from the same tumor), in which neurite outgrowth occurs in response to nerve growth factor, there is no morphological change or alteration in growth rate of PC-G2 cells after exposure to nerve growth factor.


Kainic acid and synaptic transmission in the stellate ganglion of the squid. Kainate, a conformational analogue of glutamate, blocks synaptic transmission across the giant synapse of the squid. In the presence of blocking doses of kainate, impulses continue to propagate into the nerve terminal, but action potentials are slightly reduced in size and the subsequent hyperpolarization is greatly diminished. Kainate depolarizes the postsynaptic axon. Since the depolarizing action of kainate is confined to the postsynaptic membrane, it appears that kainate can combine with the receptors which are normally activated by the transmitter. This results in a diminished effect of the transmitter released by a presynaptic nerve impulse.


Structural correlates of recurrent collateral interneurons producing both electrical and chemical inhibitions of the Mauthner cell. Intracellular injections of horseradish peroxidase provided a basis for morphological identification of inhibitory interneurons belonging to the recurrent collateral network of the Mauthner cell. Their axons dilate to form unusually large bulbs surrounding the axon cap. The morphological appearance of these bulbs as well as intracellular recordings at their level indicate that they behave as nodes and serve as a final source of current for electrical inhibition of the Mauthner cell. The axon of each interneuron gives rise to two different groups of fibres which are respectively fitted for the mediation of electrical and chemical inhibitions of their target cell.


Brain catecholamines metabolism in offspring of amphetamine treated rats. Previous observations have pointed out that treatment with amphetamine during pregnancy produces behavioral modifications in adulthood. In order to elucidate some possible brain biochemical mechanisms that could explain the behavioral changes observed we have determined the endogenous content of brain dopamine and noradrenaline, the in vivo rate of conversion of tyrosine-C14 in such amines and the activity of tyrosine-hydroxylase, the rate limiting enzyme in catecholamines biosynthesis. We did not observe modifications in the endogenous content of dopamine and noradrenaline but did observe an increase in the conversion rate of tyrosine-C14 in such amines and also in the tyrosine-hydroxylase activity. These results indicate that treatment with amphetamines during fetal age produces catecholamine metabolism modifications that persist throughout adulthood, although the influence of behavioral modifications of the mothers cannot be ruled out. The relationship with behavioral changes is discussed.


Role of neuroleptic agents on mouse pulmonary cyclic nucleotide systems. The norepinephrine (NE)-induced accumulation of cyclic AMP in incubated tissue slices of mouse lung was inhibited by chlorpromazine (CPZ) and to a lesser extent by haloperidol. In particulate lung fractions both agents blocked dopamine-sensitive adenylate cyclase to a greater degree than the NE-responsive enzyme. Again CPZ was more potent than haloperidol. Acute injections (1/2--8h) of the neuroleptics usually resulted in lower steady state levels of pulmonary cyclic AMP and cyclic GMP following rapid (0.5 sec) tissue inactivation by microwave irradiation. On a subchronic injection schedule, the in vivo levels of pulmonary cyclic AMP tended to increase.


[Planning of psychotropic drug trials. Statistical evaluation. Hypotheses and methods]. Any reasonable evaluation presupposes a precise question. Furthermore it is necessary to eliminate all factors of disturbance, which are able either to simulate or to mask a result of evaluation. The most important of these factors is the psychiatrist himself. Therefore, experimental designs have to taken in account the factor psychiatrist. Criteria of the effects of any drug must be relevant with regard to comparison of two or more drug effects. The reproduciability of criteria is very desirable, but a wish-fulfilment under the most circumstances. Because criteria should be independent and mutually exclusive, all scales like the Hamiltons one are not suitable for evaluation. Finally one should use as few criteria as possible. Models of evaluation are described for the most frequent questions in connection with clinical trials in psychopharmacology.


Effect of alcohol and benzodiazepines on performance as related to personality characteristics. Personality characteristics among healthy "placebo reactors" and nonreactors. For 2 weeks 40 volunteers received either 5 mg diazepam, t.i.d., or 10 mg chlordiazepoxide, t.i.d., and placebo. A choice reaction test, two coordination tests, and an attention test were administered to the subjects on the 14th day of each treatment. Thirty minutes before the tests, the subjects ingested either alcohol., 5g/kg or a placebo drink, incombination with the last capsule. After the test the subjects rated the quality of their treatment as placebo, tranquilizer, or stimulant. The psychological tests taken before the treatments were Eysenck's EPIC-NESI, Taylor's Manifest Anxiety Scale (MAS), and Cattell's 16 PF inventory. A multiple regression analysis was computed. Personality factor scores found to be associated with a strong effect of the benzodiazepines were 16 PF's A, C, L, N, and Q, and EPIC's E. The effect of alcohol was associated with a high score of 16 PFs B factor. Personality factors associated with "placebo reactors" and nonreactors were investigated, as well. Those subjects on placebo indicating their treatment to be active were classified as "placebo reactors". A discriminant analysis revealed that 16PF's O and I factors discriminated effectively "placebo reactors" from nonreactors, and EPIC's SE and 16 PF's L factor nonreactors from "reactors".


[Further developments of the AMP-system. A report on the 2nd AMP-symposium and training seminar (author's transl)]. This is a report of a symposium and training seminar of the "Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie" (AMP). Video-recordings of two psychiatric interviews were shown during the seminar and rated by the participants using the AMP-3-Scale (Psychopathology). Aim of the seminar was a rater training and the preparation of an expert standard rating. These videotapes with the corresponding standard ratings will enable the different clinics using the AMP-System to compare their rating behaviour. The process of achieving an expert standard rating is described. The training seminar was followed by a symposium during which a series of lectures was presented on "Standardized Assessment in Psychiatry", The different working groups of the Association reported about their work and future prospects of the Association were discussed.


Indication of an antipsychotic action of the opiate antagonist naloxone. In 20 psychotic patients with frequent hallucinations and/or actual delusional experience a possible antipsychotic action of the opiate antagonist naloxone (N-allyl-noroxymorphone) was investigated, using a double-blind placebo-controlled cross-over design. 18 of these patients were not treated with neuroleptic drugs; 13 suffered from an acute episode of schizophrenia. Psychopathological changes were assessed by the use of the IMPS-scale and of a symptom-specific rating scale (VBS). Intravenous injection of naloxone (in most cases 4.0 mg) induced a reduction of psychotic symptomatology (especially hallucinations) in the majority of patients. Compared with placebo this effect reached statistical significance within 2-7 hours after injection. From this result a possible involvement of endogenous ligands of opiate receptors in the pathogenesis of schizophrenia may be concluded.


[Influence of the Benzodiazepine-derivative Ro 06-9098/000 on choreo-athetotic syndromes (author's transl)]. Five patients suffering from choreo-athetotic syndromes of different genesis were treated with the benzodiazepine-derivative Ro 06-9098/000 (7-Nitro-1(methylmethoxy)-1,3-dihydro-5-phenyl-2 H-1,4-benzodiazepin-2-one). The existing hyperkinesias could be well influenced in four cases of male patients, sufficiently in one case of a female patient. The sedative effect, accompanied by a muscle hypotonia appearing simultaneously under the medication, did not represent and essential limiting factors at the chosen dose of 5--20 mg/die. The observed successes in therapy point at the result and effect of benzodiazepine derivatives on extra-pyramidalmotoric hyperkinesias which got little attention until now.


[The preprogramming of behavior patterns by changing the neurotransmitter metabolism in the early postnatal ontogenesis of albino rats]. Changes in neurotransmitter concentrations, which are brought about by the administration of neurotropic pharmaceuticals to albino rats at the time of differentiation of the brain, may have a lasting effect upon the reactivity and adaptability of adult animals to environmental factors and give rise to specific patterns of behavior. 1. Pargyline, when administered neonatally, resulted in a reduction of learning power, decrease in the power of retention, as well as reduction of the decision-making ability. 2. Reserpine gave an improvement of learning power, but simultaneously decreased both the power of retaining what had been learnt and the decision-making ability. 3. Pyridostigmine gave a marked improvement of adaptability which was evidenced in higher learning power, greater retentiveness, and better decision-making ability.


The striatonigral fibres and the feedback control of dopamine metabolism. It proved possible to make lesions which interrupted the striatonigral GABA-containing pathway in the rat brain without causing concomitant damage to the nigrostriatal dopamine containing system. Estimations of striatal concentrations of dopamine (DA), dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA) inducated that these lesions had no influence either on normal striatal DA turnover or on the enhancement of DA turnover induced by neuroleptics. Behavioural experiments suggested a motor output function for the striatonigral pathway.


Benzodiazepines and behavioral effects of reward (water) omission in the rat. Two behaviors related to nonreward (omission of water in an enclosure where the rats were habituated to drink) were studied. The time spent licking the bottles during water omission and the time spent drinking during a subsequent 5-min drinking session (water available) were recorded. The drinking session was performed 30 min after the water-omission session. Rats subjected to water omission showed an enhanced drinking time that varied with the length of the water omission session, with the motivational state of the animals, and with the previous number of water-omission sessions. Diazepam, chlordiazepoxide, lorazepam, and meprobamate (i.p., 30 min before water omission), increased the time spent licking the empty bottles, but failed to abolish subsequently enhanced drinking. However, some of our data suggested that minor tranquilizers weakly reduced the increased drinking induced by nonreward, despite their direct stimulation on water drinking. It is proposed that either minor tranquilizers are devoid of general antifrustration activity or nonreward-induced frustration and nonreward-induced drive enhancement may not be correlated.


Pulmonary complications associated with the prune-belly syndrome. Eight patients are presented who demonstrate many of the pulmonary complications seen in the prune-belly syndrome. The patients are divided into two major groups: Group I includes pulmonary hypoplasia; Group II includes lobar atelectasis and pneumonia. The etiology, pathogenesis, and radiographic features of these complications are discussed. Pulmonary complications become more important as renal dialysis and transplantation spare more of these patients from an early uremic death. Prompt recognition of the type and the extent of pulmonary disease in patients with the prune-belly syndrome may lead to increased survival.


Activation of guanylate cyclase by arachidonic acid in mammary gland homogenates from mice. Arachidonic acid stimulated guanylate cyclase activity about two fold in homogenates of mammary glands obtained from midpregnant mice; effects of arachidonic acid were observed during incubation periods between 5 and 20 minutes. Stimulatory effects of arachidonic acid on guanylate cyclase activity were observed when 10 to 100 microgram arachidonic acid was added to the reaction mixtures (150 microliter). When 250 microgram or more arachidonic acid was added to the reaction mixtures, the activity of guanylate cyclase was inhibited. Other fatty acids including linoleic acid, linolenic acid and oleic acid also stimulated guanylate cyclase activity but neither arachidic acid nor stearic acid had an effect. The arachidonic acid stimulation of guanylate cyclase activity was abolished by incubation with indomethacin and aspirin, thus suggesting the arachidonic acid effect may be carried out via the prostaglandins. A variety of prostaglandins, however, at several concentrations did not stimulate guanylate cyclase activity when added to the reaction mixtures. The failure of the prostaglandins to have an effect may be due to several reasons which are discussed.


Effect of beta-fluorophenethylamine analogs on monoamine oxidase substrate preference. A novel potentiometric assay was employed to evaluate the effects of beta-fluorination of phenethylamine (PEA) on brain MAO substrate preference. Through the use of the substrate selective MAO inhibitors clorgyline (type A) and Deprenyl (type B), F-PEA and F2-PEA were found to be preferred substrates for MAO type B. Since various degrees of fluorination of the parent PEA molecule proportionally decrease the pKa values, as well as their substrate activity for MAO, it is suggested that the protonated form of PEA and its respective mono and difluoro analogs are the preferred substrate forms for catalysis by brain MAO.


Survival of Leptospira interrogans serovar pomona in an acidic soil under simulated New Zealand field conditions. Leptospira interrogans serovar pomona was found to survive for at least 42 days in a typical New Zealand soil under simulated winter field conditions. The soil was markedly acidic with a pH of 5.5 and survival times were not reduced even when its water content was only 23%. The values of both these parameters are considerably less than previously recorded for the survival of leptospires in soil. Two methods were used to recover leptospires from the soil microflora. One was the culture of a membrane filtrate in EMJH media with or without contaminant-suppressing additives and the other was the direct inoculation of soil-washings into hamsters. Both techniques proved to equally sensitive. It was estimated that following the addition of 5 X 10(8) leptospires to the soil samples less than 2 X 10(4) were present after six weeks.


Tissue and blood distribution of gamma-glutamyl transferase in the lamb and in the ewe. Gamma-glutamyl transferase distribution was studied in 10 ewes and 10 lambs; in both groups kidney was the most active organ, followed by pancreas, liver and lungs. In kidney and liver, GGT was bound mainly to cellular structures. Blood GGT activity of 48 lambs was 44 +/- 11 iu/litre and 33 +/- 7 iu/litre of 45 ewes.


Subcellular fractionation studies on peroral jejunal biopsies from the dog. Portions of closed jejunal biopsies from the dog were homogenised and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles were determined using highly sensitive assay procedures. The following organelles, with assayed marker enzymes and modal densities between brackets were characterised: peroxisomes (catalase, 1.21); brush borders (zinc-resistant alpha-glucosidase, leucyl-beta-naphthyl-amidase, gamma-glutamyl transferase, alkaline phosphatase, 1.20); lysosomes (N-acetyl-beta-glucosaminidase, alpha-mannosidase, 1.19); mitochondria (malate dehydrogenase, 1.18); endoplasmic reticulum (Tris-resistant alpha-glucosidase, 1.16); basal-lateral membranes (5'-nucleotidase, 1.11) and cytosol (lactate dehydrogenase). Homogenisation in isotonic sucrose containing digitonin (0.12 mmol/litre) selectively disrupted lysosomes and increased the equilibrium density of brush border and basal-lateral membranes. This procedure will be used to study the subcellular pathology of naturally occurring intestinal disease in the dog.


Gill ventilation in the sturgeon, Acipenser transmontanus: unusual adaptations for bottom dwelling. Measurements of branchial cavity water pressures and flow patterns, arterial blood PO2 and pH, and oxygen utilization and uptake have been made in undisturbed, free swimming sturgeon, Acipenser transmontanus. Although the jaws are degenerate and the oral apparatus is highly modified for feeding, gill ventilation is nonetheless powered by a buccal force pump and an opercular suction pump common to most bony fishes. The reduced spiracles play little or no role in gill ventilation. In sturgeon in which water intake through the ventrally located mouth was experimentally eliminated, a condition which may often develop when these fish forage in mud and sand on river substrates, effective ventilation of the gills was maintained with water drawn into the branchial cavities in a retrograde fashion solely through permanent openings in the upper regions of the opercular slits. O2 uptake and transport also remained at control levels. It is suggested that this unusual alternative mode of gill ventilation in the sturgeon represents an important respiratory adaptation to bottom dwelling and feeding.


Hemoglobin-ligand interaction in fetal and maternal sheep blood. Hemoglobin-ligand interaction was studied in maternal and fetal sheep blood as a function of oxygen saturation. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of NaOH or HCl at constant PCO2 (fixed acid Bohr effect). For maternal blood, CO2 Bohr factor was -0.41 at 50% oxygen saturation, increasing in magnitude at lower saturation and decreasing in magnitude at higher saturation. For fetal blood, CO2 Bohr factor was -0.45 at 50% oxygen saturation, unchanging at lower saturation and decreasing in magnitude at higher saturation. Fixed acid Bohr factor was relatively saturation independent with a value of -0.36 for fetal blood and -0.27 for maternal blood. The pH-independent effect of molecular CO2 on oxygen affinity was markedly saturation dependent being greatest at low oxygen saturation. The CO2 effect was greater in maternal blood than fetal blood. However, the magnitude of the saturation dependency of Bohr factor is not great enough to have major physiological significance in oxygen transfer across the sheep placenta.


Pulmonary gas exchange, diffusing capacity in natives and newcomers at high altitude. At high altitude, in resting conditions, no differences have been observed between High Altitude Natives (HAN) and acclimatized Sea Level Natives (SLN) in AaDO2, aADCO2 or venous admixture. In acclimatized SLN, AaDO2 is smaller than at sea level because of: (1) The minor effect on arterial oxygenation of the probably constant venous admixture. (2) The reduction of VA/Q inequality as shown by a smaller aADCO2. In HAN, DLCO is greater than in SLN; the contribution of DM or VC in this difference remains unsettled, mainly because of the difficulties of measurement of DM and VC in HAN suddenly exposed to acute hyperoxia. In SLN, in acute hypoxia, DLCO increased transitorily. Asynchronous mechanisms of adaptation to high altitude are evoked.


Oxygen affinity in the blood of sheep.

Oxygen affinity in the blood of sheep. The oxygen affinity in the blood of adult Dorset sheep with HbB was studied by determining several oxygen equilibrium curves under different conditions of pH and PCO2 by a method that allowed strict control of pH, PCO2, and HCO3- concentration over the entire curve. Nomograms and equations were derived that allowed the estimation of the oxygen saturation in a sample of blood in the range 0 to 100%, either from pH, PCO2 and PO2, or from PO2 and known P50. The advantage of this approach is that no assumptions about the shape of the oxygen equilibrium curve need be made (i.e. the Hill parameter, n, is not required to be constant), since the entire curve was measured.


Separator isoelectric focusing for identification of alpha-1-antitrypsin (Pi M) subtypes. A modified analytical isoelectric focusing procedure on polyacrylamide gel slabs, offering increased resolving capacity, has been developed for identification of six subtypes of the most common alpha-1-antitrypsin (A-1-AT) phenotype, Pi M. Combination of commercial Ampholine and other ampoteric substances, so called separators, produces pH plateaus, determined by the properties of the the additatives. Equilibrium is reached after extended focusing time, whereby stabilization of A-1-AT through alkylation is advantagous. The significance of this high resolution method for applications of the Pi system in genetic studies, and the general relevance of the modifications for other analytical purposes are discussed. A new nomenclature recommendation is presented.


Purification and properties of human amniotic fluid diamine oxidase. Diamine oxidase (DAO) was purified from amniotic fluid. The activity was separated in two DAO fractions with pI values of 5.8 and 4.0. Molecular weight were found to be 245,000 and 485,000, respectively, with subunit molecular weight of 110,000. This indicated that they probably are dimer and tetramer of the same DAO subunit. The enzyme was active against putrescine and histamine and was strongly inhibited by carbonyl group reagents. A Ping Pong Bi Ter enzyme reaction mechanism is probable. The diamine, with one amino group protonized, is suggested to be responsible for interaction with the enzyme.


Determination of plasma or serum haemoglobin by peroxidase activity employing 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen. A procedure is described for the determination of plasma or serum haemoglobin employing the peroxidase activity of the haemoprotein using 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen. The method gives equal results for free haemoglobin, methaemoglobin and haemoglobin complexed to haptoglobin. It is designed to measure haemoglobin in the range 0--12 mumol/l. The peroxidase activity of myoglobin is similar to that of haemoglobin, whereas haemin in free solution, bound to haemopexin or to albumin (methaemalbumin) shows much lower activity. The precision within run is satisfactory, +/- 5%.


Viruses and bacteria associated with acute respiratory illnesses in young children in general practice. The results obtained and the laboratory methods used for the isolation of viruses and bacteria from Malaysian children with acute respiratory illnesses seen in a private clinic are described. Of the 65 children studied virus isolations were obtained from 26 children, bacteria from 10 and both virus and bacteria from another 5. The agents isolated were influenza viruses, parainfluenza viruses, adenoviruses, Bordetella pertussis, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus pyogenes.


Current concepts of the undescended testis. Abnormalities of testicular descent represent the most common genitourinary anomaly in men. Many aspects of testicular maldescent remain controversial. The etiology of the undescended testis is still not known, but results of experimental work in rats strongly support the hormonal theories. Distinction between the truly undescended testis and the retractile testis remains a problem, making retrospective analysis of previous data confusing. Newer aspects of diagnosis of nonpalpable testes include the human chorionic gonadotropin test, herniography, venography and arteriography. Routine aspects of surgical therapy have changed little in recent years, although newer techniques, such as microsurgical procedures and innovative scrotal anchoring methods, are now available. Malignant tumors and infertility are the most worrisome complications. Evidence is presented to suggest that prognosis is related not only to choice of therapy but also to its timing. The recent evidence for Sertoli cell dysfunction, if substantiated may resolve some of the controversies.


Takayasu's disease: association with HLA-B5. The frequency of HLA-B5 (66%, n = 38) in Japanese patients with Takayasu's disease was significantly higher than in controls (32%, n = 160). The level of significance was x2 = 13.53, P less than 0.0005 and corrected P less than 0.009.


The lethal effects of the cibarial and pharyngeal armatures of mosquitoes on microfilariae. Microfilariae of Wuchereria bancrofti and Brugia pahangi were killed by the chewing action of the cibarial and pharyngeal armatures and other papillae and spines in the fore-gut of mosquitoes. The proportion of ingested microfilariae that were killed was largely dependent on the presence and shape of the cibarial armature. Anopheles farauti No. 1 and Anopheles gambiae species A and B have well developed cibarial armatures and killed 36 to 96% of the ingested microfilariae. Culex pipiens fatigans has a poorly developed cibarial armature and killed only 6% of the microfilariae. Aedes aegypti and Aedes togoi lack cibarial armatures but have the remaining fore-gut structures. They killed only 2 to 22% of the microfilariae. The significance of these observations in relation to the control of filariasis with diethylcarbamazine is discussed.


Mouse Peyer's patches contain T cells capable of inducing the graft-versus-host reaction (GVHR). The potential of cells from the Peyer's patches (PP) of normal adult DBA/2 Tru mice (DBA/2) to induce a graft-versus-host reaction when injected into (C57BL/6 Tru x  DBA/2 Tru)F1 hybrid (B6D2F1) mice was studied. The injection of 10(6) to 10(7) DBA/2 PP or spleen cells i.p. into neonatal F1 mice produced a striking splenomegaly. Comparable doses of parental PP or spleen cells injected into a rear footpad of adult F1 mice also induced a marked enlargement of the draining popliteal lymph node. In addition, PP cells were also capable of producing a lethal runting syndrome when injected i.v. into sublethally irradiated adult F1 recipients. In all assays, injection of syngeneic B6D2F1 cells had little or no effect. Treatment of the DBA/2 PP cells with anti-theta serum and complement abolished their capacity to induce splenomegaly in neonatal F1 mice. The graft-versus-host reaction activity of the PP cells could also be eliminated by thymus deprivation of the donor DBA/2 mice. These data are contradictory to previous findings in which it was observed that mouse PP cells were unable to induce graft-versus-host reaction.


ABO-incompatible marrow transplants.

ABO-incompatible marrow transplants. Seventeen patients with aplastic anemia or acute leukemia received transplants from donors who had major ABO incompatibilities. Antibody titers were decreased by plasma and whole blood exchanges prior to marrow infusion. All 17 patients were successfully engrafted, and there was one possible rejection in the patient with the highest pretransplant anti-A IgG titer. Nine of 17 patients are currently alive. A review was carried out of transplants performed in Seattle between HLA-matched siblings with aplastic anemia and leukemia. Two hundred forty-six evaluable patients with ABO-compatible donors were compared with 46 with minor ABO-incompatible donors. There was no effect of minor ABO incompatibility on graft rejection, incidence and severity of graft-versus-host disease, or survival.


Lipoprotein-lipase activity in subcutaneous, adipose tissue in healthy subjects: variation of activity in a population of 60-year-old men. The lipoprotein-lipase activity (LPLA) in the abdominal, subcutaneous, adipose tissue was studied in a random sample (n = 69) of 60-year-old men. A new method for the quantification of LPLA was applied. The mean value was 67 mU/g when expressed per gram (wet weight) of adipose tissue. Several subjects within the lower part of the range of adipose-tissue LPLA values had low concentrations of serum-triglycerides (S-TG). There was no correlation between the LPLA and S-TG concentrations in the fasting state. Among the 69 subjects, four had newly detected diabetes mellitus and had significantly lower LPLA in the adipose tissue than the control group. The fat-cell size and the LPLA per gram of adipose tissue were not correlated. Thus, obesity without diabetes mellitus does not imply a low LPLA concentration in adipose tissue. The variation of the concentration of adipose-tissue LPLA in the fasting state in this population was explained only to a minor extent by the variation of S-insulin and blood-glucose parameters, when analysed statistically by a stepwise multiple-regression technique.


Postpubertal untreated cryptorchidism. Anatomical relationship between Leydig cells and tubular sclerosis. A histological study of the postpubertal untreated cryptorchid testis establishes a direct anatomical relationship between Leydig cells and tubular sclerosis, an age-related process ranging from mild fibrosis of the tubular tunica propria to complete tubular hyalinization. Two separate processes are involved. Mild or moderate tunical fibrosis is related to pretubular hyperplastic Leydig cell nodules, while severe tubular sclerosis and hyalinization depends on the development of intratunical Leydig cells, a finding hitherto undescribed. More probing studies are needed to define the mechanisms whereby these abnormal Leydig cells cause tubular tunical fibrosis.


Reversal of the storage lesion of CPD bank blood: a problem in clinical medicine. The effect of phosphate buffer on the course of pH, ATP, and 2,3-PDG of CPD red blood cells stored at three temperatures was observed. Basic phosphate at an equilibrated level of 10 mM (as iP) maintained pH above 7.00 and ATP and 2,3-DPG above 70 per cent of initial value in cells stored at 37 C for 24 hours. In contrast however, at 25 and 4 C no buffering was obtained with basic phosphate concentrations up to 50 mM, but values for both ATP and 2,3-DPG were higher in phosphate treated aliquots than in controls throughout storage. When the pH of blood stored at 4 C was adjusted into the range 7.15 to 7.25 with tromethamine and the level of iP raised to 10 mM by addition of Na2HPO4 on day seven, it was found that ATP and 2,3-DPG levels were maintained at 90 and 120 per cent, while control levels fell to 60 and 12 per cent, respectively at 21 days. The process described parallels the normal repair of damaged red blood cells of bank blood that occurs in vivo following transfusion.


Alpha-blockers and urethral pressure in neurological patients. In 11 patients with upper motor neuron bladder paresis due to spinal trauma, 2 patients with lower motor neuron bladder paresis, and 4 patients with multiple sclerosis, alpha-adrenergic blockade with 10 mg Regitine intravenously decreased the maximum urethral closure pressure to an average of 42%. The decrease was most pronounced in a patient with lower motor neuron bladder paresis and a flaccid pelvic floor. Treatment with phenoxybenzamine was found valuable in patients with multiple sclerosis and poor bladder emptying as well as in patients with lower motor neuron bladder paresis. In patients with detrusorsphincter dyssynergia this treatment was of no value.


Detrusor hyperreflexia in female urinary incontinence treated pharmacologically. Detrusor hyperreflexia was found in 54 patients or 14.6% of 369 consecutive patients referred for urinary incontinence and/or genital prolapse during a 2-year period. The dominant symptom was urge incontinence. The urological investigation consisted of a medium fill water cystometry in the supine position. 20 patients (37%) suffered from cerebral or pyramidal nervous disorders. The treatment of choice was pharmacological with parasympatholytica, methantheline bromide (Banthine). The follow-up examinations performed in 33 patients after 6 months treatment showed an improvement rate of 82%. The importance of performing a cystometry in all female patients referred for urinary incontinence is stressed.


Effect of beta-adrenoceptor stimulation on the human bladder in vivo. The effect of beta-adrenoceptor stimulation on the volume of the urinary bladder in 16 neurologically normal humans without symptoms of micturition disturbances was investigated into. Terbutaline, a selective beta2-receptor-stimulating agent, was tested in 9 persons and isoprenaline, a general beta-receptor-stimulating agent, was tested in 7 persons. After terbutaline the maximum increase in the bladder volume was 10% and on an average around 5%. After isoprenaline the maximum increase in the bladder volume was 15% and on an average around 5%.


Effects of beta-adrenergic stimulating and blocking agents on the dynamics of the human bladder outlet. The alpha-adrenergic innervation of the functional urethra is a well-known fact, while beta-adrenergic influence is rather unknown until now. We studied the influence of beta-stimulating and beta-blocking agents on the human urethra by the urethral pressure profile (UPP). A decrease of the UPP under orciprenaline sulfate and an increase under propranolol could be mentioned.


Twenty-five-year experience with prune belly syndrome. Thirty cases of prune belly syndrome with no stillborn deaths seen over a twenty-five-year period at a university pediatric hospital are reviewed and the management, findings, and prognosis discussed.


Urinary tract reconstruction in prune belly syndrome. Fifteen boys with prune belly syndrome cared for over a ten-year period required surgical treatment because of uncontrolled infection and/or progressive azotemia. Five died of renal dysplasia. Primary or staged reconstruction resulted in significant improvement when ureteral reimplantation was combined with tailoring of ureteral caliber.


[Age-dependent adaptation of erythrocytes in the model of haemoglobinolysis (author's transl)]. 1. The erythrocyte is suitable as a model of investigating the mechanism of  adaptation as a function of aging. 2. By hemolysis experiments in isotonic solutions of various pH-values changes of the resistance of human erythrocytes during the mechanism of aging in the organism are established. 3. In isotonic alkaline solutions the resistance of the human erythrocytes changes according to the "curve of vitability" of the human organism.


[Effect of low temperatures on the functional state of the membranes of the hepatic endoplasmic reticulum]. Oxidation of fluorescent substrates--NADPH and 4-dimethylamine chalcone (DMC) by microsomes from liver endoplasmic reticulum was studied after freezing and thawing of these cells organelles. Slow freezing to -25 degrees or quick freezing to -196 degrees did not affect distinctly the rate of NADPH oxidation after thawing, but oxidation of DMC by microsomes was decreased in both cases. Freezing and subsequent thawing of microsomes impaired apparently the terminal sites of electron transfer and/or the systems of hydroxylation, including cytochrome P-450. Slow freezing to -25 degrees impaired microsomes more markedly than quick freezing to -196 degrees.


[Concentration of cyclic nucleotides, activity of adenylate cyclase, 3',5'-AMP phosphodiesterase and guanylate cyclase in plasma membranes from liver and hepatomas of different degrees of malignancy]. Adenylate cyclase activity as well as intracellular content of sAMP were decreased 2.5-4-fold, as compared with normal state, in plasmatic membranes (PM) of hepatoma 22 and of Ehrlich ascites carcinoma--the tumors characterized by high level- of malignancy. Activity of cAMP phosphodiesterase exceeded distinctly the normal value in all the tumors studied. In less malignant hepatoma 48 the adenylate cyclase activity and content of cAMP were similar to those found in normal liver cells. The guanylate cyclase activity did not differ markedly from values found in normal liver cells in PM of all the tumors studied and in liver tissue of the tumor-bearing animals. Distinct alterations were not found in content of cGMP in the tumors, except of hepatomas 60 and 22, in which the nucleotide level exceeded 2-fold the normal value. The ratio cAMP/cGMP was decreased in the most malignant tumors. At the same time, the ratio was distinctly elevated in tumors with the middle level of malignancy (hepatomas 60 and 61).


[Lipids and lipoproteins in early changes of arteriosclerosis]. LDL, fibrinogen and other plasma macromolecules are retained in intima in substantial amounts. In areas where lipid is accumulating a large part of LDL is immobilized possibily by binding to fibrin. Lipid may be deposited from LDL as a result of degradation by a cathepsin in intima.


[The coincidence of visceral lupus erythematosus and epilepsy]. It is reported on course and problems of the diagnosis of a lupus erythematodes visceralis with epilepsy. In the demonstrated case the initial stage was characterized by the nearly simultaneous appearance of relapsing arthritides and epilepsy. The diagnosis was made in the stage of an acute exacerbation with cardiac symptomatology which began after the medicamentous treatment with diphenylhydantoin. Up to this moment an oligosymptomatic lupus erythematodes visceralis had not yet been diagnosed. Anamnestic data and the laboratory-clinical findings of the further course of the disease proved the actual lupus erythematodes visceralis. It is referred to the necessity of an aimed anamnesis and a determination of the antinuclear factors before every application ofhydantoin derivations when an epilepsy and joint symptomatology are present.


[GLC-data of 19 hydrolysis-derivatives rised from 12 important benzodiazepines and 17 main-metabolites (author's transl)]. Analytical investigations of extracts after acid hydrolysis are in use especially considering benzodiazepine screening methods. The article describes the gas-chromatographic data of 19 hydrolysis-derivatives which are formed by hydrolysis of 12 important 1,4- and 1,5-benzodiazepines and 17 main metabolites.


[Use of phenazepam in the treatment of neurotic conditions]. The report contains data concerning clinical studies of a new Soviet tranquilizer of benzodiazepine derivative--phenazepam. Treatment of 100 patients gave a good therapeutical effect in 82%. The best results were attained in the treatment of generalized hystero-neurotical states, somewhat less in the group of neurotic states with a prevalence of affective disorders and the less effective in the obsessive-phobic syndrome. On the basis of comparative studies, the conclusion is made that phenazepam is not worse by its psychotropic activity than ativan (lorazepam) and exceeds diazepam (seduxen), most likely because of its myorelaxing action. The drug exerted an expressed hypnotic effect being not less than eunoctin and other eunectics.


Cytochrome P-450 and alkane hydroxylase activity in Candida guilliermondii. In the investigated Candida guilliermondii strain after growth on n-alkanes as the only carbon and energy source 5--10 nMol cytochrome P-450 per g cells (wet weight) could be detected. Cytochrome P-450 and alkane hydroxylase activity was found in the 100 000 xg pellet. Cofactor studies and inhibition experiments revealed the existence of a NADPH-dependent cytochrome P-450 alkane hydroxylase system.


Methotrexate and citrovorum factor after histoincompatible allogeneic bone marrow transplants in dogs. Methotrexate (MTX) followed by citrovorum factor (CVF) rescue was evaluated for its effectiveness in reducing graft-versus-host disease (GVHD) in lethally irradiated dogs transplanted with bone marrow from unrelated histoincompatible donors. Animals were given no immunosuppressive therapy (group A) or a combined regimen of MTX and CVF (group AMC). These two groups were compared with a group of animals transplanted earlier given MTX alone (group AM). Ainmals in the AMC group lived significantly longer than the A group (p less than 0.05). Engraftment rate, hematopoietic recovery and incidence of GVHD were similar in all three groups. Incidence of early deaths was significant in the AM group (p less than 0.05). It is concluded that MTX combined with CVF increases survival and is an effective posttransplantation immunosuppressive regimen with minimal toxicity.


Comparison between the unsaturated plasma folate binder and in vivo labelled plasma folate binder. Endogenous plasma folate binder denuded of folate by dialysis at pH 3, subsequently bound more methylfolate than folic acid, in contrast with the minor unsaturated plasma binder which bound folic acid in preference to methylfolate. On Sephadex DEAE-A50 chromatography 14C-CH3H4PteGlu bound to acid-denuded endogenous binder, eluted like the endogenous binder-radioactivity, labelled in vivo after oral 14C-CH3H4PteGlu. It is suggested that the endogenous plasma folate binder is not identical with the unsaturated binder.


Peripheral platelet count in response to salbutamol before and after adrenergic beta-receptor blockade. The effect of salbutamol (a comparatively selective adrenergic beta2-receptor agonist) on the peripheral platelet concentration was studied before and after the ingestion of either 50 mg metoprolol or 40 mg propranolol. The study was carried out on healthy males volunteers and autologous 51Cr-labelled platelets were employed at the experiments. Salbutamol was infused intravenously over a period of 6 min in a dose of 0.27 microgram.kg(-1). min(-1). Prior to metoprolol and propranolol administration a statistically significant lowering in platelet-bound radioactivity (PBR) was obtained in response to the salbutamol infusions. This salbutamol-induced fall in PBR was completely blocked by propranolol but was left unaffected by metoprolol. It is concluded that adrenergic beta2-receptor stimulation induces a transient lowering of the peripheral platelet count.


Clinical restitution following cerebral ischemia in hypo-, normo- and hyperglycemic rats. Rats with different levels of blood glucose concentration were exposed to 10 min of complete brain ischemia achieved by compression of neck vessels by a pneumatic cuff. All normoglycemic rats survived the ischemic period and made the best clinical recovery. Hyperglycemic rats died within 12 h. Seizure activity was observed in all animals in this group. Three of eight hypoglycemic rats died between 3 and 16 days. The clinical recovery was less complete than in the control group. Thus, recovery from cerebral ischemia depends upon preischemic blood glucose concentration. Hyper- and hypoglycemia hamper the clinical recovery after transient cerebral ischemia.


beta-Glucosidase activities in the Norrbotten type of juvenile Gaucher's disease. beta-Glucosidase and N-acetyl-beta-glucosaminidase activities were measured with synthetic substrates in peripheral leucocytes, urine and serum from patients with juvenile type of Gaucher's disease. Our findings in urine and serum make it clear that diagnosis by using synthetic substrate is not possible. In peripheral leucocytes reduced level was found for beta-glucosidase activity in patients with Gaucher's disease but also there occurred some overlapping with controls. The possible explanation to these findings are discussed.


The effect of stannous fluoride on human plaque acidogenicity in situ (Stephan curve). A system employing an Ingold glass electrode was shown to give reliable measurements of pH drops in dental plaque in situ (Stephan curve readings). The system was used to demonstrate that mouthrinses of 0.2 per cent aqueous solutions of stannous fluoride reduced the pH drops markedly for at least seven hours. A reduction of the stannous fluoride concentration increased the pH drops and decreased the duration of the inhibiting effect. A commercial toothpaste containing stannous fluoride and stannous pyrophosphate had an effect similar to the 0.2 per cent mouthrinse. It was shown that tin accumulated in dental plaque after application of solutions containing stannous fluoride. About 40 per cent of the amount of tin present in the plaque immediately after the mouthrinse was still retained seven hours later. It is suggested that the reduction in acid formation may be caused by stannous ions adsorbing to the bacterial cell wall thus disturbing membrane transport mechanisms, or through inhibition of enzyme systems essential in the fermentation of sugars. The observed effect may be a part of the mechanism involved in the caries preventive function of stannous fluoride.


Observations of otoconial membranes from human infants. The microdissection technique was used to study otoconial membrane from 30 human infants ranging from newborn to 2 years of age. Both saccular and utricular membranes were quite variable in overall shape. During the neonatal period, the gelatinous layer of the otoconial membrane appears to thicken and become less adherent to the macular surface than in the fetal period. In many infants older than 6 weeks, otoconial membranes were found at autopsy to be completely dislodged from the maculae, with abnormally large saccular otoconia present in four specimens. Fourteen of the infants studied died of sudden infant death syndrome and 16 died of other causes. The incidence of detached otoconial membranes was approximately the same in both groups. Although the majority of these membranes were apparently dislodged post mortem, the present findings suggest that otoconial membranes are susceptible to pathological alteration due to disease or head trauma.


Bacteriology of maxillary sinusitis in relation to quality of the retained secretion. The bacteriological findings in 200 patients with acute maxillary sinusitis are reported. It is concluded that the sampling technique--by antral aspiration--is highly significant in the evaluation of the bacteriological background of sinusitis, whereas the anerobic transport of the sample seems to be of less importance. By aspiration the purulent secretion can be properly separated from the non-purulent secretion. Pneumococci, H. influenzae and anaerobic bacteria can be isolated in about 90% of the patients with true sinus empyema, while sterile conditions are rare.


Base pairing mRNA-rRNA. The arrangement of nucleotides in the message for coat protein of phage MS 2. The relation of the nucleotide sequences in the message and of the short nucleotide sequence in 3' terminus of 16 S ribosomal RNA was found to differ from statistical expectancy. The observation is interpreted in terms of both the ribosomal interactions and the molecular evolution.


Antigenic glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin. I. Gel filtration in 6 M guanidine hydrochloride. Highly purified glycopolypeptides HA1 and HA2 were separated from bromelain-released haemagglutinin of influenza virus A/Dunedin/4/73 (H3N2) by gel filtration in 6 M guanidine hydrochloride under reducing conditions. The purity of both glycopolypeptides was proved by extensive studies. Despite the lack of C-terminal end, the isolated HA2 glycopolypeptide displayed some hydrophobic properties.


UV-inactivation of Epstein-Barr virus: differences in early antigen expression in two different non-productive cell lines and influence of caffeine. Two non-productive Epstein-Barr (EB) virus genome-carrying lymphoblastoid cell lines, namely Raji and NC37, were used for studying the effect of UV irradiation on the ability of P3HR-1 EB virus to induce early antigen (EA) formation. In NC37 cells infected with UV-irradiated virus the formation of EA was delayed; thus the slope of inactivation curve based on the early (24 hr) reading was steeper than that based on the late (72 hr) reading. This was not observed in Raji cells. Caffeine did not influence the percentage of EA positive cells in cultures infected with untreated virus; however, the drug exhibited a marked inhibitory effect on EA production after infection with UV-irradiated virus. The sensitivity to caffeine effect decreased more rapidly with time after infection of Raji than of NC37 cells, suggesting a higher degree of readiness of the host cell repair system in the former than in the latter cells. The caffeine effect was merely directed against the synthesis of R (restricted) component of EA; its influence on the D (diffuse) component formation was negligible.


Suppression of an arenavirus by a togavirus in experimental acute double infection. Lymphocytic choriomeningitis virus (LCMV) and tick-borne encephalitis virus (TEV) were inoculated in young and old chick embryo cell (CEC) and in L-cell cultures at various multiplicities per cell, simultaneously or 17 hr apart. The yield of infective LCMV was inhibited in double infection, most in old CEC with elevated interferon mechanisms, and least in L cells producing no interferon. In young CEC, TEV-induced interferon was stimulated by coinfecting LCMV; LCMV alone never has induced interferon. The reproduction of TEV was little affected. In doubly infected L cells the fluorescent antibody techniques revealed more cells positive for each viral antigen than in single infections, but the yield of LCMV per one antigen-positive cell was decreased. The course of TEV infection in cerebrally infected mice was not changed by co-infection with LCMV. The titre of LCMV in the brains of doubly infected mice was markedly suppressed when compared with LCMV monoinfection. High interferon levels in brains of all mice infected with TEV were not affected by LCMV co-infection.


Variations in biological properties of geographic strains of western equine encephalomyelitis virus before and after passage in Culex tarsalis and Culiseta melanura. Western equine encephalomyelitis (WEE) virus strains from the eastern and western United States were compared using two biological markers: antigenic properties measured by cross complement fixation (CF) tests and the size of plaques produced in Vero cell cultures. Slight antigenic differences were discernible on a geographic basis, and all of the virus strains from the West produced significantly larger plaques than the eastern isolates. One virus strain from each region was serially passaged in Culex tarsalis and Culiseta melanura by intrathoracic inoculation. No change in plaque size was detected as a result of mosquito passage. After passage of the eastern strain of WEE virus in C. tarsalis, its mouse brain CF antigen titer was increased to resemble the high CF antigen titer produced by the western strain. However, the antisera titers did not change when tested with this antigen. A cross plaque reduction neutralization test (PRNT) with the two virus strains before and after passage in mosquitoes failed to reveal any antigenic changes.


Improved detection by immunodiffusion of type-specific influenza antibody in avian sera. Various solvents and kinds of agar and agarose as well as various ribonucleoprotein (RNP) antigen preparations were tested in a search for optimal conditions for the detection of low levels of type-specific influenza antibody in avian sera by gel double diffusion. The best results were obtained with one kind of agarose in a solvent with lowered ionic strength (approx. 0.075 M). A hypertonic solvent usually gave worse or negative results, with the exception of one kind of agarose. In general, agarose yielded better results than agar. The results of immuno-precipitation were affected by the strain of influenza virus used for the preparation of RNP antigen.


Experimental infection of hare (Lepus europaeus) with Coxiella burnetii and Rickettsia slovaca. Hares (Lepus europaeus L.) infected subcutaneously (s.c.) or per os with Coxiella burnetii and s.c. with Rickettsia slovaca overcame an inapparent infection accompanied by irregular rickettsaemia and distribution of rickettsiae to different organs and variable antibody response. Neither riskettsia could be detected in faeces of infected animals, but C. burnetii was found in the urine of one hare, which died on day 13 post infection (p.i.). Antibodies against C. burnetii persisted for one year of observation period, those against R. slovaca up to the 181st day p.i. Based on the results obtained and data on other lagomorph species, the hare could play an important role as host of C. burnetii and R. slovaca in nature.


H-1 and X14 parvovirus antibodies in women with abortions or still-births. Antibodies against H-1 and X14 parvoviruses were found 13.71 and 9.14%, respectively, of 350 sera from women affected by repeated abortions or still-births. On the contrary, only 2.66 and 1.66% of 300 control sera were positive to the two viruses. The difference in the incidence of antibodies appears highly significant (p greater than 0.001). Therefore a possible role of the parvoviruses in inducing abortions or still-births in humans is suggested.


Depression: a new approach to an old syndrome. Depression is a medical illness related to an interplay of genetic, biochemical and environmental/experiential factors. Careful diagnosis, using contemporary psychiatric criteria, simplifies treatment by the family physician. Awareness of these criteria may lead to improved selection of candidates for drug treatment and early intervention in recurrent illness. The new nosology in psychiatry avoids much confusion and should take some of the guesswork out of psychiatric treatment in the family physician's office.


Binding of bile acids by dietary fiber.

Binding of bile acids by dietary fiber. Binding of bile salts to food residue was studied in vitro and in vivo. In the in vitro experiments, residues of a number of foods were incubated with each of several bile salts at different concentrations and pHs. All food residues tested adsorbed more dihydroxy than trihydroxy bile salts. Bile salt binding increased as bile salt concentration increased and was greater at a low pH. The extent of bile salt adsorption to some food residues could be clinically important. In patients with short ileal resections, we compared the rates of fecal excretion of labelled cholic and chenodeoxycholic acids and of a nonabsorable marker during ingestion of an ordianry diet (approximately 5 g of fiber) and a residue-free liquid diet. Coefficients of bile salt adsorption were calculated. Both bile acids were absorbed more efficiently during the liquid diet. Chenodeoxycholic acid was preferentially bound to the particulate matter of stools of patients eating the fiber-containing diet. It seems possible that dietary fiber could affect the enterohepatic circulation of bile salts in certain patients with ileal resection.


Accuracy and precision of urinary pH determinations using two commercially available dipsticks. The accuracy and precision of urinary pH determinations using commercially available dipsticks were studied. Two products were evaluated by 17 MT(ASCP) technologists over the pH range 4.5 to 9.0. The study included accuracy, reproducibility, variation among technologists, and variation between products. The results demonstrated considerable variation among technologists, products, and true pH levels in dipstick urinary pH determinations, and that very good or very poor results could be obtained, depending on the true pH level being sampled and on the choice of technologist.


Urinary nitrite and urinary-tract infection. Two dipstick procedures and an automated quantitative urinary nitrite assay were used to study nitrite in 786 samples of urine submitted to the bacteriology laboratory for routine culture and sensitivity testing. Many samples that had more than 100,000 nitrite-reducing organisms/ml and no detectable nitrite were studied. Limited nitrate concentration in urine was not a significant cause of false-negative nitrite results. However, in some urine samples nitrite added in vitro was lost during a four-hour incubation in vitro at 37 C in the presence of more than 100,000 nitrite-reducing organisms/ml. Ascorbic acid, abnormal amounts of urobilinogen, and urinary pH below 6.0 are all possible causes of false-negative nitrite determinations.


Inhibition of canine gastric acid secretion by an H-1 receptor antagonist to histamine. Histamine H-2 receptors are thought to mediate gastric acid secretory responses, whereas H-1 receptors supposedly regulate mucosal vascular responses to histamine. In an in vivo chambered canine stomach flap preparation, the H-1 receptor antagonist, tripelennamine, injected intraarterially (22.1 mumol/kg) into the stomach flap reduced histamine-stimulated (1.25 micron/kg/min intravenously) acid secretion by approximately two thirds with a secondary reduction in gastric mucosal blood flow. This antisecretory action does not appear to be due to nonspecific mucosal damage. The H-2 receptor antagonist, metiamide, injected intraarterially (2.5 mumol/kg) also inhibited gastric acid secretion by about two thirds as did intravenously injected metiamide (4.5 mumol/kg), whereas intravenously administered tripelennamine (40.8 mumol/kg) was ineffective as an acid secretory inhibitor. Intraarterial tripelennamine reduced the secretory actions of the H-2 agonist, 4-methylhistamine (2.2 micron/kg/min intravenously), while intravenous metiamide depressed the gastric mucosal dilator responses to the H-1 agonist, 2-methylhistamine (5 micron/kg/min intravenously). Both histamine-receptor antagonists also reversed the systemic circulatory depressor effects of histamine and its analogs. These results suggest the need for reevaluation of inferences based upon the assumed specificity of H-2 and H-1 agonists and antagonists.


Impairment of secretin release in celiac sprue. Plasma secretin concentrations and pH in the second portion of duodenum were measured in the fasting state and during duodenal infusion of HCl in five patients with untreated celiac sprue, five celiac sprue patients after gluten-free diets, and five normal subjects. Mean fasting plasma secretin concentrations were insignificantly lower in untreated sprue patients (4.1 +/- 1.4 pg/ml) than in normal subjects (5.7 +/- 0.59 pg/ml). During 30-min intraduodenal infusions of 0.1 N HCl at 0.20 mEqH+/min, mean plasma secretin concentrations were significantly lower in untreated sprue patients (5.8 +/- 1.8 pg/ml) than in normal subjects (25.4 +/- 1.60 pg/ml, P less than 0.01). The increases in mean secretin concentrations over fasting were 2.1 +/- 0.82 pg/ml in untreated sprue patients compared to 19.7 +/- 1.47 pg/ml in normal subjects (P less than 0.01), a ninefold difference. The results indicate that endogenous release of secretin in response to duodenal acidification is impaired in patients with celiac sprue.


Rapid emesis from high-dose ipecac syrup in adults and children intoxicated with antiemetics or other drugs. The effect of ipecac syrup as an emetic in adults as well as children who had ingested antiemetics or other drugs was evaluated. Adults or children over five years of age were given 30 ml of ipecac syrup followed by 360 ml of water; children aged one to five years were given 15 ml ipecac syrup followed by 240 ml of water. If emesis was not induced within 30 minutes, a second dose was administered. Of 232 patients studied (199 adults and 33 children), 188 (81%) vomited following the first dose, 34 (15%) required two doses and seven (3%) did not vomit. Of 63 patients who had ingested drugs with antiemetic properties, 51 (81%) vomited following the first dose, nine (14%) required a second dose and three (5%) did not vomit. The time from ipecac administration to the onset of emesis in all 232 patients averaged 24.2 minutes. Ipecac was successful in inducing rapid emesis in both adults and children who had ingested antiemetics or other drugs, probably as a result of its irritating effect on the gastric mucosa.


Cardiac systolic time intervals in fetal monkeys: pre-ejection period. The systolic time intervals of the fetal cardiac cycle were studied by means of simultaneous recordings of electrocardiogram (ECG) and ultrasound Doppler cardiogram (DCG) in chronic preparations of fetal rhesus monkeys. Recordings were made under physiologic conditions as well as during various experimental stresses. The pre-ejection period (PEP) showed no significant relationship with heart rate in the unstressed fetuses, but the acceleration of heart rate induced by epinephrine was accompanied by shortening of PEP. The PEP increased with advancing fetal age. The PEP was inversely correlated with left ventricular end-diastolic pressure and arterial pulse pressure, but showed a positive correlation with both systolic and diastolic arterial blood pressure. The PEP also exhibited strong negative correlation with arterial blood pH. the prolongation was essentially the same whether acidosis was of respiratory or metabolic origin. The PEP increased slightly but significantly during nonacidemic hypoxemia; however, there was no correlation between Pao2 and PEP Epinephrine shortened the PEP significantly, whereas the effect of atropine was inconsistent. Alteration of the plasma glucose level by injection of insulin or glucose did not affect PEP. These findings demonstrate that the PEP may be a useful indicator of fetal cardiac performance, reflecting both myocardial contractility and the hemodynamic state of the cardiovascular system.


Withdrawal syndromes associated with antipsychotic drugs. Withdrawal symptoms frequently follow abrupt discontinuation of antipsychotic compounds. In addition to other somatic symptoms, withdrawal-emergent dyskinesias may be observed. "Covert dyskinesia" refers to a masked form of tardive dyskinesia that becomes clinically detectable only after antipsychotic drugs are withdrawn or their dosage is reduced. Withdrawal dyskinesia appears under similar circumstances but disappears spontaneously in 6 to 12 weeks. Cholinergic overactivity and changes in dopamine-acetylcholine balance in the basal ganglia may underlie these withdrawal syndromes. The principal value of the concept of covert dyskinesia is in the secondary and tertiary prevention of tardive dyskinesia through early discovery and treatment.


The social context of schizophrenia.

The social context of schizophrenia. During the past 25 years psychiatry has increased its understanding of the social context of schizophrenia in four major areas. Reasonable reliability can now be achieved in describing and recognizing many of the acute and chronic syndromes, so that comparability can be achieved between different research teams. Much is now known about the proximate social causes of symptoms and disabilities. The relationship between social and pharmacological treatments is now better understood. A more rational approach to the planning and prescription of services and to the counseling of patients and relatives can be made. Each of these lines of advance promises to lead to further progress in the future.


[Medical check-ups and selection of subjects: some results from a gerontological field-study (author's transl)]. In a gerontological field-study in Cologne, West-Germany, 1114 subjects of a random sample of elderlies were successively offered three modalities for a medical check-up, which covered a physical examination and a psychiatric interview: 1. in the out-patient department of a psychiatric hospital (Rheinische Landesklinik Köln) (38% of the subjects); 2. in the subjects' home by a psychiatrist of the hospital (13%); 3. by having the general practitioner fill out a questionnaire (21%). There remained a fourth group of subjects who refused any medical check-up (28%). Data on social and economic problems had been obtained for all subjects in a preceding interview. These data were used to find out to what extent selection mechanisms were effective. Results indicate that to a certain extent the modality of the medical check-up chosen by the subject is related to some of the variables analyzed.


[Collecting data on the state of health of the elderly by mail survey of family doctors (author's transl)]. In connection with a gerontological research project data on the physical of the persons being investigated were, amongst other sources, also obtained through a mail survey of family doctors. How far survey shortcomings have a distorting effect was studied. The results indicate that a mail survey of family doctors may yield appropriate data even if some of the physicians named by the persons being investigated do not respond.


[Study on the effectiveness of the "Berlin Letters for Seniors (author's transl)]. The effectiveness of the "Berlin Letters for Seniors" (LFS) will be tested by a longitudinal study. Two Measurement Points (MP) are scheduled: 1976 and 1978. The total sample (N = 3000) comprehends two subsamples of receivers and non-receivers. Data were/will be collected by a questionnaire. A preliminary analysis of the MP I data shows that the two subsamples are comparable as to demographic variables and relevant attitudes; so they may serve as experimental versus control group. An examination of what the readers' concept of the LFS was like, proved that though reservation was recognizable approval prevails.


[Stress of the elderly (author's transl)]. Author examines the suicide-motives of elderly people in connection with stress and describes the Hedri-Mallisons disease, which has a very high suicide-rate.


[Survived brain infarction in old age - clinical and morphological findings. II. Risk factors (author's transl)]. 208 hospitalized patients, nearly 80 years old, were investigated because of risk factors and complicating diseases. Hypertension (58.2%), typical myocardial infarctions (37.2%) and diabetes (45.2%) were twice often as in our comparable cases without stroke. Corresponding we found signs of left ventricular hypertrophy in more than 50% post mortem. The dimensions of heart failure by hypertension are visible in ECG indicating LVH with many dysrhythmias. Early mortality (40%) as survival time are dependent on the size of the stroke. Cardiovascular causes of death were found mainly. The differences to younger patients with brain infarction seem to be only of gradually nature and especially to refer to the more intensive damaged heart.


[Prosthetic fitting in the geriatric leg amputee (author's transl)]. This retrospective study regarding prosthetic fitting in geriatric amputees showed that only about 50 per cent of the patients could be fitted with a prosthesis. The time interval from the amputation until the patients walked adequately with the prostheses was very long. This was due to problems with the healing of the stump, as well as insufficiencies in the medical organization. An increased coordination of the care of these patients before and after an amputation would improve the whole course of events. It is suggested that the main responsibility for these patients should be transferred to physicians, specialized in long-term care medicine.


[Application of laser rays in surgery (author's transl)]. Some years will have to pass, until there will be evidence, if application of leaser beam in surgery of Breastcancer, Melanomas or Basaliomas was justified and whether it is possible or not to interrupt or reduce intraoperative tumor cellspread. As an increasing number of surgeons have started to use laser rays in these illnesses, result of laser surgery and those of traditional methods could be compared in a couple of years. Possibly other indications will be outlined in general surgery for the use of laser beside those we have been working out. It may happen that surgeons working with laser beam might bring the method into discredit putting indication not rigorous enough. I should like to remind everybody who starts working with laser rays, to do so with greatest possible care. Collaboration with a technician is recommended. Periodic he should control the machine and handle arising technical problems.


[The cardiotropic effect of antidepressants in aging patients (author's transl)]. All antidepressants now used have a cardiotropic, for some instances also cardiotoxic effect. This quinidine-like effect prolongs the QT-interval of ECG and can induce reentry and ventricular fibrillation. When quinidine and antidepressants are combined in the same patient the risk of such cardiac complications increases.


[Autoimmune phenomena in the aging, cerebral atherosclerosis, Parkinsonism (author's transl)]. Studies were undertaken on the immune reactions in aging at cerebral atherosclerosis and parkinsonism. With age a number of changes occurred, which were characterized by a decrease in specific and non-specific immunity, against the background of which the autoimmune reactions were developing. There was an increase in the frequency of the detection of antibodies to antigens of the brain as well as in those of the aorta, heart, liver and pancreatic gland. The "peak" of autoimmune reactions was registered at 65 years in men and 75 years in women. There were lymphocytes in the peripheral blood, which together with homologic antigens inhibited the migration of macrophages. In subjects aged 90 years and over the autoantibodies occurred in a lower percent of cases as compared with the subjects aged 60--74. In subjects aged 45--55 with cerebral atherosclerosis the indices under study appeared to be close to those in healthy persons aged 60--74. Still more marked immunological shifts were found in patients with parkinsonism. The findings may suggest a certain role of the autoimmune mechanisms in pathogenesis of some forms of nervous pathology at late stages of ontogenesis and atherosclerosis.


[A meaningful antibiotic therapy of diseases of the ear, nose and throat in old age (author's transl)]. Each stage of life is characterized by the prevalence of certain affections; among others, inflammatory diseases of the ear, nose and throat are frequent in old age. Therefore, specific problems of chemotherapy in old age are dealt with in general terms in the introduction, with special stress being placed on the functions of individual organs, mainly of the kidneys, and on questions of disturbed absorption. Inflammations caused by streptococci, requiring at least ten days of antibiotic treatment, always deserve particular attention, and so do staphyloccocal diseases, requiring the selective administration of semi-synthetic pencillines (sioxazol preparations). Penicillin is still the first choice among all antibiotics, penicillin substitutes, to be used in case of allergies, are listed according to their order of value. As anaerobic germs may also be present in the ENT area, the effective modern therapy by means of special antibiotics is also referred to. Finally, due consideration is given to local antibiotic therapy, with an emphasis on the ototoxicity of chemotherapeutical agents, such as amino-glycosides.


[Stereological investigation in the cerebral cortex of aging subjects (author's transl)]. Involving cortical regions, capillaries of the human cerebrum of two 19 and 27 years old men, a 69 years old woman and a 72 years old man were stereologically investigated by optical-electronic image-analysis. The cortical capillary net work was demonstrated by the alkaline phosphatase activity. Each cortex region comprised a determination of the stereological parameters diameter, projected area, specific surface area, capillary distances in linear direction of TV-lines and total length per unit cortex volume. A comparison between different cortex regions revealed a good correlation between increased values of the diameter and the projected area, a decreased specific surface area and diminished capillary distances, which entail a shortened distance of oxygen diffusion through the cortical tissue. During aging a diminished capillary surface area, which results from increased values of diameter and projected area is compensated by shortened capillary distances. Presumably an augmented capillary length is due to a condensation of the capillary net per unit cortex tissue. The behaviour of the registered stereological parameters seems to be an accommodation of the capillary net in the human cerebrum to metabolic and circulatory changes during aging.


Leucocyte migration test and hypersensitivity to glafenin. The leucocyte migration test (LMT) was performed on 20 patients with an intolerance to glafenin--a non-narcotic analgesic drug. LMT was found to be positive in 50% of the subjects with intolerance, a highly significant percentage as compared with the control groups. HSA-glafenin was found to be the most appropriate method for presenting the antigen, but glafenin and its hydroxylated metabolites were only found to induce a migration inhibition in the subjects intolerant to glafenin.


Increasing halothane concentrations reduce nitroprusside dose requirement. There has been no description of the hemodynamic dose-response relationship between halothane and sodium nitroprusside (SNP), although these drugs are used together frequently for induction of deliberate hypotension. Utilizing aortic root cannulation and thermister-tipped pulmonary artery catheterization, this relationship was studied in 6 beagles receiving a standard 100 microgram/kg infusion of SNP solution administered at 3 different infusion rates (5, 10, and 20 microgram/kg/min) while anesthetized with 3 different concentrations of halothane (0.5, 1, and 2%). Sodium nitroprusside infusion resulted in dose-related reductions in mean arterial pressure, systemic vascular resistance, and left ventricular stroke work. Increasing concentrations of halothane significantly potentiated the hypotensive effects of SNP. Cardiac output increase as the SNP infusion rate increased, whereas increasing the halothane concentration resulted in a reduction of cardiac output at each SNP infusion rate studied. Pulmonary artery wedge pressure was significantly reduced by SNP infusion at all 3 halothane concentrations, whereas mean pulmonary artery pressure was unchanged. Arterial pH fell in response to each SNP infusion, from 7.46 at the beginning of the study to 7.32 at the end (p less than 0.001). Sodium nitroprusside predictably induced hypotension during halothane anesthesia at the cost of a dose-related metabolic acidosis. Increasing the depth of halothane anesthesia afforded a greater percentage reduction in arterial pressure at each SNP infusion rate studied. Metabolic acidosis, however, developed no more rapidly at 2% halothane than it did at 0.5 or 1%.


Low-frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R): an experimental study. We describe a new form of mechanical pulmonary ventilation, low-frequency positive pressure ventilation with extracorporeal CO2 removal (LEPPV-ECCO2R). In a series of animal studies the rate of mechanical ventilation was 0.66, 1, 2, and 4 min-1 at a tidal volume of 3, 10, and 15 ml kg-1. We were able to maintain normal blood gases and normal lung volumes and lung mechanics even at the lowest ventilator rate with tidal volumes of 10 or 15 ml kg-1. Each experiment lasted 7 hours. Our data suggest a possible new dimension in the management of a difficult patient on mechanical pulmonary ventilation.


[Perforations of the dura mater during epidural anesthesia. The value of epidurography]. The authors propose a pathogenic classification of perforations of the dura mater occurring during continuous epidural anaesthesia: according to the flow through the communication with the subarochnoid space. Two clinical forms of anaesthesia affecting the cord itself may be distinguished on this basis, one frequent and of immediate onset, diagnosed by the "test dose" and the other rare, of delayed onset, where this safety measure does not suffice. Routine prior epidurography is suggested, in order to ensure the diagnosis of dura mater perforation. In the case of the latter, it show either a more or less typical appearance of radicolography only or, more rarely, a picture which combines opacification of the epidural space with the subarachnoid passage of the contrast medium. This "mixed" appearance, although rare, should be known since it makes it possible to prevent delayed total spinal anaesthesia.


Effects of pH on protein binding of lidocaine. Protein binding of lidocaine (2.5, 5, 10, and 20 microgram/ml in fresh plasma was studied from pH 5.6 to pH 9.8. Percent binding of lidocaine was inversely related to hydrogen-ion and lidocaine concentrations.


[Psychiatric complications in patients under intensive care]. Ten adult patients with psychiatric disorders in the intensive care ward were examined. The length of stay varied from one week to four months and mechanical ventilation was necessary for all patients. Their experience of intensive care and their psychosensorial problems were as follows: temperospatial disorientation, perturbation of the sense of posture, hallucinations which could go as far as oneiric delirium, anguish and symptoms of depression. No psychotic syndrome, literraly speaking, was observed objectively. In the monthes that followed the stay under intensive care many patients presented important psychosomatic disorders. Organic factors are responsible for these complications, though the environment of the intensive care could induce a marked disafferentation. An effort by the attending staff, aimed at orientating or "reafferenting" these patients, could reduce these problems.