Optimization of high-dose methotrexate with leucovorin rescue therapy in the L1210 leukemia and sarcoma 180 murine tumor models. An analysis of dose and schedule dependence of calcium leucovorin rescue during high-dose methotrexate therapy of ascitic forms of l1210 leukemia and Sarcoma 180 is reported. Schedules with very delayed "low-dose" leucovorin rescue following lethal doses of methotrexate were highly effective in preventing toxicity and achieved a pronounced antitumor effect in both ascites tumor models. Best results were obtained on a schedule of methotrexate (400 mg/kg s.c.) followed 16 to 20 hr later by calcium leucovorin (12 mg/kg s.c.) given once every 2 hr for a total of 5 doses. Progressive increases in the calcium leucovorin dosage on any schedule reduced both toxicity and the antitumor effect of methotrexate in each model. Following a single course of therapy, essentially no toxicity was observed, and the antitumor effects were 2-fold (L1210 leukemia) and 4-fold (Sarcoma 180) greater than a single, maximally tolerated dose (24/kg s.c.) methotrexate alone. An increase in the methotrexate dosage to 800 mg/kg s.c. with or without an increase in calcium leucovorin dosages on the same schedule did not appreciably increase the antitumor effect observed. Two courses of high-dose methotrexate (400 mg/kg s.c.) with leucovorin rescue (24 mg/kg s.c. 16, 20, and 24 hr after drug) given with an 8-day interval between courses doubled the total antitumor effect in each model with no substantial increase in toxicity and gave long-term survivors with Sarcoma 180. The results, overall, are in close agreement with prior prediction for schedule and dose dependence made on the basis of related pharmacokinetic and biochemical studies in murine tumor models reported from this laboratory.


Pharmacokinetics of high-dose methotrexate with citrovorum factor rescue. The methotrexate (MTX)-plasma concentrations of 172 high-dose infusions over the range of 50-200 mg/kg were measured over the 72-hour period following the beginning of infusion. Pharmacokinetic analysis shows that a biexponential function adequately describes the plasma decay for all doses. The distribution of plasma clearances over the patient population at a given dose has been characterized by a biexponential clearance function and associated time-dependent variance. It is found that when each of the plasma clearance functions are scaled by their respective dose, the 1 SD bands about the resulting unit dose curves overlap throughout their time ranges and are therefore insignificantly different from one another. Thus, the plasma clearance over the 50-200-mg/kg range may be represented by a single dose-scalable biexponential model with half-lives of 1.8 +/- 0.1 and 8.4 +/- 0.5 hours. For a given maximum allowable plasma-MTX level (eg, 10(-5) M at 24 hours), the variance of the clearance distribution is shown to predict the expected fraction of patients who will require intensified rescue. Urinary clearance has been determined at 104 +/- 8 ml/minute over the dose range of 50-300 mg/kg and only 60% of the MTX was excreted in the urine by 72 hours.


Ipsilateral diminution of CRF-granules after unilateral hypothalamic lesions. Axons terminating in the outer layer of the median eminence of rats contain light microscopically visible granules. The granules are assumed to represent a corticotropin-releasing factor and, therefore, are called CRF-granules. To find out whether neurons containing CRF-granules originate and run together with the neurons of the hypothalamus-neural lobe system (HNS), the effect of unilateral lesions in the HNS on the amount and distribution of CRF-granules was studied in bilaterally adrenalectomized rats. HNS lesions prevented the adrenalectomy-induced increase in CRF-granules on the side of the lesion. Lesions outside the HNS or sham lesions did not influence the amount and distribution of the granules. The findings suggest that CRF-granules are located in terminals of neurons whose perikarya are situated in magnocellular hypothalamic nuclei. It can also be concluded that the axons of these neurons run within the HNS and do not decussate.


Isolation of an arenavirus closely related to Lassa virus from Mastomys natalensis in south-east Africa. Five unidentified virus strains were recovered from the multimammate mouse ,Mastomys natalensis, during the course of studies on arbovirus infections in Mozambique. These agents were found to be morphologically and immunologically related to Lassa virus. Four of 19 sera from Mastomys captured in the study area had antibodies to both Lassa virus and one of the unidentified strains. Although not definitive, the differences noted in results of complement fixation and indirect immunofluorescent tests suggest that these viruses from south-east Africa are not identical to West African Lassa virus.


Nine-year study of WHO virus reports on fatal viral infections. In 1963, the World Health Organization established a system for the collection and distribution of information on viruses. The present study is based on 2737 reports of fatal viral infections received from laboratories in 39 out of a total of 47 countries participating in the scheme. In the industrially developed countries, from which most of the reports came, more than one-third of the total number of deaths were associated with influenza A virus, while in the developing countries, the enteroviruses, and in particular poliovirus, came high on the list.In general, a steady increase in the number of reports received by WHO has been noted, especially during the last three years. The greatest variations in the yearly number of reports were seen in those concerning influenza A virus, and coincided with the clinical and epidemiological patterns observed since the advent of the A/Hong Kong/68 strain.In children, death was most frequently associated with enteroviruses, and in adults, with influenza A virus. However, some of the viruses, and in particular herpesvirus, were reported in both children and adults.Overall, respiratory diseases were the most frequent cause of death, mainly because of influenza A virus infection; next most frequent were herpesvirus infections, especially of the central nervous system, and particularly among young adults. The findings in this study confirm that it is the most serious central nervous system viral infection in the developed world.In contrast to the above, the enteroviruses are still the most important killers in the developing world and the cases occur among infants and young children. Poliovirus, in particular type 1, is still the most prevalent.


Rickettsioses studies. 3. Natural foci of rickettsioses in south Bohemia. Antibodies against Coxiella burnetii and against rickettsiae of the spotted fever group were found in human sera and in sera from domestic and wild animals collected in south Bohemia. Spotted fever group rickettsiae were also discovered in the tick Ixodes ricinus. These results indicate the presence of both types of rickettsiae in this part of Czechoslovakia. As no epizootics or epidemics of Q fever have as yet been reported in the area, it can be assumed that C. burnetii occurs in the latent state. The occurrence of spotted fever group rickettsiae is probably endemic among I. ricinus ticks and among small and larger wild mammals.


The presentation and use of height and weight data for comparing the nutritional status of groups of children under the age of 10 years. This paper presents recommendations for the analysis and presentation of height and weight data from surveillance or surveys involving nutrition and anthropometry in young children up to the age of 10 years. These recommendations are only for the analysis of data collected on a cross-sectional basis. The basic indices recommended are height for age and weight for height, each considered either in terms of centiles or in a cross-classification scheme using standard deviation scores. It is hoped that these methods of analysis and presentation will prove widely acceptable, so that international comparisons will be made easier.


A synopsis of the nematodes occurring in blackflies (Diptera: Simuliidae). Larvae, pupae, and adult blackflies (Simuliidae) are capable of harbouring several groups of nematodes. Multiple parasitism involving nematodes of the same or different species, or various developmental stages of the same nematode may also occur. Thus, blackflies can serve as paratenic, intermediate, or definitive hosts of nematodes. The present study reviews the literature pertaining to the association between nematodes and Simuliidae and provides a key to various groups of nematodes found in blackflies. Emphasis is placed on the commoner filarial and mermithid nematodes, but several other unusual and rare roundworm parasites are also discussed.


The morphology of cirrhosis: definition, nomenclature, and classification. This article provides guidelines on the definition, nomenclature, and classification of cirrhosis, hepatic fibrosis, and chronic hepatitis. Cirrhosis is considered according to its etiology and morphological characteristics, these being complementary rather than alternative.


Study of the plate agglutination test with rose bengal antigen for the diagnosis of human brucellosis. This study presents the results of a number of serological tests, in particular the plate agglutination test using acid antigen stained with rose bengal, in the examination of 440 human sera for brucellosis. In addition, the sera were examined for the presence of specific antibodies of various classes (IgM and IgG). These investigations showed the rose bengal plate agglutination test to be highly specific and sensitive as a rapid method for the diagnosis of human brucellosis.


Methods for the detection of haemophilia carriers: a memorandum. This Memorandum discusses the problems and techniques involved in the detection of carriers of haemophilia A (blood coagulation factor VIII deficiency) and haemophilia B (factor IX deficiency), particularly with a view to its application to genetic counselling. Apart from the personal suffering caused by haemophilia, the proper treatment of haemophiliacs places a great strain on the blood transfusion services, and it is therefore important that potential carriers should have precise information about the consequences of their having children.The Memorandum classifies the types of carrier and describes the laboratory methods used for the assessment of coagulant activity and antigen concentration in blood. Particular emphasis is laid on the establishment of international, national, and laboratory (working) standards for factors VIII and IX and their calibration in international units (IU). This is followed by a detailed account of the statistical analysis of pedigree and laboratory data, which leads to an assessment of the likelihood that a particular person will transmit the haemophilia gene to her children. Finally, the problems and responsibilities involved in genetic counselling are considered.


Ecological studies of Bulinus rohlfsi, the intermediate host of Schistosoma haematobium in the Volta Lake. In the present ecological study of cercarial transmission of Schistosoma haematobium in the Volta Lake, Ghana, habitat observations and sampling of Bulinus truncatus rohlfsi were conducted within a 60-km stretch of shoreline. Observations revealed that human water contact sites in each village undergo constant changes in shape and vegetation. Snail sampling surveys in water contact sites were carried out monthly (for 27 months) in 8 villages using newly designed palm-leaf traps, and in 8 additional villages (for 16 months) using a modification of Olivier & Sneidermann's man-time method. Results to date confirm the finding by Chu & Vanderburg that cercarial transmission in the lake takes place almost exclusively within water contact sites. Additional results indicate that even within individual water contact sites this transmission is focal, most infected snails being found very close to the shoreline. Transmission also varies significantly according to shape, vegetation, and geographical location of the water contact sites, and is distinctly seasonal in most villages. These findings lead us to conclude that control of cercarial transmission in the Volta Lake is both attainable and feasible with existing methods.


The microfilarial load in the anterior segment of the eye. A parameter of intensity of onchocerciasis. The presence of microfilariae of Onchocerca volvulus in the eye is associated with an increased risk of deterioration of existing eye lesions. An opthalmological and parasitological examination of 630 persons was carried out in a hyperendemic focus of onchocerciasis in northern Togo. The prevalence of microfilariae increased in the cornea as well as the anterior chamber up to the age of 40-50 years, then decreased. The prevalence of onchocercal punctate keratitis, on the other hand, showed a peak for the age group 10-20 years. In two-thirds of the cases microfilariae were present in the anterior chamber as well as in the cornea. The relative distribution of microfilariae between the anterior chamber and the cornea did not change with the development of severe anterior lesions but in cases with severe posterior lesions relatively more microfilariae were found in the anterior chamber than in the cornea. In all cases of severe ocular lesions the numbers of microfilariae both in the anterior chamber and in the cornea were increased. The average number of microfilariae in the eye can be used as a parameter to enumerate the severity of ocular onchocerciasis.


The upper tolerance limits of nonepidemic daily morbidity for influenza and other acute respiratory diseases in the epidemic season. The start of an influenza epidemic may be detected by comparing actual daily morbidity from influenza and other acute respiratory infections with the upper tolerance limits of this morbidity for nonepidemic years. A method of constructing such tolerance limits for the autumn-winter season, when the probability of an influenza epidemic is greatest, is described. The results are illustrated by data relating to Moscow.


Treatment of nonunion with constant direct current. Laboratory experiments show the following relationships between electricity and bone: (1) stressed bone exhibits electronegativity in areas of compression, (2) living, nonstressed bone exhibits electronegativity in areas of bone growth and healing, and (3) the application of low magnitude direct current to bone induces osteogenesis at the negative electrode or cathode. Based on the above principles, a clinical study was performed in which 10-20 microamperes of constant direct current was used in treating nonunion in 57 patients. The results suggest that specific electrical parameters are required for successful osteogenic stimulation in patients. When these electrical parameters are met, a successful healing rate of 70 per cent can be achieved in treating nonunion with direct current. As experience is gained with this new technique in the treatment of nonunion, the results should improve even further. Basic studies exploring the mechanism(s) whereby electricity induces osteogenesis are opening new vistas into our understanding of bone growth and repair. The extension of these basic studies has far-reaching clinical implications.


Electrical stimulation of human fracture healing by means of a slow pulsating, asymmetrical direct current. Twenty-eight tibial fractures were treated with external fixation by means of a Hoffmann apparatus. Through two electrode-screws in the Hoffmann apparatus a slowly pulsating, asymmetrical direct current was applied to the fracture site in each patient. The stimulated patients experienced a 30 per cent acceleration in healing as determined by mechanically stressing the Hoffmann apparatus used for immobilization of the fracture.


Treatment of congenital pseudarthrosis of the tibia with direct current. Bone possesses a bioelectric property that is important in maintaining its structural and architectural integrity. In vivo experiments demonstrate that bone formation can be accelerated by the application of direct current. We hypothesize that bone formation occurs through an electrochemical rather than an electromechanical effect. Two cases of congenital pseudarthrosis of the tibia treated by direct current stimulation are presented. A bone graft may be added to enhance bony union in conjunction with direct current. The implications of this work are that there is need for further fundamental studies including ultrastructural observations.


Clinical experiences with low intensity direct current stimulation of bone growth. Low intensity direct current stimulation of bone growth involves the continuous application of cathodic currents in the nanoampere range. The technique has been applied to 13 patients with a variety of non-unions and pseudarthroses with a success rate of 77 per cent. Preliminary data indicate that a range of total energy, from 0.6 to 2.5 Joules, is maximally effective. The technique has been combined with anodic control of local bacterial infection with promising results. Both the osteogenic stimulation and the bacterial suppression techniques as described in this paper, appear to be safe and effective.


The electrical induction of callus formation and external skeletal fixation using methyl methacrylate for delayed union of open tibial fracture with segmental loss. A case of delayed union of an open tibial fracture with segmental loss is presented in which electricity was applied to the bone defect through two screws that were connected to a methy methacrylate skeletal fixation device. The fracture developed electrically induced callus formation around the cathode, callus extended to the anode, and solid bony union ensued. External skeletal fixation using methyl methacrylate is convenient and is a suitable adjunct to electrical stimulation of fracture healing.


The electrical enhancement of periosteal proliferation in normal and delayed fracture healing. Normal fracture healing in long bones is a poorly defined process which to a great extent is dependent on periosteal response to injury. When this normally effective mechanism fails, electrical enhancement may prove an effective adjunct and less morbid solution than standard bone grafting procedures for periosteal reactivation.


T and B lymphocytes in pleural effusions. To determine the diagnostic significance of the determination of T and B lymphocytes in pleural fluid, we studied these cells in peripheral blood and in pleural fluid by means of surface markers. Our study comprised 30 patients suffering from pulmonary tuberculosis, pulmonary malignancy, connective tissue disease, nonspecific pleurisy or congestive cardiac failure. In pulmonary tuberculosis, both the percentage and absolute numbers of T lymphocytes in pleural fluid were significantly higher than in peripheral blood. In patients with pulmonary tuberculosis, pulmonary malignancy or nonspecific pleuritis, the percentages and absolute numbers of B lymphocytes were significantly lower in pleural fluid than in peripheral blood. Considered together with other clinical and laboratory indices, these determinations may aid in the differential diagnosis of pleurisy of various etiology.


Effect of erabutoxin B on acetylcholine release and root potentials of the frog spinal cord. Erabutoxin b (ETX), a sea snake neurotoxin with neuromuscular blocking properties, slightly reduced resting ACh release from the isolated fron spinal cord. ETX did not affect ACh release evoked by antidromic stimulation of ventral roots but reduced the ventral-dorsal root potential and prolonged the dorsal-ventral root potential. The latter effect was associated with a reduction in the orthodromically evoked ACh release. It is suggested that ETX did not affect the presynaptic terminals of the motor axon collaterals and that its effects occurred at postsynaptic sites.


Bacterial lipopolysaccharide (LPS) enhances concanavalin A reactivity of thymocytes from the low-LPS-responder mouse strain C3H/Hej. The capacity of LPS to enhance Con A reactivity of thymocytes was studied comparatively in the low-LPS-responder C3H/Hej mice and the high-LPS-responder CBA mice. The extent of synergism LPS + Con A was found similar in both strains.


A differential effect of L-serine on the incorporation of 3H-deoxycytidine and 3H-thymidine into DNA of rat thymocytes. The addition of L-serine to short-term cultures of rat thymocytes stimulated the incorporation of 3H-deoxycytidine into DNA, but simultaneously depressed the incorporation of 3H-thymidine into DNA.


On the function of cilia in the female reproductive tract. A recently discovered syndrome is characterized by congenital immotility of the cilia. It consists of chronic infections in the respiratory system, male infertility, and, in about one-half of the cases, situs inversus. The syndrome thus includes Kartagener's syndrome. The syndrome provides a unique opportunity to gain insight into the role of the cilia in the human body. Five women evidently suffering from this syndrome were examined. They had no gynecologic disorders. Three of the five women had tried to become pregnant and two have suceeded. A review of the literature indicates that men with Kartagener's syndrome are usually infertile, whereas the women are not. This fact and the data presented herein constitute strong evidence that ciliary motility is not essential for female fertility. More conclusive proof could be obtained if any of the affected women would consent to ultrastructural investigation of the oviductal cilia.


[Partially common antigenicity of macrophages, epitheloid cells and foreign body giant cells. Experimental studies on rats]. By means of antimacrophage sera it is possible to demonstrate partially common antigenicity of monocytes with peritoneal macrophages, reticulum cells capable of phagocytosis, mast cells and Kupper's cells. The authors continued these studies important for the explantation of cytogenetical interrelations using a special method on epitheloid and giant cells of rats. The experiments aimed for the detection of possible partially common antigenicity with the above mentioned monocytes/macrophages system.


[Resting potential and action potential of an individual frog muscle fiber during reciprocal inhibition]. In single muscle fibres of the frog m. tibialis anticus longus resting membrane potential and parameters of the action potential were studied in situ during rest and during the resiprocal inhibition of its spinal center. Development of the reciprocal inhibition increased the resting membrane potential, the amplitude of the action potential, but decreased the time course and latency of the action potential. The changes in functional properties of single muscle fibres seem to occur as the result of deprovation of central influences due to the reciprocal inhibition.


Photocontact dermatitis from P-aminobenzoic acid. A 6-year-old girl with xeroderma pigmentosum was contact and photocontact sensitized to PABA which had been used as a sunscreening agent. The activating wavelengths for photocontact dermatitis were in long-wave ultraviolet light. The experimental photocontact sensitization was not induced in guinea pigs. Although PABA is the most effective and harmless sunscreening agent for normal skin, it could induce photocontact sensitivity especially in diseased or damaged skin.


Effect of somatostatin on platelet aggregation and plasma factor VIII level in normal man. As impairment in coagulation and platelet function has been reported following acute administration of somatostatin, a reevaluation of the effects of the cyclic and linear form of the peptide was undertaken. In vitro somatostatin had no effect by itself on platelet aggregation and no effect on ADP- or ristocetin-induced aggregation. In vivo ten healthy men infused with cyclic or linear somatostatin (loading dose of 250 microgram and three hour-infusion with 1,500 microgram) and five control subjects were investigated during the infusion and for three hours after the end of the infusion. With this dose, sufficient in man for maintaining plasma growth hormone and insulin at fasting levels under arginine stimulation, no abnormalities in platelet count, in ADP-induced platelet aggregation and in plasma VIII von Willebrand factor, factor VIII procoagulant activity and factor VIII related antigen levels were observed.


The differentiation of T lymphocytes. IV. Net increases in low theta cells, maintenance of biological activity and death of high theta cells during short-term culture of mouse thymocytes. Dissociated mouse thymocytes were cultured under optimized conditions in Marbrook vessels in order to follow some aspects of T-cell differentiation. Under particular conditions it was possible to obtain a 50% net increase in the total number of the peripheral T-cell like, minor low theta thymocyte subpopulation over the first day of culture, although this increase was lost with further incubation. The increase arose from proliferation of preexistent low theta cells,and not from transformation of the major, high theta population. Under all conditions the high theta cells died rapidly in culture. These results are in accordance with the view that the high theta and low theta thymocytes represent separate streams of T-cell development. There was a striking increase in responsiveness to phytohemagglutinin and concanavalin A after culture of thymocytes under these conditions. However, this was ascribed, not to the development of new immunocompetent T cells, but to selective cell death in the cultures eliminating some inhibitory elements. No increase in progenitors of cytotoxic lymphocytes was obtained. The results demonstrate some potential artifacts in assessing the immunocompetence of cultured thymocytes.


Changes in the cellular membrane surface coat of lymphocytes and thymocytes after incubation in vitro with cystein as revealed with electronmicroscopy. Changes in the cellular membrane surface coat of lymphocytes and thymocytes after incubation with cystein in vitro were revealed with electronmicroscope, while performing the reaction with Ruthenium Red and Concanavaline A. Lymphocytes and thymocytes not incubated with cystein to which reaction with Ruthenium red and Cocanavaline A was applied have shown a well developed and preserved surface coat of the cellular membrane. Contrary to this finding when lymphocytes and thymocytes were incubated with cystein and thereafter treated with Ruthenium Red and Concanavaline A no reaction product on the surface of the cellular membrane was observed. The experimental results could indicate on the influence of cystein on the glycoside bonds.


[Pharmacological studies on carprofen, a new non-steroidal anti-inflammatory drug, in animals (author's transl)]. The pharmacological profile of carprofen as a new non-steroidal anti-inflammatory drug has been established in various experimental inflammation models in animals. This compound possesses marked effects on prevention of adjuvant arthritis, cotton-pellet granuloma formation and hyperalgesic edema (scalding) and the extent is similar to that observed with indomethacin and piroxicam. The anti-inflammatory potency of carprofen is markedly stronger than those seen in cases of phenylbutazone, mefenamic acid, ibufenac and acetylsalicylic acid, almost equal to that of diclofenac and slightly lower than that of indomethacin in the following parameters: carrageenin-edema, granuloma-pouch, UV-erythema, and bradykinin and histamine-induced capillary permeability. As is the case with other non-steroidal anti-inflammatory drugs, carprofen has no inhibitory effect on lethal anaphylactic shock, passive cutaneous anaphylaxis and hyperuricemia. Carprofen induces ulcerogenicity and fecal occult bleeding to a extent markedly less than those seen with indomethacin and piroxicam. These investigations on anti-inflammatory drugs indicate a probable dissimilarity to the extent of anti-inflammatory effects and induction of gastrointestinal disturbances. Repeated administration of carprofen has no effect on spontaneous excretion of corticosterone and aldosterone into adrenal vein of rats.


[Studies on absorption and metabolism of drugs in febrile animals. (III). Antipyretic effect of acetylsalicyclic acid and aminopyrine and their plasma concentrations in febrile rabbits induced with lipopolysaccharide (author's transl)]. The present investigation was an attempt to clarify the mechanism of combined effect of acetylsalicylic acid (ASA) and aminopyrine (AMI) in febrile rabbits as induced by lipopolysaccharide (LPS). In addition, the possible synergic effect of both agents was studied in relation to the plasma concentration. In febrile rabbits, the plasma concentration of ASA (500 mg/kg, p.o.) was a higher level than in the control, but the concentration of salicylic acid (SA), the metabolite of ASA, was similar to that in the control. The plasma concentration of AMI (100 mg/kg, p.o.) in febrile rabbits was lower than in the control. A dose-dependent antipyretic effect was seen in the successive doses from 125 to 500 mg/kg of ASA, and a similar tendency was also observed in AMI from 25 to 100 mg/kg. To observe the synergic effect of ASA and AMI, we prepared the following three combinations: I (ASA/AMI; 125 plus 75 mg/kg), II (ASA/AMI; 250 plus 50 mg/kg) and III (ASA/AMI; 375 plus 25 mg/kg). Plasma concentrations of ASA, SA and AMI were measured after oral administration of the preparations and these concentrations were lower than in the separate administration of ASA ans AMI. The antipyretic effect of the three preparations was weaker than the expected value, respectively.


[Anti-inflammatory property of 6-chloro-5-cyclohexyl-1-indancarboxylic acid (TAI-284) (author's transl)]. Anti-inflammatory activity and the mode of action of TAI-284 were investigated in animal models and compared with the activities of indomethacin. TAI-28 inhibited the increased vascular permeability in rats and mice which is the primary stage of inflammatory process, but the activity was less than that of indomethacin. The compound was as active as indomethacin in inhibiting acute rat paw edema induced by carrageenin and fracture. Furthermore, in the inhibitory effects on ultraviolet erythema in guinea pigs, durable paw edema induced by mustard and wound healing in rats, TAI-284 showed the same or more potent activity than indomethacin. Therefore, TAI-284 proved to have the same anti-inflammatory activity as indomethacin. TAI-284 protected rabbits from sudden death caused by intravenous injection of arachidonic acid, but the activity was about one twentieth less than that of indomethacin. The anti-inflammatory action of TAI-284 was derived from the mode of action of non-steroidal anti-inflammatory drugs, judging from the effects on ultraviolet erythema and death by arachidonic acid. On the other hand, the compound was more potent on secondary or thema and death by arachidonic acid. On the other hand, the compound was more potent on secondary or late stage than on primary stage of inflammation, and to some extent showed the mode of action seen with steroid antiinflammatory drugs. TAI-284 displayed marked inhibitory activity on nystatin induced paw edema in rats. It is suggested that the antinflammatory action of TAI-284 may be due to the lysosomal stabilizing effect.


[Clinical experiences in supplementary treatment of pseudarthroses using electromagnetic potentials]. In 22 cases of pseudarthrosis following fractures of the limbs, 5 osteotomies and one fresh fracture of the lower leg postoperative treatment with the electro-magnetic alternating field according to Kraus/Lechner was performed in addition to osteosynthesis. Except in one unsuccessful case all patients showed a complete and obviously even quicker osseous bridging. Especially in preoperated and problem-cases such as pseudarthrosis of the femoral neck and defect-pseudarthrosis with inflammation of the tibia this method provided an additional success.


Record-keeping in a state hospital: a modification of the Weed system. The Weed problem-oriented medical record has been modified for use in a state psychiatric hospital that has a large proportion of long-term patients and uses  an interdisciplinary team approach to treatment. Three new record forms were developed during a pilot study at the hospital: the processed-problem list, the problem card, and the unprocessed-problem list. The modified problem-oriented record system is being used in 28 wards providing both short- and long-term psychiatric care.


The problem-oriented medical record as a training tool for staff. After numerous deficiencies were found in a psychiatric center's medical records, a task force devised a system that incorporated the four components of the problem-oriented medical record plus other elements required by the center's structure. They divided the record into ten sections and also developed a four-page form for recording the patient's assessment and treatment plan. Two-hour mandatory training sessions were held to teach all levels of mental health staff how to use the new system; various kinds of follow-up instruction were also given. That training, the authors say, was a valuable way to teach staff not only proper record-keeping but also clinical thinking and logical treatment planning.


New approaches to the treatment of scoliosis. Customary methods of correcting curvature of the spine--surgery for severely afflicted adults and use of the so-called Milkwaukee brace for youngsters--have a number of drawbacks. Among the improved approaches now becoming available are lighter, less obtrusive braces such as an orthoplast jacket molded to the individual's torso, electrostimulation of paraspinal muscles, and implantation of a rod to distract the spine.


A population genetic study of the Vania Soni in Western India. A total of 267 blood samples from persons belonging to the Shrimali Vania Soni caste group in Gujarat State, Western India have been analyzed for 6 blood group, 4 serum protein and 19 red cell enzyme systems, for haemoglobin and beta-thalassaemia and for red-green colour blindness. A number of rare genetic variants were detected, including a unique electrophoretically fast variant of superoxide dismutase. Genetic distance comparisons with other caste groups in Gujarat State show that Vania Soni from Surat are a distinctive group clustering with another subdivision of the Vania. The remaining Vania Soni cluster together and are distinct from the other caste groups examined in Gujarat. However, on the basis of individual genetic markers the Vania Soni appear not to be genetically differentiated in any remarkable way from other Hindu populations in western and northern India.


Comparison of various procedures for the detection of antigen-antibody complexes. The described test of inhibition of AA activity proved to be a procedure of exquisite sensitivity and specificity for detection of immune complexes. This could have been expected since AA is an antibody specifically combining with IgG antibody that suffered molecular transformation in the reaction with its corresponding antigen. Complexes formed at or close to the equivalence zone were most active in inhibiting AA, whereas those at extreme antigen excess did not inhibit it at all. Inhibition of AA was capable of detecting circulating immune complexes as well as immune complexes deposited in the tissues. It was also shown that by using this procedure, identification of the antigen participating in immune complex formation is feasible since excess of the specific antigen converts inhibitory complexes into inactive complexes.


Cell-mediated immunity in pregnancy evaluated using lymphocyte transformation tests and rosette tests for T and B lymphocytes. A cross-section analysis. In vitro tests of cellular immune response using lymphocyte transformation tests and rosette tests for T and B lymphocytes were studied in a cross-section analysis of a total of 55 patients in six groups (non-pregnant, 2-3 month pregnant, 4-5 month pregnant, 6-7 month pregnant, at parturition and 3 months after parturition). No pregnancy-related changes were found in the numbers of T, B or nil cells, nor changes in PHA, PWM or MLC responses. However, a significant reversible depression of the PPD response was found in the second half of pregnancy.


Experimental autoimmune orchitis in T-cell-deficient mice. Experimental autoimmune orchitis (EAO) was induced in inbred strains of mice by injection of mouse testis homogenate (MTH) in Freund's complete adjuvant with pertussis vaccine. Although all mice injected with MTH and adjuvants developed signs of EAO, there were marked strain variations in susceptibility to EAO suggesting that genetic factors may be involved in the response to antigen or to adjuvants. Studies in hypothymic BALB/c. nu/nu mice indicated that a source of T cell was required for induction of EAO. Thus BALB/c. nu/nu mice were not able to develop EAO, despite adequate orchitogenic challenge; reconstitution of nu/nu mice with syngeneic thymocytes completely restored the capacity of such mice to develop orchitis. Transfer of EAO was effected in nu/nu mice with lymphoid cells from appropriately immunized donors but not with immune serum. However, both T cells and antibodies may be necessary in the effector stages of the disease since the capacity of lymphoid cells to transfer EAO was only partially inhibited by anti-Thy-1.2 treatment.


Glycolysis in quiescent cultures of 3T3 cells. Stimulation by serum, epidermal growth factor, and insulin in intact cells and persistence of the stimulation after cell homogenization. Addition of serum to quiescent cultures of 3T3 cells rapidly increases lactic acid formation and subsequently stimulates cell division. The stimulation of lactic acid production is seen at high, saturating concentrations of extra-cellular glucose. It is dependent on the time of exposure and on the dose of serum and is not blocked by the addition of cycloheximide, puromycin, or actinomycin D. In contrast, serum only marginally affects glycolysis by rapidly growing 3T6 or SV40-3T3 cells. In addition to serum, epidermal growth factor (0.1 to 10 ng/ml) and insulin (10 to 500 ng/ml) cause a striking stimulation of glycolysis in quiescent 3T3 cells. Neither exogenous cyclic nucleotides nor ouabain effect the glycolytic response, but the presence of Ca2+ markedly influences the activation of glycolysis by epidermal growth factor and by insulin. A novel finding in this study is that homogenates prepared from quiescent cells treated with serum, epidermal growth factor, or insulin show increased glycolysis as compared with homogenates from nonstimulated cultures. This finding will allow further experimental analysis of the cause of increased glycolysis in rapidly proliferating cells.


Control of normal differentiation of myeloid leukemic cells. XIII. Inducibility for some stages of differentiation by dimethylsulfoxide and its disassociation from inducibility by MGI. There are clones of myeloid leukemic cells that can be induced to differentiate by the normal differentiation-inducing protein MGI to form Fc and C3 rosettes, mature macrophages and granulocytes. One of these clones (MGI+DMSO+) was also inducible by dimethylsulfoxide (DMSO) for C3 but not Fc rosettes, and for mature macrophages but not for mature granulocytes. Other clones (MGI+DMSO-) were inducible by MGI but not DMSO and a third type of clone (MGI-DMSO-) was not inducible by either compound. Clones that differed in their inducibility by DMSO showed a similar inhibition of cell multiplication by DMSO. The results indicate, that some stages of differentiation can be induced by DMSO in an appropriate clone of myeloid leukemic cells and that there are different cellular sites for induction by DMSO and MGI.


Epithelioid and fibroblastic rat kidney cell clones: epidermal growth factor (EGF) receptors and the effect of mouse sarcoma virus transformation. Fibroblastic and epithelioid clones have been isolated from the normal rat kidney line, NRK. These clones were studied for their ability to bind epidermal growth factor (EGF), susceptibility to transformation by mouse sarcoma virus (MSV), and alteration in EGF binding upon sarcoma virus transformation. The epithelioid clones bound much more EGF than the fibroblastic clones; Scatchard plots on two of these clones, one epithelioid and one fibroblastic, showed that the higher EGF binding (1.3 x 10(5) molecules per cell for the epithelioid clone and 1.3 x 10(4) molecules per cell for the fibroblastic clone) was due to a greater number or receptors on the epithelioid cells rather than to a difference in the apparent affinity constant. When the clones were transformed by Moloney murine sarcoma virus the EGF binding decreased, the effect being greater with the fibroblastic clones. In 20 out of 20 independently isolated sarcoma virus transformed fibroblastic clones, the level of EGF binding was either greatly reduced or completely eliminated. In contrast to EGF, another growth factor, multiplication stimulating activity (MSA), bound to a greater extent to the fibroblastic clones than the epithelioid clones, and its binding was not decreased by sarcoma virus transformation. The results show that loss of EGF binding ability correlates with expression of the murine sarcoma virus transformation.


Scanning electron microscopy of human lymphocytes during transformation and subsequent treatment with methotrexate. Preparations of human peripheral blood lymphocytes containing 72-87% T-cells and 10-16% B-cells were shown by scanning electron microscopy to consist almost exclusively of cells bearing numerous microvilli, whereas thymocytes were of mixed surface morphology, with both smooth and encrusted forms numerous. T-lymphocytes purified on long nylon columns were all covered with numerous short villi. Stimulation with phytohaemagglutinin for 2 days produced T-lymphoblasts almost exclusively, and as the T-cells enlarged the microvilli lengthened, the increase in length reaching 5-fold by day 3. Addition of sufficient methotrexate on day 3 to arrest proliferation (50 nM) caused progressive loss of microvilli from the cell surface, with the eventual production of large numbers of smooth cells, the surfaces of which later became pitted, followed by the complete dissolution of the cell. T-lymphocytes were shown to form rosettes with sheep erythrocytes through direct contact of the cell membranes over a significant area, but when, as a result of methotrexate treatment, the lymphocytes had become denuded of microvilli or had reached an advanced state of dissolution, rosettes were no longer formed.


Treatment of lupus nephritis in adult (NZB + NZW)F1 mice by cortisone-facilitated tolerance to nucleic acid antigens. Adult female (NZB + NZW)F1 mice were treated with cortisone, cortisone with tolerogen (isologous NZB IgG-nucleosides conjugates) or cortisone with isologous IgG free of nucleosides. Other treatments also included tolerogen or isologous IgG alone, and cortisone together with denatured DNA. All untreated mice died by 10 mo of age. Cortisone prolonged the survival rate. This effect was further improved by combined treatment of cortisone and tolerogen. Prolonged survival was accompanied by a decrease in proteinuria. Other treatments failed to influence either survival or proteinuria. Although cortisone did not prevent the appearance of antibody to denatured DNA, cortisone and tolerogen suppressed them in most of the animals. Preexisting antibody to denatured DNA was reduced by cortisone and cortisone and tolerogen, but not by cortisone and IgG. In contrast, antibody to native DNA bore no relationship to therapy. Animals living beyond 1 yr of age, regardless of the treatment, fall into three histopathological categories: (a) severe nephritis, as in untreated animals, (b) moderate nephritis (with absence of severe alteration of the glomerular basement membrane, i.e. the histological counterpart of prolonged survival), (c) minimal nephritis. In a small number of animals treated with cortisone or cortisone and IgG and in 6/20 animals treated with cortisone and tolerogen, minimal lesions as judged by light, fluorescent, and electron microscopy were found. These last mice were in good health at 15-16 mo of age, twice the life-span of untreated mice. In conclusion, these data suggest that tolerance to nucleic acid antigens facilitated by cortisone offers a promising new approach to treat established murine lupus nephritis.


Distribution of peripheral blood T and B lymphocyte markers in atopic children and changes during immunotherapy. Peripheral blood lymphocytes from children undergoing evaluation for allergic disease were examined for T and B lymphocyte markers. Patients were evaluated at intervals to determine differences in these markers between atopic and nonatopic children and relative changes during immunotherapy. T lymphocytes were identified by the sheep RBC rosette technique. Surface immunoglobulin was detected by immunofluorescence following incubation with fluorescein-labeled antihuman IgG, IgA, IgM, and IgE. At initial examination, atopic patients differed from controls only in the increased percentage of lymphocytes bearing surface IgM. There were no differences between patient and control values in T lymphocyte distribution or in cells bearing surface IgG, IgA, or IgE at any point in the study. The increased percentage of IgM-bearing lymphocytes is reduced to the control level after four months of immunotherapy but remains elevated in the untreated atopic group. Serum IgM levels remained constant. This study shows that the distribution of lymphocyte markers may be altered in atopic children. Patients treated with immunotherapy demonstrated a return to control values of IgM-bearing lymphocytes. The elevated serum IgE seen in atopy was not reflected in an elevated percentage of IgE-bearing lymphocytes.


Cytofluorometric quantitation of 5-hydroxytryptamine and heparin in individual mast cell granules. Cytofluorometric quantitation of 5-hydroxytryptamine (5-HT) and heparin in individual mast cell granules is described. The technique is based on micromanipulation of intact mast cells reacted with formaldehyde or stained with Berberine sulfate and the use of a cytofluorometer equipped with a sensitive peak detecting device. The quantities of 5-HT and heparin contained in mast cell granules which are of the order of 10(-16) and 10(-13) g, respectively were expressed as relative fluorescence guanta. The results of measurements on representative samples of mast cell granules indicate that all granules contain heparin as well as 5-HT, and that there are large variations in both 5-HT and heparin content within the granule populations of individual cells. A dose dependent increase in 5-HT content in both cells and individual mast cell granules occurred 24 hr after the injection of 10--50 mg L-5-hydroxytryptophan/kg intraperitoneally. There was no evidence for an increase in the heparin content of granules or cells, indicating that a new synthesis of granular macromolecules is not required for the 5-HT uptake. The results further suggest that 5-HT may be stored initially in a cytoplasmic extragranular pool and then taken up in the mast cell granules.


Effects of antigen-feeding on intestinal and systemic immune responses. I. priming of precursor cytotoxic T cells by antigen feeding. The ability of antigens administered by the intestinal route to alter the cytotoxic T lymphocyte (CTL) population in intestinal and extraintestinal sites was examined by feeding mice tumor cells bearing H-2 or non-H-2 gene-coded cell surface alloantigenic differences. Peyer's patches from mice fed tumor cells differing at H-2 demonstrated a 12-fold increase in specific CTL activity over controls after stimulation of culture but the precursor CTL population in Peyer's patches was not expanded by feeding mice cells bearing minor H gene coded alloantigenic differences. In contrast, the precursor CTL pool in spleen was increased both in mice fed cells bearing alloantigenic differences coded for by H-2 and non-H-2 gene loci. The precursor CTL population in mesenteric lymph nodes (MN) was not expanded significantly by tumor cell feeding. Feeding was nearly as effective as i.p. priming at expanding the Peyer's patch precursor CTL population when tumor cells bearing H-2 differences were used, whereas i.p. priming was more effective than feeding in expanding the precursor CTL population in spleen.


Generation of T helper cells in vitro. IV. F1 T helper cells primed with antigen-pulsed parental macrophages are genetically restricted in their antigen-specific helper activity. A sequential culture technique for the in vitro induction and subsequent assay of T helper cells is employed to examine the histocompatibility requirements for antigen recognition by murine T helper cells. F1 T cells are primed in vitro with antigen-pulsed parental strain macrophages and tested for antigen-specific helper activity in cultures containing anti-Thy 1.2 serum and C treated spleen cells from hapten-primed parental or F1 mice. A semiallogenieic system is used and appropriate controls are included to avoid possible complicating effects of allogeneic interactions. The results indicate that F1 T helper cells preferentially stimulate carrier-specific anti-hapten plaque-forming cell responses in spleen cells which are H-2 identical with the macrophage used initially to prime the T cells. Parental spleen cell cultures do not respond to F1 T helper cells which were primed with the other parental strain macrophage. Supplementing this culture with macrophages which are histocompatible with those used to prime the F1T cells is sufficient to restore T helper cell activity. Thus, the genetic restriction described here is between the primed T cell and the macrophage used to elicit secondary responses and not between the T cell and B cell. The results in this semiallogeneic system, however, do not rule out the possibility of additional allogeneic genetic restrictions in the subsequent interaction of T cells with B cells.


The occurrence of diploid ova in Rana pipiens. All 12 Rana pipiens females tested from three populations produced diploid ova. These were identified by the development of from 0.15 to 35 percent per clutch of normal diploid-like embryos among large numbers of haploid embryos following activation of R. pipiens eggs with irradiated R. clamitans sperm. Their diploid nuclear constitution was demonstrated by diploid cell size at Shumway Stage 19, and by the diploid number of chromosomes both as embryos and as mature frogs, and was confirmed by the occurrence of triploid embryos among normally fertilized progeny from the same female parents. Although the precise cytogenetic events leading to the origin of these diploid ova were not directly determined, we were led to conclude that, although diploid ova may result from polynucleate oocytes, the diploidy reported here was an expression of abnormal meiosis that occurred under genetic control. Such anomalies, at the orders of frequency we observed in R. pipiens, have important consequences for all studies using Anuran model systems.


BCG-induced suppressor cells. I. Demonstration of a macrophage-like suppressor cell that inhibits cytotoxic T cell generation in vitro. Spleen cells obtained from mice 5 to 40 days after infection with viable BCG organisms (BCG-spleens) were found to be unresponsive in vitro to both mitogenic and alloantigenic stimuli. Moreover, suppressor cells could be demonstrated in the spleens from these infected animals. When spleen cells from BCG-infected mice were added to either syngeneic or allogeneic normal spleen cells, the mixtures neither proliferated nor developed cytotoxic activity when cultured with alloantigen or with concanavalin A (Con A). The development of unresponsiveness post-infection paralleled the onset of suppressive activity. Spleen cells obtained from mice given heat-killed BCG were neither suppressive nor unresponsive. The suppressive activity of BCG-spleen cells was associated with an adherent, phagocytic cell that lacked membrane-associated Thy-1 antigen. Removal of this cell by passage through nylon wool columns resulted in a cell population that was no longer capable of suppression and that responded normally to alloantigen and to Con A. It would thus appear that BCG infection results in the development of a "suppressor" macrophage-like cell population within the spleen. The role of this cell type in regulation of the immune response in BCG-infected animals is as yet undefined.


Subpopulations of splenic T cells regulating an antihapten antibody response. I. Helper and amplifier cells. There was a pronounced quantitative difference between the helper activities of B6C3F1 splenic T cells sensitized with unmodified vs modified antigens of SRBC. Modified SRBC induced the greater helper activity which was measured by the magnitude of an anti-TNP response (IgM and IgG) elicited in vivo by virgin B lymphocytes. Antigen modification was produced by conjugating SRBC with the hapten or simply by incubating SRBC in cacodylate buffer. There were restrictions with respect to both erythrocyte species and mouse strains for this differential priming to occur. The relatively poor performance of SRBC-primed T lymphocytes was apparently not due to suppressor T cells, but rather to activation of only one of two identified T cell subpopulations required for full helper activity. Unmodified SRBC activated a subpopulation of "helper" cells characterized as sensitive to elimination by ATS and long-lived after ATx, but failed to activate in B6C3F1 mice a second subpopulation of "amplifier" cells resistant to elimination by ATS and short-lived after ATx. In contrast, modified SRBC activated both helper and amplifier cells. Under appropriate conditions these subsets of T cells were strongly synergistic in promoting antihapten antibody formation especially of the IgG class. The involvement of two distinct types of T lymphocytes in the positive regulation of antibody responses raises interesting and novel questions concerning the sequence of events in the triggering of B cells and the subsequent development of the response.


Cell-mediated lympholysis of trinitrophenyl-derivatized autologous human cells: in vitro triggering by nonspecific signals. This report describes the primary in vitro generation of human CTL that lyse TNP-derivatized autologous cells. Although in the majority of these studies, a direct cytotoxic response to the TNP-modified autologous stimulators was not achieved, in all experiments the addition of either allogeneic cells or soluble antigen triggered the generation of killer cells which destroy TNP-modified, but not unaltered, autologous targets. Fractionation of responder lymphocyte populations demonstrated that the cytotoxic activity was mediated by T cells. Killer cell specificity was tested by assaying for cytotoxicity to a variety of targets, and by blocking the cytolysis of TNP-altered autologous targets with various populations of nonradiolabeled cells. Results indicated that these CTL were cytotoxic for TNP-modified autologous cells but not unaltered autologous or TNP-modified allogeneic targets. The capacity of soluble antigen and alloantigens to facilitate the in vitro generation of altered-self reactive human CTL is not an isolated phenomenon. This "helper" effect has now been observed for the cytotoxic response to chemically modified autologous cells and MHC identical human leukemic blasts. It is possible that in vivo, similar responses to nonspecific antigenic stimuli may play a role in the maintenance of immune surveillance.


Glycolipid markers of murine lymphocyte subpopulations. We have shown previously that purified antibodies to ganglioside GM1 react with peripheral T cells and most thymocytes in several strains of mice, independent of Thy-1 phenotype. GM1 and the Thy-1.2 antigen cap independently on C3H thymocytes, which provides additional evidence that GM1 is not the Thy-1.2 antigen. In C3H and nude mice antibodies to GM1 also react with a population of cells, comprising about 25% of lymphocytes from lymph nodes or spleen, that bear surface immunoglobulin. After removal of immunoglobulin from these cells by digestion with proteolytic enzyme, the GM1+ cells regenerate their surface immunoglobulin during 18 hr in culture, which indicates that these double-labeled cells synthesize their surface immunoglobulin. Protease treatment of lymphocytes reveals receptors for antibodies to GM1 on most cells. These data indicate that T and B cells differ in the accessibility of GM1 to antibody, and not necessarily in their content of GM1. Purified antibodies to asialo GM1 react with mature T cells in all strains of mice tested. In contrast to anti-GM1, these antibodies do not react with most thymocytes, with immunoglobulin-bearing lymphocytes of C3H or nude mice, nor with pronase-treated B cells.


Studies on the platelet radioactive anti-immunoglobulin test. A platelet radioactive antiimmunoglobulin test (PRAT) has recently been introduced. In the present report, a detailed analysis the influence of varying test conditions (i.e. efficiency of iodination of anti-IgG, cell number, degree of sensitization of platelets, times and temperatures of incubation, frequency of washings) on the results of this technique is presented. A standard procedure based on these findings is outlined. It is shown that the PRAT is two to four times more sensitive than platelet complement fixation for the detection of HLA antibodies.


Defective function of T lymphocytes in psoriasis. The distribution of thymus-derived (T) and bone marrow-derived (B) lymphocytes in 100 patients with psoriasis were studied by the rosetting techniques. Depression of the number of T lymphocytes forming spontaneous rosettes with sheep erythrocytes (E rosettes) occurred in 66% of patients, whereas no difference in B lymphocytes bearing C3 receptor (EAC rosettes) was observed between psoriatics and normals. The decrease in E rosettes was associated with the active phase of the disease. This disappeared 4-6 wk after onset of remission, which suggested that the abnormality in T-cell marker distribution is transitional. Lymphocytes forming neither E nor EAC rosettes, which were found to be significantly increased in active psoriasis, were identified as T lymphocytes since they reacquired normal E rosette function during short-term preincubation with concanavalin A (Con A). A serum factor was also demonstrated which inhibited E rosette formation by normal peripheral blood lymphocytes. Its activity increased linearly within 2 mo from the onset of skin lesions. The data suggest that in active psoriasis serum factors may be coated on the lymphocyte surface membrane which may be responsible for blocking of specific receptor for sheep erythrocytes and/or interfere with T lymphocyte function.


Biologic half-life and organ distribution of radiolabeled human PiM and PiZ alpha-1-antitrypsin in the dog. Highly purified A-1-A.T., prepared from blood obtained from donors of known PiZZ and PiMM phenotype, was radiolabeled with 125I or 131I and injected intravenously into dogs. The radiolabeled proteins retained their prelabel electrophoretic and trypsin-inhibitory characteristics. The biologic t1/2 of both M and Z protein in the circulation were similar, averaging 71 hr for M protein and 80 hr for Z protein. The label was shown to remain tightly bound in vivo for 2 days after injection. The material was nonpyrogenic in rabbit and dog. No arteriovenous differences in radioactivity could be detected at 2 or 20 min after injection. However, surface scanning disclosed substantial pulmonary deposition of radioactivity for the first 9 hr after injection. At 48 hr, intense radioactivity was present in the spleen, but not in the liver. These studies indicate the feasibility of similar studies in man, including noninvasive assessment of body distribution of M and Z protein by surface scanning techniques.


Endogenous mediators of the acute-phase reaction. I. Rabbit granulocytic pyrogen and its chromatographic subfractions. LP, a saline extract of exudate-derived rabbit granulocytes, shown to be free of endotoxin contamination by sensitive LAL assay, can elicit brisk acute-phase responses in the rabbit. Following a single large intravenous dose of LP (875 mce) there is a brisk fall in serum iron at 8 hr and marked elevations in concentrations of CxRP, haptoglobin, fibrinogen, and ceruloplasmin and a lesser rise in sialic acid in the blood at 24 hr, which return toward baseline to varying degrees by 48 hr. When the crude LP solution is fractionated by column chromatography on Sephadex G75, all detectable acute-phase mediating activity elutes in a fraction (pool C) which contains all the pyrogenic activity and about 15% of the total eluted protein. Within the limitations of the methods employed, the acute phase stimulating activity and the pyrogenic activity of LP preparations appear to be closely linked.


Proteins induced by infection with caliciviruses. Three polypeptides with mol. wt. 100 (P100), 80 (P80) and 65 (P65) X 10(3) were found in calicivirus infected cells. P100 and P80 were present in sub-molar amounts compared with P65 and no precursor product relationship between the three polypeptides could be demonstrated using pulse-chase experiments or selective inhibitors of protein synthesis and of proteases. In the presence of protease inhibitors a polypeptide with mol. wt. 120 X 10(3) (P120) was demonstrated which appeared to be the precursor of P100. Possible mechanisms of translation in the caliciviruses are discussed.


Effects of general anaesthesia on size of cerebrospinal fluid spaces during and after pneumoencephalography. The mode of anaesthesia used during pneumoencephalography has a significant effect on the size of the cerebral ventricles 24 hours after the procedure. Post-encephalographic ventricular enlargement is less marked in patients examined under nitrous oxide anaesthesia. This appears to be related to passage of the gas into the ventricles during the encephalogram, and subsequent diffusion outwards. Variations in arterial carbon dioxide tension during the anaesthesia do not contribute significantly to changes in ventricular size. However, both hyperventilation and inhalation of nitrous oxide may cause apparent increase in size of the cerebral sulci.


Assessment of cellular and humoral immunity of myasthenics. A close association of autoimmune diseases or autoimmune phenomena in myasthenia gravis is well known. A comprehensive immunological study of 22 patients with myasthenia gravis showed that changes in the immune system mainly involve the thymus-derived lymphocytes (T cells). Anti-thymus antibody was present in 90% of the patients, and it paralleled the frequency of thymic abnormality in myasthenia gravis. It is postulated that in myasthenia gravis the altered T cell functions caused by anti-thymus antibody result in the formation of an array of autoantibodies including the factor which blocks the neuromuscular transmission.


Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. Fifty patients with P. carinii pneumonitis were randomized to receive either pentamidine isethionate or trimethoprim-sulfamethoxazole therapy. Those not responding favorably to the first drug after three or more days of therapy were changed to the alternate drug. Of the 26 patients initially treated with TMP-SMZ, 20 recovered (0.77)-17 after TMP-SMZ alone and three of nine who were crossed over to pentamidine. Of the 24 patients initially treated with pentamidine, 18 recovered (0.75)-14 of 15 who received only pentamidine and four of nine who were crossed over to TMP-SMZ. Abnormal values for blood urea nitrogen, creatinine, or glucose; inflammation at injection sites; or combination of these effects occurred in 14 of the 15 patients treated with pentamidine alone. Only one of the 17 patients treated with TMP-SMZ alone developed any of these abnormalities. This study shows that TMP-SMZ is as effective as pentamidine in the treatment of PCP, and that it offers the advantages of minimal adverse effects, oral administration, and ready availability.


The management of drug induced gingival hyperplasia in mentally retarded patients with hemophilia: a report of two cases. Two cases of hemophilia in severely mentally retarded patients with drug-induced gingival hyperplasia are presented. The method of management in each case is described. A conservative approach is recommended in which tissue removals and only selected extractions are performed. It is also suggested that the sequela of dilantin hyperplasia be considered when dilantin is used in patients with hemophilia or severely mentally retarded patients whose oral hygiene may be difficult to maintain. If feasible, as in the first case reported, discontinuance of the drug should be considered. In case 2 the patient is presently being weaned from dilantin therapy. It should be understood that the authors are concerned with the immediate clinical management of drug-induced gingival hyperplasia in mentally-retarded patients with hemophilia. Although this method of management has proved successful in the hands of the authors, we do not have data to show that it is the best form of treatment for these patients.


The effect of haloperidol on the ionic currents in the voltage-clamped node of Ranvier. Haloperidol (Haldol) selectively inhibits sodium currents at the voltage-clamped node of Ranvier at concentrations ranging from 0.013 to 13 muM. The action potential is reduced or abolished while the membrane potential is not significantly changed. The dose-response curve is described by a Langmuir adsorption isotherm with an apparent dissociation constant of 6 X 10(-7) M. Sodium current time-to-peak and the permeability-voltage relationship are not affected, although at higher concentrations the inactivation time constant is slightly increased. Potassium currents are not altered except at 13 muM where there is an occasional nonsystematic effect. Leakage currents are not changed at any concentration.


Influence of lithium upon the intracellular potential of frog skin epithelium. The effect of Li upon the intracellular potential of frog skin (Rana esculenta) was investigated. In the range between 1 and 25 mM Li in the epithelial bathing solution, a semilogarithmic linear relationship between [Li] and intracellular potential under short circuit conditions was obtained. The intracellular potential at all [Li] is quantitatively sufficient to explain the previously reported accumulation of Li in the intracellular space of the frog skin epithelium (Leblanc, G. 1972. Pfluegers Arch. 337:1) on the basis of a passibe entrance step at the outer border. A reduction of the intracellular potential by Li is also observed in the presence of 6 mM Na in the epithelial bathing solution. Consequences regarding the mechanism of uptake of Na across the outer border of the frog skin are discussed.


Studies of the mechanisms for the induction of in vivo tumor immunity. II. Distribution and homing of cytotoxic effector and precursor cells. Cytotoxic T (thymus)-lymphocytes (CTL) with specific cytotoxicity against the leukemia-associated antigens of FBL-3, a syngeneic Friend virus-induced leukemia in C57BL/6 mice, could be adoptively transferred to sublethally X-irradiated (350 R) syngeneic hosts and could be induced by adoptive transfer of either normal or presensitized lymphocytes obtained from immunocompetent hosts. The CTL and their precursor cells were systemically distributed in peripheral lymph nodes and spleen, although they had the tendency of homing to the lymphoid tissue of the same origin. Direct cytotoxicity was obtained with the lymphocytes from these lymphoid tissues, and cells obtained from these lymphoid tissues could produce secondary cytotoxic responses by the mixed lymphocyte tumor cell culture reactions 40--60 days after adoptive transfer. In addition, lymph node and spleen cells had a synergistic effect on the induction of cytotoxicity. These findings indicated that tumor immunity was widely distributed and that various populations of lymphocytes were involved in the generation of efficient cell-mediated cytotoxic responses.


Inhibition of host protein synthesis in vaccinia virus-infected cells in the presence of cordycepin (3'-deoxyadenosine). Cordycepin inhibited efficiently viral mRNA and polyadenylic acid syntheses in vaccinia virus-infected cells, but allowed the shutoff of host protein synthesis to occur. Therefore, cordycepin was used to study this shutoff in the absence of gene expression. Ribosome transit time was increased in infected cells, revealing an inhibition at the level of elongation and/or release of polypeptide chains. However, the disappearance of heavy polysomes in vaccinia virus-infected cells showed that the inhibition of host protein synthesis resulted predominantly from a block at the stage of initiation. This conclusion was confirmed by the recovery of heavy polyribosomes when low levels of cycloheximide were added to slow down ribosome release from the mRNA. Similar amounts of cellular mRNA (present in the polyribosomes) were found in vaccinia virus-infected cells and in mock-infected cels (exposed to cordycepin), showing that the cellular mRNA was not inactivated in these conditions. It was concluded that a component of the vaccinia virion inhibits, in the absence of viral RNA and polyadenylic acid syntheses, host protein synthesis at the level of initiation and, to a lesser extent, at the level of elongation (and/or release) of polypeptide chains.


Achilles tendon rupture owing to rheumatoid disease. Case report with a nine-year follow-up. Rheumatoid disease as a cause for achilles tendon rupture has been inferred but never reported to my knowledge. A patient with confirmed achilles tendon rupture from rheumatoid disease has been free from disease for nine years following tenoplasty and synoviobursectomy of the achilles tendon.


Reactivity of HLA typing sera against cultured lymphoblastoid cell lines and purified peripheral B and T cells from the same original donors. Anomalous cytotoxicity reactions are observed in some HLA typing sera when cultured lymphoid cells are used as targets. These extra reactions are also detected when the purified B cells from the original donors of the cell lines are used. This observation strongly indicates that these extra reactions are directed to the B cell alloantigens which are normally expressed on B cells of the original donor.


[Typical monochromacy, congenital deafness, and resistance to intracellular action of thyroid hormone (author's transl)]. A 9-year-old boy, the product of a consanguineous marriage, had visual acuity of 6/60, pendular nystagmus, and a bull's-eye type of macular atrophy. A sensorineural deafness was present. The photopic electroretinogram was extinguished; the electro-oculogram was normal. There was associated mental retardation and failure of inhibition of the pituitary gland by high levels of circulating thyroid hormone. Two older siblings although not examined, had similar endocrine abnormalities. Non-involvement of three half-siblings suggested autosomal recessive inheritance.


[Cytarabine treatment of herpes zoster (author's transl)]. Systemic treatment of herpes zoster becomes possible by cytarabine. Complications of herpes zoster ophthalmicus such as relapsing corneal ulceration, perforation or scarring, secondary glaucoma, Argyll Robertson pupils, extraocular muscle palsies, and optic atrophy, as well as postherpetic neuralgia can be prevented by the use of this drug. For this reason the authors believe treatment with cytarabine to be the therapy of choice in herpes zoster.


[Prolonged jaundice by heterozygous alpha-1-antitrypsin-deficience? (author's transl)]. Of 28 newborns with prolonged jaundice and lowered or subnormal values of alpha-1-antitrypsin in the serum six patients were found to have a Pi-type MZ, three a Pi-type MS and one patient a Pi-type MP. One of the newborns had Pi-type SZ (double heterozygous), one infant was a homozygous carrier of the Pi-type S. It seems to the possible that one of the reasons for the not yet explained cases of prolonged jaundice of the newborns period can be found in the high frequency of homozygous or heterozygous genotype carriers of Pi-system.


Early decline of thymic effect on T cell differentiation. Thymic lobes of B6C3F1 mice ranging in age from 1 day to 11 weeks were implanted under the kidney capsule of T cell deprived syngeneic young adult TXB mice, and the capacity of the thymus grafts to influence the maturation of T cells was assessed at 6 and 12 weeks after the implantation in terms of (a) regenerative activities of the grafted thymus, (2) splenic T cell dependent anti-SRBC response, and (c) mitogenic reactivity of spleen and lymph node cells to T cell specific mitogens. The results revealed that: (1) thymic tissues from 1 week old donors were most efficient in restoring the immune potential of adult TXB mice; (2) a decline in mitogenic reactivities of spleen and lymph node cells was observed in recipients of thymus grafts from donors of 1 month and older; and a decline of splenic helper T cell function was observed in recipients of thymus grafts from 11 weeks old donors. The significance of this early decline in the thymic effect on T cell differentiation is discussed.


Immunological senescence in mice and its reversal by coenzyme Q10. A pronounced suppression of the humoral, hemolytic, primary immune response in old (22 months) mice was demonstrated as compared with this response in young (10 weeks) mice. The suppression is associated with a lower thymus weight:body weight ratio. In contrast, the ratios spleen weight:body weight and liver weight:body weight in 10 weeks and 22 months old mice remain almost constant. A single administration of coenzyme Q10--a non-toxic, non-specific stimulant of the host defense system--partly compensates the age-determined suppression of the humoral, immune response. This suppression probably results from an age-dependent imbalance of T cells: B cells ratio and a decline of their immunological responsiveness which is compensated by the administration of coenzyme Q10.


[Sensory components of optokinetic nystagmus in exposure to the action of angular accelerations]. The relationship between the vestibular and optokinetic nystagmus was investigated using a special vestibulooptokinetic trainer. A correlation between the objective index of the angular velocity of the slow component of the optokinetic nystagmus and concomitant sensory reactions responsible for the visual perception of optokinetic stimuli was examined. It was shown that tolerance of the optokinetic system can be characterized by the differential criterion +/-deltaw that is the difference between the angular velocity of the slow component of the optokinetic nystagmus and the angular velocity of optokinetic stimuli. A group of people whose optokinetic system is highly resistant to vestibular noise had been identified. It is suggested that these findings can be used for special selection.


Colitis, cancer, and colonoscopy.

Colitis, cancer, and colonoscopy. Colonoscopy has added a new dimension to the diagnosis of colonic diseases. In the field of inflammatory bowel disease, colonscopy is indicated only when certain specific problems arise. Patients with acute colitis and those who are too sick to withstand cleansing enemas should not undergo colonoscopy. A major use of the colonoscope is in the detection of carcinoma in the colitic colon either in the form of colonic strictures or filling defects discovered by barium enema x-ray, or in the long-term surveillance of patients with universal ulcerative colitis. Criteria are listed to assist in the colonoscopic differential diagnosis between ulcerative and granulomatous colitis. By using different criteria than the radiographer, and with the help of biopsy specimens, a high degree of accuracy in proper diagnosis can be achieved.


[Antimycotic sensitivity of Candida (author's transl)]. We studied on the sensitivity of 184 candida species from various samples isolated in our mycology laboratory, to nystatin, miconazole and pimaricine by using both the agar disc diffusion and dilution methods and then compared the results. Our findings showed that antimycotic sensitivity could largely vary in different candida species. Therefore, we came to the conclusion that the use of sensitivity tests in infections caused by candidas, as used in bacerial infections, would play an important role for cure effectiveness and in the fight against resistance increases as well. In addition it is well observed that the practical characteristics of agar disc diffusion techniques in valid also for candidas.


Evaluation of nephrotoxic and ototoxic effects of tobramycin in worldwide study. Tobramycin sulphate, a bactericidal aminoglycoside antibiotic, has been evaluated worldwide in 3,506 patients. Drug-related adverse effects were reported by the investigators in 3.9% of the cases, and included reactions in the nervous system (ototoxicity) in 0.6% and in the kidney in 1.5%. Effects of doubtful relationship to tobramycin occurred in 6.6% of the cases. The effects were usually reversible, although infrequently altered renal or eighth-nerve function appeared to persist in some of the patients. There were no deaths or instances of renal shutdown as a result of tobramycin therapy. Therefore, under the clinical conditions in which it was evaluated, tobramycin appeared to be well tolerated. The association of toxicity with various "risk factors" is discussed.


[On the antipyretic effect of paracetamol. Clinical investigation with two different forms of application (author's transl)]. 144 children, aged between 15 days and 12 years, suffering from febrile condition of various etiology, were treated with differentiated single doses of paracetamol (N-acetyl-p-aminophenol) in form of syrup, suppositories and a combination of syrup with the antihistamine doxylaminsuccinate. During investigation periods of four hours, applying reduced doses, the syrup application showed the same antipyretic effects as those obtained with paracetamol suppositories. When administering the combination with doxylaminsuccinate, the antipyretic effect was reduced and the psychomotoric superactivity did not improve. A control of the actual rectal dosage scheme for repetitive applications is recommended and the combination of paracetamol with sedatives is to be discussed.


Expression of hexosaminidase isoenzymes in childhood leukemia. Because differences in hexosaminidase isoenzyme profiles of granulocytes and lymphoyctes suggested that such profiles might help to distinguish between various types of leukemia, was examined leukocyte extracts from 55 untreated children and 12 controls by automated anion-exchange chromatography. In 23 of 27 cases of the common form of childhood acute lymphoblastic leukemia, the activity of hexosaminidase component I was greatly increased; the activity ratio of hexosaminidase I to hexosaminidase A was greater than 0.5 in 18 of these cases, whereas for other types of leukemia and for all normal cells tested, the ratio was less than 0.2. A raised hexosaminidase I was shown to be associated with leukemic cells by the finding of normal isoenzyme profiles of bone-marrow cells from 17 patients in remission who had such an increase either at diagnosis or in relapse. Hexosaminidase isoenzyme analysis had diagnostic value and may provide a new marker for study of leukocyte differentiation.


Measurements of the normal ventricular system and hemispheric sulci of 100 adults with computed tomography. The brains of 100 normal adults were examined with 160 X 160 matrix computed tomography (CT). The left lateral ventricle was found to be larger than the right in both sexes, and both lateral ventricles were larger in the male. There was a statistically significant increase of all cerebral parameters with age, and the cella media index showed a correspondingly small decrease with age. The linear measurements of the lateral ventricles demonstrated positive correlation to cranial size, while the widths of the third ventricle and of the hemispheric sulci were independent of the size of the skull.


Age and sex dependence of the size of normal ventricles on computed tomography. Several parameters of the normal ventricular size have been measured routinely on more than 170 computed tomographic scans of patients with normal neurological findings. All patients have been classified into age groups of 15 years each. Means and further statistical values, separate for male and female, have been calculated and figured in a table and histograms.


Histoplasma meningitis with hyperactive suppressor T cells in cerebrospinal fluid. Histoplasma meningitis usually occurs in conjunction with disseminated histoplasmosis. We studied a patient with common variable hypogammaglobulinemia who manifested meningitis without disseminated histoplasmosis. No histoplasma antibody was detected in cerebrospinal fluid (CSF) or blood. Evaluation of lymphocyte function in the blood revealed normal numbers of T cells with increased numbers of B cells. Most blood lymphocytes were identifiable, but most lymphocytes in CSF were null cells. Lymphocyte proliferative response to phytohemagglutinin or pokeweed mitogen was poor. T cells in CSF suppressed proliferative responses to histoplasma antigen by cells from blood or CSF, whereas T cells from blood did not. This difference suggested compartmentalization of T-cell function. The lack of humoral and cellular response to histoplasma in CSF may have allowed meningitis to develop, while the cellular response to histoplasma elsewhere prevented development of disseminated histoplasmosis.


[Unusual case of headache of psychogenic origin]. A case of attacks of short-lasting pains in the midfrontal region is reported. The attacks occurred several dozen of times per day, no drugs were effective. Contrast radiological investigations failed to show presence of an expanding lesion. After psychotherapy (suggestion reinforced with faradic current) the attacks disappeared completely.


[Porto-systemic anastomosis in the treatment of portal hypertension due to intrahepatic block. Advanced surgical technics]. A physiopathological interpretation is offered of the possibilities given by recent selective or portally regulated reduction of pressure in achieving a balance between reduction of pressure and diversion. Classic demonstrations, in fact, prove effective in the prevention of haemorrhage due to rupture of oesophageal varices. On the other hand, by over-diversion of the portal flow from the liver, they may cause a further deterioration in liver performance and more imposing the greater the flow of portal blood through the liver preoperatively. Procedures aimed at de-tension of the portal system, particularly the gastro-oesophageal segment, and at ensuring an intrahepatic venous flow sufficient to obviate steal syndrome damage, are described. Some of these procedures are still at the experimental stage. The techniques involved are explained, along with the underlying principles achieved by or prospected for each of them.


Systemic lupus erythematosus. Management during pregnancy. The course of 27 pregnancies in 13 patients with systemic lupus erythematosus (SLE) is presented. The overall incidence of fetal wastage was 33.3%, a figure significantly higher than that observed in the general population. Although serum C3 complement levels rise during normal pregnancy, mean C3 levels remain within the normal range. Since it is a fall in complement levels in patients with SLE which may herald the onset of symptoms and provide a guide to therapy, assay of serum C3 complement levels remains a valid monitoring device in management of these patients during pregnancy. Flares of SLE during pregnancy generally should be treated vigorously with corticosteroids rather than by therapeutic abortion. Continuation of corticosteroid treatment during the first 2 months postpartum is advised to limit the incidence of exacerbation of SLE activity following delivery.


Immunosuppressive effect of serum in patients with ovarian carcinoma. Cell-mediated immune response was measured in 23 patients with ovarian cystadenocarcinoma, 38 patients with benign ovarian tumor, and 44 healthy volunteers. The method used two indexes: the lymphocyte response per unit volume of peripheral blood to phytohemagglutinin (PHA) and the immunosuppressive effect of serum on the response of normal lymphocytes to PHA stimulation. The lymphocyte response per 50 microliter peripheral blood did not differ significantly between patients with ovarian cancer and healthy volunteers. The serum effect, in contrast, differed significantly between malignant and benign ovarian tumors, and was found to increase significantly even when the cancer masses were as small as about 5 x 5 x 5 cm in size, ie, in FIGO Stage I. It is our belief that the measurement of the serum effect in patients with any ovarian tumor enables the early detection of ovarian cancer.


Preoperative topical antibiotics and lash trimming in cataract surgery. Fifty patients admitted for cataract extraction had their lids and conjunctive cultured two days preoperatively, on the morning of surgery, and on each of the first four postoperative mornings. Multiple topical preoperative antibiotics given for forty-eight hours before surgery produced a marked reduction in the periocular bacterial flora, an effect which persisted throughout the postoperative period. Lash trimming prior to surgery did not alter the periocular bacterial flora present on the morning of surgery or at any time during the first four postoperative days. While multiple preoperative topical antibiotics may reduce the incidence of postoperative endophthalmitis through suppression of periocular bacterial flora, no such role can be postulated for lash trimming.


The dangers of metal-loop intraocular lenses. The author implanted 500 intraocular lenses (IOLs) during intracapsular surgery. Data from the 60 lenses with metal posterior loops showed a markedly high incidence of complication compared to plastic loops: twice as many overall complications, three times the cystoid mascular edema, three times the rate for subsequent corrective surgical procedures, and 30 times more IOLs had to be removed. IOL manufacturers are advised to abandon metal loops for intracapsular implantation. Polypropylene is suggested as the apparent ideal loop material.


[Duodenal ulcer in a newborn infant with gastro-intestinal hemorrhage (author's transl)]. A newborn infant was transferred to our hospital because of gastro-intestinal hemorrhage, starting a few hours after birth. Because of fetal distress a cesarean section had been necessary. The clinical examination as well as the results of the laboratory tests revealed nothing abnormal. In an upper gastro-intestinal X-ray series there was evidence for a duodenal ulcer. Under conservative treatment the baby recovered and has remained in a good condition without any bleeding episode  until now. A repeat upper gastro-intestinal X-ray series was done at the age of 5 months and no evidence of ulceration could be found. The incidence and the reason of such an ulcer in the new born period is shortly discussed.


The effect of the CO2/HCO3- buffer system on the membrane potential of frog skeletal muscle. 1. The membrane potential of frog skeletal muscle was measured in various solutions, in the presence and in the absence of the CO2/HCO3- buffer. 2. The CO2/HCO3- buffer (PCO2 = 38-593 mm Hg; [HCO3-] = 5-25 mM/1) generally induced a reversible depolarization. 3. In the presence of C1-, there was a slowly developing but marked depolarization. 4. In the absence of C1-, there was an early depolarization which increased in high-PCO2 or low-K+ solutions, and decreased in low-PCO2, high-K+ or Na+-free solutions. Changing the HCO3- concentration did not modify the depolarization. 5. The early depolarization and contractions observed in C1--free Ringer persisted in presence of tubocurarine chloride (2.5-10(-5) M/1). 6. Possible mechanisms for the depolarization are discussed.


[Biosynthesis of folic acid in Eimeria tenella (Coccidia)]. The inhibitory analysis has shown that E. tenella does not include ready folic acid into metabolic process but synthesizes its metabolite, 7:8-dihydrofolic acid (DHFA), from its precursor, para-aminobenzoic acid (PABA), which enters the host's organism. PABA can be fully substituted in the process of metabolism by sulphadimesin (SD) at the molar ratio PABA: SD=1: 16.7. As a concurrent antagonist of PABA SD is 6 times stronger in the parasite-host system of Coccidia than in bacteria in cultural medium. The increase in PABA content in relation to SD more than 1: 16.7 intensifies the viability of Coccidia that is expressed in higher lethality of chicks, which reaches its maximum at PABA : SD=1 : 1.25. A further increase in the content of PABA does not affect the host's lethality. The decrease in PABA in relation to SD lower than 1 : 16.7 reduces the viability of Coccidia. Nucleic bases G, A transforming in the organism into corresponding nucleotids and aminoacids, 1-metionin and glycine, which are the products of biosynthesis with a participation of DHFA, do not stimulate the viability of E. tenella that apparently is associated with the non-capability of the host to assimilate timidin.


Influence of the saccule, lagena and vertical posterior canal on the ipsilateral horizontal and vertical anterior semicircular canals in Rana esculenta: role of receptor-receptor fibres. The influence of the efferent vestibular system being eliminated, the spontaneous activity of single afferent fibres of the ampullary nerves of the horizontal and vertical anterior semicircular canals was recorded in the frog. By stimulating electrically the nerves of the vertical posterior canal, lagena or saccule as well as by sectioning these nerves and then using statistical methods, it is shown that the receptor-receptor fibres arising from the above mentioned receptors have generally an inhibitory influence on the afferent activity from the horizontal and vertical anterior canals.


Effects of the replacement of chloride by methylsulphate on the membrane currents in frog atrial trabeculae. The effect of the replacement of extracellular chloride by methylsulphate was investigated on isolated frog atrial trabeculae using the voltage clamp technique. In methylsulphate solution, the following results were obtained: 1. After a transient depolarization of the resting potential, the action potential was lengthened and the diastolic depolarization rate of the repetitive activity was reduced. 2. In voltage clamp conditions, the current-voltage relationships and the steady-state inactivation curves of both early and secondary inward currents were unaffected. 3. The study of the evolution of the instantaneous backgroundd current with membrane potential showed a decrease of the current values. 4. The first component of the time-dependent outward currents was unaffected but the second component was reduced without change of its time-constant value. Assuming the absolute value of the chloride equilibrium potential at about -30 mV, it was suggested that the lengthening of the action potential in methylsulphate solution might be explained by the decrease of an influx of chloride ions which should participate in the repolarization. The reduction of the diastolic depolarization rate might be due to the decrease of an outflux of chloride ions which should be involved in the inward background currents unmasked by the deactivation of the time-dependent outward currents.


Problem-orientation: an experimental study to test its heuristic value. Using a two-group before--after experimental design, this study explored the effect of problem-orientation on a nursing staff's ability to identify underlying patient problems. Nursing service staff members (registered nurses, licensed vocational nurses, and corps personnel) from two small naval hospitals who met the criteria for inclusion and consented to participate were utilized. Because of staff turnover, the composition of the groups differed from preto posttesting phases. The pretest sample consisted of 47 control/48 experimental subjects; the posttest sample included 38 control/39 experimental subjects. The experimental group was instructed on the independent variable, problem-orientation, by the investigator through a six-hour workshop on the problem-oriented nursing record after which the system was instituted in the experimental setting. After a five-month period posttesting was done to determine if changes had occurred. Analysis of the data supported the hypothesis that problem-orientation does, in fact, substantially increase a nursing staff's ability to identify patient problems. The incorporation of this system into nursing services could provide a vehicle for pinpointing underlying patient problems and dealing with them in a systematic way, thereby upgrading patient care.


The role of serotonergic and cholinergic systems in the aggression-stereotypy complex produced by amphetamine in mice. The aggression--stereotypy complex (ASC) was produced in mice by administration of 15 mg/kg of amphetamine. The elevation of cerebral serotonin level in the mouse brain by administration of L-tryptophan or DL-5-hydroxytryptophan suppressed the aggressiveness without affecting significantly the stereotypy. Serotonin antagonists: methysergide and cyproheptadine, did not potentiate clearly the aggressive component of ASC. Cholinomimetics, pilocarpine and physostigmine, strongly suppressed the aggressive component, while a cholinolytic, scopolamine, evidently potentiated the elements of aggressive behavior. The aggressiveness observed in the ASC in the mouse receiving a large dose of amphetanine is predominantly dependent on the increase of activity of dopaminergic system, but seems to be functionally dependent also on the serotonergic and cholinergic systems.


Ly phenotype of T cells cytotoxic for syngeneic mouse mammary tumors: evidence for T cell interactions. Specific cell-mediated cytotoxicity (CMC) of lymph node cells from immunized C3Hf mice, against syngeneic C3H/Umc mammary tumor cells, assayed in vitro, is effected by T lymphocytes. This CMC response is biphasic, with an early peak attained within 6 hr and a second major peak beginning at about 18 hr. Effector cells of both the early minor and late major phases of the response belong to the Ly23 set. Other T cell sets evidently play no part in the early effector response. But specifically activated Ly1 cells help or amplify the major late-phase response. Nevertheless, the mixture of specifically activated Ly1 and Ly23 sets still does not completely reconstitute the late response, which implies that the Ly123 set is also needed for maximal expression of CMC in this system. These Ly123 cells must come from specifically immunized donors. It appears, therefore, that maximal CMC is achieved by the participation of specific Ly123 cells which in the late phase directly or indirectly give rise to Ly23 killer cells. Thus, although killing of syngeneic mammary tumor cells in the CMC assay is invariably effected by cells of the Ly23 set, specifically activated cells of the Ly1 set, and probably of the Ly123 set also, are participants in the interactions needed to produce a maximal CMC response.


Cultured aortic endothelial cells from pigs with von Willebrand disease: in vitro model for studying the molecular defect(s) of the disease. Aortic endothelial cells from normal pigs and pigs with von Willebrand disease have been established in long-term cultures. Both cultures appeared similar in terms of general growth characteristics, morphologic features and ultrastructure. Immunofluorescent staining of these cultures with chicken (or rabbit) antiporcine ristocetin-Willebrand factor sera (or IgG) resulted in extensive perinuclear staining of the cells in both cultures. Additionally, staining of semiconfluent cultures of normal cells for ristocetin-Willebrand factor revealed an extensive meshwork of distinct, immunologically identifiable ristocetin-Willebrand factor-containing filaments between cells. Immunoreactive material was considerably decreased and more diffuse between cells in semiconfluent cultures from affected pigs. Through immunocytochemical staining with peroxidase-coupled antiserum, the filaments (of indeterminate length) were found to have a diameter of approximately 300 A. Finally, washed porcine platelets interacted extensively with scrape-damaged cultures of affected endothelial cells. This interaction of platelets with damaged normal cultures was abolished by pretreatment of the cultures with rabbit antiporcine ristocetin-Willebrand factor IgG.


Rectal bleeding secondary to fecal disimpaction: angiographic diagnosis and treatment. Two cases of bleeding caused by manual disimpaction of fecal material are presented. Angiography played a critical role in the diagnosis and treatment. One case was managed with balloon tamponade, and the other was successfully treated by selective intra-arterial vasopressin infusion, after prior intravenous infusion had been ineffective. A history of fecal disimpaction should suggest the possibility of low rectal bleeding which can be diagnosed and treated angiographically.


[Radiological diagnosis of tumours of brain stem (author's transl)]. Cerebral pneumography, positive ventriculography and vertebral angiography were employed in the examination of 154 of tumour of brain stem at Departments of Neuroradiology in the city of Naples between 1962 and 1974. The findings in various sites are described and discussed and several examples are presented.


Effectiveness of murine leukemia chemotherapy according to the immune state: reconsideration of correlations between chemotherapy, tumour cell killing, and survival time. Cyclophosphamide (CPM) chemotherapy (134 mg/kg) of L1210 leukemia is less efficient in mice previously immunodepressed by antithymocyte serum (ATS) than in non-ATS pretreated mice. On the other hand, administration of a higher dose of CPM (403 mg/kg), which kills a greater number of leukemic cells but induces an immunodepression, according to the skin graft test, results in a shorter survival time than does the administration of a lower dose of CPM (134 mg/kg), capable of killing fewer leukemic cells but not inducing such an immunodepression. Thus, it appears that: (1) the antileukemic effect of the same dose of a chemotherapeutic drug is less efficient in immunodepressed than in nonimmunodepressed hosts, and (2) calculation of the number of neoplastic cells killed by a given chemotherapy by extrapolation from the survival time may lead to erroneous conclusions.