[Clinical evaluation of oxypertine in anxiety conditions]. Oxypertine, a new anxiolytic drug related to the indolylazine compounds, was evaluated in a group of 30 patients, the majority with severe anxiety (acute or chronic) : in some cases depression was associated. The study was performed in the Psychiatric Department at the Centro Femenil de Rehabilitación Social, in Mexico City. A special feature of this study was that patients were confined for a legal process and consequently with restricted liberty. All were females between 19 to 44 years old, with an average age of 32.05 years. The methodology applied in this case was a modified double blind randomized procedure, using different color capsules with placebo or the active drug (yellow oxypertine and blue placebo). Patients received a 10 mg capsule every 12 hours (20 mg daily). The clinical measurement of anxiety was performed using the Visual Anxiety Scale (Murphy), evaluating each of its 11 parameters. The intensity was qualified from 0 to 3; at the end of each consultation a global assessment was made. Most of the patients were interviewed in five occasions during the treatment period. For each of the nine patients receiving during 4 weeks only oxypertine capsules (group I), the scores of the parameters of the scale were added, observing the following results: in seven excellent respond, fair in one and one abandoned the study since the beginning. In eight of the patients who received placebo (group II) also for a 4 weeks period, results were evaluated as follows: five excellent one good and two poor. It can be observed that both groups gave a similar final score at the end of the study, meaning that no significant benefits were obtained between the active drug and the placebo, in spite that anxiety decreased in most of them. In group III, seven cases initiated with placebo and after 2 weeks the capsule had to be changed to oxypertine due to stablization or increase in the anxiety. Results were excellent in three, good in two, poor in one and another case suspended the treatment when placebo was to be substituted. In this same group, six cases initiated treatment with oxypertine, and after two weeks or more the medication was changed to placebo due to the same reasons mentioned above. Results were fair in one and poor in five. A significant response was observed in those cases where oxypertine replaced placebo and no response was obtained when placebo substituted oxypertine. Few cases abandoned mainly for two reasons: satisfactory remission of the anxiety or symptoms exacerbation. Investigators emphasize that the psychological conditions of the patients studied in this trial were different from the ones who ordinarily assist to the out patient clinics or private practice, mainly because were subjects with legal and social problems, as already mentioned, confined in a rehabilitation center. The conclusion of the stldy is that the administration of oxpertine at the dosage of 20 mg to patients with severe anxiety and with the special conditions mentioned above, provides a relative anxiolytic effect.


Benzodiazepine-induced modifications of dream content: the effect of flunitrazepam. The purpose of this study was to investigate the effect of flunitrazepam, a benzodiazepine with strong hypnotic properties, on dream content. Eight normal subjects were studied in laboratory by the awakening technique, and the dream contents were rated by two judges according to nine scaled dimensions: unreality, participation of the dreamer, pleasantness, unpleasantness, verbal aggresivity, physical aggressivity, sexuality, sensoriality and time of reference in the dreamer's life. By comparison with placebo condition, flunitrazepam induced more unpleasantness, more verbal aggressivity, more physical aggressivity, and more sexuality in dreams. This increase of emotionally loaded contents can be related to a disinhibitory effect of this drug, and the possible involvement of dopaminergic or serotoninergic systems is discussed.


[Cases of enuresis nocturna treated with single reflexotherapy. Clinical and therapeutic evaluation]. Treatment of children with nocturnal enuresis by means of acupuncture, auriculotherapy, etc. is reported. The aetiopathogenetic background, the results of treatment, and the neurophysiological mechanisms through which the action of reflexotherapy can be explained are discussed.


Practolol and the safety of other beta blockers. Recognition of the "occulomucocutaneous syndrome" related to practolol administration has caused the safety of other beta-blocking agents to come under close scrutiny. No satisfactory means of screening for at-risk patients is available. ANF estimation, has considerable limitations as both a screening and a diagnostic procedure. Patients with skin lesions alone may not be positive, while even advanced cases often show very low titres. There are important technical difficulties with the assay and interpretation of results is hindered by an increase in incidence of the antibody with age, in females, and in patients on a wide variety of other therapeutic agents.


Primary uterine tumors and multiple endocrine adenomatosis, type I. Multiple endocrine adenomatosis, Type I was initially diagnosed in a 35-year-old woman with primary chief cell hyperplasia of the parathyroids. Approximately 5 years later, vaginal bleeding developed and a well-differentiated endometrial adenocarcinoma was recognized. An adenomatoid tumor of the uterus was discovered in addition to a nonfunctional islet cell tumor of the pancreas. Multiple endocrine adenomatosis is reviewed in relation to possible gynecologic neoplasms.


Phenylalanine hydroxylase and tyrosine aminotransferase in human fetal and adult liver. The mean value of phenylalanine hydroxylase activity in adult human liver was almost twice as high as that in the fetal ones; no consistent variations were seen with sex, fetal age (between the 11th and 22nd week of gestation), or with hours between delivery and death. The tyrosine aminotransferase levels did not correlate with sex, age, or method of abortion; however, they were 5 times higher in the two fetuses which survived for more than 1.5 hr after delivery. The mean concentration of tyrosine aminotransferase (excluding these two fetuses) was about 15 times lower than in the adult liver. Phenylalanine hydroxylase is known to appear in rat liver on the 20th to 21st day of gestation. Tyrosine aminotransferase, on the other hand, emerges on the first postnatal day and, as shown here, can be evoked by premature delivery. Thus, in man as in the rat, (1) phenylalanine hydroxylase approaches physiologically significant levels at an earlier development stage than does tyrosine aminotransferase and (2) extrauterinization stimulates the synthesis of tyrosine aminotransferase but not of phenylalanine hydroxylase. Speculation There is a greater analogy than is usually assumed between human and rat liver with respect to the time schedule of enzymic differentiation and the factors which regulate it.


Failure of parathyroid hormone and cyclic AMP to inhibit renal carbonic anhydrase. It has been suggested that the parathyroid hormone and cyclic AMP produce their bicarbonaturic effects through inhibition of renal carbonic anhydrase. In the present study, the incubation of renal carbonic anhydrase with parathyroid hormone or cyclic AMP in presence of ATP, Mg++ and K+ ions, did not produce any inhibition of the enzyme when the pH of the solution was maintained above 7. It is concluded, that parathyroid hormone and cyclic AMP produce urinary bicarbonate excretion by a mechanism independent of carbonic anhydrase inhibition.


polA6, A mutation affecting the DNA binding capacity of DNA polymerase I. The polA6 mutation is an allele of the polA gene of Escherichia coli which produces a DNA polymerase I species readily distinguishable from that produced by the wild type allele. Experiments described here show that this enzyme has an altered pH optimum for polymerization and a lower binding affinity for DNA. The defect clearly lies within the carboxyl-terminal large fragment of the enzyme produced by in vivo or in vitro proteolysis since the fragment has the same pH optimum for polymerization as the intact enzyme. The polA6 enzyme and its fragment are more sensitive to phosphate ions than the wild type polymerase, and the large fragment is less efficient at binding poly d(AT) in in vitro binding assays. Although the specific nucleolytic activity of the polA6 enzyme is higher than that of the wild type, there is no apparent alteration in pH optimum for the hydrolysis of eigher double or single stranded DNA.


Implications of electrostatic potentials on ribosomal proteins. Potentiometric studies of ribosomal particles 30S, 50S, and 70S, were designed to investigate possible implications of the electrostatic potentials developed by the 16S and 23S rRNA fractions. Release of protons and proton titrations of these ribosomal fractions were examined as a function of Mg2+ and K+ concentrations. The effects of these cations fit the polyelectrolyte theory remarkably well and are discussed accordingly.


Volume changes in binding of ligands to methemoglobin and metmyoglobin. The volume changes for the binding of various ligands to metmyoglobin and methemoglobin have been determined from the effect of pressure on the binding constants (for metmyoglobin) and by direct dilatometry (for methemoglobin). The volume changes associated with the binding of cyanide and azide ions to methemoglobin are pH-dependent. The volume change for the binding reaction is evidently affected by the same subtle structural variations that have been judged to be present from the variation with pH of enthalpy and entropy for the binding reactions in these proteins. Hydration changes and spin state changes which have been postulated to be linked with structural variations in these proteins must be pH-dependent.


Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug. In order to develop a better dopamine receptor radioligand, [3H[apomorphine was prepared and tested for dopamine-like binding properties in both calf and human brain tissues. Specific binding of [3H]apomorphine was defined as that binding which occurred in the presence of 1 muM (-)-butaclamol (an inactive neuroleptic) minus that occurring in the presence of 1 muM (+)-butaclamol (active neuroleptic). The specific binding was saturable, the number of sites being double that of specific [3H]dopamine binding, and occurred primarily in dopamine-rich regions of postmortem human brains. The binding had a dissociation constant of 0.9 nM for human caudate (2 nM for calf caudate) and was blocked by dopamine and norepinephrine, but not by isoproterenol or (-)-propranolol, distinguishing it from a beta-adrenergic receptor. Since there was little desorption of [3H]apomorphine, the ligand permits extensive washing during routine assays for dopamine receptors, and facilitates biochemical purification of the receptor.


[Effect of several factors on the process of protein solution ultrafiltration]. Ultrafiltration of protein solutions was investigated, using deoxyribonuclease of Actinomyces streptomycini filtered through a membrane based on vinylpyrrolidone-methyl methacrylate copolymers. It was shown that ionization of the protein molecule, level of the applied pressure as well as the protein concentration in the initial solution influenced particle adsorption on the surface and in pores of the molecule and the formation of gel layer reducing the rate of the solution filtration. The following parameters were found to favor the process: pH=7.5 (the value corresponds to the highest stability of the enzyme and the presence of the total negative discharge on the surface of the protein molecule). DNase concentration not more than 2 mg/ml, pressure 2 atm. The retaining capacity of the membrane was 85% and DNAase losses were 20%.


Isolation of 3-phosphohistidine from phosphorylated pyruvate, phosphate dikinase. Pyruvate, phosphate dikinase (EC 2-7-9-1) catalyzes formation of phosphoenolpyruvate, AMP, and inorganic pyrophosphate from pyruvate, ATP, and orthophosphate. A pyrophosphoryl and phosphoryl form of the enzyme is involved in this transfer. The [32P]phosphoryl form of pyruvate, phosphate dikinase was prepared with enzyme isolated from Bacteroides symbiosus. The [32P]phosphoryl enzyme was found to have properties corresponding to a phosphoramidate linkage and this was confirmed by isolation of 3-[32P]phosphohistidine from alkaline hydrolysates of the enzyme. The histidyl residue is considered to be the pyrophosphoryl- and phosphoryl-carrier between the three substrate sites of this enzyme.


Phosphorus nuclear magnetic resonance studies on normoxic and ischemic cardiac tissue. The intact heart of a young rat was excised rapidly and cooled to 0 degree C; its energy-rich compounds were examined by 31P Fourier Transform nuclear magnetic resonance. The heart showed the characteristic spectrum of sugar phosphates, inorganic phosphate, phosphocreatine, and magniesium phates, inorganic phosphate, phosphocreatine, and magnesium ATP, characteristics of the energizing state of the nonbeating tissue. Warming to 30 degrees C imposes an energy load upon the heart consistent with short-term resumption of beating, concomitant intracellular acidosis, and decomposition of all detectable energy-rich compounds. The intracellular acidity causes a shift from pH 7.0 to 6.0. The effects of possible interferences with this pH measurement are considered. The method appears to have wide usefulness in cardiac infarct models for detecting the fraction of the total volume occupied by the infarct and for studying the effect of various proposed therapies upon this infarcted volume.


Role of the intrinsic transglutaminase in the Ca2+-mediated crosslinking of erythrocyte proteins. Transamidase (i.e., "transglutaminase") activity of human erythrocytes, lysed by a single freezing and thawing to 37 degrees, was measured by a method of incorporating [14C]putrescine into N,N'-dimethylcasein. In the absence of added calcium ions, virtually no enzyme activity could be detected. An increase in concentration of the cation to about 0.5 mM, however, turned on the enzyme to appreciable levels of activity. Simultaneously, Ca2+ produced formation of high molecular weight, nondisulfied bonded protein polymers either directly in the lysate or in fresh cells when the cation was added together with the A23187 ionophore. The polymers could be readily identified in the isolated cell ghosts by means of disc gel electrophoresis. If the Ca2+-promoted formation of polymers was allowed to take place in the presence of 14C-putrescine, then this tracer became incorporated into the polymeric material. The incorporation indicated that polymerization occurred through gamma-glutamyl-epsilon-lysine bridtes. It is suggested that the intrinsic transamidase mediates protein crosslinking of the erythrocyte membrane whenever there is an increase in intracellular Ca2+ concentration. The presence of suitable transglutaminase substrates, e.g. histamine, inhibited crosslinking when the cells were incubated with Ca2+ and ionophore.


Proline and glycine uptake by renal brushborder membrane vesicles. Uptake of L-proline and glycine by rat renal brushborder membrane vesicles was seen to be osmotically sensitive, pH dependent,and occurred in the absence of proline and glycine metabolism. The uptake system for proline was Na+ gradient dependent, and exhibited a dual system for entry, Km1 = 0.067 mM and Km2 = 5.26 mM. The uptake of glycine was also Na+ gradient dependent, and exhibited a two Km system, Km1 = 0.22 mM and Km2 = 4.00 mM. Studies of proline and glycine interactions indicate a shared site which has a lower affinity and higher capacity for glycine than for proline. The high affinity glycine site and low affinity proline site do not appear to be shared.


Discriminative stimulus properties of fentanyl and morphine: tolerance and dependence. Using a food-reinforced two-lever operant procedure, rats were trained to discriminate 0.04 mg/kg fentanyl from saline. At different time intervals after the establishment of discriminative responding, stimulus generalization experiments were performed with equivalent dose ranges of fentanyl (0.0025 to 0.02 mg/kg) and morphine (2.5 to 20 mg/kg). It was found that the ED50 values of both compounds for generalization with the narcotic discriminative stimulus complex, did not change over a 4-month period. The subjects used in this study demonstrated marked tolerance to narcotic analgesia, but none of them showed signs reminescent of narcotic dependence. It is concluded that the discriminative stimulus properties of narcotic analgesics are not subject to tolerance.


Early processing of visual information.

Early processing of visual information. An introduction is given to a theory of early visual information processing. The theory has been implemented, and examples are given of images at various stages of analysis. It is argued that the first step of consequence is to compute a primitive but rich description of the grey-level changes present in an image. The description is expressed in a vocabulary of kinds of intensity change (EDGE, SHADING-EDGE, EXTENDED-EDGE, LINE, BLOB etc.). Modifying parameters are bound to the elements in the description, specifying their POSITION, ORIENTATION, TERMINATION points, CONTRAST, SIZE and FUZZINESS. This description is obtained from the intensity array by fixed techniques, and it is called the primal sketch. For most images, the primal sketch is large and unwieldy. The second important step in visual information processing is to group its contents in a way that is appropriate for later recognition. From our ability to interpret drawings with little semantic content, one may infer the presence in our perceptual equipment of symbolic processes that can define "place-tokens" in an image in various ways, and can group them according to certain rules. Homomorphic techniques fail to account for many of these grouping phenomena, whose explanations require mechanisms of construction rather than mechanisms of detection. The necessary grouping of elements in the primal sketch may be achieved by a mechanism that has available the processes inferred from above, together with the ability to select items by first order discriminations acting on the elements' parameters. Only occasionally do these mechanisms use downward-flowing information about the contents of the particular image being processed. It is argued that "non-attentive" vision is in practice implemented by these grouping operations and first order discriminations acting on the primal sketch. The class of computations so obtained differs slightly from the class of second order operations on the intensity array. The extraction of a form from the primal sketch using these techniques amounts to the separation of figure from ground. It is concluded that most of the separation can be carried out by using techniques that do not depend upon the particular image in question. Therefore, figure-ground separation can normally precede the description of the shape of the extracted form. Up to this point, higher-level knowledge and purpose are brought to bear on only a few of the decisions taken during the processing. This relegates the widespread use of downward-flowing information to a later stage than is found in current machine-vision programs, and implies that such knowledge should influence the control of, rather than interfering with, the actual data-processing that is taking place lower down.


Modification of the noradrenaline related effects of smoking by beta-blockade. Increases in plasma noradrenaline were found in a group of 12 subjects smoking cigarettes. The associated rises in pulse rate, blood pressure and plasma free fatty acids could be prevented by beta-blockade with oxprenolol. This inhibition of the peripheral effects of catecholamines did not affect subjective satisfaction, indicating that central effects or other rewards are more important reinforcers. It is suggested that noradrenaline release in the hypothalamus is the final common pathway to pleasure in many situations, including smoking.


Psychoactive drug effect on behavioural changes induced by prolonged socio-environmental deprivation in rats. Several so-called 'non-specific' or 'non-drug' factors are known to interfere with the response to psychotropic drug administration. Animal emotionality has been reported to change the outcome of psychoactive drug administration, so that the response to a stimulant or depressant drug may considerably change according to the baseline state of activity of the central nervous system. Prolonged socio-encironmental deprivation or isolation has been shown to produce in rats three different types of abnormal behaviour which have been tentatively defined as 'friendly', 'indifferent' and 'muricide'. Such unusual changes in rat behaviour are assumed to reflect a series of different emotional changes. The present experiments show that psychoactive drugs can exert a different effect in relation to the different kinds of animal behaviour used in the experiments. The investigation of the properties of psychoactive compounds, as performed in experimental animals showing behavioural alterations, is then suggested as being more fruitful in providing much information closer to the clinical results than that achieved with the experiments performed in normal laboratory animals.


Amino acid precursors of monoamine neurotransmitters and some factors influencing their supply to the brain. There is evidence that changes in the concentrations of the monoamine neurotransmitters within the brain are associated with changes in mental processes, with disorders of control of movement and with certain neuropsychiatric diseases. These neurotransmitters are synthesized in the brain from aromatic amino acid precursors that have to be obtained from the circulating blood. In this study some factors which alter the rates of entry of four amino acids (the important neurotransmitter precursors L-tyrosine and L-tryptophan, as well as L-phenylalanine and L-histidine) into the brain have been studied and the findings considered in relation to conditions in which the quantities of one or more of the monoamine neurotransmitters formed within the cerebral cells may be either too large or too small. Thus too little neurotransmitter will be formed if competition between amino acids for the carriers transporting them into the cerebral cells causes the exclusion of a large proportion of any of the aromatic amino acid precursors from the brain. ,or example, L-tryptophan is partially excluded from the brain if a raised level of any one of several other amino acids is maintained in the circulation. Of these, L-phenylalanine inhibits the transport of L-tryptophan into the brain most effectively, while aromatic amino acids in general exclude L-tryptophan more effectively than do other neutral amino acids. Over-production of one or more of the monoamine neurotransmitters is likely to occur when there is too much of one of the aromatic amino acid precursors in the brain cells as a result of abnormally high uptake from the blood, or as a result of their release by an excessive breakdown of the protein within these cells. Underproduction of neurotransmitters may occur in certain disease states, such as some aminoacidurias or Parkinsonism. We have listed some conditions associated with altered mental states or motor disability in which over- or under-production of monoamine neurotransmitters may occur and have tried to relate the findings in human disease with our experimental results.


Effects of chlordiazepoxide, ripazepam and d-amphetamine on conditioned acceleration of timing behaviour in rats. The lever-pressing behaviour of three rats was maintained by a schedule in which food reinforcement was obtained by any response which was emitted at least 15 s after the previous response (DRL 15s). When performance on this schedule had stabilised, the animals were presented intermittently with 1-min periods of a white noise stimulus, the termination of which was accompanied by the delivery of a mild electric footshock. This procedure let to reliable increases in response rates furing the stimulus although responding at other times continued to be appropriate to the DRL 15-s schedule. Administration of the benzodiazepine chlordiazepoxide (1, 3, 10, 17 and 30 mg/kg) and of ripazepam (1, 3, 10, 30 and 56 mg/kg), a non-benzodiazepine reported to have anxiolytic properties, increased response rates on the DRL baseline while decreasing the acceleration of responding produced by the preshock stimulus. Baseline response rates were also increased by d-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg) and at the higher doses this drug completely abolished the accelerated responding during the preshock stimulus. Although the effects of chlordiazepoxide and ripazepam are consistent with the suggestion that these drugs may attenuate the behavioural effects of aversive stimuli, in this experiment the behavioural effects of d-amphetamine were similar in many respects.


Head twitches induced by benzodiazepines and the role of biogenic amines. Clonazepam, one of the benzodiazepines, induced head twitches in mice in a dose-dependent manner and sustained them for at least 120 min. Some of the benzodiazepines such as nitrazepam, fludiazepam, and nimetazepam also significantly induced head twitches at doses higher than 10 mg/kg, but other benzodiazepines like diazepam, flurazepam, oxazepam, medazepam, and chlordiazepoxide did not significantly induce head twitches at doses up to 60 mg/kg. The head twitches induced by clonazepam were more strongly blocked by a n antiserotonin drug, cyproheptadine than catecholamine receptor blocking drugs, haloperidol, propranolol, and phentolamine, and were not blocked by GABA receptor blocking drugs, bicuculline and picrotoxin, as well as by a glycine receptor blocking drug, strychnine. Clonazepam also increased the head twitches induced by mescaline, a serotonin receptor stimulant. These results indicate that the head twitches induced by clonazepam might be mediated via serotonergic neuron systems.


Action of enpiprazole on emotional behavior induced by hypothalamic stimulation in rats and cats. Action of enpiprazole on emotional behavior elicited by hypothalamic stimulation in rats and cats was investigated and comparisons were made with effects of diazepam. Two behavioral patterns were elicited by stimulation of the postero-medial part of the hypothalamus in rats: a food-carrying response beginning with exploratory movement and an analogue of fear. Enpiprazole frequently changed the food-carrying response into food-taking response and occasionally analogues of fear into food-carrying and /or food-taking responses. Thresholds for these behaviors were also elevated. Diazepam showed the same effects on the thresholds as enpiprazole, having but little effect on the behavioral patterns.  In cats, enpiprazole evelvated the thresholds for affective-defensive responses induced by hypothalamic stimulation in 6 of 8 cases, but lowered them in 2 cases. This suggests that enpiprazple has a 'biphasic effect' in the central nervous system. By contrast,diazepam consistently elevated thresholds. Comparing the action of enpiprazole with that of diazepam it can be presumed that the former is a different type of anxiolytic drug than the latter.


Single and repeated administration of neuroleptic drugs to rats: effects on striatal dopamine-sensitive adenylate cyclase and locomotor activity produced by tranylcypromine and L-tryptophan or L-Dopa. Injection of tranylcypromine and L-tryptophan results in rats displaying behavioural changes including hyperactivity, probably due to stimulation of post-synaptic 5-hydroxytryptamine (5-HT) receptors. Increased locomotor activity of a different type is elicited by injection of tranylcypromine and L-dopa, a procedure which increased dopaminergic function in the brain. It has now been demonstrated that the neuroleptic drugs, chlorpromazine, alpha-flupenthixol, haloperidol and spiroperidol block both syndromes. The inhibition produced by these drugs on 5-HT-induced hyperactivity is probably because a dopaminergic system is involved in the behavioural expression of the 5-HT induced hyperactivity. The structurally related drugs with no neuroleptic activity (ethopropazine, promethazine and beta-flupenthixol)are without effect on thses hyperactivity syndromes. Also ineffective were the neuroleptics pimozide and clozapine. Striatal dopamine sensitive adenylate cyclase activity in vitro was inhibited by the administration of chlorpromazine (100 mg/kg) in vivo. Rats treated for 4 or more days with chlorpromazine, alpha-flupenthixol, spiroperidol and haloperidol subsequently showed enhanced locomotor activity in response to tranylcypromine and L-Dopa. Administration of those drugs which did not block hyperactivity acutely did not result in enhancement. Only chlorpromazine, when given for 4 days, enhanced the hyperactivity response following tranylcypromine and L-tryptophan, probably because the drug also blocks 5-HT receptors. In rats displaying enhanced behavioural responses no evidence was found for enhanced sensitivity of striatal adenylate cyclase to dopamine.


Effects of pyrroxan and chlordiazepoxide on biogenic amine metabolism in the rat brain. Pyrroxan (20 mg/kg, i.p.), a new potential antianxiety agent, increased brain norepinephrine (NE) turnover in rats, reflecting a possible central alpha-adrenergic receptor blocking activity. In contrast, chlordiazepoxide (20 mg/kg, i.p.), a widely used antianxiety agent, did not alter the NE turnover. Pyrroxan did not affect overall DA turnover although it did appear to accelerate DA turnover initially. The initial potentiation of DA turnover may indicate a short-lasting blocking action on DA receptors. In comparison, chlordiazepoxide (20 mg/kg, i.p.) decreased the turnover rate of DA. Effects of both drugs on 5-HT indicate a decrease in turnover with no significant monoamine oxidase activity or blockade of the 5-HT reuptake mechanism. Both drugs antagonized the decline in intraventicularly-injected 14C-5-HT. Neither drug caused consistent changes in endogenous 5-HT, 5-hydroxyindoleacetic acid, or tryptophan levels. Neither drug potentiated the behavioral effects of L-Dopa nor increased the 5-HTP behavoiral syndrome in the mouse. Pyrroxan may be expected to exhibit a spectrum of activity between that of minor and major tranquilizers, characterized by antianxiety action together with sedative or tranquilizing activity.


Investigations of the mechanism of central action of kinins. The effects of kinins on the level of norepinephrine, dopamine, and serotonin and on their metabolites, i.e., normetanephrine, homovanillic acid, and 5-hydroxyindoloacetic acid in the brain tissue divided into cerebellum, corpus striatum, cortex, hippocampus, hypothalamus, medulla oblongata, and midbrain were investigated. It was shown that bradykinin in a dose of 4 mug decreased the content of norepinephrine in corpus striatum, midbrain, and cerebellum. It also decreased the level of dopamine in corpus striatum but increased the level of serotonin in corpus striatum and midbrain. Similar changes were observed with 100 Mu/kg of kallikrein. It was that changed levels of investigated neuromediators are accompanied by changed levels of their metabolites. Bradykinin, in a dose of 4 mug, decreased the level of normetanephrine in corpus striatum, hippocampus, and midbrain and the level of homovanillic acid in corpus striatum, and increased the level of 5-hydroxyindoloacetic acid in corpus striatum and hippocampus. It was also shown that bradykinin increased norepinephrine uptake by the blood platelets when its level in the platelets was low, and released the absorbed norepinephrine into the medium when the level of norepinephrine was higher. The above results confirm the existence of an interaction of kinins with neuromediators in the central nervous system.


Sleep disorder and psychobiological symptomatology in male psychiatric outpatients and male nonpatients. Sleep disturbance was studied in relation to psychiatric and physical symptoms for 214 male psychiatric outpatients and 248 male nonpatients. Our self-report instrument required that subjects describe the frequency of symptoms precisely on a five-point scale from "every day" to "not at all." Percentages are based on the numbers of subjects reporting a symptom as occurring "every day" or "several times a week." More patients reported sleep disturbance symptoms (75%) than nonpatients (25%) (P less than 0.001). Sleep loss symptoms were reported by 63% of patients and 20% of nonpatients. Twelve percent of patients and 6% of nonpatients reported trouble with excessive sleep problems. Sleep disturbance was not strongly related to specific diagnoses. Fewer schizophrenics (21%) than other patients (50%) reported trouble "falling asleep" (P less than 0.02). Finally, for both patients and controls, disturbed sleepers reported more psychiatric and physical symptoms than undisturbed sleepers (P less than 0.001). It is suggested that sleep disturbance might be a useful clinical clue to previously unsuspected psychiatric and physical illness.


Intraperitoneal and retroperitoneal hemorrhage. Besides blunt and penetrating trauma, many diseases spontaneously produce abdominal hemorrhage. Here the term "spontaneous" implies the lack of observable injury, but the likelihood that unrecognized trauma initiates blood loss which continues unabated when clotting factors are absent or depleted. Survival of the patient often depends on rapid and accurate diagnosis.


Stages of bone marrow transplantation: a psychiatric perspective. Patients undergoing bone marrow transplantation were closely followed by a psychiatric service functioning as part of a multidisciplinary team. A somewhat predictable pattern of psychological reactions to the stress of various stages of the procedure appeared to emerge. Approaches to patient evaluation, typical patient responses, and suggestions for working with these patients and their families are described.


The chemical structure of prostaglandin X (prostacyclin). The chemical structure of prostaglandin X, the anti-aggregatory substance derived from prostaglandin endoperoxides, is 9-deoxy-6, 6alpha-epoxy-delta5-PGF1alpha. The stable compound formed when prostaglandin X undergoes a chemical transformation in biological systems in 6-keto-PGF1alpha. Prostaglandin X is stabilized in aqueous preparations by raising the pH to 8.5 or higher. The trivial name prostacyclin is proposed for 9-deoxy-6, 9alpha-epoxy-delta5-PGF1alpha.


Biosynthesis of thromboxane B2: assay, isolation, and properties of the enzyme system in human platelets. The microsomal fraction of human platelets catalyzed the conversion of arachidonic acid to an unstable platelet-aggregating factor and a hydrolyzed product on the thin-layer chromatography (TLC). This product was isolated on TLC, purified by silica gel column chromatography and identified by combined gas chromatography-mass spectrometry as the hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5, 10-heptadecatrienoic acid (thromboxane B2). The enzymatic activity was dependent upon methemoglobin and tryptophan as cofactors. Reduced glutathione had no effect either alone or in combination with other cofactors. Methemoglobin could be replaced by hematin or hemin; and tryptophan by 3-indolacetic acid or catecholamines. The apparent requirement for methemoglobin is due to the reductive activity of ferriprotoporphyrin IX. The reaction, however, catalyzed by the ferriprotoporphyrin IX in the thromboxane synthesizing system is different from that described for the decomposition of lipid peroxides. Certain transition metals and hydrogen donors, such as hydroquinone and ascorbate, which have been shown to stimulate the catalytic activity of ferriproroporphyrin IX in the decomposition of 15-hydroperoxy-prostaglandin E1 are inhibitors of thromboxane B2 formation. This enzyme preparation also transformed eicosa-8. 11, 14-trienoic acid to an unknown product on TLC. The enzyme system was rapidly inactivated upon incubation in the reaction mixture.


[Effect of the ionic environment and of various neurotransmitters on spontaneous motility in snail intestine (author's transl)]. A spontaneous rhythmic motility of the isolated intestine in snail, Chryptomphalus hortensis, has been registered at 30 degrees C with the aid of an electronic transductor and an appropriate amplification. These slow regular movements are affected by ionic composition changes in the suspension medium. Na+, K+ and Ca++ ions prove to be important in this motility, and the addition of Ba++ markedly stimulates it. ACh produces hypermotility from 1.8 X 10(-11) g/ml. Its effect decreases in the presence of atropine and increases in that of pyridostigmine. The intestine is sensitive to 5-HT from 10(-10) g/ml, which stimulates its activity. The effect of histamine is weak. Low concentrations of adrenaline tend to increase the amplitude, whereas concentrations from 10(-5) g/ml onward produce a cease of motility in relaxation.


Participation of leukemia cells in immune responses. Cells of a transplantable lymphoid leukemia of mice were tested in vivo and in vitro to see which features of normal lymphoid cells were retained in spite of malignant transformation and lack of growth control. Leukemia cells phagocytosed, adhered to glass, possessed receptors for immunoglobulin, participated in the immune response against SRBC (probably by amplifying a normal response through attachement of antibodies on their surfaces), became recruited into inflammatory reactions elicited by grafting allogeneic of syngeneic skin, and apparently joined graft-versus-host and host-versus-graft reactions, contributing toward damage of hemopoietic target tissues.


[The concept of risk in parasitic diseases with special reference to malaria (author's transl)]. The concept of risk, its components and their interrelationship are described. Emphasis has been placed on the value of the variables to be taken into account in the selection of intervention measures: -- for the mosquito: the daily frequency of blood meals taken from man, the duration of the sporogonic cycle, the daily survival rate and the proportion of people with gametocytes in the peripheral blood; -- for man: the number of anophelines feeding on man in a unit of time, the proportion of mosquitoes with sporozoïtes in their salivary glands and the proportion of sporozoïtes able to infect man. Using these variables, it is possible to calculate the various risks incurred both by man and vector. Whenever possible and in order to be of greater value, the interventions should be directed against the variable which have the highest power. However, in view of the complexity of relations, it is better to construct a mathematical model able to simulate with the use of a computer, real epidemiological situations. A model has been recently developed for the study of the malaria dynamics and for the comparative evaluation of various methods of control.


Antagonism by naloxone of morphine-induced single-dose dependence and antinociception in mice. Single-dose physical dependence on morphine, as indicated by the mouse withdrawal jumping test, was reduced in a dose-related fashion by co-administration of naloxone. In the same dose range, naloxone also antagonized the antinociceptive effect of morphine in the mouse writhing test. Dose-response data revealed essentially the same ED50's for naloxone in both tests. These results indicate that naloxone does indeed block the development of morphine-induced single-dose physical dependence in mice and that it does so as effectively as it blocks morphine-induced inhibition of writhing.


Changes in brain catecholamines and spontaneous locomotor activity in response to thyrotropin releasing hormone. Repeated exposure of rats to thyrotropin releasing hormone produced a dose- and time-dependent increase in spontaneous locomotor activity accompanied by an increase in brain stem tyrosine hydroxylase. Dopamine levels in cerebral cortex were increased maximally by 34% in animals receiving thyrotropin releasing hormone at a dosage of 2 mg/kg for 10 days. The concentrations of brain stem tyrosine and cerebral cortex norepinephrine remained unaltered in response  to thyrotropin releasing hormone treatment. Our data suggest that administration of thyrotropin releasing hormone increases the synthesis and perhaps the turnover of brain catecholamines and that this may constitute an underlying mechanism for the anti-depressant action of this synthetic hormone.


Vasomotor rhinitis: psychosomatic conditions and treatment. The importance of the autonomic nervous system in vasomotor conditions of the nose was outlined. The symptoms, findings and differential diagnosis of the vasomator rhinitis were reviewed. Reference is made to the applied treatment and results obtained with different antistaminics in 2150 patients.


Improvement in the quality of enzyme determinations by Scandinavian laboratories upon introduction of Scandinavian recommended methods. The last annual Scandinavian proficiency survey (January 1975) offered an opportunity to evaluate the effect of the introduction of recommended methods for ASAT, ALAT, LD, and ALP on routinely performed enzyme determinations in clinical chemical laboratories. The results obtained by the recommended methods showed a marked improvement in precision, bringing the interlaboratory variations down to levels that have previously been achieved only for the determination of non-enzymic constituents. Enzymes for which no recommended method have been proposed were still determined with low interlaboratory precision.


A method for enzymatic determination of citrate in serum and urine. A method for determination of citrate in serum and urine using citrate lyase is described. The influence of pH, zinc, magnesium, and calcium ions on the reaction velocity is studied. Citrate lyase activity is found rather insensitive to variations in pH round the pH-optimum at 8.2. Zinc ions activate the reactions. The optimal concentration of zinc ions in the reaction mixture is found to depend on the calcium concentration of samples. Perchloric acid is used for precipitation of proteins. The perchloric ion inhibits the reaction,  and a procedure for removing perchlorate is given. Sensitivity of analysis is  0.005 mmo1/1 for serum and urine samples, respectively. No contamination of citrate lyase is found, and therefore addition of lactate dehydrogenase is considered unneccessary.


Clinical assessment of cryptorchid boys by determination of urinary testosterone glucuronide following large doses of human chorionic gonadotropin (hCG). Urinary TG and fractionated 17-ketosteroid (Drosdowsky) determinations were performed before and after the intramuscular administration of 15,000 IU of human chorionic gonadotropin (hCG) in 10 sexually immature healthy boys and in 12 bilaterally cryptorchid boys. The same basal determinations were made in 11 gonadless girls. Basal serum FSH and LH were determined (by radioimmunoassay) in controls and also in cryptorchid boys. If 15mug/24 h (three SD's of basal excretion in controls) is considered the smallest adequate response, the TG but not the fractionated 17-KS determination assessed fairly well either the presence or the functional capacity of the Leydig cell-containing tissue. Agonadic girls had significantly higher basal excretion of steroids and this is presumably due to their greater absolute body size and to their more advanced bone age.


Transferrin and iron uptake by isolated rat liver mitochondria. Isolated rat liver mitochondria accumulate iron from the suspending medium when [59Fe]transferrin is used as a model compound. The accumulation proceeds by two different mechanisms, i.e. by an energy-independent and an energy-dependent (uncoupler sensitive) mechanism, which have different time, pH, and temperature dependencies. The energy-dependent accumulation, which is inhibited by ruthenium red and sulphydryl reagents, reaches a saturation level of approx. 30 pmoles iron/mg protein during 30 min incubation. The energy-independent accumulation of iron-transferrin reveals no saturation kinetics, it is inhibited neither by ruthenium red nor by N-ethylmaleimide, and it proceeds linearly for at least 90 min. With [125I]transferrin as a model compound, quantitatively the energy-independent accumulation is as reported for [59Fe]transferrin. There is, however, no energy-dependent accumulation of [125I]transferrin. The results indicate that the energy-dependent accumulation of [59Fe]transferrin represents a process by which mitochondria accumulate iron from transferrin.


[Use of a monomaxillary curved splint in maxillofacial surgery]. We describe a prefabricated monomaxillary arch, fitted with perpendicular supports with a main bar which provides dento-maxillary setting in the antero-posterior direction and also vertically since it is possible to attach it to the free edge of the teeth. The indications concerning the use of this arch are given in detail. It offers the advantage of being readily adaptable and is therefore easy to use in an emergency.


Microcalorimetric measurements of heat production in human erythrocytes. III. Influence of pH, temperature, glucose concentration, and storage conditions. Heat production in human erythrocytes has been measured under different conditions of pH, glucose concentration, and temperature. Storage conditions have also been varied. The erythrocytes, which were from healthy subjects, were suspended either in autologous plasma or in phosphate buffer. The heat effect, P, was shown to increase linearly in the physiological pH range: 1.2% per 0.01 pH unit. Variation of the glucose concentration within a wide range, 3-32 mmol/1, did not affect the P value. The temperature coefficient for P was determined to be Q10 = 2.8 for the temperature range 32-42 degrees C. A constant energy of activation was found, 82.6 kJ/mol, for the temperature range 25-42 degrees C. When the erythrocytes were stored at 4 degrees C, P values (measured at 37 degrees C) increased initially by 6%/h. After 24 h of storage P was about 50% higher than the initial value. Determinations of glucose consumption were made in parallel with most of the calorimetric experiments.


The absorption of acetylsalicylic acid from the stomach in relation to intragastric pH. A comparative study on the effect of a buffered (pH 6.5) and an unbuffered (pH 2.9) solution of acetylsalicylic acid (ASA) on gastric pH, gastric emptying, and gastric absorption of ASA was performed in 10 healthy volunteers. Gastric pH was recorded using radiotelemetry. Gastric emptying and gastric absorption was studied with an aspiration technique and phenol red as nonabsorbable marker. Administration of the unbuffered solution to the fasting subjects resulted in a gastric pH of about 2 and absorption of ASA from the stomach was found to occur. The buffered solution of ASA increased gastric pH to above 5 and gastric absorption of ASA was found to be significantly less than after the unbuffered solution. The buffered solution was emptied from the stomach more rapidly than the unbuffered one.


[Endocrinological studies in arterial hypertension. Search for phaeochromocytoma]. Elevated urinary catecholamines and their metabolites are the only findings which confirm the presence of pheochromocytoma. This examination is of particular interest if carried out in urine produced after spontaneous hypertensive episodes. Pharmacologic tests when carried out under standard conditions have proven to be a reliable aid in cases of suspected pheochromocytoma. Roentgenographic studies, determination of local plasma catecholamine concentrations and blood volume control should be undertaken in these patients before surgical procedure.


[Paralytic ileus in pheochromocytoma. Possible correlation with an attempt at adrenal phlebography]. Following adrenal phlebography, obstruction of the large bowel associated with adrenergic crisis was observed in a 60 year old patient with pheochromocytoma. As in other published cases of ileus associated with pheochromocytoma, high urinary catecholamine concentrations were found in our patient and the tumor resected at surgery was large. As phlebography immediately preceded the onset of ileus and hypertensive crisis, it is postulated that angiography led to massive secretion of catecholamines, which caused the hypertensive crisis as well as the ileus. The possible mechanisms by which phlebography may lead to adrenergic crisis are discussed. It is concluded that in suspected pheochromocytoma all angiographic examinations should be carried out under simultaneous treatment with alpha-blocking agents.


[Pharmacokinetics of two beta blocking drugs: detection of a pharmacogenetic abnormality]. 10 healthy male volunteers received orally either 100 mg tolamolol or 20 mg bufuralol. These experiments were repeated by intravenous administration of 10 and 5 mg respectively of these two drugs. Plasma levels of the parent drugs and their main metabolite were measured. In one subject, the apparent half-life of elimination was increased from 2.5 h (normal subjects) to 5 h for both drugs. This prolongation of the half-life is associated with low plasma levels of the metabolites, a peculiarity which can be explanined by a decreased rate of metabolism for these two drugs. This anomaly may explain the marked orthostatic hypotension observed only in this subject. The likelihood of a pharmacogenetic defect is discussed.


[Contribution to the treatment of threatened abortion]. 460 cases of threatened abortion were divided into 3 different treatment categories. Group A was treated with a combined antihistamine and antispasmodic, and Group B with tranquilizers and synthetic gestagens. Group C consisted of patients who refused therapy. The percentage of delayed abortions in group A was 79.3%, in group B 84.7% and in group C 54.8%. According to the x2-test, the difference between the treated and untreated groups is statistically significant. The mode of action of the prescribed drugs is substantiated and their effectiveness was compared with published data on other therapies. Complications of pregnancy, at delivery and during the puerperium were not more prevalent than in normal pregnancies. However, the percentage of premature births (22.9%) and of perinatal mortality (5.4%) was strikingly high. Accordingly, successfully treated threatened abortions are to be followed up as "risk" pregnancies and closely supervised as such. It is especially important to avoid a premature birth. The frequency of congenital defects and functional disturbances was 11.9%; their existence is independent of the type of therapy. Since the defects are usually of minor consequence and reversible, we advocate treatment of the threatened abortion.


Lysogeny in pneumococci freshly isolated from man. Twelve strains of encapsulated pneumococci isolated from patients with pneumococcal disease were examined for the presence of bacteriophage. Four of the strains yielded phage lytic for a noncapsulated indicator strain of pneumococcus. Three of the newly isolated bacteriophages differ serologically from pneumococcus bacteriophages described previously. The ability to yield lytic phage was lost by two of the lysogenic pneumococcal strains on repeated subculture.


Control of gamete formation (exflagellation) in malaria parasites. The only stages of malaria parasites capable of establishing an infection in a mosquito are the gametocytes that circulate in the blood of the veterbrate host. Within minutes of ingestion by a mosquito the gametocytes transform into mature gametes in the process of "exflagellation." This process is controlled in vitro solely by the change in pH in the blood as it moves from the environment of the circulation to that of the atmosphere, the pH rise being mediated by the fall in carbon dioxide tension as the blood equilibrates with the atmosphere.


Beta-adrenoceptor blocking drugs and their use in hypertension. Beta-adrenoceptor blocking drugs have been found to be effective antihypertensive agents of similar efficacy to sympathetic inhibitory drugs and methyldopa. They have the advantage of not causing postural or exercise hypotension. While the antihypertensive effect is a function of beta-receptor blockade, the precise mode of action is unknown.


Acid-base determinations in normal and asphyxiated term infants during the first 24 hours of life. Vigorous term infants who are born normally initially have a moderate metabolic and respiratory acidosis which is corrected by the time the infant is 6 hours old. Asphyxiated infants consistently show a greater degree of acidosis, both metabolic and respiratory. Caesarean section results in higher pCO2 values, especially when 'diffusion apnoea' occurs. Indications for the correction of acidosis in asphyxia are proposed.


A metabolic approach to the evaluation of peripheral vascular disease. Thirty-five patients with occlusive disease of the arteries underwent metabolic studies. The arteriovenous differences of lactate, glucose and oxygen varied with the severity of the ischemic process, as assessed clinically. Lactate release and glucose extraction were significantly different from control values of patients with rest pain or with ischemic gangrene, while values in patients with claudication were comparable with those in the control group. Percutaneous muscle surface pH measurements, which reflect lactate release, decreased directly with diminished perfusion. Metabolic assessment of arterial occlusive disease may prove to be a useful clinical approach.


Leukocyte phagocytic function and dysfunction. Although some species of bacteria are killed in vitro by humoral factors in cell-free serum, the in vivo experience with leukopenic patients illustrates the critical role played by phagocytic leukocytes in host resistance to infection. Effective ingestion and killing of micro-organisms requires the sequential and integrated function of the elements of the phagocytic system. Each step in the phagocytic process is also a potential crack in the armor of host defense, and an increasing number of clinically significant disorders of phagocytic function are being recognized and described (5). The phagocytic leukocytes are equipped with a variety of intracellular microbicidal mechanisms which provide a degree of overkill capacity and allow these cells to meet the challenges posed by the many and varied microbial transfressors. Undoubtedly, other phagocytic disorders will be discovered and other important aspects of the intraleukocyte killing mechanisms will be elucidated. For instance, little is known about the function of leukocytes within the relatively hypoxic environment of injured tissue where so many bacterial infections begin. As our understanding of phagocytic function develops, new ways may be found to augment host resistance by preservation or stimulation of the phagocytes.


Scanning electron microscopic and electrophoretic studies on clotting factor adsorbents. Physical studies carried out on a range of protein and clotting factor adsorbents revealed marked morphological and charge differences. Their appearance in the scanning electron microscope could be used to classify the insoluble precipitates, calcijm phosphate, barium sulphate and citrate, as either amorphorous or crystalline. Surface charge is difficult to define but the present studies on the sparingly-soluble salts, based on calcium and barium, have revealed that they can be subdivided on the basis of the presence or absence of a charge reversal point in the pH-mobility curve. The anion component appeared to determine this characteristic; it was noted that phosphate and citrate ions had a marked effect and gave a biased negative potential at all pH values. We concluded that where a divalent cation is cohabiting with a trivalent anion, the greater potential-determining ability of the latter will dominate the overall charge at the surface of a particle, even below pH7 and the absence of a positive potential gives a monophasic pH-mobility curve. Differences in both the physical appearance and electrophoretic mobility of the adsorbents studied reflect the wide variation in their chemical composition, especially among the various forms of calcium phosphate which, unlike barium sulphate, can include substituted ions such as hydroxyl, in their crystal lattice. The definition of these characteristics allows their behaviour towards clotting factors to be more easily predicted.


Competitive inhibition by lithium and hydrogen ions of the effect of calcium on the aggregation of rabbit platelets. ADP-induced platelet aggregation and shape change were monitored optically in citrated rabbit platelet-rich plasma (PRP) diluted with isotonic salt solutions. Lithium (Li) produced a concentration-dependent reduction in the rate of platelet aggregation but had no discernible effect on the shape change which precedes aggregation. When PRP was pre-incubated with Li, the inhibitory effect of the ion was independent of the duration and temperature of the treatment. The inhibitory effect of Li also was observed in heparinized PRP or when 5-HT was used as the aggregation-inducing agent. When Li was combined with aggregation inhibitors which enhance platelet cyclic AMP content either by activating adenylate cyclase or by inhibiting phosphodiesterase, only additive effects were observed. The inhibitory effect of Li was opposed by added calcium. Kinetic evaluation of the interaction between Li and Ca indicated that their antagonism was competitive. Added calcium also displayed competitive antagonism toward the aggregation inhibiting effect of increased hydrogen ion concentration in the pH range between 6 and 8.


Effects of bupranolol, a new beta-blocker, on platelet functions of rabbit and human in vitro. The effects of bupranolol, a new beta-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known beta-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased. Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4-3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the beta-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8-3.3 times as effectively as propranolol. From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis.


Effects of ions on ADP-induced aggregation of bovine or human platelets. Effects of divalent cations on ADP-induced aggregation response were examined. Bovine platelets were transferred by Sepharose 2B gel filtration from citrate-PRP into citrate free buffer (buffer-GFP). Response increases, reaches a maximum and decreases with increasing calcium and/or magnesium concentration. For either calcium or magnesium alone, increasing response is proportional to a rate coefficient and, through an apparent ion-platelet association constant, to the fraction of platelet critical sites bound to cation. With both ions present, bound magnesium appears to inhibit bound calcium in excess of that accounted for by competition and a lower rate coefficient for bound magnesium. With citrate present in buffer-GFP, apparent association constants increase, excess magnesium inhibition is present, but systems are path dependent. Initial conditions appear to establish a response which is thereafter immutable to environmental magnesium alteration. Citrate-PRP resembles buffer-GFP: response is sensitive to the selective removal of calcium and excess magnesium inhibition is present. With heparin-PRP, response is immutable to the selective removal of approximately 90% of initial calcium. The dependency of response inhibition observed at high divalent cation concentrations indicates that aggregation is not due to interplatelet cross linking by ions. Ion effects are similar for bovine and human platelets.


Chemical studies of marine invertebrates. XXIII. A novel polyhydroxylated sterol from the soft coral Litophyton viridis (Coelenterata, Octocorallia, Alcyonacea). The structure of 24-methylenecholest-5-en-3beta,7beta,19-triol (II) isolated from the soft coral Litophyton viridis, has been established by X-ray diffraction analysis. The compound is accompanied by its 7-monoacetate derivative.


Induction of increased graft-versus-host disease by mouse spleen cells sensitized in vitro to allogeneic tumor. The aim of our study was to sensitize cells in vitro, follow their proliferative and cytotoxic responses, and determine their ability to cause lethal graft-versus-host disease (GVHD). C57BL/6 (H2b) spleen cells were incubated with irradiated BALB/C (H2d) Moloney lymphoma cells (LSTRA) in mixed leukocyte culture conditions for 2, 4, or 6 days and then tested. The maximal proliferative response occurred after 4 days. In vitro cytotoxic reactivity against 51Cr-labeled LSTRA was generated by 4 days (76.3+/-3.1% 51Cr released) and 6 days (133.0+/-4.8%) of sensitization but not by 2 days (-0.2+/-1.1%). Induction of fatal GVHD was assayed by injecting graded doses of the C57BL/6 spleen cells i.v. into adult BALB/c mice pretreated with cyclophosphamide, 180 mg/kg. Cells sensitized for 2 days were effective but no more so than were (control) cells cultured with irradiated C57BL/6 spleen cells. However, cells sensitized longer were far more active than the control cells. Cells sensitized for 4 days killed 70 of 88 mice (80%), and those sensitized for 6 days killed 37 of 48 mice (77%), whereas control cells killed only 42 of 90 mice (47%) (P less than 0.005). Thus, cells sensitized in vitro exhibited an increased ability to induce GVHD in vivo, which was temporally associated with the development of cytotoxicity in vitro.


The hydro-chemical and physical conditions of the environment of the immature stages of some species of the simulium (Edwardsellum) damnosum complex (Diptera). Water samples were collected from breeding sites of species of the Simulium (Edwardsellum) damnoslm complex in Upper Volta, Liberia and Cameroon during the dry season; and in Tanzania and Kenya at various seasons during a period of two years. The following 20 factors were analysed at 45 breeding sites: water temperature, current velocity, pH value, conductivity free carbon dioxide, oxygen content, calcium, magnesium, potassium, sodium, alkalinity, chloride, sulphate, nitrite, nitrate, ammonium, phosphate, silicate, total iron and organic substance (consumption of potassium permanganate). A number of notable differences in the chemical composition of the water of the breeding sites of 13 S. damnosum complex species were found, particularly with regard to the pH and conductivity. On the basis of these differences the various species can be divided into three main groups: Group I: 3 species (S. sanctipauli, S. yahense, "Menge"); breeding in sites with pH values always below 7 and conductivity values below 50 mumhos. Group II: 8 species (S. sirbanum, S. sudanense, S. damnosum s.s., S. squamosum, "Sanje", "Nkusi", "Nyamagasani", "Jovi"); breeding in watercourses with neutral, weakly acid or weakly alkaline reactions and conductivity values ranging from 50 to 150 mumhos. Group III: 2 species ("Kibwezi", "Kisiwani"); breeding in watercourses characterized by highly alkaline reactions with pH values between 7.7 and 10 and by conductivity values between 400 and 950 mumhos. The vectors of Onchocerca volvulus are included in group I and II only.


[Effect of a urea diet on glutamate dehydrogenase and glutamine synthetase activity in various organs of chickens]. The total values were determined for the activity of glutamate dehydrogenase, glutamine synthetase, and dehydrogenase with pyruvate in broilers fed a diet with a 0, 2 and 4% content of urea for three weeks. A statistically significant increase of glutamate dehydrogenase activity was ascertained in the liver and kidney of broilers. The increase of the activity of glutamine synthetase in liver was close to the threshold of statistical significance. Dehydrogenase activity with pyruvate increased in liver.


3H-deoxythymidine incorporation in graft-versus-host disease in the Norway rat. I. Liquid scintillation studies. Graft-versus-host-disease was produced in newborn Brown Norway (BN) rats with an intravenous (iv) injection of adult allogeneic Lewis (L) lymph node cells (experimental) and the response was compared to littermates injected with adult syngeneic BN cells (control). By 4 days the reaction in the spleen of experimental animals was such that the spleen index was 1.70 and 2.58 on day 7, and continued to increase until death. A one hour iv pulse of tritiated deoxythymidine (3HdT) administered to experimental and control animals revealed a whole organ peak incorporation of 3HdT on day 6 in experimental spleens. A second larger peak occurred on day 10 in the experimental spleen as compared to a single peak at days 6 or 7, respectively, in the experimental mesenteric and combined superficial lymph nodes. However, analysis of the incorporation of 3HdT with respect to organ weight revealed a peak incorporation in animals receiving L cells on day 4--6 with a second smaller peak on day 10 in the experimental spleen and again a single peak on day 5 or 6 in the lymph nodes. Total 3HdT incorporation within both experimental lymph node compartments became less than controls by day 15 even though experimental nodes had a larger mass. 3HdT incorporation per milligram tissue weight decreased in all tissue compartments of experimental animals by day 13--14. The contribution of donor and host cell proliferation to the various peaks observed is discussed.


3H-deoxythymidine incorporation in graft-versus-host disease in the Norway rat. II. Autoradiographic studies. A sequential analysis was made of various areas within the lymph nodes and spleen of newborn Brown Norway (BN) rats suffering from graft-versus-host disease (GVHD) subsequent to an allogeneic injection of adult Lewis (L) lymph node cells (experimental). One micron thick autoradiographs were compared between such experimental and control littermates having received the same number of syngeneic adult BN cells. Both experimental and control animals received tritiated deoxythymidine (3HdT) one hour before killing. The autoradiographs revealed a 2.25 and 2.50 times higher thymidine labeling index of lymphocytes in the deep cortex of mesenteric lymph nodes and white pulp of the spleen, respectively, for experimental animals. The experimental effect occurred within one day. The majority of the labeled cells in experimental animals were large lymphoblasts with prominent nucleoli. The labeling index within these areas remained significantly higher than control values until day 8 in the spleen and through day 14 within the lymph nodes. However, differences in labeled cells present in high powered microscopic fields reached a peak on day 3 within compartments in experimental animals but fell significantly below control values by day 9 owing to a pronounced disappearance of both small and large lymphocytes from these areas, and a decreased intensity of individual cell labeling as the reaction progressed. In contradistinction the concentration of labeled cells present in high powered microscopic fields of lymph nodes' medulla became 3.13 times controls by day 4. Most of these labeled cells contained a more basophilic cytoplasm than those found in the deep cortex and some were distinctly plasma cell precursors. In contrast to the deep cortex their concentration remained approximately three times control values until death. The data indicates that the major proliferative events within the spleen and lymph nodes in neonatal rat GVHD are initially restricted to donor cell localization areas of these tissue compartments. Subsequently the GVHD-related events may be attributed to other areas and possibly cell types. Thus any proliferation contributing to splenomegaly in the latter stages of GVHD appears to occur in the red pulp and that contributing to lymph node enlargement a medullary response.


[Interaction of complex esters of hydroxyethylsulfones with DNA in vitro]. The effect of a number of alkyl disulphones on the parameters of DNA melting following its treatment with the substances involved was studied under in vitro conditions: it was found that bis(acetyl oxyethylsulphonyl) methane and bis (formyl oxyethylsulphonyl) methane reduced the temperature of DNA melting. As a result of decomposition of oxyethylsulphone esters the corresponding vinylsulphones were formed. It is suggested that the parameters of DNA melting change under the influence of vinylsulphones being formed. There is some correlation between antitumor activity of alkyl disulphones and their capacity to interact with DNA. Inactive or insignificantly active substances would not influence the parameters of DNA melting, while the two substances under consideration possessed a high antitumor effect on ascites forms of animal tumors.


Contributions to the optimal use of human blood. VIII. Stability of blood coagulation factor VII during collection and storage of whole blood and plasma. Investigations were performed concerning the influence of the pH on the stability of factor VIII during the collection of blood and during the storage of blood and plasma for varying periods and at varying temperatures. It was found that the low pH of ACD anticoagulant solution (pH 4.9) caused a loss of factor VIII procoagulant activity of 10-15% during the collection of blood. However, when less acidic anticoagulant solutions were used, substantial losses of factor VIII occurred during the storage of blood. We concluded that the optimal pH of both the anticoagulant solution and the stored blood, should be between 6.7 and 7.0. However, no anticoagulant solution is known that meets these requirements. In practice ACD ensures the highest recovery of factor VIII in cryoprecipitate, at least in those cases where the blood donations are stored for several hours before separation and freezing of the plasma.


In vivo and in vitro activation of T-antigen receptors on leukocytes and platelets. Serological studies on a patient whose red cells are polyagglutinable due to T activation have demonstrated concomitant T activity of the separated leukocytes and platelets. Normal leukocytes and platelets are not T active, but activation can be induced in vitro by treatment with neuraminidase or with pneumococcus type III filtrate. Such T-active cells absorb anti-T from Arachis hypogea lectin. Tests on idfferent types of separated leukocytes show that both neutrophils and lymphocytes have latent T antigen receptors. Neuraminidase treatment of platelets does not change their ability to promote clot retraction, to aggregate with ADP, or to take up serotonin.


Neurochemistry and behavior in man.

Neurochemistry and behavior in man. The distribution and functions of certain neurotransmitter substances seem to correlate with clinical, anatomical and physiological evidence about the mediation of normal and abnormal behaviors in man, though much remains to be learned. The biosynthetic and metabolic pathways, receptors and reuptake mechanisms, and relationships to cyclic nucleotides for several major neurotransmitters are characterized, as well as the specific actions of many behavior-modifying drugs employed clinically. Experimental systems, including nerve cells in culture, permit tests of molecular actions inferred from biochemical and neurophysiological analyses in intact brain. This selective review emphasizes advances in neurochemistry which provide a context for current and future research on neurological and psychiatric disorders encountered in clinical practice.


[Fermentation of pyruvate by 7 species of phototrophic purple bacteria]. The dark, anaerobic fermentation of pyruvate under growth conditions was examined with the following species of phototrophic purple bacteria: Rhodospirillum rubrum strains Ha and S1, Rhodopseudomonas gelatinosa strain 2150, Rhodopseudomonas acidophila strain 7050, Rhodopseudomonas palustris strain ATCC 17001, Rhodopseudomonas capsulata strains Kb1 and 6950, Rhodopseudomonas sphaeroides strain ATCC 17023, and Chromatium vinosum strain D. Fermentation balances were established for all experiments. Under fermentative conditions cell protein and dry weight increased only slightly, if at all. The species differed considerably in their fermentative activity; R. rubrum and R. gelatinosa exhibited the highest rates (2-8 mumoles pyruvate/mg protein-h). R. acidophila and R. capsulata showed an intermediate fermentation rate (0.4--2.0 mumoles pyruvate/mg protein-h), while the other strains tested fermented at quite low rates (0.2-0.4 mumoles pyruvate/mg protein-h). The extremes of fermentation times were from 30-380 hours. Based on the products of fermentation which were formed in addition to acetate, formate, and CO2, the species can be grouped as follows: a) R. rubrum, R. gelatinosa, and R. sphaeroides additionally form propionate. b) R. gelatinosa, R. palustris, R. capsulata, R. sphaeroides, and C. vinosum additionally form lactate. R. palustris also produces butyrate. c) R. acidophila and R. capsulata additionally form much 2,3-butanediol, acetoin, and diacetyl. Small amounts of acetoin were formed by the rest of the strains. A comparison of the fermentation of pyruvate by normal and starved cells (4 days in the light without a carbon source) of R. rubrum and R. gelatinosa shows that the latter ferment more slowly and produce less acetate and formate, but more propionate or lactate. The fermentation of pyruvate by R. rubrum was also studied in cultures in which the pH fell (7.2--6.6). Compared with the fermentation at neutral pH (7.3, 7.4), the following differences were found: a slower fermentation rate, an increased production of dry weight, an increased formation of propionate, but a reduced formation of acetate and a very low production of formate.


Purification and some properties of factor D of the human properdin system. Factor D has been purified by gel and ion exchange chromatographies, and by ultrafiltration through different membranes. The final preparation appeared pure in various analytical tests. The molecular weight of human D is 21,500 according to gel chromatography, the isoelectric point was found at pH 7.8. Factor D is an active esterolytic enzyme, it cleaves N-alpha-acetyl-L-lysine methyl ester and N-alpha-acetyl-L-glycyl-L-lysine methyl ester. Both peptide esters inhibit the hydrolytic activation of factor B by D in the presence of cobra venom factor. D is also inhibited by diisopropyl-fluorophosphate and by penylmethyl-sulfonyl-flouride.


Volatile degradation products of l-dehydroascorbic acid. Volatile degradation products were isolated from a solution of L-dehydroascorbic acid in phosphate buffer solution of pH 2,4,6 and 8 heated under reflux for 3 h or left at 25 degrees C for 200 h. The products were identified by comparison of their gas chromatographic retention data, infra-red and mass spectra with those of authentic compounds. Fifteen products were identified,  among which 12 had not yet been reported as degradation products of L-dehydroascorbic acid. Concentrations of 5 main degradation products, i.e. 3-hydroxy-2-pyrone, 2-furancarboxylic acid, 2-furaldehyde, acetic acid and 2-acetylfuran depended on the pH values and temperature; the presence of oxygen had no pronounced effect.


Surface tension activity and paramorphogenic effect of sorbose, sodium desoxycholate, and griseofulvin on the growth of colonies of Chaetomium aureum Chivers. Sorbose at 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1.0% levels, sodium-desoxycholate at 0.025, 0.050, 0.075, 0.1 and 0.125% levels, and griseofulvin at 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, and 0.010% levels restrict the growth of colonies of Chaetomium aureum, both at pH 6.5 and 7.0. Restriction of colonies was most effective with 0.7% sorbose, 0.1% sodium-desoxycholate, and 0.006% griseofulvin in the medium adjusted to pH 6.5. Surface tension activity of sorbose, sodium-desoxycholate, and griseofulvin in different concentrations was determined, following the usual standard method.


[New findings on human prolactin].

[New findings on human prolactin]. Since prolactin (HPRL) occurs as a separate pituitary hormone in man the paper will discuss results about the mechanisms involved regulation of HPRL secretion. A number of factors which lead to an increase in HPRL secretion are named. The clinical relevance of HPRL inhibiting substances as L-DOPA and 2-Br-alpha-ergocryptine is mentioned. The influence of HPRL in pregnancy and lactation period is described also the regulative effect of HPRL on hormone-dependent breast tumors.


[Production of obstetrical reports using a computer]. A rational method of production of medical reports in obstetrics is reported. The basis of this method is the approved computer guided system (DOKUMEDA) in clinics of radiology. Advantages and disadvantages of using are discussed.


Chitinase and beta-N-acetylglycosaminidase in the digestive juice of Helix pomatia. A beta-N-acetylglucosaminidase from Helix pomatia digestive juice was separated and partly purified by gel chromatography. The optimal pH for the degradation of p-nitrophenyl-N-acetyl-beta-D-glucosaminide was 3.4. The molecular weight was around 160 000 and the pI = 4.95. In the same gel chromatography run two chitinase active peaks were also obtained. These chitinase active peaks were also obtained. These chitinases, with molecular weights around 26 000 and 13 000, had somewhat different pH activity curves with optima at 4.2 and 4.3. By isoelectric focusing the first peak with molecular weight around 26 000 was divided in two chitinase active regions with pI at 5.7 and 3.5. The second peak with molecular weight around 13 000 had a pI at 7.3.


Absorption of free and antibody-conjugated horseradish peroxidase to fixed glial cells in tissue culture, a possible source of error in immunohistochemistry. Incubation of cellular preparations with antibody-conjugated peroxidase result in a very strong unspecific staining, for one electropolar binding of the basic enzymic protein with the cell structures. In immunohistochemical practice, it may represent an evil as import as when dealing with immunofluorescence techniques. This background can to a great extent be avoided by rinsing the preparations in buffer at pH = 6.2.


Effect of continuous positive airway pressure breathing on cardiorespiratory function in infants with respiratory distress syndrome. A method of investigating the cardiorespiratory responses to continuous positive airway presslre (CPAP) in infants with respiratory distress syndrome is described. All measurements were made immediately before and within five minutes of application or any change in level of CPAP. Ventilation was derived from a pneumotachograph and dynamic compliance calculated. We have also measured arterial pH, oxygen and carbon dioxide tensions, arterial blood pressure and central venous pressure. Arterial oxygen tension increased in association with a decrease in the alveolar-arterial oxygen gradient. No consistent changes occurred in pH or carbon dioxide tension. Heart rate and mean arterial blood pressure remained the same but the arterial pulse pressure narrowed and the increase in central venous pressure averaged 17% of the applied airway pressure. There were less variations in both tidal volumes and instantaneous respiratory rates with CPAP compared with spontaneous breathing without CPAP. The respiratory rate decreased, but there were no consistent changes in tidal volume, resulting in a lesser reduction of minute ventilation. Dynamic compliance decreased on CPAP. With correct use of CPAP, and improvement in oxygenation generally occurs without obvious adverse cardiorespiratory effects. CPAP must nevertheless be used cautiously and in conjunction with close monitoring; because when the appropriate pressures are exceeded, it is possible that both circulatory and ventilatory function might be severely compromised.


The protective action of certain anaesthetics and tranquilizers against the effects of hyperbaric oxygen. The protective effects of pentobarbitone, hydroxydione and diazepam against acute and chronic toxicity of high-pressure oxygen (HPO) were studied in rats. During exposure to hyperbaric oxygen body temperature was measured and ECG as well as EMG tracings from the diaphragm were obtained. Long term observations of animals after the exposure to HPO were conducted. Pentobarbitone and hydroxydione reduced the manifestations of acute toxicity but increased those of chronic toxicity. Diazepam reduced the manifestations of acute toxicity and seemed to counteract those of chronic toxicity. Lowering of body temperature of the animals which occurred during exposure to HPO was probably connected with manifestations of chronic toxicity. Observation of the cardiorespiratory functions suggested a possible connection between their disturbances and an onset of seizures and development of oxygen-induced paralysis.


Present state of alpha and beta adrenergic drugs III. Beta blocking agents. The beta blocking agents are valuable drugs in cardiology. They are effective in any fast arrhythmia. Together with nitroglycerin, beta blockers are drugs of first choice in angina. As antihypertensives, they have advantages that should make them drugs of first choice. For migraine the beta blockers are equal to any other type of drug. With more study their place in treating anxiety will be clarified. And without question other uses will be found. It is difficult for this author to understand the attitude of the FDA to this class of drugs. To limit the American physician to only one drug in this large group of drugs is unheard of. Although it can be argued that propranolol is the best one, there are obvious cases where another drug would be better. For example, propranolol induces nightmares in a few patients. There is evidence to show that timolol does this less frequently. FDA delay in approval of propranolol for essential hypertension is totally incomprehensible. Other approved drugs are less effective and much more toxic. Propranolol, and the other beta blockers, are safe and effective. The adverse beta effects are easily controlled or avoided. The other adverse effects are no more frequent than with any other class of drugs, and all are reversible. It is to be hoped that science and common sense will prevail over bureaucratic indecision.


Effects of the H1-antagonist promethazine and the H2-antagonist burimamide on chronotropic, inotropic and coronary vascular responses to histamine in isolated perfused guinea-pig hearts. On guinea-pig atria part of the inotropic response to histamine is attributable to a concomitant increase of the frequency [7]. Since the chronotropic effect of histamine is mediated by a stimulation of H2-receptors a direct interaction of histamine with H1-receptors a direct interaction of histamine with H1-receptors mediating the inotropic response on heart may be overlooked. For this reason the ability of the H1-antagonist promethazine and the H2-antagonist burimamide to inhibit the positive chronotropic, inotropic and coronary vascular responses to histamine was determined in spontaneously beating and electrically driven perfused guinea-pig hearts. (1) Burimamide produced a competitive blockade of the positive chrono- and inotropic responses to histamine. (2) On the other hand, promethazine in concentrations that had no effect on cardiac function by itself, proved to be ineffective against the positive chrono- and inotropic responses produced by histamine on spontaneously beating and electrically driven heart preparations. (3) The predominant coronary vasodilation observed after infusion with histamine was competitively antagonized by promethazine and burimamide. This blockade was not attributable to an interaction with myocardial H2-receptors mediating increases in heart rate and contractility and was, therefore, direct in nature. (4) Based upon the present study and former investigations [7] the following distribution of different histamine receptors in the guinea-pig heart does exist: H1-receptors are present in the atrial muscle and the coronary vascular bed. H2-receptors are located in the sinus node, the ventricular myocardium and the coronary vessels.


Takayasu's arteritis. Clinical study of 107 cases. The clinical experience derived from the retrospective study of 107 cases of TA over a 19 year period is presented. The disease predominated in females (8.5:1), with age of onset usually less than 20 years. In half of the cases an acute inflammatory phase was observed, characterized mainly by systemic and cardiovascular symptoms. Subsequently the natural course of TA was toward chronicity with gradual  deterioration. The most frequent variety of TA (65 per cent of the patients) was Type III, in which the supra-aortic trunks and the abdominal aorta were involved. The predominant clinical features were reduction of amplitude of peripheral arterial pulses (96 per cent), vascular bruits (94 per cent), and raised blood pressure (72 per cent), mainly resulting from renal arterial involvement (62 per cent). Heart failure (28 per cent) is rarely the result of direct coronary arteritis. TA is most often confused with aortic coarctation, but usually the aortogram distinguishes these. The etiology of TA is discussed. The high incidence of previous and present active tuberculous (48 per cent) in the present series and previous experimental work suggest that tuberculosis may play an important role in the etiology of TA. Treatment for antihypertension and heart failure should be employed when indicated. Treatment with corticosteroids requires further evaluation. Treatment for tuberculosis is not justified in all cases until the exact role of tuberculosis is well established.


Effect of antiserum on transplantable hematopoietic colony-forming units during Rauscher leukemia development. Studies have been carried out to determine the sensitivity of hematopoietic CFU-S from Rauscher leukemic mice to an antiserum against the disease prepared in syngeneic mice. Test of this antiserum against Rauscher virus prior to injection showed it to be effective both in vitro and in vivo. At the same time, normal serum was shown to be without effect either against the CFU-S or against the virus. Spleen CFU-S were obtained from control and leukemic mice over a sequence of days following Rauscher virus injection and assayed by transplantation technique. Prior to transplantation these were incubated in vitro in either normal syngeneic serum or syngeneic antiserum. Incubation with antiserum had no effect on CFU-S obtained from the spleens of normal mice. However, incubation in this antiserum of spleen CFU-S from Rauscher leukemic mice resulted in a reduction of up to 50% in their colony-forming ability. Additional tests with guinea pig complement suggested that the levels of inactivation seen are not complement limited. This antiserum-induced reduction in colony formation was first evident in the second week after the injection of virus, coincident with the onset of splenomegaly in the leukemic mice. Thereafter, sensitivity of CFU-S to the antiserlm could be detected up to the terminal point of the leukemia (44 days).


Multiple endocrine adenomas in a patient with the Maffucci syndrome. A patient with multiple cutaneous hemangiomas and skeletal dyschondroplasia (the Maffucci syndrome) was found to have a pituitary chromophobe adenoma, a parathyroid adenoma and two other neoplasms. The presence of two endocrine tumors suggested the syndrome of multiple endocrine adenomatosis, and raised the issue of an etiologic relationship between this disease and the Maffucci syndrome. Dyschondroplasia, however, has no known influence on the secretion of parathyroid hormone or any of the pituitary hormones. The Maffucci syndrome is associated with a high incidence of malignancy, but it involves primarily mesodermal derivatives whereas multiple endocrine adenomatosis affects tissues of ectodermal origin. The association of the two in our patient is probably fortuitous.


A study of the relationship between Goodwin's high-risk score and fetal outcome. Correlation between Goodwin's high-risk score and Apgar score was studied in 266 pregnancies managed with the use of the information from clinical monitoring. The correlation coefficients between Goodwin's score and Apgar scores were -0.3178 for one-minute Apgar scores and -0.2668 for five-minute Apgar scores. Both are significant at the level of p less than 0.001. When the patients were divided into two groups by Goodwin's score, fetuses of the group with the higher score (greater than or equal to 4) were significantly more acidotic than those of the group with the lower score. Therefore, Goodwin's high-risk scoring system is simple and useful in the selection of potential risk patients.


Pathologic scar formation. Morphologic and biochemical correlates. Morphologic and biochemical analyses were performed to compare normal skin and mature scars to hypertrophic scar and keloid. Correlation of morphologic findings with biochemical profiles of the skin and scar samples proved feasible and enlightening. Scanning electron microscopy (SEM) was used to characterize the architectural arrangement of collagen fibers in skin and scars. Cultured fibroblasts from each specimen were also examined with the SEM. A biochemical profile of each tissue specimen was constructed, characterizing the collagen component of the specimen by sequential molecular sieve and ion exchange chromatography to determine a) the degree of intermolecular crosslinking, b) amino acid analysis, and c) levels of lysyl oxidase activity. Results indicate that collagen fibers and fiber bundles display a decreasing level of organization as the clinical degree of scar abnormality increases, and this structural gradient correlates with the gradient of intermolecular crosslinking in the same tissue--normal skin and mature scar being highly crosslinked, hypertrophic and keloid successively less so. Surprisingly, the level of the crosslinking enzyme lysyl oxidase is normal or elevated in hypertrophic scar and keloid despite the relative lack of crosslinking. Amino acid content was uniform for all specimens. Scanning electron microscopy examination of cultured fibroblasts from the tissue specimens demonstrated three phenotypically distinctive fibroblasts whose numerical and volumetric proportions correlated with the tissue of origin.


Hyperlactatemia and hemolysis in G6PD deficiency after nitrofurantoin ingestion. A 69-year-old man with glucose-6-phosphate dehydrogenase deficiency was treated with nitrofurantoin for pyuria. Four days later he presented with metabolic acidosis due to excess lactic acid, a decline in curculating hemoglobin, reticulocytosis, elevated serum transaminase levels, and hyperbilirubinemia. The drug was withdrawn and the hyperlactatemia subsided in three days without specific treatment. In vitro, nitrofurantoin is capable of stimulating erythrocyte glucose utilization aand lactate production, and inhibiting the generation of reduced glutathione. In vivo, this drug is capable of producing hemolysis in susceptible subjects and hepatocellular injury. The temporal proximity of drug ingestion and hemolysis, increased glucose utilization, lactate excess, and hepatic insufficiency suggests that nitrofurantoin may have been responisble for precipitating the clinical and chemical abnormalities observed.


Effect of pH on ammonia production by renal mitochondria. NH3 production by renal cortical mitochondria was studied under conditions of metabolic acidosis induced in vivo and with pH manipulations of the media bathing mitochondria from normal rats. A HCO3- medium equilibrated with O2 and CO2 was utilized with glutamine concentrations of either 10 or 0.5 mM. With chronic acidosis NH3 production increased significantly at either substrate concentration. Similar results were obtained with rotenone in the media, both with chronic acidosis and with acidosis of 3 h duration, indicating that increased glutamine entry and/or phosphate-dependent glutaminase (PDG) activity accounts for the increased ammoniagenesis. In contrast to acidosis induced in vivo, mitochondria from normal rats subjected to a diminution in medium pH, either by manipulation of HCO3 concentration or PCO2, significantly decrease NH3 production. Mitochondrial studies with rotenone, as well as studies of solubilized PDG, suggest that a low pH diminishes NH3 production by directly altering PDG activity. Furthermore, regardless of the specifics of the mechanism, these studies indicate that adaptation to metabolic acidosis is not the immediate, direct result of a change in pH.


Renal hemodynamics in drug-overdosed patients. Effective renal plasms flow (ERPF) and glomerular filtration rate (GFR), as determined by a radioisotopic method, were evaluated in seven heroin-overdosage patients (Group I) and 7 hypnotic-sedative-analgesic overdosage patients (Group II). No patient had evidence of shock. There was no significant intergroup differences in PaO2, PaCO2, pH, blood pressure, pulse rate, respiratory rate, cardiac output, or serum creatinine levels. Group I patients had lower ERPF and GFR compared to Group II (271 +/- 182.8 vs. 580 +/- 62 cc/min and 62.4 +/- 32.6 vs. 102.9 +/- 12.8 cc/min, respectively, p less than 0.005). We conclude that compared to hypnotic-sedative-analagesic overdosed patients heroin overdosed patients heroin overdosed patients have more profoundly altered renal hemodynamics.


pH environmental of red cells in the spleen. Intrasplenic pH in vivo was deduced from measurements on blood drained from cat spleen during contraction with the inflow occluded. The pH of blood in the red pulp is normally 7.20, but stasis or reduced flow through the pulp causes pH to fall toward 6.8. The splenic pulp contains blood of high hematocrit. To evaluate the role of buffering by the red cells themselves, intrasplenic p/ in red cell-free spleens was, therefore, estimated atering and leaving the spleen during red cell washout. At inflow pH less than 6.8 the outflow pH was raised, at inflow pH = 6.8 there was no change, b,t at inflow pH greater than 6.8 the outflow pH was lowered. These results indicate that the pH environment of red cells in the spleen results indicate that the pH environment of red cells in the spleen results from the interplay of two separate factors: i) pH-determining elements of the splenic tissue that buffer at 6.8, and ii) buffering provided by red cells passing through the pulp.


Response to angiotensins I and II and to AI-converting-enzyme inhibitor in a shark. The spiny dogfish shark, which does not have renal juxtaglomerular cells, exhibits a strong pressor response to both angiotensin I and II. A nonapeptide, angiotensin I-converting-enzyme inhibitor, blocks the pressor response to angiotensin I in this fish. The pressor response to both angiotensin II and norepinephrine is completely blocked by the adrenergic blocking drug phentolamine.


A comparison of high- and low-dose lorazepam with amylobarbitone in patients with anxiety states. A double-blind crossover trial comparing lorazepam at two dosage levels with amylobarbitone supported previous reports of the effective anxiolytic action of the drug. Evaluation of the patients' responses during each week of treatment was based on a physician's weekly rating and on daily self-rating by patients. The results were analyzed by sequential and nonsequential analyses. The main side effect of the drug was drowsiness, which occurred to a clinically significant degree among the high-dose group of patients. The authors emphasize the value of two dosage trials, particularly in devising subsequent flexible individual treatment regimens.


Tardive dyskinesia: are first signs reversible? Although tardive dyskinesia, a serious and sometimes irreversible side effect of antipsychotic drug use, is becoming increasingly common, there is still considerable confusion concerning the course of the syndrome. The authors observed 12 psychiatric patients with tardive dyskinesia from the inception of the syndrome. They found that first symptoms rarely persisted if antipsychotics were discontinued and concluded that the length of time symptoms have persisted prior to drug discontinuation, not age at onset, may be the major variable determining reversibility of the syndrome.


Timor filariasis: epidemiologic and clinical features in a defined community. The epidemiology of Timor filariasis was observed during a clinical and parasitologic survey of persons living in a remote village on the island of Flores, Southeast Indonesia. Infection and disease was distributed evenly throughout the community, which was in accord with the breeding and feeding habits of the only identified vector, Anopheles barbirostris. Although micfofilaremia rates appeared independent of host variables of age and sexes and sex, symptoms of disease were greater among males than females, and in both sexes disease rates more than doubled between the first and second decades of life. Symptoms included recurring episodes of inguinal and femoral lymphadenitis with retrograde lymphangitis and fever, abscesses of lymph glands or vessels along the path of the great sapheneous vein and its mae highest yet reported for the Timor filaria; it is a virulent parasite causing serious ill-health among the inhabitants of eastern Flores.


Endemic eastern equine encephalomyelitis in Florida: a twenty-year analysis, 1955-1974. Research and surveillance programs relating to the circulation of eastern equine encephalomyelitis (EEE) virus in Florida between 1955 and 1974 are summarized. All available data suggest that EEE virus is 1) endemic in many Florida fresh water swamps and waterways, 2) active in a continuous cycle throughout the year with a peak between May and August, and 3) circulating in Culiseta melanura. It has been isolated also from eight other mosquito species.