Effects of beta blockers on cardiac function and myocardial oxygen consumption in the isolated supported heart preparation of the dog.

Effects of 2 different types of beta blockers, CS-359 and practolol, on mechanical performance and myocardial oxygen consumption (MVO2) in the isovolumic contraction of the isolated, blood-perfused canine heart with a support dog were studied. Two dose levels of the beta blockers were given intravenously to the support dog, one of which was enough to produce a significant beta adrenergic blocking action and other of which was a higher dose to reveal a direct depressant action on the isolated heart. CS-359 in the lower dose produced significant decreases in heart rate (HR), peak ventricular systolic pressure (peak VSP), and peak dp/dt while practolol caused no change in these parameters. The HR of the support dog was significantly decreased to the same degree in the lower dose of respective blocker. In the higher dose CS-359 decreased all parameters more definitely whereas practolol diminished peak VSP and peak dp/dt but did not significantly HR. MVO2 was decreased dose-relatedly by CS-359, but not affected significantly by practolol. From the analysis of relationships of MVO2 to peak VSP and HR in the isolated heart it is concluded that the effective reduction in MVO2 by CS-359 resulted mainly from a reduction in the peak VSP in the lower dose and additional decrease in HR in the higher dose of CS-359.


Effect of starvation on renal metabolism in the rat.

The effects of starvation on the acid-base status of the rat and on the glucoeogenic and ammoniagenic capacity of rat renal-cortical slices were examined.  Starvation for 48 or 72 hr did not affect acid-base status, and urinary ammonia production did not change.  Kidney cortical slices from starved as compared to fed rats showed increased gluconeogenic capacity when incubated with the substrated pyruvate, succinate, fumarate, malate, 2-oxyoglutarate, glutamine and glutamate.  Renal cortical tissue from starved rats also had increased activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase.  Renal cortical slices from starved rats did not differ from those from fed rats in the ability to produce ammonia from glutamine or glutamate, nor was there any difference inhe activity of glutaminase between these groups.  These results show that renal gluconeogenic capacity is increased in starved rats in the absence of systemic acidosis, and starvation does not lead to an increase in urinary ammonia excretion or renal ammoniagenic capacity.


Effects of nephron reduction and dietary protein content on renal ammoniagenesis in the rat.

Urinary ammonium excretion, in vitro ammoniagenesis and the activities of renal cortical phosphate-dependent glutaminase (PDG) and glutamic dehydrogenase (GLDH) were measured in rats with a reduced renal mass. Following contralateral nephrectomy, ammonium excretion per nephron, ammonia production and the activities of PDG and GLDH were all increased significantly in remnant kidneys of rats fed high protein diets. In rats fed low protein diets, although PDG activity increased, GLDH activity and ammonia production and excretion did not increase in remnant kidneys following contralateral nephrectomy. Ammonia production and excretion were greater in rats fed high than low protein diets, a difference that was corrected by the addition of mineral acid to the diets of low protein-fed rats. Acid supplementation to the low protein group did not result in enhanced ammonia production or GLDH activity following a reduction in renal mass. The data indicate that the increased rate of ammoniagenesis which occurs following nephron reduction is markedly influenced by dietary protein content. A lack of enhanced GLDH activity may underlie the lack of increased ammonia production of low protein-fed rats following nephron reduction.


Renal secretion of diphosphonates in rats.

Diphosphonates, characterized by a P--C--P bond, are relatively new experimental drugs used for the treatment of myositis ossificans, dental calculus, nephrolithiasis and Paget's disease. These compounds are not metabolized and the fraction which is not taken up by the skeleton is excreted unchanged in the urine. In the present study, the renal clearances of two 14C-labelled diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (CEHDP) and disodium dichloromethylene diphosphonate (CC12MDP) have been measured in conscious rats. The clearances have been found to be higher than the glomerular filtration rate (GFR), Cdiphosphonate/GFR being about 1.5. This observation indicates net tubular secretion of both drugs. High plasma concentration of EHDP or Cl2MDP significantly depressed CEHDP, whereas CEHDP was not influenced by varying urine pH, by infusing NH4Cl or NaHCO3, or by simultaneous administration of high doses of para-aminohippurate (PAH), probenecid, N-methylnicotinamide or Ca-EDTA. High plasma concentration of inorganic phosphate depressed CEHDP and also depressed the in vitro ultrafiltrability of EHDP. In conclusion, these results provide evidence of an active renal transport of diphosphonates which appears distinct from the mechanisms handling organic acids, organic bases and EDTA in the rat kidney.


[New views on the significance and treatment of undescended testis (author's transl)].

Undescended testis is of clinical importance because there are increased risks of milignancy and torsion and disturbances of fertility and psychosexual development. New quantitative morphologic investigations show that human prepubertal testicular maturation does not occur in phases but is continuous. This made it necessary to investigate afresh the causes of disturbance of fertility and the treatment of indescended testis. Our own investigations show that damage to the germ epithelium need not be congenital but may develop because of its ectopy. If, in dogs, a testis is placed into the abdomen, not only this but also the normally placed testis in the scrotum is damaged. The diameter of the tubules and their surfaces as well as the numbers of pachtenous primary spermatocytes are significantly reduced both in the displaced and the normally placed testis. Nuclear surfaces and density of the cells involved in spermatogenesis differ from those in the controls. The findings support the plea for early hormonal or surgical treatment in order to prevent later disturbances of fertility.


Neuroleptanalgesic drug combinations in the anaesthetic management of small laboratory animals.

Trials of different drug combinations for use in rabbits, guinea-pigs, rats, hamsters and mice are described in detail and experience over a 5-year period evaluated. Combinations of fentanyl citrate, fluanisone and diazepam provided exceptionally good anaesthesia in each species and were considered superior to other injectable agents.


Women alcoholics. A review of social and psychological studies.

Research on social-history variables, personality characteristics, social roles and role confusion, and possible treatment methods for women alcoholics is reviewed. Suggestions for additional studies involving factors motivating drinking in women, theories of personality, new treatment methods, and differentiation between subgroups of women alcoholics are discussed.


Dimensions of psychopathology among alcoholic patients.

Responses of hospitalized alcoholics to the Minnesota Multiphasic Personality Inventory and the Differential Personality Inventory were intercorrelated and factor analyzed. Considerable heterogeneity of psychopathology within the sample was found.


Psychological test results at three stages of inpatient alcoholism treatment.

Improvement in intellectual, perceptual-motor and personality functioning was observed in men alcoholics after 30 and 60 days of treatment. On the basis of results with the Minnesota Multiphasic Personality Inventory, four consistent personality clusters were identified.


Alcoholism and schizophrenia: the search for perspectives. A review.

The historical search for meaningful relationships between alcoholism and schizophrenia is reviewed. The results are considered inconclusive and further lines of research are suggested.


Relationships between specific drinking problems in early adulthood and middle age. An exploratory 20-year follow-up study.

Specific drinking problems were remeasured in a panel study after a 20-year interval. The nature of the problems at both measurement points is assessed and the associations between them explored.


Drinking behavior and "alcoholism".

Drinking is viewed as a functional behavior, an active response to environmental conditions, and excessive drinking as a compromise behavior resulting from ineffectiveness in mediating goals and resolving problems.


Alcohol consumption and personal resources. A general hypothesis and some implications.

A general hypothesis is formulated in which alcohol consumption is largely determined by the resources available for drinking, the activities competing for those resources, and the costs associated with drinking in the context of a particular social status. Implications in terms of drinking patterns of occupational subgroups, longitudinal changes in alcohol consumption, and vulnerability to the development of pathological drinking are suggested.


Mixed models of alcoholism. Definitions, etiology, treatment and prognosis in health education textbooks.

The information on alcoholism presented in college-level health education textbooks was compared with eight models of alcoholism. No model was cited consistently; diverse knowledge bases, models of alcoholism and moral views were implicit in the texts. The utility of the models is also discussed.


Training paraprofessionals in the treatment of alcoholism. Effects on knowledge, attitudes and therapeutic techniques.

Participation in a training program for paraprofessional alcoholism counselors increased the trainees' knowledge of alcoholism, modified their attitudes toward alcoholism and affected their therapeutic techniques.


Physicians and alcoholics. The effect of medical training on attitudes toward alcoholics.

The over-all ratings assigned by first- and second-year medical students and housestaff (residents and interns) to alcoholics on a 16-adjectivee bipolar semantic differential measure differed significantly. Mean ratings by the housestaff were lowest and the ratings by the second-year students were lower than those of the first-year students on 5 of the 6 adjective pairs on which the groups differed significantly.


Drinking-driving behavior of young men in relation to accidents.

To determine the role of drinking in the accidents of young men, data were examined from a representative survey sample of 1670 young men in south-eastern Michigan and from official accident statistics of 4 states. By age 20 over half the sampled men drank at least once weekly and drove at least once monthly after drinking. Alcohol was involved in 3-8% of all crashes of 20-year-olds. The highest accident rates without alcohol involvement occurred at ages 18-20, whereas the most alcohol-involved accidents occured at ages 22-24.


Cross-fostering of DBA and C57Bl mice. Increase in voluntary consumption of alcohol by DBA weanlings.

Weanling mice of the alcohol-avoiding DBA strain cross-fostered to mothers of the alcohol-selecting C57Bl strain drank twice as much alcohol as did nonfostered DBA mice. In contrast, C57Bl mice cross-fostered to DBA mothers drank the same amount of alcohol as did nonfostered C57Bl mice. Differences in maternal behavior seem to be responsible for differences in alcohol selection by weanlings.


Drinking patterns of institutionalized and noninstitutionalized Wyoming youth.

The drinking attitudes and patterns among institutionalized and noninstitutionalized Wyoming youth were examined. The majority appeared generally to support a norm of approval of drinking but those institutionalized for antisocial behavior were more likely to drink often, to become drunk and to have gotten into trouble with parents or the police because of drinking.


An intake group in the alcoholism outpatient clinic.

At an outpatient clinic, alcoholics who attended group meetings dealing with basic communication skills during the admission process missed fewer appointments and more often completed the process than did alcoholics who did not attend the meetings.


Transplantation models using the regional lymph node.

Several transplantation models, using the regional lymph node, to study the transplantation reaction in strictly defined and simple conditions were devised. Lymphoid cells were transplanted to inbred rats and mice at the sites drained by one regional lymph node; the experimental design was chosen so as to permit theoretically a one-way reaction, either the host-versus-graft (HVG) or the graft-versus-host (GVH) reaction. The changes in the lymph nodes draining the site of cell injection (weight increase, histology, lymphocyte activation) were very similar in both transplantation reactions. They were ascribed to a humoral mediator released upon the contact of lymphoid cells from two genetically different individuals. The direct demonstration of a mediator which is capable of activating the regional lymph node in vivo introduces some new aspects into the process of sensitization after transplantation.


[Restoration of articular movement after injury using the Volkov-Oganesian appliance].

Volkov-Oganiesian's apparatus takes over the whole statical and dynamical load and releases the articulation completely. The apparatus fills the gap created between the articular surfaces both in statical and dynamical respect, it eliminates the friction and overcomes also the effect of the reflex muscular contracture. In the same time it eliminates also the superfluous muscular movements, since the apparatus is fixed firmly to the bone, and the exact centring of the articular ends (being of extreme importance in the surgical treatment of the luxation and subluxation) promotes the formation of the newly developed articular surfaces.


[Infection in bone surgery].

After surgical interventions carried out in the bone different occurrence of infections in various institutes has been observed, - the infections are in general more infrequent in the specialized institutes and departments. In the authors' opinion, - besides the general asepsis the special conditions of work and the working tools play important role in the prevention of infections. In the indication of surgical intervention in the bone the surgeon must have self-criticism, - this may lead to the reduction of infections. Several data have shown that all interventions are not allowed everywhere and always.


[Primary excision of burn wounds].

After the clarification of the pathophysiology of the shock suffered in burns and after working out the successful shock therapy -, as well as after the surgical removal of the necrosed tissues and the introduction of the up-to-date dermoplasty the prognosis of the thermic trauma has undergone fundamental change. The tangential and laminal excision - that is the removal of the necrosed areas with dermatological knife - has been introduced in 1968. Ater the review of the secondary surgical interventions the new method, its advantages and limits, as well as their experiences are discussed by the authors. This method has elevated the primary care of the burns to the level of the therapy of the mechanical wounds and it has allowed the application of Friedrich's principle also in the surgical treatment of the thermic trauma. The proportion of the contractures decreased considerably, - and this may be considered as a great progress, even in the case that the mortality of the severe burns could not be reduced in greater degree. The institution and the use of the tangential excision is already of beneficial effect.


[Results of panastragal arthrodesis performed on basis of different indications].

The indications of pantalar arthrodeses - performed in 21 years - and their results are discussed. In the authors' opinion, the compression arthrodessis carried out in one sitting is the method of choice.


[Possibilities of treatment of arthrogryposis].

The results of the treatment of 90 patients with arthrogryposis are resumed. The possibilities of the conservative treatment are discussed and on the basis of their experiences and the data of the literature the details of the surgical technique are given for each articulation. Besides conservative therapy 86 different surgical interventions have been performed on 21 patients. The treatment necessitates utmost care and good collaboration is necessary between the doctor and the patient, or the patients relatives, resp. The therapeutical program yields often after several years satisfactory result.


[Fenestrated rib fracture, a disease entity?].

The problems of the paradoxical respiration - observed in the case of fenestrated rib fracture - are discussed by the authors. On the basis of the data of the literature and of 348 own cases with covered rib fracture, as well as on the basis of the course and the clinical analysis of the lesion the authors refuse to admit the role of the "pendelluft" and of the mediastinal flutter in the development of circulatory and respiratory disorders occurring in the case of fenestrated rib fractures. In the authors' opinion, there are only quantitative differences between the consequences of the various rib fractures. The thoracal lesion is considered by the authors as functional unity. The treatment is always prescribed according to the degree of the functional disorder and also the classification of the injured patients is to be made on this basis.


[Positive contrast arthrography in the diagnosis of ligament lesions in the upper ankle joint].

There are a great number of open questions in the diagnosis and the management of ligament lesions of the ankle joint. On the basis of the data of the literature and the author's experiences the advantages of the contrast arthrography of the ankle-joint may be resumed in the following: 1. No narcosis is necessary. 2. More exact determination of the site of the lesion is possible. 3. Therefore proper treatment may be chosen. 4. The incidental technical errors are more easily to be verified. (Paraarticular administration of the contrast medium is immediately demonstrable, whereas faulty observance of the prescriprions becomes not always evident from the roentgenogram). 5. No comparative roentgenograms are necessary. 6. The X-ray staff is not exposed to X-ray radiation.


[Supplying patients with orthopedic shoes after panastragal arthrodesis].

After the arthrodesis of the upper and lower articulations and of the Chopart's articulations (panastragal arthrodesis) the foot's functions undergoes a change, which may be substituted only with properly constructed orthopaedic shoes. Partly the foot's function - altered in consequence of the intervention - and partly the considerations to be respected at the preparation of the orthopaedic shoes are discussed in the paper.


[Experience with artificial hibernation of patients with severe craniocerebral injuries].

The artificial hibernation (hypothermia) of patients with severe cranio-cerebral lesion is discussed. The authors' experiences have shown that re-establishment of the normothermia reduces considerably the symptoms of the neurovegetative syndrome, thus it contributes to the improvement of the prognosis and in many cases it assures the patient's survival. Artificial hibernation is an important task during the intensive therapy of patients with cranio-cerebral lesions.


[Experience with the treatment of longitudinal oblique and spiral fractures of the leg by Goetze's percutaneous cerclage].

After the short review of the literary data in respect of Goetze's percutaneous cerclage 25 cases are presented: in all cases satisfactory functional results have been obtained. With proper use this method is useful for the treatment of long oblique and spiral fractures of the leg, if suitable technical equipment is available.


[Organization of the management of burns in mass disasters].

In war-time or in the case of other mass casualties we are compelled to have recourse to a compromise between the great number of the injured individuals and the possibilities of their management. This compromise, however, should not become distorted to an inevitable concession to our medical principles. The care of mass casualties - resulting also from burns - is an integrant area of up-to-date medicine, requiring full responsibility. It is our sublime obligation to study and to teach this discipline.


[Accidental immobilization of the proximal joint of the index finger].

In connexion with one case a rare clinical picture is described by the authors. The stoppage of movement observed in young individuals in the MP articulation of the forefinger occurs under the effect of trauma, - under normal articular conditions, - on strongly flexed finger, under the effect of powerful ulnar duction.


The heart and hyperthyroidism. Use of beta-adrenergic blocking drugs.

Many of the manifestations of hyperthyroidism are secondary to increased adrenergic activity. In recent years the beta adrenergic blocking drugs, as represented by d,1-propranolol, have become the agents of choice for ameliorating the adrenergic signs and symptoms of hyperthyroidism. Propranolol improves the tachycardia, tremor, restlessness, anxiety, and myopathy.


Purification and characterization of a Streptomyces albus endo-N-acetylmuramidase lytic for group A and other beta haemolytic streptococci.

The purification and characterization of the streptolytic exo-enzyme from the Maxted-McCarty strain of Streptomyces albus is described. This enzyme was shown to be an endo-N-acetylmuramidase with a molecular weight of 10 to 12,000 and optimal activity at pH 8 and 45 degrees C. The enzyme is lytic for streptococci of various groups, Micrococcus lysodeikticus, Staphylococcus aureus, as well as Escherichia coli. It closely resembles the F1 endo-N-acetylmuramidase described by Ghuysen et al. (1966) except for small differences in the products of lysis of streptococcal cell walls and the resistance of Escherichia coli to lysis by the F1 enzyme. Lysates of group A and A variant streptococcal cell walls prepared with purified Streptomyces albus muramidase contained serologically active M protein and C carbohydrate-peptidoglycan complexes. The chemical and immunological characteristics of these enzymmatic products of streptococcal cell walls are reported and their utility as immunologic reagents is described.


Cholesterol metabolism by Mycobacterium.

Cholesterol metabolism by Mycobacterium species ATCC Number 19652 was studied in defined media. Whole cells were found to take up 91% of the total cholesterol when incubated five days at 34 degrees C in media of pH 6.8-7.4. Uptake of cholesterol by whole cells could be significantly inhibited by 2,4-dinitrophenol and dicyclohexylcarbodiimide. Growth media supernates as well as isolated microbial cell walls were found to contain cholesterol hydrolysing activity. This activity was extractable by Triton X-100 and appeared to have a molecular weight of approximately 100-200,000.


[Change in the indices of direct count of bacteria in cultures and pond water at different pH].

Experiments were carried out with the pure cultures of Pseudomonas fluorescens and Bacillus subtilis, and with pond water. The adjustment of pH of the culture or water to 8.8--9.0 facilitates the direct count of the microorganisms, and makes the results more accurate.


[Factors influencing the biosynthesis of beta-galactosidase in Alternaria tenuis].

The effect of pH, carbon sources, and some organic substances on the biosynthesis of beta-galactosidase was studied in Alternaria tenuis on a defined medium that had been optimized by the method of mathematical planning of experiments. Optimal conditions for the production of the enzyme and its liberation into the cultural broth were maintained by adding 2 per cent soya flour to the medium and 0.1 M phosphate-citrate buffer pH 3.0. The production of the enzyme was increased by 3 to 4 times. The biosynthesis of beta-galactosidase by Alternaria tenuis is of an induced nature.


[Characteristics of a Mycobacterium mucosum culture oxidizing cholic acid].

Some physiologo-morphological and biochemical characteristics were studied with the culture of Mycobacterium mucosum 1210 which can assimilate cholic acid as a sole source of carbon. This culture is capable of spontaneous variability. Four variants of the culture were obtained which possessed different rates of the transformation of cholic acid. The variant which formed slimy colonies of pale-yellow colour was the most active. Some morphological modifications of the cells were investigated in the course of cultivation, such as the size, shape and formation of the capsules. Various growth media were tested, and the optimal values of pH were selected.


[Effect of low pH values on the chemical composition of a chemostat culture of Bacillus megaterium].

Inhibition of the growth of Bacillus megaterium was studied in the conditions of chemostat. Inhibition of the growth by hydrogen ions had almost no effect on the content of DNA, RNA, protein and polysaccharides, but the protein-synthesizing activity of RNA changed. The content of polyphosphates, of high and low molecular weight, depended on pH; the relationship was of a non-linear character. The total content of lipids increased with the concentration of hydrogen ions.


Changing concepts in the management of hypertension.

Experience in a hypertension clinic attended by 591 patients over a 13-year period has shown marked changes in the pattern of use of hypotensive agents. Thiazides have been used throughout the period in almost all cases. Methyldopa was used for most patients for almost a decade. Since 1967 there has been a steady increase in the use of beta adrenergic blocking agents, and these are now used for over 60% of patients attending the clinic. Combination beta adrenergic blocking agents with peripheral vasilodators such as hydrallazine and prazosin have provided a very effective means of controlling the blood pressure in moderate and severe hypertension. Prazosin, a new peripheral vasodilator, has been used in the treatment of 295 patients. In most cases it has been used in combination with a thiazide diuretic and beta adrenergic blocking agent. Open studies have demonstrated that this is an effective hypot  .ensive agent. Side effects are few and are counteracted by combination with a beta adrenergic blocking agent. Prazosin and hydrallazine are being compared in double-blind studies.


[Comparative characteristics of the ability to coagulate milk in different representatives of the order Actinomycetales].

The ability to clot milk was studied among 482 cultures of Actinomycetales. The highest activity was manifested by thermophilic actinomycetes, the next come globisporous, white, and gray groups of the genus Actinomyces. Cultures belonging to the genera Mycobacterium and Mycococcus did not clot milk. The ability to clot milk can be used as an additional taxonomic index while studying ray fungi.


A tw0-component ribonucleotidyl transferase from E. coli.

Some properties of an enzyme designated as a two component ribonucleotidyl transferase from E. coli are presented. The enzyme in the presence of magnesium ions catalyzes the synthesis of polyribonucleotide chains using all four nucleoside triphosphates as substrates. The enzyme consists of two components; component A in the presence of Mg2+ catalyzes the synthesis of homo- and heteropolymers using ATP, CTP and UTP but not GTP as substrates. Component B itself does not catalyze any synthesis at all, but its addition to component A affects this component in two ways: quantitatively- the activity of component A considerably increases, and qualitatively- both components together are capable of catalyzing the synthesis of polyribonucleotides consisting of all four ribonucleotides.


Interaction between membrane properties and proteins synthesis in reticulocytes - a two step inhibition of protein synthesis by valinomycin.

In this work we consider the differential effect of Valinomycin used at different concentrations both on the protein synthesis of reticulocytes and on 42K exchange. We demonstrate that there is a two step action of this antibiotic. At 10(-6)M and below the drug has no effect on the 42K exchange, but it stops, however reversibly, protein synthesis. At 10(-5)M the drug has a very sharp action on the 42K exchange and stops protein synthesis in an irreversible way. Ribosomal population checked by two ways, sucrose gradient and direct counting on E.M. sections shows that at low concentrations of Valinomycin (10(-8)M to 10(-6)M) there is no breakdown of the polysomes which can be detected by either one of these methods. On the contrary, after short incubation with 10(-5)M of Valinomycin the breakdown of ribosomes is very clear, as evidenced by sucrose gradient analysis. By direct ribosomes clusters counting on E.M. sections this breakdown is seen only after long incubation.


"In vivo" release of endogenous neurotransmitters in cat limbic regions: effect of chlorpromazine and of electrical stimulation.

The effect of chlorpromazine (10 mg/kg i.v.) on the spontaneous release of endogenous dopamine (DA), noradrenaline (NA) and acetylcholine (ACh) within limbic areas perfused by means of the push-pull cannula was investigated in the gallamine-immobilized cat. Chlorpromazine increased the liberation of DA and NA in the nucleus accumbens septi, indicating blockade of the amine receptors. However, the drug did not change the output of ACh from this nucleus nor from ventral and dorsal hippocampal formations which receive a cholinergic input from the septum as indicated by several published findings and by the increased liberation of ACh after electrical stimulation of the homolateral nucleus medialis septi. These results seem to exclude that cholinergic neurons of some limbic areas mediate the effect of the blockade of DA (and of NA) receptors which is possibly involved in the antipsychotic action of neuroleptic drugs.


Inhibition of striatal dopamine synthesis in rats injected chronically with neuroleptics in their early life.

3H-dopamine synthesis from L-3,5-3H-tyrosine was reduced in striatal slices of 40 days old rats treated during their early life with neuroleptics. Animals were first injected intra-utero with thioproperazine (5 mg/kg) or with the palmitic ester of pipotiazine (32 mg/kg); the thioproperazine-treated rats were then injected every day from day 1 to day 37; the animals injected with the long acting neuroleptic were injected once more with the drug on day 15 after birth.


Hydrophobic interactions responsible for unspecific binding of morphine-like drugs.

The unspecific binding of four narcotic analgesics 3H-dihydromorphine, 14C-morphine, 3H-etorphine and 3H-fentanyl to human albumin, human plasma, rabbit plasma and several tissue homogenates from rabbits was investigated using equilibrium dialysis and ultrafiltration. At a drug concentration of 10(-7) M in human plasma, dihydromorphine is bound to an extent of 14%, morphine to 23%, etorphine to 88% and fentanyl to 70%. These differences in binding are due to different degrees of hydrophobic interaction between the drugs investigated and the plasma or tissue components. The hydrophobic interactions are due to the unionized form of the drugs. The ionized form is bound to a negligible extent with all four compounds, possibly in part by ionic mechanism. Binding increased with increasing ionic strength of the protein solution, with raising temperature between 0 degrees C and 37 degrees C and with increasing pH values of the protein solution, features which are characteristic of hydrophobic interactions. Scatchard plots of the binding data, from which the total binding constants nk were derived, indicated high concentrations of binding sites compared with drug concentrations found analgesically effective in vivo.


Antagonism by d-amphetamine of learning deficits in rats induced by exposure to antipsychotic drugs during early postnatal life.

The acquisition of a conditioned avoidance response (CAR) was investigated in rats of nursing mothers given pimozide 0.5 mg/kg on days 1, 2, 3, 4, 5, 6, and 7 after delivery. Four weeks after birth, the male litter-mates were tested for CAR acquisition in a two-way avoidance situation or for correct CAR acquisition in a brightness discrimination situation. Offspring of mothers treated with pimozide were markedly inferior in the CAR acquisition in both behavioural situations as compared to those of mothers given glucose. The administration of d-amphetamine 15 min prior to the training session specifically counteracted the behavioural impairment obtained in the offspring of pimozide-treated mothers. The results obtained in the present investigation lend further support to the contention that the behavioural deficits in offspring of nursing mothers treated with neuroleptic agents are due to a developmental disturbance in central catecholamine neurones.


Selectivity for catecholamines of presynaptic alpha-receptors involved in feedback control of sympathetic neurotransmitter secretion in guinea-pig vas deferens.

The aim of the study was to quantitatively compare the relative affinities of noradrenaline, adrenaline, dopamine and isoprenaline for the, probably neural, receptors mediating feedback control of sympathetic neurotransmitter secretion. The experiments were carried out in isolated superfused field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline. Desipramine and normetanephrine were added to prevent rebinding of transmitter. Exogenous noradrenaline was found to cause a dose-dependent and reversible depression of the secretion of tracer noradrenaline evoked by field stimulation. Since the depressing effect was not affected by a ten-fold rise in the desipramine concentration, it seems likely that it was not due to uptake and preferential secretion of unlabelled exogenous noradrenaline, but was truly due to depression of the secretory mechanism. Adrenaline was significantly more potent than noradrenaline, as inhibitor of the secretion of tracer transmitter, while dopamine, at the same molar concentration, was without effect. The beta-agonist isoprenaline did not depress, but rather tended to enhance, the secretion of tracer noradrenaline. It is concluded that the receptors controlling the secretion of noradrenaline from the sympathetic nerves of guinea-pig vas deferens quantitatively-with regard to sensitivity-as well as qualitatively-with regard to order of preference for different catecholamines-resemble the "classical" alpha-receptors of e.g. smooth muscle in the same tissue.


Tyrosine hydroxylase: allosteric activation induced by stimulation of central noradrenergic neurons.

Electrical stimulation of the rat locus coeruleus cases about a 300% increase in the activity of the tyrosine hydroxylase prepared from the hippocampus on the stimulated side and assayed in the presence of subsaturating concentrations of tyrosine and pteridine cofactor. Addition of calcium or cAMP to soluble preparations of tyrosine hydroxylase isolated from the hippocampus produces a similar activation of tyrosine hydroxylase. The activation of tyrosine hydroxylase produced by calcium is reversed by addition of the calcium chelator, EGTA, while the activation produced by cAMP addition or by electrical stimulation of the locus coeruleus is unaffected by addition of EGTA to the assay medium. The activation of tyrosine hydroxylase produced by electrical stimulation or by addition of calcium or cAMP to the assay medium appears to be mediated in part by alterations in the kinetic properties of the enzyme. All treatment causes the enzyme to have an increased affinity for substrate and pteridine cofactor and a decreased affinity for the endproduct inhibitor, norepinephrine. These results are suggestive that the activation of tyrosine hydroxylase which occurs during periods of increased impulse flow in noradrenergic neurons may be initiated by alterations in calcium fluxes or by changes in the steady state levels of cAMP which accompany neuronal depolarization.


Evidence for an involvement of GABA in the mediation of the cerebellar cGMP decrease and the anticonvulsant action diazepam.

Subcutaneous injections of isoniazid or picrotoxin increase the cerebellar content of 3',5'-cyclic guanosine monophosphate (cGMP) without changing the 3',5'-cyclic adenosine monophosphate cAMP. This increase was dose dependent and the threshold for the cGMP increase was lower than that for convulsions. In cerebellum the increase of cGMP content elicited by isoniazid but not that caused by picrotoxin was paralleled by a decrease of GABA content. Diazepam doses starting from 1.74  mumol/kg intraperitoneally produced a dose dependent decrease of cerebellar cGMP concentration without changing cAMP or GABA content. Smaller doses of diazepam (0.5 mumol/kg i.p.)failed to decrease the basal cerebellar content of cGMP. However, this dose of diazepam antagonized the increase of cGMP produced by isoniazid but not that produced by picrotoxin. Higher doses of diazepam were necessary to block the increase of cerebellar cGMP elicited by picrotoxin. Low doses of diazepam (0.14 mumol/kg) antagonized the convulsions in 50% of the rats injected with 3.3 mmol/kg of isoniazid. The doses of diazepam required to block picrotoxin, pentylenetetrazol or strychnine convulsions were 7, 25 and 40 times higher than those required to block isoniazid convulsions, respectively. Desmethyldiazepam, chloridiazepoxide, oxazepam were also several times more potent in antagonizing isoniazid than picrotoxin, pentylenetetrazol, or strychnine convulsions. In contrast, barbiturates were equipotent against all the convulsants studied. These experiments suggest that diazepam may act in the CNS either by altering the disposition of endogenous GABA or by mimicking the action of GABA at specific synaptic receptors.


The beta-adrenergic receptor-adenyl-cyclase system of rat reticulocytes: effects of adrenergic stimulants and inhibitors.

Non-nucleated red blood cells from rats contain adenyl cyclase, the activity of which is predominantly localized in the reticulocytes. Basal enzyme activities in membrane preparations from reticulocyte-rich blood (pretreatment of rats with acetyl-phenylhydrazide: about 60% reticuloytes) are about 5 times higher than in preparations from reticulocyte-poor blood (untreated animals: 2-3% reticulocytes). The enzyme activities are stimulated 10-fold by sodium fluoride (10(-2)M) and 6 to 8-fold by isoprenaline (10(-4)M). Adenyl cyclase activities in membrane preparations from reticulocyte-rich and reticulocyte-poor blood can be ascribed to identical enzymes since identical apparent Km (ATP; 3 times 10(-4)M, Ka (isoprenaline; 3 times 10(-6)M) and Ki (propranolol vs. isoprenaline; 3 times 10(-7)M) values were obtained in both preparations. Besides NaF, only phenylethanolamine derivatives with beta-adrenergic receptor stimulant properties were effective as stimulators of adenyl cyclase activity. The affinities (apparent Ka values) of the investigated compounds decreased in the order isoprenaline--hexoprenaline--fenoterol--salbutamol--adrenaline--terbutalin--noradrenaline--phenylephrine. For maximal intrinsic activity, the catechol structure was essential; the relative intrinsic activities of resorcinol derivatives did not exceed 0.6. The isoprenaline-stimulated adenyl cyclase activities in erythrocyte membrane preparations were competitively inhibited by beta-adrenergic blocking drugs, the affinities (apparent Ki values) decreasing in the order prindolol--penbutolol--propranolol--practolol. The dextrorotatory enantiomers of penbutolol and propranolol were 1/100 to 1/200 as active as the resp. levorotatory enantiomers. From experiments with alpha-adrenergic agonists (e.g. phenylephrine) and antagonists (e.g. phentolamine), it is concluded that alpha-adrenergic receptors do not interfere with the beta-adrenergically-mediated cAMP formation in these particular membranes. A variety of hormones and drugs known to stimulate denyl cyclase activities in various tissues, e. g. ACTH, glucagon, STH, erythropoietin, prostaglandin E1 etc. did not affect adenyl cyclase activity in reticulocyte-rich erythrocyte membrane preparations. In contrast to adenyl cyclase activity, phosphodiesterase activities in erythrocyte membrane and cytoplasmic fractions were only twice as high in reticulocyte-rich as in reticulocyte-poor preparations. From the experiments described, it is obvious that the adenyl cyclase of the rat reticulocyte is subject to monovalent-hormonal, i.e. beta-sympathomimetic stimulation. Moreover, the premature red blood cell provides a useful model for quantitative studies of the interaction of drugs with the beta-adrenergic receptor.


Acute and subacute effects of neuroleptics dopamine synthesis and release in the rat striatum.

The effects of acute and subacute treatments with moderate doses of thioproperazine and haloperidol on dopamine synthesis and release have been examined in rat striatal slices. Synthesis and release of dopamine were determined by measuring the rate of formation of 3H-H2O during the conversion of L3,5-3H-tyrosine into 3H-Dopa and the accumulation of newly synthesized 3H-dopamine in striatal slices and their incubating medium. Possible effects of the treatments on tyrosine striatal levels or tyrosine specific activity were also investigated. Dopamine synthesis rate was markedly accelerated 2.5 hrs after the acute injection of thioproperazine, but was equal to control levels 24 hrs later. The effects of thioproperazine and haloperidol were thus determined 2.5 and 24 hrs after an acute injection and following the last injection of a repeated daily treatment of 11 days. Dopamine synthesis and release were still markedly increased 2.5 hrs after the last injection of the subacute neuroleptic treatments when compared to controls, but these effects were less pronounced than those observed 2.5 hrs after an acute injection of either drug. Conversely, dopamine synthesis and release were significantly decreased 24 hrs after the last injection of the subacute neuroleptic treatments when compared to controls. Two hypotheses are proposed to explain the changes in dopamine synthesis induced by repeated treatments with neurolptics.


[4-allyloxy-3-chlorophenyl-acetic acid (alclofenac) in the treatment of painful arthroses in the aged. Double-blind controlled clinical trial].

The antiarthrosic effectiveness with respect to spontaneous pain upon movement and pressure, of alclofenac (4-allyloxy-3-chlorophenyl-acetic acid) was tested in a homogeneous group of elderly patients and compared with orally administered indomethacin. The research was carried out in strictly controlled, double-blind experimental conditions. The results obtained suggest that 500 mg of the new anti-inflammatory analgesic have the same action as 25 mg of indomethacin but with a lower incidence of the side effects common to all anti-inflammatory substances. Thanks to its good tolerability and high effectiveness, the new drug should be of considerable utility in the treatment of arthrosis in the elderly and in painful, inflammatory complications.


[Study of the tolerability and effectiveness of a new sleep-inducing preparation].

Flurazepam hydrochloride was experimented on 43 patients aged 33-83 yr with various forms of insomnia over a period of 4 to 23 days (mean 11.66). There were no changes in the laboratory data and gastroenteric tolerance was also excellent. Chi-square analysis showed that both the quantity and quality of sleep were significantly improved (P less than 0,001). There was no evidence of assuefaction or withdrawal symptoms.


Successful management of severe aortocaval compression in twin pregnancy.

In a patient with severe aortocaval compression, simultaneous brachial and femoral blood pressure measurements demonstrated the need for a 30 degrees left-down tilt to avoid significant obstruction of the vessels. When emergency cesarean section became necessary, proper positioning of the patient was readily accomplished.


Acute neonatal nonketotic hyperglycinemia: normal propionate and methylmalonate metabolism.

Propionyl-CoA carboxylase and combined methylmalonyl-CoA (MMA-CoA) racemase and -mutase activities were studied in liver and fibroblasts of two patients with the acute neonatal form of nonketotic hyperglycemia. In all experiments, these enzyme activities studied in tissues of the patients were within the range of healthy control subjects, whereas no propionyl-CoA carboxylase activity was measurable in the fibroblasts of a patient with propionic acidemia. Subcellular fractionation of liver and fibroblasts indicated that the normal amounts of MMA-CoA found after incubation of whole tissue homogenate were formed by propionyl-CoA carboxylase, a mitochondrial enzyme, and not be acetyl-CoA carboxylase, which theoretically could also be involved in the carboxylation of propionyl-CoA. From the above data as well as from clinical and biochemical observations in three patients, it was concluded that there exists a true nonketotic hyperglycinemia which is not related etiologically to the different disorders of the ketotic hyperglycinemia syndrome. True nonketotic hyperglycinemia is not associated with ketoacidosis even after loading with propionate- and MMA precursors. It must be distinguished by exclusion from mild forms of the ketotic hyperglycinemia syndrome which may present clinically as hyperglycinemia without ketosis.


Early growth and development in low-birthweight infants following treatment in an intensive care nursery.

Sixty-seven appropriate-for-date infants with gestations less than 33 weeks were followed for 12 months after their term dates. All had been born after September 1970. None received hypercaloric alimentation as neonates. Growth from the expected date of delivery was compared with that of 24 normal full-term infants and with accepted growth standards. The boys did not differ from the controls or the standard in mean weight, length, and head circumference, in weight and height indices, or in velocity of weight and linear growth. The girls had a slower velocity of weight growth for the first six months and had significantly lower weight indices at 12 months than did their controls. Velocity of linear growth, height indices, and mean length and head circumference for the girls were similar to those of the control standards. Gross central nervous system defects occurred in 22.5% of the boys but in none of the girls. More than one half of the abnormalities were hydrocephaly. The mean post-conceptional developmental quotient was 110 for the girls and 108 for the boys.


Assisted ventilation in infants with meconium aspiration syndrome.

In a retrospective analysis of infants born with meconium staining over an 18-month period at Cook County Hospital, 32 infants met two of the three criteria for the diagnosis of meconium aspiration syndrome: (1) history of meconium in the oropharynx or trachea; (2) clinical evidence of respiratory distress; and (3) x-ray evidence of aspiration pneumonia. Seventeen infants developed respiratory failure; nine of these infants died. One infant without respiratory failure died of sepsis. Analysis of sequential arterial blood pH and gas tension showed that nonsurviving infants had persistently high PCO2 and A-a gradient in spite of initiation of assisted ventilation. These changes seem to be related to severe right-to-left shunting and ventilation perfusion abnormalities. The data further suggest that asphyxia and acidosis occur well before the infant is born and that intrapartum monitoring to recognize fetal asphyxia may help in improving morbidity and mortality from meconium aspiration syndrome.


Medex: a time-motion study.

Six Medex working with family practitioners were followed by an observer for a total of 18 days to gain an objective profile of how Medex spent their workday. Medex on the average spent 30% of their time with office patients and saw 38% of all office patients. Medex saw between 25% and 100% of all pediatric office patients and spent on the average 37% of their office patient time with pediatric patients. On the average, Medex saw 8 pediatric and 11 adult office patients per day. Well-child examinations, the largest pediatric diagnostic category, accounted for 30% of Medex pediatric office patient time. Minor surgery accounted for the second largest portion of pediatric office patient time (21%) while respiratory illness ranked third (11%). In view of the increasing role family practitioners and their assistants will undoubtedly play in the provision of child health care, pediatricians are urged to work closely with family physicians in developing and implementing health care services for children.


[Treatment of bone marrow aplasia by allogenic bone marrow grafts].

Three patients with severe aplastic anemia were treated by bone marrow transplantation using the method described by Santos and Thomas. Two of the patients, both successfully grafted have survived for more than 5 and 6 months respectively. Chimerism was proved by cytogenetic analysis and erythrocytic phenotypes. In one case, a severe graft versus host reaction was cured with ATG and prednisone. Graft rejection in the third case was related to the immunisation caused by many previous transfusions. Although bone marrow grafting is limited by the necessity of using a matched sibling as donor, its success this far is very encouraging and represents a new hope for the treatment of aplastic anemia.


[Post-hepatitic aplasia treated by grafts of allogenic bone marrow. Remission for more than 2 years. Persistance of a total hematopoietic chimera. Graft versus host reaction].

A successfull bone marrow transplant was achieved in a case of post hepatitic aplastic anemia after cyclophosphamide immunosuppression. Caryotype analysis, erythrocytic phenotype and IgG Gm allotype demonstrated evidence of complete chimerism. Anti-thymocyte serum undoubtly was able to suppress a life threatening episode of graft versus host reaction. Severe long lasting skin lesions are now persisting 2 years after the graft.


The spectrum of systemic vasculitis: a classification to aid diagnosis.

Determining the cause of systemic vasculitis can be facilitated by a clinicopathologic classification of the syndrome. The considerations in differential diagnosis include periarteritis nodosa, leukocytoclastic angiitis (hypersensitivity angiitis, Schonlein-Henoch purpura, other disease-associated vasculitis), Wegener's granulomatosis, allergic granulomatosis (granulomatous angiitis), and giant cell arteritis.


Respiratory problems complicating burn injury: recognition, assessment, and treatment.

Postburn pulmonary injury is a common and frequently overlooked concomitant of burn injury. The lesion may be secondary to direct damage to the respiratory apparatus from the inhalation of smoke or of toxic or superheated chemicals or from mechanical mechanisms or it may be secondary to indirect damage from hypovolemia, shock, central nervous system disturbances, or drug usage. Therapy comprises establishment of a clear airway and administration of humidity and oxygen in amounts appropriate to maintain adequate blood oxygen tension and pH. Sequential monitoring of oxygen and pH status is required. The diagnosis of postburn pulmonary injury is made on clinical grounds, and sequential management of the patient, closely supported by laboratory studies, is essential. Surface decompression of the thorax, antibiotics given systemically, and sequentially increasing respiratory support (with later de-escalation) may be needed.


Lipid biosynthesis in the chick. A consideration of site of synthesis, influence of diet and possible regulatory mechanisms.

Studies in vitro and with intact chicks support the view that liver is the major site of lipid biosynthesis in the chicken. Adipose tissue is relatively unimportant as a site of fatty acid biosynthesis in this species although it does have the ability to esterify fatty acids to triglycerides. The available evidence, therefore, suggests that in the chicken, and presumably other avian species, fatty acids are synthesized in liver and are transported as triglycerides in the plasma low-density lipoproteins to the adipose tissue for storage. Fasting, even for short periods of time, markedly depresses the capacity for hepatic lipogenesis in the chick. Food restriction for 2 hr. depresses hepatic lipogenesis by about 90% and refeeding for 1 hr./or/the intravenous administration of glucose or fructose restores the lipogenic capacity. Feeding diets high in fat or protein cannot be adequately explained on the basis of the reduction of dietary carbohydrate which accompanies increased dietary protein or fat levels. Dietary fat and protein appear to exert their effects on hepatic lipid synthesis by different mechanisms. The depression in hepatic fatty acid synthesis brought about by fasting or fat-feeding is accompanied, and probably preceded, by an increased plasma free fatty acid level. Under these conditions hepatic fatty-acyl CoA levels increase while free CoA levels are reduced. Long-chain acyl CoA derivatives are capable of inhibiting acetyl CoA carboxylase activity as well as citrate transport. The reduced availability of free CoA may limit the citrate cleavage reaction. Dietary alterations influence the hepatic lactate-pyruvate ratio of chicks, however the changes observed are not always consistent with the changes observed in rat liver. Chicks fed high-protein diets have a decreased hepatic lactate/pyruvate ratio indicative of a more oxidized cytoplasmic environment. This change in redox state may be associated with control of fatty acid synthesis in chicks fed high-protein diets. Thyroxine and glucagon affect hepatic fatty acid synthesis in the chick, however insulin appears to play a lesser role.


Radical mechanisms for 1,5-dihydroflavin reduction of carbonyl compounds.

A discussion of the expected mechanism of radical reduction of carbonyl compounds by dihydroflavin as it relates to the structure of the carbonyl compound is provided. Factors which must be taken into account are the free energies of formation of the radical anions (CR2O), THE ACIDITY OF THE CONJUGATE ACID OF THE CARBONYL FUNCTION (R2C negative charge OH), and the stability of the carbanion species of the product [(-)CR2(OH)]. It is proposed that in those instances where the product alcohol can flavin radical to CR2O or CR2OH occurs, otherwise H transfer is the terminal step for dihydroflavin reductions. The free energy of formation of the radical species CH2OH obtained by acid-catalyzed electron transfer from dihydroflavin (Fred) to formaldehyde is shown to be less than the experimentally determined free energy of activation (increment F is not equal to exp) for the reduction of formaldehyde by dihydroflavin (i.e., Fred plus CH2O leads to Fox plus CH2OH). Therefore, the radical pair composed of dihydroflavin radical species serve as an intermediate in the reduction. Our proposed mechanism is: Fred plus CH2O ka[H3O] forms k-a[H2O] Frad CH2OH leads to kc Fox plus CH3OH. The value of kaah/k-a has been obtained from the calculated standard potential Eo' for Fred plus CH2O plus H forms Frad plus CH2OH. Assuming ka to represent a two-step process (i.e., Fred plus CH2O plus H k'a forms k'-a Fred plus CH2OH kb forms k-b Frad CH2OH, where ka equals (k'akb)/(k'-ak-b), the value of k'-a will equal 10-10 M-minus 1 sec-minus 1 and kb 10-9 M-minus 1 sec-minus 1. From k'a/k'-a and kb there can be computed the expected value of increment F is not equal to calc as a function of pH. Comparison of increment F is not equal to calc to increment F is not equal to exp reveals that increment F is not equal to calc varies from increment F is not equal to exp by only about 2kcal mol-minus 1 (8.4 kJ mol-minus 1) between pH 5 and 9. Similar considerations establish that radical intermediates should serve eminently well in dihydroflavin reduction of ethyl pyruvate, pyruvic acid, etc. In these cases, 1 e transfer should compete with H transfer to yield the carbanions as the immediate products. Similar comparisons suggest that dihydronicotinamide reduction proceeds via RPyH plus C negative charge O forms RPyH plus C-0minus +H forms -H RPyH plus C-OH forms RPy plus HC-OH.


Studies on the stability of injectable solutions of some phenothiazines. Part 1: Effects of pH and buffer systems.

The stability of phenothiazines is affected by the pH-value of the solution. At the pH-values of maximum stability, triflupromazine hydrochloride and chlorpromazine hydrochloride are more stable than promazine hydrochloride. The stability of chlorpromazine hydrochloride in the Sörensen's phosphate buffer is slightly higher than that in the McIlvaine's citric acid-phosphate buffer system. On the other hand, the stbility of promazine hydrochloride and triflupromazine hydrochloride in the latter buffer system is slightly higher than that in the former one.


Studies on the stability of injectable solutions of some phenothiazines. Part 2: Effect of chelating agents and antioxidants.

Chelating agents (disodium EDTA, DTPA, HEDTA and NTA) exhibit a stabilizing action towards phenothiazines to different extents. This could be correlated to the stability constants of their metal chelates as well as to the dependency of these constants on the pH-value of the solution. Antioxidants (sodium bisulphite, sodium dithionite, and sodium metabisulphite) also exert a stabilizing effect which could be correlated--in the first place--to the pH-value of the solution. The sulphur content of the antioxidant might also be relevant to such an effect.


The alpha-chain-termination mutants and their relation to the alpha-thalassaemias.

The structure, synthesis, genetic transmission, clinical associations and distribution of the elongated alpha-chain haemoglobin variants has been described. The data indicate that the most likely molecular basis for these common abnormal haemoglobins is a single base substitution in the alpha-chain termination codon. Because these variants are produced inefficiently they give rise to the clinical picture of alpha-thalassaemia. When these findings are taken together with recent work regarding the molecular basis for other forms of alpha-thalassaemia it is possible to build up a fairly complete picture of the molecular pathology of the alpha-thalassaemias.


Correlation between plasma levels of prolactin and chlorpromazine in psychiatric patients.

Plasma levels of chlorpromazine (CPZ) and prolactin were measured repeatedly in 14 psychiatric patients throughout CPZ treatment.  Mean prolactin level was elevated in 11 subjects (all six women and five of eight men).  Mean plasma prolactin correlated significantly with mean plasma CPZ but not with the dose of the drug.  Only patients with mean plasma prolactin above 35 ng/ml developed Parkinsonian side-effects.


Auditory signal detectability and facilitation of simple reaction time in psychiatric patients and non-patients.

Patients diagnosed on the basis of structured interviews as having affective psychoses were less sensitive in detecting the presence of a transient auditory signal than were schizophrenic patients or non-patients. Patients with affective psychoses also benefited more (their reaction time was more reduced) than the other two groups from the presence of a second auditory transient.


Dopaminergic mediation of the interoceptive cue produced by d-amphetamine in rats.

After rats were trained to differentiate between the effects of d-amphetamine and saline in a state-dependent task, pretreatment with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, significantly decreased amphetamine discrimination. Pretreatment with the dopamine-beta-hydroxylase inhibitor, disulfiram, or with the tryptophan hydroxylase inhibitor, p-chloro-phenylalanine, was observed to have no effect on the rats' ability to discriminate d-amphetamine. Administration of haloperidol, a selective dopamine receptor blocker, completely abolished the amphetamine discrimination, whereas alpha- and beta-adrenergic receptor blockade had no effect. Apomorphine, a dopamine receptor stimulant, produced amphetamine-like responses and this was, likewise, abolished by pretreatment with haloperidol. These data suggest that dopaminergic systems mediate the interoceptive cue produced by d-amphetamine in rats, and these results are discussed in relation to possible dopamine mediation of amphetamine psychosis and paranoid schizophrenia.


Differential effects of heart rate modification training on college students, older males, and patients with ischemic heart disease.

Seventy male subjects participated in a six session study of feedback-mediated heart rate modification. Three groups of subjects were compared: (1) college students, (2) patients with ischemic heart disease, and (3) healthy males, age-matched to the patients. The groups did not differ in heart rate during rest or in response to a perceptual-motor tracking task. However, the college students produced significantly larger changes in cardiac rate than the other two groups when instructed to modify heart rate (speed or slow) and provided with exteroceptive feedback. The patients showed the poorest overall feedback performance. These differences between groups were greater for speeding than for the slowing task. Relationships were explored between feedback performance and resting heart and respiration rate, drug regime, and personality questionnaires. The results were consistent with the hypothesis that interdependence between psychological stimuli and cardiovascular events is reduced in heart disease.


Work in progress. Occurence of phospholipase A1 and A2 in human decidua.

Phospholipase A2, an enzyme which may regulate the formation of polyunsaturated fatty acids utilized for prostaglandin synthesis, was found to have significant higher activity in decidual than in myometrial tissue. The major part of phospholipase A2 in the decidua had an acid pH optimum, which indicates that most of the enzyme is stored in the lysosomes of this tissue. These findings, together with previous observations, lend further support to the view that lysosomal phospholipase A2 released within decidual cells might be a trigger of abortion and parturition.


Studies on closure of the ductus arteriosus. X. In vivo effect of prostaglandin.

The effect of prostaglandins F2alpha, E1 and of 7-oxa-13-prostynoic acid on the newborn rabbit ductus can be studied using the whole-body freezing technique. PGF2alpha and PGE1 were able to re-open the closing ductus arteriosus in adequately oxygenated animals. PGF2alpha administration was accompanied by a strong physical reaction in the rat but less in the rabbit. PGE1 had sedative effects in both animals. A prostaglandin antagonist, 7-oxa-13-prostynoic acid had no effect on normal ductal closure nor did it counteract the effects of PGF2alpha and PGE1. The role of prostaglandins in homeostasis during the fetal and newborn period may be to modify ductal tone.


Prostaglandin synthetase activity from human rheumatoid synovial tissue and its inhibition by non-steroidal anti-inflammatory drugs.

1. Prostaglandin synthetase activity was found in a microsomal fraction from human rheumatoid synovia. 2. The microsomes produced PGE2 and a small amount of PGF2 when incubated with arachidonic acid. 3. The pH optimum of the enzyme from this source was similar to that found with microsomal preparations from rabbit renal medullae and bovine seminal vesicles. 4. The enzyme was inhibited in vitro by the non-steroidal anti-inflammatory drugs flurbiprofen, indomethacin and aspirin in the same rank order of potency as prostaglandin synthetase from other tissues.


[Purification and properties of guinea pig liver ornithine transcarbamylase].

Ornithine transcarbamylase, the enzyme which catalyzes the formation of citrulline from ornithine and carbamoylphosphate, has been purified from guinea pig liver. By the procedure indicated in the present paper a 200 fold purification of the enzyme has been achieved. Using both the purified fraction and the crude extract, a parallel determination of some physicochemical properties has been carried out. The pH of maximal activity of OTC was 7.8 for both preparations. The maximal stability of the enzyme with respect of pH showed a plateau over the range of pH 7 to 9.5 in the purified fraction, whereas the crude extract exhibited a major stability which lay between pH and 10. Both OTC preparations showed similar behavior regarding thermal stability, the enzyme being still active at a 50 degrees C temperature. The values of the apparent Km's proved to be 4.4 mM for the substrate ornithine and 5 mM for carbamoylphosphate.


A comparison of some methods for determining oxygen dissociation curves of fish blood.

A brief description is given of four different methods for determining the oxygen dissociation curve of trout blood at pH 7.8 and 15 degrees C. A comparison of the results obtained indicates that the methods give similar results, especially when used by experienced workers. The relative advantages and disadvantages of the methods for determination of some O2-carrying parameters of fish blood are discussed.


[Physiopathology of hepatitis B virus infection].

Hepatitis B associated antigen (HB-Ag) may be observed in the serum in subjects either apparently healthy or exhibiting a number of disease symptoms. Its incidence among the Geneva voluntary blood donors is 0.48% with 54% exhibiting the surface antigen ad and 34% ay. While the HB-Ag positive blood donors appeared clinically healthy, minor pathology was found in the majority of them (thrombocytopenia, histological evidence of inflammatory foci, of persistent hepatitis and of chronic aggressive hepatitis). In 82 patients suffering from hepatitis B the same ad-ay type distribution of the HB-Ag has been found. In 11 out of 31 patients increased Clq binding suggests the presence of circulating complexes. Diminutions in the level of complement components also indicates participation of complement in the formation of immunocomplexes. In 2 out of 3 patients with Hb-Ag positive polyarteritis nodosa, the Clq binding test was also positive. The pathophysiologic implications of hepatitis B infection are discussed in connection with the authors and other findings. It appears that the main defense mechanism leading to elimination of the viruses within the hepatocytes lies in cell mediated immunity. Hepatitis would then represent the side reaction of this defense mechanism. Antibodies are probably useful in preventing the virus from entering the cell, but also in the course of the cell mediated defense mechanism (elimination of viral material liberated during the T-cell hepatocellular interaction). Immune complexes may be operative in certain extrahepatic manifestations such as arthralgia. Polyarteritis nodosa may result from local antibody interaction with antigen fixed within arterial walls.


[Acquired ulcero-mutilating acropathies in adults. Critical study of 150 personal cases].

The authors review critically a series of cases, followed up by the authors, of acrodynia and trophic ulcers occurring either in alcoholics (119 cases) or in diabetics (28 cases), who were also often alcoholic as well. The symptoms were similar in both groups. However, the poor nutrition was generally more market in the alcoholics. The trophic disorders were very similar, together with the sensory disorders. However, the deep sensitivity was less rarely involved in diabetics. Above all, the study of the rate of conduction of the motor nerve fibers showed axonal involvement in alcoholics and segmental demyelinisation in diabetics. The treatment was mainly dietary, together with proper hygiene and immobilisation of the foot.


Renal artery stenosis--then and now.

Diagnostic approaches evolve steadily. Selective renal arteriography and determination of renal vein renins have replaced differential clearances and translumbar aortography. The hydrated intravenous pyelogram remains helpful in assessing physiologic significance and complements both aortography and renin determinations. Except for young patients, medical treatment rather than surgical management usually is preferred.


The use of lorazepam as a soporific and for premedication.

An open study, in which 48 patients scheduled for elective surgery received either 1,25 mg or 2,5 mg of lorazepam (orally) as a soporific the night before surgery and as premedication immediately prior to surgery, revealed that lorazepam produced a good night's rest and a desirable calm immediately prior to surgery. Vital signs remained stable throughout the operative procedure, and vomiting and other reactions were virtually absent.


Bicarbonate excretion in kwashiorkor.

Children with kwashiorkor have an impairment of bicarbonate excretion which may result in the inappropriate production of acid urine in the presence of systemic alkalosis. This defect has resolved after 2 weeks of treatment.


Hepatitis B (surface) antigen in mothers and their infants.

Hepatitis B (surface) antigen (HBSAg) was found in the serum of 8 out of 4 245 women attending the antenatal clinic of the Queen Victoria Maternity Hospital Seven (0, 16%) were asymptomatic carriers of the antigen, while the eigth suffered from polyarteritis nodosa. Seven of the 8 babies born to these mothers were followed-up over periods of up to 18 months, and 1 has become a chronic carrier of HBSAg. The antigen was not detected in the colostrum (breast milk) of the 6 positive mothers tested, but it was present in amniotic fluid, placenta and cord blood of some of the mother-infant couples. The possible routes of transmission of the hepatitis B virus from mother to baby are discussed in the light of these findings. No cases of acute virus B hepatitis occurred in the latter months of pregnancy nor in the puerperium, among 4 088 women delivered at the hospital during this period.


Resistance of the Candida albicans filamentous cycle to environmental change.

The filamentous growth cycle in C. albicans was resistant to changes in environment brought about either by the serial transfer of growing cells to fresh nutrients or by sudden changes of temperature after the first h of growth. In further experiments older culture filtrates, exhausted of their ability to induce mycelial growth, were reactivated by addition of fresh nutrients or water. The data provided evidence against the existence of both a mycelial stimulatory and inhibitory compound in the growth medium. It is concluded that although the environment initially dictates what proportion of blastospores are committed to filamentation it has no further effect on the process.


Operative technique in myocardial revascularization.

This article necessarily deals exclusively with vein and artery bypass grafts. The venous autograft remains the most versatile operation and data thus far compiled verify its reliability. We advocate normotensive, normothermic perfusion and recommend the interrupted suture technique for most anastomoses. Our guidelines for IMA grafting indicate its applicability for most anterolateral wall vessels, except for unstable emergency patients and those with a large left ventricular mass. We emphasize that the technical details are far more important than the steps involved in coronary artery operations. The operative techniques described and discussed herein are deceptively simple, and direct coronary artery surgery often appears uncomplicated to the inexperienced observerer. However, one should not attempt myocardial revascularization without the benefit of high quality cinecoronary arteriograms. An organized and experienced operative team is mandatory and, above all, the procedure itself must not be an endurance contest between surgeon and patient. Expeditious revascularization produces less morbidity and better overall results.


Effects and distribution of acute fat embolism in spontaneously breathing dogs using radioactive carbon triolein.

The acute effects of a triolein infusion in dogs were secondary to the mechanical effects of this neutral fat which was distributed in the pulmonary and systemic vascular tree of all organs without inflammatory change. Hypoxia developed immediately and became progressively worse as the infusion was continued. Pulmonary hypertension developed during the fat infusion without pneumonia, congestive heart failure or pulmonary edema. There was a slow leak of 14C triolein into the systemic circulation rather than a rapid shower, and this radioactive fat was recirculated between the pulmonary and systemic vasculature. Seventy-six per cent of the 14C triolein was retained in the lungs. Terminally, the dogs had a respiratory arrest without cardiac decompensation, cardiac arrest or pulmonary edema; cerebral fat embolism in addition to severe hypoxia appears to be the cause.


Cryptorchism and related defects in dogs: epidemiologic comparisons with man.

In a study of 1266 dogs with cryptorchism from a large clinic/hospital series 8 breeds were found to be at excess risk of the defect and 3 breeds at significantly low risk. Review of the medical histories revealed that hip dysplasia, patellar dislocation, defects of the penis and prepuce, and umbilical hernia were excessively associated with cryptorchism. Testicular tumors were diagnosed 10.9 times more commonly among cryptorchid dogs. The epidemiologic features of canine cryptorchism were compared with those in man. Cryptorchid dogs could be used as models for etiologic research.


Physiological effects of hypoxia and trypan blue in 17-day chick embryos.

Seventeen-day chick embryos were divided into 5 groups and treated as follows: (1) untreated, (2) yolk-sac injected with 0.1 ml of saturated trypan blue solution solution in sterile saline, (3) saline, (4) hypoxia, i.e., 10.5% oxygen, and (5) hypoxia plus trypan blue. After 5 h  hypoxia-treated embryos had an increased mortality rate, severe hypoglycemia, reduced blood pH, elevated plasma potassium, and reduced CO2 content. Trypan blue treatment induced few deaths and few physiological imbalances. Hypoxia plus trypan blue was without synergistic effects and had effects that did not differ significantly from hypoxia alone. This lack of response of 17-day chick embryos to high doses of trypan blue may be related to a marked decline in oxygen consumption by the yolk at this age.


[The protein distribution in  the postischemic edema of dogs in reference to pathogenesis (author's transl)].

A postischemic edema in hind limbs of dogs occurred after a 5 hours tourniquet ischemia. The protein distribution of edematous liquid, serum and lymph has been investigated by immunoelectrophoretic analysis. Using different identification reactions it could be demonstrated, that edematous liquid only differs from serum because of additional appearance of fibrinogen, so corresponding qualitatively and in so far estimated quantitatively to serum plasma. In connection with the osmotic pressure factors and postischemic hyperemia, as they have been demonstrated up to now, the severe changes of permeability seem to be a main factor in pathogenesis of postischemic edemas.


[Comparison of tolerance to ischemia in human and animal myocardium during various forms of induced cardiac arrest (author's transl)].

In a total of 16 patients the tissue pH was determined on myocardium both during surgery and on isolated samples. Cardiac arrest was induced by hypothermal infusion cardioplegia and external cooling. In the isolated human myocardium section pH values were continuously determined at 15 degrees C. Parallel to these measurements samples were taken for electron microscopic examinations. In this way the pH limit under which the human myocardium cannot be revived could be visualized by additional morphologic examination. These results and those from the intrasurgical measurements with a fixed heart muscle surface probe were compared with each other and with results from animal experiments.


Modification of hybrid responsiveness in the local graft-versus-host reaction by injection of parental lymphocytes.

The local graft-versus-host reaction in F1 hybrid rats, assayed by popliteal lymph node enlargement, is specifically depressed by pretreating the host with parental lymphocytes. The conditions for demonstrating specific depression are injection of a small dose of parental lymphocytes and assay 7 days later. Pretreatment with cells from thymus and bone marrow is ineffective, as is pretreatment with purified B lymphocytes. The structures which stimulate the suppressed response of F1 hybrids are not present on parental B lymphocytes.


[Cryopreservation of hemopoietic stem cells (author's transl)].

The CFU-S potential of mouse bone marrow, the transplantation capacity of autologous and allogeneic monkey bone marrow and the CFU-C potential of human bone marrow can be cryopreserved without loss of viability. It is critical for an optimal stem cell recovery to avoid an osmotic shock after thawing. The intracellular cryoprotectives glycerol and DMSO which provide a high osmotic pressure should be removed from the thawed cells by a slow stepwise dilution procedure.


Induction of neurogenic tumors by nitrosotrialkylureas in rats.

Four nitrosotrialkylureas were each fed to groups of 15 male and 15 female Sprague-Dawley rats for 50 weeks in drinking water at the same molar concentration. Tumors of nervous origin arose after treatment with nitrosotrimethylurea (3/30), notrosotriethylurea (7/30), nitrosomethyldiethylurea (23/30), and nitrosoethyldimethylurea (8/30). A comparison of the relative stabilities of the four nitrosoureas in aqueous solution at various pH's showed no correlation with the tumorigenicities of the compounds.


[Oxygen transport in the blood of children with congenital heart defects].

In 55 children with congenital heart defects (aged 6 months and older), hematocrit, hemoglobin concentration, acid-base status, oxygen pressure, oxygen saturation, and 2,3-DPG content of erythrocytes were determined in blood taken from the vena cava superior. The data were correlated with each other as well as with parameters obtained during cardiac catheterization. Whereas an increased hematocrit was seen only at a difference in arteriovenous oxygen saturation of more than 30%, or a central venous saturation below 65%, a close correlation between 2,3-DPG concentration in erythrocytes and these parameters was obtained already in the normal range (r = 0.79, and r = 0.78, respectively). A relatively close correlation was also found between 2,3-DPG concentration and half-maximal oxygen saturation pressure (T50 value; r equals 0.73), and the T50 values and the central venous oxygen saturation (r equals 0.61), respectively. Because of the shift to the right of the O2-binding curve the functional oxygen transport capacity was increased by an average 15% in children with acyanotic heart defects (mean T50 value of 31.6 mm Hg), and by 40% in children with cyanotic heart defects (mean T50 value of 34.6 mm Hg), as compared to healthy children (mean T50 value of 28.1 mm Hg). A marked influence on the position of the O2-binding curve and hence on oxygen release of the blood in the periphery is therefore exerted by the 2,3-DPG concentration, whose effect was about twice that of the Bohr effect in the pH range measured.


[Identification of a group A arbovirus isolated in the Far East].

Strains Nos. 296 and 260 isolated from Aedes vexans and Culex pipiens mosquitoes in the USSR Far East in 1971 and 1973, respectively, were identified. The size of the viruses was found to be about 50 nm. Both strains were pathogenic for 2--3-day-old and 3--4-week-old mice by the intracerebral, subcutaneous and intraperitoneal routes, agglutinated goose red blood cells at the optimal pH 6.0. The strains were identical to each other and by their antigenic structure were classified as Semliki Forest virus.


[Effect of potassium-magnesium aspartate on hemodynamics and myocardial metabolism of coronary disease patient during beta receptor stimulation].

2 series of patients with angiographically proven coronary artery disease were studied under the influence of an infusion of a beta-receptor stimulating drug (heptaminole) and of kalium-magnesium-aspartate (KMA) in high (series: I: 1000 mg of heptaminole in 25 min) and low doses (series II: 200 mg of heptaminole in 25 min) of beta-receptor stimulation. The results confirm the finding that high dose beta-receptor stimulation in patients with severe coronary artery disease results in failure of the contractile mechanism of the heart with the beta-receptor angina. However, administration of KMA simultaneously with the beta-receptor stimulator seems to be able to prevent the expected decrease of lactate extraction and results in no change in lactate AVD in series I and even in an 11% increase in lactate AVD in series II. Experimental data concerning the biochemical effects of KMA suggest that its ability to provide adequate amounts of oxaloacetone and hence to improve the function of the bricarbonic acid cycle seems to be of special importance. For this action to become relevant in coronary artery disease a situation would have to be postulated, in which an additional limiting factor of oxydative metabolism would be an inadequate supply of Krebs-cycle intermediates.


The effect of an antiserum to plastocyanin on various chloroplast preparations.

A monospecific antiserum to tobacco plastocyanin agglutinates stroma-free swellable chloroplasts from wild type tobacco, (Nicotiana tobacum var. John William's Broadleaf) from the tobacco aurea mutant Su/su2, (Nicotiana tabacum var. Su/su2) from Antirrhinum majus and spinach (Spinacia oleracea). In this condition the antiserum inhibits linear photosynthetic electron flow in tobacco and spinach chloroplasts. This inhibition of electron transport as well as the agglutination are not observed if the chloroplasts have been sonicated prior to antiserum addition. This is due to the fact that plastocyanin is removed by ultasonication. The antiserum stimulates a number of photophosphorylation reactions in tobacco chloroplasts. This stimulation is always larger in the aurea mutant chloroplasts from yellow leaf patches of a variegated tobacco mutant (N. tabacum, var. NC 95) than in the green type chloroplasts. The stimulation appears to be a consequence of the inhibition of linear electron transport. The antiserum does not affect PMS-mediated cyclic photophosphorylation in tobacco chloroplasts from the wild type whereas the reaction appears stimulated in the tobacco mutant chloroplasts. However, menadione-mediated cyclic photophosphorylation is inhibited upon addition of the antiserum. The same is true for noncyclic photophosphorylation coupled to electron transport in the aerobic system diaminodurene/ascorbate leads to methylviologen in the presence of N-tetraphenyl-p-phenylenediamine in spinach chlorplasts. If the lamellar system of Antirrhinum and spinach has lost is swellability neither agglutination nor inhibition of electron transport is observed. However, also in this state antibodies to plastocyanin are specifically adsorbed onto the surface to the thylakoid membrane. This state which is characterized by a morphologically well preserved lamellar system is realized in chloroplast preparations from Antirrhinum and spinach and is termed stroma-freed chloroplasts. In both states of the molecular structure of the thylakoid membrane, plastocyanin is located in the outer surface of the thylakoid. However, it cannot be excluded that functioning plastocyanin is also located in the interior of the thylakoid membrane.


[The importance of the substrate for the induction of tyrosine-alpha-ketoglutarate-transaminase in RLC-cells (author's transl)].

1. Dexamethasone phosphate causes approximately a threefold increase of the tyrosine-alpha-ketoglutarate transaminase in the culture of RLC cells. 2. The induction of the enzyme depends on the presence of L-tyrosine. Omission of L-leucine or L-tryptophan, respectively, has no effect. 3. Omission of L-tyrosine influences the activity of the lactate dehydrogenase and malate dehydrogenase not at all and that of the glucose-6-phosphate-dehydrogenase only to a small extent. 4. In the absense of L-tyrosine an superinduction takes also place by actinomycin.


[Investigations of the influence of pH on the oxidative degradation of glucose by E. coli (biochemical glucose demand) (author's transl)].

The oxidative degradation of glucose by E. coli was studied in the Warburg manometer. The pH of the medium was established in these studies at values between 5.5 and 8.0. Analysis of the reaction kinetics by plotting time/consumption curves shows that three consecutive reactions can be distinguished as the substrate is eliminated from the medium: An adaptation phase which is generally relatively brief is followed by two reactions, of which the first proceeds more rapidly or more slowly than reaction 3, depending on pH. The important feature in reactions 1 and 2 is that the oxygen demand is evidently independent of the initial concentration of substrate. In spite of these differences, if the reaction is regarded as a whole, there are no relations involving significant dependence on pH of medium. Neither the substrate-specific biochemical oxygen demand nor the reaction time necessary for catabolism show statistically significant dependence within the range of pH examined. It can be assumed therefore that E. coli possesses a regulation mechanism which compensates for unfavourable environmental conditions. The division of substrate catabolism into constituent reactions, combined with a change in concentration of pacemaker enzyme and a "competitive inhibition" may be of significance in this regulations.


Acid-base relationship between mother and fetus in gestosis (pre-eclampsia) and in pregnant women with a labile blood pressure.

Simultaneous blood microsamples were taken from the maternal ear and uterine cervix and the fetus of healthy pregnant women, those with labile hypertension, and those with severe gestosis (pre-eclampsia). The po2, pH, BE and pco2 were studied. The fetuses showed no signs of asphyxia. The differences in BE values between the women withe gestosis and their fetuses were significantly greater than in the cases of healthy pregnancy. No differences were seen between healthy and gestotic gravida groups in po2, pH and pco2 values. This favours the opinion that in gestosis of the mother the fetus has a tendency to metabolic acidosis, which apparently places it in a poorer position than the fetuses of healthy mothers, should acute asphyxia occur. At the time of study the po2 of the fetuses of gravidas with a labile blood pressure was lower than that of fetuses of healthy gravidas.


Respiration and acid-base balance of blood after diffuse experimental brain injury.

Diffuse brain injury in rabbits was caused by injecting olive oil and saline into one internal carotid artery. In this report, the fourth of a series, the effects of this experimental brain injury on respiration and acid-base balance of blood are analyzed. The animals that withstood the injury best were those that had a lower pre-traumatic pCO2; the animals that suffered a rise in intracranial pressure and succumbed to the injury quickly did so in spite of pronounced hyperventilation after the injury. Arterial pCO2 immediately before the injury was the only significant prognostic factor in this analysis. Respiratory rate only dropped immediately before respiratory arrest and death. The findings concerning pCO2 tally with results after experimental ligation of a cerebral artery, but less so with results after other types of experimental brain injury. This emphasizes again that conclusions drawn from one type of brain injury must not be extrapolated to other types.


Sympatho-adrenal development in perinatally addicted rats.

Chronic morphine administration in adult rats results in neurogenic secretion of adrenal catecholamines and compensatory increases in basal catecholamine levels, in activities of catecholamine biosynthetic enzymes and in the number of storage vesicles in the tissue. Perinatally addicted developing rats demonstrated changes completely different from those seen in adults; catecholamine levels and dopamine beta-hydroxylase activity were reduced compared to controlscsnnofinduction of tyrosine hydroxylase was observed. The time course of adrenomedullary maturation was delayed throuth the first 10-20 days of age, with reduced numbers of storage vesicles and larger proportions of partially filled vesicles. On exposure to morphine, continued until weaning, perinatally addicted rats did not display any of the changes in catecholamine synthesis or uptake seen in adult rats. The differences between adults and developing rats can be partly explained by the absence of functional innervation of the neonatal adrenal medulla.


Pathogen transmission in relation to feeding and digestion by haematophagous Arthropods.

The blood feeding habit, especially among opportunist feeders such as tabanids and Stomoxys is known to result in transmission of diseases for which the vectors are not the obligate or alternate hosts. Thus, mechanical transmission of trypanosomes such as T. vivax can occur in cattle herds outside tsetse fly areas where tabanids are actively feeding. In the case of Yaws, mechanical transmission of the spirochaetes by eye flies (Hippelates pallipes) in the West Indies is thought to be most likely. The spirochaetes remain motile in the pharynx and oesophageal diverticula for several hours but are apparently immobilised in the midgut (Kumm & Turner, 1936). There is apparently no development ofspirochaetes in the fly. They have been shown to pass through houseflies, but in mechanical transmission, biochemical transformation or adaptation of the pathogen is not implied. Virus transmission is common among arthropods and transovarial transmission to succeeding generations is frequent in mites and ticks. Although Yellow Fever virus is not transovarially transmitted by its vector Aedes aegypti, the mosquito only becomes infective some time after ingesting an infected blood meal (Chandler, 1955). Thus, metabolic or biochemical changes or adaptations in the virus or in the vector are in some way implicated, as they must also be in transovarially transmitted viruses. However, the causal relationships between virus infectivity and vector physiology are poorly understood. As with virus infections, those disease organisms possessing a cyclical host/vector relationship will possess a variable infectivity potential which is not necessarily related to the abundance of any of the organisms in the cycle. Clearly, feeding behavior and host preferences of the vector are important in determining the rate and extent of disease transmission, and such parameters can be quantified in epidemiological studies. However, a complete understanding of the factors concerned in cyclical disease transmission also depends on a knowledge of the physiology of the organisms involved, and particularly of the interdependence of their physiologies. The subject is vast, and it is proposed to illustrate the problems involved and the progress made, by reference largely to trypanosome transmission by tsetse flies (Glossina spp.).


Skin-piercing blood-sucking moths I: ecological and ethological studies on Calpe eustrigata (Lepid., noctuidae).

The Noctuid Calpe [Calyptral] eustrigata Hmps. was reported as a skin-piercing blood-sucking moth for the first time in Malaya (Bänziger, 1968) and is so far the only lepidopteran proved to suck blood by means of a piercing act. A few field observations and the description of the piercing behaviour of caged moths were given. Apart from a taxonomic study of the genus Calpe (Berio, 1956), a single record (Büttiker, 1969) and some notes on the moth's proboscis and possible evolutionary pathway (Bänziger, 1970, 1971, 1972) to our knowledge no other data have been published on the moth after its description as a new species (Hampson, 1926). The life cycle is completely unknown. From the scanty museum specimens available, it appears that the species inhabits South and Southeast Asia. A closely related, though less rare species, the fruit-piercing C. thalictri Bkh., has been used for a detailed study of the piercing mechanism likely to be adopted by Calpe (Bänziger, 1970); the feeding turned out to be as unusual as the feeding habits. Little or nothing is known about other Calpe species. C. eustrigata is not the only adult lepidopterous parasite of mammals. Lachryphagous ("eye-frequenting") moths feed as "marginal" parasites upon eye-secretions of ungulates, elephants and occasionally man (Shannon, 1928; Reid, 1954; Büttiker, 1964, 1967; Bänziger, 1966). Arcyophora species and the eulachryphagous Noctuid Lobocraspis graseifusa Hmps. which apparently feeds exclusively upon eye discharges, are suspected as vectors of eye diseases (Guilbride et al., 1959, Büttiker, 1964; Bänziger, 1972). While no lachryphagous moth is able to suck blood by a piercing act, there are a number of facultative lachryphagous moths which lick up the blood freely present at wounds, or that excreted anally by mosquitoes (Bänziger, 1969, 1972). Because of the scientific interest in C. eustrigata, research has been carried out to investigate different biological aspects of the species in Malaysia, Thailand. Laos and Indonesia (May 1971-May 1973). The first account presented here will be continued with a paper (in prep.) on the piercing mechanism and soon, it is hoped, with more information on the physiology, life cycle and medical importance of the moth.


Haemolytic activity in the blood clot of Aedes aegypti.

In the present study it was demonstrated that mosquito blood clots contain a haemolytic principle which achieves haemolysis of washed erythrocytes in an isotonic medium. Proteinases are thought to play a role in this process. No final proof could be given for the existence of phospholipase activity although some results suggest the presence of this group of enzymes.


Effects of carbon dioxide anaesthetic on Glossina.

Exposure of 2 day old virgin females of Glossina fuscipes fuscipes, G. pallidipes, G. brevipalpis, and G. morsitans centralis to carbon dioxide anaesthesia for 15 sec has the effect of suppressing their subsequent insemination frequency. This insemination-inhibitory effect of the gas is more pronounced in G. f. fuscipes and G. pallidipes than in G. brevipalpis and G. m. centralis. In G.f. fuscipes the adverse effect on insemination persists, albeit to a lesser degree, at least up to 72 hr. Carbon dioxide anaesthesia also reduces the insemination capability of G.f. fuscipes males; this effect, however, is less marked than in females. Exposure of wild non-teneral G.f. fuscipes, G. pallidipes, G. brevipalpis, and 3 day old G.m. centralis to the gas for 30 min causes some mortality during anaesthesia, which increases with increasing exposure period. G. m. centralis is most tolerant to the lethal effect of the gas within the 10-90 min exposure periods. Wild females of G.f. fuscipes and G. pallidipes seem to be more sensitive to carbon dioxide in this report than males. In view of these adverse effects produced by carbon dioxide anaesthesia, its use on tsetse is not to be recommended.


Comparative systemic and regional hemodynamic effects of dopamine and dobutamine.

Dopamine and dobutamine are sympathomimetic amines with divergent peripheral vascular actions. The renal, mesenteric, and femoral vascular and total systemic hemodynamic effects of these amines were compared in pentobarbital-anesthetized dogs. Both agents increased myocardial contractility. Infusion rates of dopamine greater than 5 mug per kilogram per minute increased mean aortic pressure. Dobutamine increased mean aortic pressure. Dobutamine in creased the systolic pressure but did not alter mean aortic pressure. Dobutamine increased cardiac output more than dopamine. Dopamine infusions up to 10 mug per kilogram per minute increased renal and mesenteric blood flow and decreased vascular resistance. Dobutamine had negligible effects on the renal or mesenteric blood flow but produced dose-related increases in femoral blood flow. Dopamine did not significantly alter femoral hemodynamics. These results more clearly define the systemic and regional vascular hemodynamic effects of these agents.


Paroxysmal hypertension in aortitis syndrome.

Three patients with aortitis syndrome ehibited paroxysmal hypertension which seemed to result from baroreceptor dysfunction. All of the patients had signs of active inflammation of aortitis syndrome and stenotic carotid and subclavian arteries. During the attacks, the blood pressure rose to at least 230 mm. Hg systolic and the heart rate exceeded 100. However, with prolonged administration of steroid hormones, the attacks ceased. In two patients with dilated thoracic aortas and aortic regurgitation, the attacks of paroxysmal hypertension occurred without apparent precipitating factors and were followed by anginal pain with marked ST depression. The sympathicotonic state resulting from the disturbance of the baroreceptors was considered to be responsible for the attacks. In another patient, the attacks occurred in the course of treatment with a steroid hormone and were provoked only by voluntary micturition. This post-micturition hypertension was presumed to be an expression of abnormal overshooting following a fall in blood pressure after voiding.


Serum gamma-glutamyl transpeptidase. Evaluation in screening of hospitalized patients.

Evaluation in screening of hospitalized patients. Am J Clin Pathol 64: 311-314, 1975. The specificity of the serum gamma-glutamyl transpepidase (GGT) was evaluated by its determination in 1,040 unselected adult inpatients. GGT was elevated in 139 (13.4%) patients, but was only rarely elevated in the absence of elevation of other enzymes in the routine chemistry profile. Of the elevations, 32.4% occurred in patients with primary hepatobiliary disease. An elevated serum GGT is a strong indicator of hepatobiliary dysfunction. However, proper interpretation of a serum GGT elevation requires correlation with clinical data and other tests.