The replacement of trideuteromethyl by methyl groups when using methane as a reagent gas in chemical ionization mass spectrometry. The methane chemical ionization spectra of a number of tertiary and quaternary amines with a N-trideuteromethyl group show substitution of this group by methyl. The isotopic purity of the original amines was shown to be greater than 99% using ammonia as a reagent gas.


Chemical ionization and field desorption mass spectrometry of the gentamicins. Gentamicin sulphate employed in therapeutics consists of a mixture of three major aminoglycoside components, the gentamicins C1, C1a and C2. In the electron impact mass spectra of these components weak parent ions may be observed but they are of no diagnostic value in the commercial mixture. Chemical ionization and field desorption spectra of individual gentamicin components and commercial mixtures are reported and discussed. Isobutane chemical ionization spectra exhibit some fragmentation, but under optimum field desorption conditions little glycosidic cleavage is observed and [M + H]+ ions dominate the spectra.


Mass spectrometric investigation of peptide amides. The reaction products of trifluoroacetic anhydride with peptide amides are identified as stable heterocyclic imidazolin-5(4)-ones, which can be analysed by gas chromatography mass spectrometry. The mass spectra show intense molecular ions and allow the assignment of the amino acid sequence.


Field desorption mass spectra of methotrexate and folic acid analogs. Field desorption mass spectra of methotrexate and folic acid analogs yield abundant molecular or quasimolecular ions. At emitter currents above the best anode temperature, fragment ions which are useful as further confirmations of structures are observed.


The analysis of terbutaline in plasma and urine at therapeutic levels using mass fragmentography. A sensitive method for the qualitative and semiquantitative determination of terbutaline in plasma and urine has been developed. After a single oral dose of 5 mg terbutaline sulphate the drug could be analysed easily. The detection limit in plasma is less than 1 ng ml-1.


Specific deuteromethylation by the Eschweiler-Clarke reaction. Synthesis of differently labelled variants of trimethylamine and their use for the preparation of labelled choline and acetylcholine. Reductive methylation (the Eschweiler-Clarke reaction) was used as a route for the synthesis of differently deuterium labelled variants of trimethylamine with the ultimate aim of preparing labelled variants of choline and acetylcholine. Combinations of unlabelled and labelled formaldehyde and formic acid yielded symmetrically labelled trimethylamines of high isotopic purity. The labelled congeners to acetylcholine and choline that were prepared subsequently provide suitable internal standards and tracers to be used in mass spectral analysis and in the evaluation of the pharmacokinetics of the parent compounds.


Hereditary angioedema: modification of clinical manifestations with androgens. HAE is an autosomal dominant trait of decreased levels or function of circulating and tissue C'1 esterase inhibitor. The clinical illness is characterized by disabling episodes of peripheral, oropharyngeal and gut-wall edema. Long-term fluoxymesterone treatment of 5 affected males (393 patient-months) and oxymetholone treatment of 6 affected females (204 patient-months) has significantly decreased the frequency of attacks of edema without substantive side effects.


Heterogeneity in the campomelic syndromes: long and short bone varieties. There appears to be definite heterogeneity within the campomelic syndromes. We are broadly classifying these into the classic or long bone campomelic syndromes and 2 distinct short bone varieties designated as the normocephalic short-boned and craniosynostotic short-boned types, respectively (Table 1).


Abnormal hemoglobins in a quarter million people. Hemolysates of erythrocytes from more than a quarter million people in Alabama were electrophoresed on cellulose acetate, pH 8.4, and those samples exhibiting an abnormality were also electrophoresed in citrate agar, pH 6.0. The globin chains of mutants other than Hb S and C were electrophoresed in urea-mercaptoethanol buffers at both pH 8.9 and pH 6.0, and 60 of them were also analyzed structurally. Of about 6000 samples from whites, only three contained abnormal hemoglobins--Hb D Los Angeles, Hb J Baltimore, and one unidentified. Of 249,000 samples from blacks, about 29,000 contained electrophoretically detectable abnormalities, most of them associated with Hb S or C, present in a frequency of about 9% and 3%, respectively. About 1000 samples resolved into patterns of potential clinical significance. Twenty other mutant hemoglobins were detected, in various genetic combinations in 164 kindreds; four of these-Hb Alabama, Montgomery, Titusville, and Mobile--were previously unknown. The methods used are rapid, economical, and well suited for large scale surveys. They provide highly specific characterizations of many mutant hemoglobins, and no discrepancies were found between the presumptive identifications based on these characterizations and the definitive identifications obtained from structural analyses.


Hemoglobin M equon beta 41 (C7) phenylalanine leads to tyrosine. A severe hemolytic crisis was observed in a 34-yr-old female of English-Irish extraction following a viral illness treated with acetaminophen. Heinz bodies and heat instability were present only during a transient hemolytic event. A challenge dose of acetaminophen caused no detectable hematologic abnormality. Structural studies of the hemoglobin during hemolysis and again after complete recovery localized the abnormality to tryptic peptide beta Tp-5, and automated sequencing of I 125-labeled beta chains indicated a replacement of phenylalanine (C7) beta 41 by tyrosine. Substitution of the next residue, phenylalanine (CD1) beta 42 by serine (Hb Hammersmith), has resulted in chronic severe Heinz body hemolytic anemia. The lack of chronic anemia in the present disorder may reflect the different relationships of beta41 and beta 42 and/or the similarities in volume and hydrophobicity of tyrosine and phenylalanine. It is suggested that substitution of tyrosine for phenylalanine in Hb Mequon may disturb the critical environment around the heme group and render it susceptible to oxidative denaturation in the presence of infections and/or drugs.


Red cell membrane deformability: new data. Red cells arrested by fine fibers and subjected to drag forces in a moving stream of fluid can be stressed beyond the point of rupture. The technique, which is basically an in vitro analogue of the microangiopathic hemolytic state, thus permits a study of red cell behavior over the entire range of stress that the membrane can withstand. Measurements made by this approach show an exponential relationship between the velocity of fluid flow and the resultant membrane deformation. Such exponential membrane deformation is consistent with the morphology of red cell fragments and appears to explain their mechanism of formation.


Reticulocyte size in nutritional anemias. Alterations in reticulocyte size occur 2-3 days after the onset of iron deficient or megaloblastic erythropoiesis and precede, by several weeks, changes in mean corpuscular volume (MCV). Iron-deficiency anemia induced in a normal subject by repeated phlebotomies was characterized by the initial development of larger than normal reticulocytes followed by an abrupt decrease in reticulocyte size. Microreticulocytes appeared 3 days after the fall in per cent iron saturation and antedated the decrease in MCV to below normal by 6 wk. Mean reticulocyte size was disproportionately smaller than normal in patients presenting with iron deficiency. In contrast, reticulocyte size increased abruptly in a patient (and rats) 2-3 days after administration of methotrexate. Mean reticulocyte size was disproportionately larger than normal in patients presenting with folate or vitamin B12 deficiency. Specific replacement therapy with iron, folate, or vitamin B12 was quickly followed by normalization of reticulocyte size.


Specific chromosomal aberrations in polycythemia vera. The chromosomes of bone marrow cells from ten patients with polycythemia vera (PV) were identified by Q-, G-, and C-banding techniques. Four of the patients had received no treatment with cytotoxic drugs, while three had received 32P only and the other three, in addition, had received busulfan or busulfan and procarbazine. One 73-yr-old male patient treated with venesection only for 4 yr lacked the Y chromosome and had a deletion of the long arm of chromosome 20 (20q-) in all cells investigated. One of the other three patients who had received no drugs had a chromosome abnormality, but only in 1 of 19 identifiable metaphases. However, the abnormality was the same (+9) as the most common one in treated patients. In the group of treated patients, an extra chromosome 9 (+9) was found in three patients, an extra chromosome 8 (+8) in one, and a deletion of the long arm of one chromosome 20 (20q-) in one patient. Multiple aberrations in addition to the extra chromosome 9 were found in one patient in whom the disease had transformed into acute myeloblastic leukemia. The finding of identical chromosomal aberrations (20q- and +9, respectively) in two patients who had received no drugs and in four patients who had received 32P and busulfan or procarbazine favors the view that these aberrations are specifically associated with the disease and not induced by the drugs. With the exception of the patient with acute myeloblastic leukemia, all other patients are alive 1-11 mo after chromosome analyses and 1-229 mo after diagnosis.


Size distribution, electronic recognition, and counting of human blood monocytes. During a study on the separation of human blood monocytes from lymphocytes, a method was developed to recognize and count monocytes by electronic means. Lightscattering (Cytograf, Bio/Physics), and changes in electrical resistance (Channelyzer, Coulter) were used to size mononuclear leukocytes directly in cell suspensions. Both methods revealed a size distribution profile in which two populations of mononuclear leukocytes could be distinguished. The largest cells were virtually eliminated after phagocytosis of iron particles. We confirmed that these cells were monocytes by three different criteria: the intracellular lysozyme activity, the number of phagocytes, and the percentage of cells with kidney-shaped nuclei. The highly significant correlations we found showed that monocytes could be recognized and counted by electronic sizing. For this method, purified mononuclear leukocyte preparations had to be used, since the presence of erythrocytes, platelets, and polymorphonuclear cells interfered. Statistical analysis revealed that electronic sizing permitted discrimination of differences in monocyte content of 4.5%, with a probability of 95%. It was calculated that this sensitivity of electronic monocyte counting was about three times higher than the sensitivity of microscopic methods. Since 100,000 cells can be sized within a few seconds, not only the efficiency of the preparation but also minor changes in the size of monocytes and lymphocytes introduced during the isolation can be followed.


Surface markers of human eosinophils.

Surface markers of human eosinophils. Peripheral blood eosinophils from patients with eosinophilia and from healthy subjects were studied for surface immunoglobulins, receptors for the Fc region of IgG, complement receptors, and spontaneous rosette formation with sheep and mouse erythrocytes. Eosinophils were found to have receptors for complement and for aggregated IgG, and to have the same two types of complement receptors as do lymphocytes and monocytes. Immune adherence type receptors were specific for C4 or C3b, while C3d receptors were specific for C3d but unreactive with C4. Eosinophils differed from fully mature neutrophils in that the former had C3d receptors and relatively weak immune adherence (C4 or C3b) receptors, while the later did not have the C3d receptors and had strong immune adherence receptors. Eosinophil phagocytosis of complement-receptor bound erythrocytes was dependent on the presence of IgG in the antibody coating the red blood cells; this requirement for IgG resembled that found in neutrophil phagocytosis. No surface Ig or spontaneous erythrocyte rosette formation was observed with eosinophils.


Stimulation of megakaryocytopoiesis by acute thrombocytopenia in rats. Rats were made acutely thrombocytopenic by injection of antiplatelet serum. Marrow sections and squash preparations were made at intervals during 120 hr. Determinations were made of mitotic index, stage of maturation, ploidy level, and cell size of megakaryocytes; number and size of platelets were measured. Increased endomitosis among megakaryocytes was followed by an increase in the proportion of immature megakaryocytes, a greater average ploidy level of recognized megakaryocytes, and larger megakaryocytes. Maximum changes in these several parameters occurred between 32 and 72 hr after induction of thrombocytopenia. By 120 hr all megakarocyte parameters were near normal. For about 3 days, beginning at about 36 hr, platelet numbers increased rapidly. Average platelet size rose and returned to normal within about 60 hr. Changes in ploidy and size of megakaryocytes were measured in the immature and mature maturation stages. The results suggest that the initial stimulus in response to acute thrombocytopenia acts primarily on diploid precursors, programming them to mature into a population of megakaryocytes with an average ploidy approximately one level greater than in normal rats and a proportionate increase in cell size. The larger megakaryocytes presumably produce more platelets, accounting for a major part of the increased rate of platelet production. Since the changes in megakaryocytes begin to reverse before circulating platelet numbers have reached the normal level, reversal of the stimulus appears to be initiated by some change other than platelet mass.


Collagen metabolism during the early stages of cholesterol-induced atherogenesis in rabbits. The involvement of collagen in cholesterol-induced atherosclerosis in rabbits was investigated. Rabbits were fed a 2% cholesterol diet for 8, 16, 30, 60 and 90 days. Histological sections were taken and aortic free and esterified cholesterol were determined after separation on thin-layer chromatography. Prolyl hydroxylase activity was used as a measure of collagen synthetic rate and hydroxyproline levels as an estimate of collagen content. Cholesterol content was a significantly increased after 8 days, while at this time there were no gross aortic lesions. After 30 days there was some aortic disease and by 60 days most of the rabbits exhibited pronounced aortic lesions. Histologically, the lesions consisted mainly of intimal foam cells. There was no alteration in collagen synthetic rate or content at 8, 16, 30 or 60 days. These data indicate that 60 days of continuous cholesterol feeding results in a foam cell aortic lesion with no alteration in collagen metabolism. After 90 days of cholesterol feeding there was significant increase in collagen synthetic activity in the thoracic aorta. These data suggest that alteration of collagen synthetic activity is secondary response, resulting from injury induced by the aortic accumulation of large amounts of cholesterol.


A comparative study of the role played by some inactivation pathways in the disposition of the transmitter in the rabbit aorta and the saphenous vein of the dog. The aim of this study was to determine the relative importance of neuronal uptake, catechol-O-methyltransferase (COMT) and diffusion in the disposition of endogenous nor-adrenaline (NA) in the rabbit aorta and dog saphenous vein. Helical strips of dog saphenous vein and rabbit aorta were stimulated transmurally, relaxation occurring either in oil or in Krebs-Henseleit solution. The rate of inactivation of NA by various mechanisms was assessed from the decrease in the rate of relaxation after blockade of one or more of these processes. Cocaine was used to inhibit neuronal uptake and COMT was blocked with 3,4-dihydroxy-2-methyl propiophenone. Diffusion out of the tissue was prevented by replacing the Krebs-Henseleit solution in the muscle bath with mineral oil. Neuronal uptake was the primary mechanism of inactivation in the saphenous vein whereas diffusion and COMT appear to be more important in the aorta. The differences in the relative importance of the inactivation mechanisms (neuronal uptake, O-methyltransferase and diffusion) existing between these two vessels are attributed primarily to differing density and distribution of the adrenergic innervation.


Phospho-accepting proteins in bovine sera. Phospho-accepting proteins in bovine sera have been detected by the use of immobilized protein kinase from rat muscle and (gamma32P)-ATP in an in vitro system. A partial biochemical characterization points to the generation of typical phosphoproteins. Differences in the phosphorylation pattern between fetal serum and calf serum as demonstrated by electrophoresis in the presence of dodecylsulfate are described.


Decrease of normotest/thrombotest discrepancy in non-contacted coumarin plasma after glass or ellagic acid activation. Activation of coumarin plasmas in glass tubes for 60 min resulted in a clear shortening of Thrombotest clotting times. Normotest clotting times were shortened too but to a much lesser extent. As a consequence the Normotest (NT)/Thrombotest (TT) discrepancy which was quite large at 0 time, became progressively smaller. This phenomenon was observed both in undiluted and 6:10 diluted plasma. After ellagic acid activation a similar phenomenon was noted even though a less pronounced shortening of Thrombotest was noted. These data suggest that Thrombotest is very sensitive to contact phase and to factor VII activation and not to any coumarin-induced inhibitors.


Lead in tissues of mallard ducks dosed with two types of lead shot. Mallard ducks (Anas platyrhynchos) were sacrificed one month after ingesting one number 4 all-lead shot or one number 4 lead-iron shot. Livers, kidneys, blood, wingbones, and eggs were analyzed for lead by atomic absorption. Necropsy of sacrificed ducks failed to reveal any of the tissue lesions usually associated with lead poisoning in waterfowl. Lead levels in ducks given all-lead shot averaged about twice those in ducks given lead-iron shot, reflecting the amount of lead in the two types of shot. Lead in the blood of ducks dosed with all-lead shot averaged 0.64 ppm, and 0.28 ppm in ducks given lead-iron shot. Lead residues in livers and kidneys of females given all-lead shot were significantly higher than in males. In both dosed groups, lead levels in wingbones of females were about 10 times those in males, and were significantly correlated with the number of eggs laid after dosage. Lead levels in contents and shells of eggs laid by hens dosed with all-lead shot were about twice those in eggs laid by hens dosed with lead-iron shot. Eggshells were found to best reflect levels of lead in the blood. Our results indicate that mallards maintained on a balanced diet and dosed with one lead shot may not accumulate extremely high lead levels in the liver and kidney. However, extremely high lead deposition may result in the bone of laying hens after ingesting sublethal amounts of lead shot as a result of mobilization of calcium from the bone during eggshell formation.


Plasticizers as interferences in pollutant analyses. Airborne compounds from two groups of plasticizers used in air conditioner filters and caulks as well as flexible polyvinyl chloride and related plastics have been identified as major sources of low level laboratory contamination that can cause serious interferences in pollutant analyses especially at the low levels requiring GCEC for quantitation. Two compounds from the phthalic acid ester group (PAE'S) OF PLASTICIZERS THAT ARE ENVIRONMENTAL POLLUTANTS AS WELL WERE FOUND INCORPORATED ON AIR CONDITIONER FILTERS LEADING TO CONTAMINATION OF CLEAN AND OIL FILMED DISHES FROM AIR FALLOUT. Solvents, inorganic reagents and hand-to-glass transfer were found to contribute to sample contamination by PAE's. Several PAE's are easily detectable at 0.1 ng levels under some conditions on GCEC and have retention times on several columns of differing polarities that can interfere with analyses of chlorinated pollutants especially p,p'-DDT. Aroclor 1254, a member of the polychlorinated biphenyl group (PCB's) of plasticizers, was found in a caulk around a laboratory window. On oil filmed, but not clean dishes, the compounds collected from air fallout produced chromatograms on GCEC with a close correspondence to Aroclor 1242.


Some aspects of orthopaedic surgery in childhood. The aetiological role of immunodeficiency in acute septic arthritis of the hip in infancy, the management of the condition after the acute infection has subsided, and the special hazards of infection in the region of the hip joint in the older child are discussed. The principles of treatment of congenital dislocation of the hip are examined in relation to the maintenance of acetabular growth potential. The factors determining the outcome of treatment in Perthes' disease are discussed and a comparison of the result in a series of cases treated by femoral osteotomy with those in untreated controls is presented.


Steroid induced avascular necrosis of bones in eighteen sites: a case report. A patient with idiopathic thrombocytopenia purpura who was treated with high dosage corticosteroids for ten years, developed 18 separate lesions of avascular necrosis in 12 different bones. Despite spontaneous revascularization of many of the lesions, subchrondral collapse caused symptomatic secondary degenerative arthritis in many joints. Pathological examination of both resected femoral heads showed no intravascular thrombosis.


Irreducible fractures of the distal phalanx of the hand. Fractures of the distal phalanx of the hand occur usually by crushing can be irreducible, if the nail fold is interposed between the fracture fragments. Details of the regional anatomy producing the deformity and the management are discussed.


Flexor digitorum superficialis rupture: a case report. A rupture of the musculotendinous junction of the flexor digitorum superficialis to the index finger in a baseball pitcher is described. No underlying abnormality could be detected. Because of loss of strength and dexterity, repair of the rupture was accomplished with an improved result.


Studies of the corrosion susceptibility of metallic cement restrictors: comparative corrosion behavior of stainless steel and cobalt-chromium alloys. Passive film and accelerated corrosion tests were performed on both wrought AISI 316L stainless steel and wrought Vitallium (Haynes Stellite 25) Charnley Type cement restrictors. The morphology and incidence of corrosion at the wire-wire crevices and the methacrylate-metal crevices were determined by scanning electron microscopy. The results are interpreted in view of the previously-documented crevice corrosion susceptibility of these two alloys.


Pain and the pronator teres syndrome.

Pain and the pronator teres syndrome. Extremely painful paresthesias and mild motor weakness of the hand were relieved by sectioning the deep head of the pronator teres muscle and the fibrous arch of the flexor digitorum superficialis, thereby freeing the median nerve and its anterior interosseous branch. The characteristic pinch deformity of the thumb and index fingers usually described in anterior interosseous-nerve syndrome was not present. A Tinel sign at the level of the pronator teres was present.


On the uses of diversity.

On the uses of diversity. An examination is made of the uses of diversity in medical library activities and personnel. This concept is extended also to the broader field of librarianship and to some forecasts of future directions for medical libraries.


Planning for meaningful change in libraries and library networks: a first step. The Program Planning Model (PPM) is a planning and management tool that facilitates development and acceptance of significant programs. PPM assists program planning by systematically involving consumer or user groups in the development and review of new programs. While user participitation is important throughout PPM, this involvement is especially important during the problem exploration phase, when the problems or needs of these users are surveyed. The Nominal Group Technique (NGT), a variation of the "brainstorming" process, is a structured but flexible group process used in the problem exploration phase to generate a high number of useful responses concerning problem areas. NGT ensures maximum contribution of ideas by all participtants. NGT and its application in the planning and management efforts of several libraries and library networks are described in detail.


Nonmediated use of MEDLINE and TOXLINE by pathologists and pharmacists. Pathologists and pharmacists have used terminals in their departmental areas successfully to perform searches on MEDLINE and TOXLINE, during the period from fall 1974 through August 1975; MEDLINE has been used more than TOXLINE. In the Department of Pathology at the University of Maryland Health Sciences Center, the annual rate of combined mediated and nonmediated use of MEDLINE increased from 142 search sessions to 432, over half of the identified use being by three individuals. About half of the total potential users from each group tried MEDLINE or TOXLINE at least once. Nine pathologists and seven pharmacists used MEDLINE five or more times. Five of the individuals in each group were "intensive" users, who concentrated more than half of their sessions within two months. Vocabulary experience and systems problems are touched on. Most individuals learned to use the systems from one another or in individual sessions with the authors, although a twenty-five page "minimanual" has also been used by a limited group.


Primary journal selection using citations from an indexing service journal: a method and example from nursing literature. Although serial literature is extremely important to a library collection, it is also the source of many problems. Specialty journal selection is difficult, particularly for the librarian of a small or intermediate-size library that is not in a position to develop or maintain an exhaustive or inclusive collection in a particular field or discipline. Steadily increasing journal costs and recent economic trends necessitate establishment or reexamination of a periodical collection policy. In this investigation, the technique used analyzes citations assigned to medical subject headings (MeSH) and subheadings by indexers who prepare the MEDLARS data base. Citations have been retrieved by exploiting the on-line nature of the MEDLARS data base. A four-year time period is used to identify specialty journals in the area of nursing. Results given include a separate rank-order listing arranged by decreasing frequency of productivity for each MeSH term searched. A composite listing is given for the 16,355 unique citations retrieved. The approach illustrated and data presented may be useful in establishing library policy for questions of periodical subscription and setting of priorities for binding and microform purchases. The purpose of the approach described is to predict collection demand with efficiency and economy.


New library buildings. Part VIII. The Library of the Health Sciences, University of Illinois at the Medical Center, Chicago. The new Library of the Health Sciences at the University of Illinois at the Medical Center is described and illustrated. The building was under construction for thirteen months, using phased construction techniques, and opened in October 1973. The library is a self-contained and physically independent building consisting of three levels above ground and one lower level, comprising an area of 130,000 sq. ft. gross and 88,000 sq. ft. net. The building provides space for 350,000 volumes, 1,037 readers, and a staff of 100. The cost of construction was $5,140,500 plus $858,500 for furnishings and equipment. Among the special features are a twenty-four-hour multimedia services department and a full-circulating style book detection system. Included in the article is an evaluation of the library after two years of occupancy.


Leptospirosis as an animal and public health problem in Latin America and the Caribbean area. As a major livestock disease, leptospirosis cuts significantly into the world's supply of animal protein through its consequences of abortion and calf mortality, retarded growth, and reduced milk production. Evidently, such losses have severe economic implications as well. The disease's impact has been somewhat diminished in the developed countries thanks to mechanization of rural activities, improved personal and environmental hygiene, and broad application of preventive measures, including the administration of bacterins, in domestic animals. Still, even in these circumstances it remains a serious problem. In the developing countries, in which large percentages of the population live in close contact with animals, the spread of infection is much greater. Moreover, the ecology of tropical and subtropical America--with its abundant rainfall, natural water courses, and high temperatures--is particularly favorable for the transmission of leptospires. In such conditions the human disease is a growing threat as well. The spread of leptospirosis, both in animals and man, is facilitated by the fact that inefection from many of the serotypes can exist without presenting serious clinical manifestations. Hence the importance of laboratory diagnosis. Systematic studies over time of serotype distribution, coupled with wide and improved surveillance, will be a key factor in bringing the disease under control. According to the limited seroepidemiologic data available, 3 to 18 per cent of the general human population, 2 to 32 per cent of those belonging to exposed occupational groups, and 10 to 50 per cent of patients with fever of unknown origin have leptospiral antibody. The most predominant serogroups are Icterohaemorrhagiae, Canicola, Pomona, Hebdomadis, and Bataviae. So far more than 50 serotypes, from 15 serogroups, have been isolated from man and animals in Latin America and the Caribbean area.


Immunization against leptospirosis: vaccine trials with heat-killed whole cell and outer envelope antigens in hamsters. Heat-killed whole cell and outer envelope antigens prepared from homologous virulent and avirulent strains of Leptospira serotypes canicola and pomona were evaluated for protecting hamsters against experimental leptospirosis. The heat-killed bacterins proved at least as effective as the outer envelope antigens, or more so, in providing protection against death and infection, and they are easier and more economical to prepare.


Diarrheal diseases of infancy in Cali, Colombia: study design and summary report on isolated disease agents. For public health reasons, it is important that the etiologic agents of early childhood diarrhea be isolated and identified, and that their routes of transmission be defined. This is especially true in tropical and subtropical developing countries, where childhood patterns of exposure to diarrheal disease agents usually differ from those in developed countries, and where diarrheal illness is a frequent harbinger of death among children under five years of age. This artical describes a study designed to identify diarrheal disease agents and transmission patterns in Cali, a large city of western Colombia's fertile Cauca River Valley. The study area, composed of five working-class districts with a total population of some 40,000, appeared to provide an environment fairly similar to those of many other "average" working-class communities in Latin America. Beginning in July 1962, a cohort of 296 children being born in these districts was studied, the period of investigation starting with the date of birth and continuing until each child's second birthday or its premature withdrawal from the study. Weekly home visits were made to establish defecation patterns, feeding practices, and anthropometry. The resulting data were then analyzed in terms of defecation frequencies, occurrence of liquid stools, and the presence of blood, mucus, or pus in the stools. Differences were noted in male and female defecation patterns and in the defecation frequencies of different age groups. Stool specimens for bacteriologic, virologic, and parasitologic examination were collected monthly on a regular basis and weekly when diarrhea occurred. Numerically, viruses were isolated and identified more often than other agents. The most commonly isolated parasite species and viral and bacterial serotypes were G. lamblia (from 222 subjects), echovirus 11 (from 166 subjects), and enteropathogenic Escherichia coli 026:B6 (from 138 subjects). Compared with the findings of several studies in other countries, isolations of shigellae were relatively rare.


National service in rural areas: the case of Colombia. Sending new medical school graduates into rural areas does give underserved populations access to modern medical care, perhaps for the first time. However, these young physicians usually spend most of their time providing strictly clinical services and are generally eager to leave at the end of their assignment. Some have referred to this practice as "parachuting" a doctor into an underserved area. An alternative is to focus first on building up permanent health service facilities in rural areas that are staffed by appropriate paraprofessionals. The young physician can then play a much more important role, serving as an administrator, researcher, evaluator, and teacher of the local staff; his clinical activities would generally be confined to the more complicated medical problems that arise. Such a model has been implemented in Kenya and Tanzania. An informal field assessment in Colombia has indicated that this model could be effectively applied there as well; indeed, it has been the hope of Colombian policymakers that the rural intern would function in such a way. However, this would require developing the nation's system of health services, as well as providing specific training aimed at preparing the medical student to perform his assigned role.


Earthquake in Guatemala: epidemiologic evaluation of the relief effort. The damage wrought by the earthquake that recently struck Guatemala evoked a commendable and efficient national response. It also led to international relief activity that was clearly instrumental in assisting the country's short-term recovery efforts. At the same time, this initial recovery period caused a good deal of experience to be gained in the field of disaster management. Some of the lessons derived from the experience are examined, and a number of approaches are suggested for measurably improving both national and international response to future disasters of this kind.


An irreversible effect of lithium administration to patients. 1 Lithium administration to patients leads to a pronounced inhibition (about 90%) of the choline transport system in erythrocytes. The transport system does not recover when ghosts are prepared from the erythrocytes, thereby removing intracellular as well as extracellular lithium. 2 When a patient is taken off lithium, the choline transport in erythrocytes recovers only very slowly over a period of three months, i.e. at about the same rate at which the erythrocytes that had been exposed to lithium are replaced by new cells. 3 It is concluded that therapeutic concentrations of lithium produce an irreversible inhibition of the choline transport system in human erythrocytes.


Depression by morphine of excitatory junction potentials in the vas deferens of the mouse. 1 Intracellular recordings were made from smooth muscle cells of the mouse vas deferens. Excitatory junction potentials (e.j.ps) were evoked by stimulation of the intramural nerves. 2 Normorphine (50 nM-5muM) depressed the amplitude of the e.j.p. The ED50 was 430 nM. The latency of the e.j.p. and the resting membrane potential of the smooth muscle cells were unaffected by normorphine. 3 The depression of the e.j.p. by narcotic analgesic drugs was stereospecific. 4 Naloxone (100 nM) completely reversed the depression of the e.j.p. produced by normorphine (1 muM). Naloxone (100 nM) alone did not alter the amplitude of the e.j.p. 5 Normorphine (1 muM) did not prevent the depolarization of the smooth muscle cells produced by exogenous noradrenaline (10 muM). 6 It is concluded that narcotic analgesic drugs act directly upon the transmitter release sites to reduce the amount of noradrenaline liberated by each nerve impulse.


The cholinergic component in the reflex vasodilatation elicited by stimulation of the depressor nerves in the rabbit. 1 The effects of the stimulation of the cephalic endings of the depressor nerve on the resistance in the perfused hindlimb were studied in the rabbit. 2 The vasodilatation thus elicited in the perfused hindlimb was reduced either by administration of guanethidine or by sympathectomy and abolished by subsequent treatment with atropine. 3 These data confirm the existence of two components in the genesis of the reflex vasodilatation: a passive component, due to the inhibition of sympathetic discharge, and an active component which in the rabbit is cholinergic in nature.


Uterine receptors for oxytocin: correlation between antagonist potency and receptor binding. 1 The apparent dissociation constants (Kd) of four competitive antagonists of oxytocin were estimated from their ability to compete with [3H]-oxytocin for binding sites in particulate fractions from rat uterine homogenates. 2 These apparent Kd values were not significantly different from the Kd values calculated from the published potency of each compound as an antagonist of oxytocin-induced uterine contractions. 3 These results support the conclusion that the binding sites for oxytocin are part of the receptor complex. Furthermore, 'spare receptors' for oxytocin do not appear to be present in significant quantities, and the relative potency of each antagonist appears to depend upon its affinity for the receptor site rather than its intrinsic activity. 4 The antagonists used in these studies were [N-acetyl, 2-O-methyltyrosine]oxytocin, [1-(beta-mercapto-beta,beta-diethylpropionic acid)]oxytocin, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid)]oxytocin, and [1-(deaminopenicillamine), 4-threonine]oxytocin.


The use of different agonists in antagonist affinity constant estimations. 1 The affinities of 4 muscarinic antagonists were estimated on intact pieces of guinea-pig ileum using the agonists carbachol and pentyl trimethylammonium both in separate experiments and in the same experiment. 2 The apparent affinities were slightly but consistently higher when estimated from the responses produced by pentyl trimethylammonium than when estimated from the responses produced by carbachol. 3 This difference was greatly reduced or abolished if totally denervated logitudinal muscle strips were used rather than intact pieces of ileum. It is therefore suggested that the difference is due to the presence of receptors in the ganglionic layer. 4 To explain the difference in apparent affinity of the antagonists these receptors can not be identical to the muscarinic receptors on the smooth muscle. 5 In addition they can not be nicotinic ganglionic receptors as the difference did not appear to be affected by the presence or absence of hexamethonium.


The pharmacology of anaphylaxis in the chicken intestine. 1 The Schultz-Dale phenomenon has been demonstrated in several circular smooth muscle strips of oesophagus, crop, duodenum, jejunum and ileum taken from young and adult domestic fowl sensitized actively to crystalline bovine albumin or horse plasma. 2 The ileal strips contract to acetylcholine, histamine, 5-hydroxytryptamine (5-HT), prostaglandins E1, E2, F2alpha, bradykinin and bovine slow reacting substance of anaphylaxis (SRS-A). Marked seasonal and individual variations in the responsiveness of gut tissues to these exogenous agonists were noted. 3 Antagonism of contractions to histamine by mepyramine suggests the existence of H1-histamine receptors in chicken ileum. Blockade of 5-HT-induced contractions by methysergide shows the preponderance of 'D'-musculotropic tryptamine receptors. 4 Failure of selective receptor antagonists of acetylcholine, histamine and 5-HT to modify the Schultz-Dale reaction suggests the nonparticipation of aminergic mechanisms in this reaction. 5 Partial to complete blockade of the Schultz-Dale reaction by a prostaglandin receptor antagonist (polyphloretin phosphate, PPP); prostaglandin synthetase inhibitors (sodium meclofenamate and phenylbutazone); inhibitors of synthesis and release of histamine and SRS-A (PR-D-92-EA, M & B 22948, diethylcarbamazine citrate, and PPP) and an inhibitor of proteinases (aprotinin) strongly suggests the involvement of vasoactive lipids and polypeptides in the anaphylactic response of chicken ileum to specific antigen.


Adenosine on myocardial oxygen consumption. 1 A 3 min intracoronary infusion of adenosine (50 mug/min) produced a significant decrease in coronary artery perfusion pressure, left ventricular systolic pressure and myocardial O2 consumption in the isolated supported heart preparation of the dog perfused at a constant coronary blood flow. Heart rate was controlled at 150, 190 or 230 beats/minute. 2 Myocardial contractile force and maximal left ventricular dp/dt were not changed by adenosine infusion. 3 The absolute decrease in myocardial O2 consumption was greater at increasing heart rates whereas the decrease in coronary artery perfusion pressure and peak left ventricular systolic pressure were similar. 4 The results suggest that the reduction in myocardial O2 consumption produced by adenosine is not related to coronary vasodilatation or to a negative chronotropic or inotropic action, but may be due to a functional shunting of blood flow from high O2 extracting regions of the myocardium to low O2 extracting ones and/or important effects on myocardial substrate utilization.


Decreased phenylethanolamine-N-methyltransferase and catechol-O-methyltransferase activity in rabbit adrenal glands during pregnancy. 1 Phenylethanolamine-N-methyltransferase (PNMT) activity in adrenal gland was lower than the control values at day 24 of rabbit pregnancy and fell throughout the gestational period. 2 Catechol-O-methyltransferase (COMT) activity during pregnancy and parturition followed a similar pattern to PNMT. 3 Adrenaline content of the adrenal gland declined significantly during the last few days of pregnancy but at parturition showed a tendency to return towards normal. 4 The biochemical mechanisms which result in a decline in PNMT and COMT activities and adrenaline concentration appear to be the consequence of modifications in endocrine gland secretion during pregnancy.


Morphine-naloxone interaction in the central cholinergic system: the influence of subcortical lesioning and electrical stimulation. 1 The opiate antagonist naloxone, injected or topically applied to the cerebral cortex, had no significant effect on the spontaneous output of cortical acetylcholine (ACh) in rats. 2 Morphine (2.5 mg/kg) administered intravenously inhibited the release of cortical ACh. A subsequent injection of naloxone rapidly reversed morphine-induced inhibition, and produced a sustained increase in the release of ACh. Topical application of naloxone solutions, after morphine, produced a slow and weak reversal of its inhibitory action. 3 Destruction of the medial thalamus abolished both the inhibitory effects of morphine on the cortical ACh release, and its antagonism by naloxone administered after the agonist. 4 Injection of naloxone in a low dose (0.1 mg/kg) increased the release of cortical ACh provoked by electrical stimulation of either the medial thalamus or the reticular formation in normal rats. In the morphine-dependent rat, naloxone also facilitated the evoked release and its action was greater than in control animals. The facilitatory effect of naloxone on the cortical release evoked by stimulation of the medial thalamus was greater than its effect on the release evoked by stimulation of the reticular formation in both normal and morphine-dependent rats. 5 Naltrexone, a narcotic antagonist, also facilitated the electrically stimulated release of cortical ACh. 6 It is suggested that (a) morphine and naloxone act at a subcortical site, probably the medial thalamus, to modify the cortical ACh release and that (b) naloxone may facilitate the electrically-induced release of ACh in the CNS by antagonizing the effect of the endogenous morphine-like factor, enkephalin.


The effect of catecholamines on the influx of calcium and the development of tension in denervated mouse diaphragm muscle. 1 The nature of the catecholamine-induced contracture of chronically denervated mouse diaphragm muscle has been investigated and compared with the contractural response evoked by acetylcholine. 2 The time course of onset of catecholamine-sensitivity in denervated diaphragm muscles was similar to the development of acetylcholine sensitivity. However, catecholamine contractures were absent in tissues denervated for periods longer than 90 days whereas acetylcholine-sensitivity was still evident several months after denervation. 3 The catecholamine-induced contracture of the denervated muscle was inhibited specifically by beta-receptor blocking drugs and was unaffected by alpha-receptor blocking drugs and cholinoceptor antagonists. 4 Catecholamine-induced contractures of denervated muscles, unlike contractures to acetylcholine, were dependent upon the presence of spontaneous fibrillation and the amplitude of spontaneous fibrillation was increased by catecholamines. Fibrillation was absent in the presence of tetrodotoxin (1 muM), 2,4-dinitrophenol (10 muM), potassium cyanide (10 muM), ouabain (100 muM), in lithium chloride Ringer solution and at low temperature. Under these conditions catecholamine-induced contractures, but not those to acetylcholine, were abolished. 5 Labelled calcium was found progressively to enter denervated muscle fibres and this entry of calcium was increased by catecholamines. It is suggested that this calcium entry may represent either an increased calcium permeability of denervated muscle fibres which is increased further by catecholamines or the presence of a calcium current that occurs during the fibrillatory potentials of denervated muscle.


Effects of L-tryptophan and L-methionine on activity in the rat. 1 The effects of an intraperitoneal dose of 20 mg/kg L-tryptophan and doses of 100 and 150 mg/kg of L-methionine were investigated on activity in the rat. 2 Activity was measured by a time sampling behaviour categorization procedure, and began 15 min after compound administration, lasting for a total of one hour. 3 Total active behaviour in the first half hour was reduced after 20 mg/kg tryptophan, 100 or 150 mg/kg methionine. Only 20 mg/kg tryptophan led to a significant reduction in active behaviour during the second half hour. 4 Administration of 100 mg/kg methionine plus 20 mg/kg tryptophan, and 150 mg/kg methionine plus 20 mg/kg tryptophan had no discernible effect on activity. 5 The results draw attention to the role of another amino acid in the modification of the behavioural effects of tryptophan.


Influence of dopamine and noradrenaline on isolated cerebral arteries of the dog. 1 Effects of dopamine and noradrenaline were compared in helically-cut strips of canine cerebral arteries. 2 Dopamine caused a greater maximal contraction than noradrenaline, although the ED50 for noradrenaline was appreciably less. The contraction induced by these amines was reversed to a relaxation by treatment with phenoxybenzamine. 3 Relaxation induced by dopamine in phenoxybenzamine-treated and prostaglandin-contracted cerebral arteries was not influenced by 1 muM propranolol, while relaxation induced by noradrenaline at low concentrations (2 muM and 10 muM) was significantly attenuated. Neither aminophylline nor atropine affected the relaxant effect of dopamine. 4 A mechanism other than beta-adrenergic, cholinergic or adenosine-related appears to be involved in the relaxation elicited by dopamine in cerebral arterial strips.


The actions of natural secretin on the small intestinal vasculature of the anaesthetized cat. 1 A plethysmographic preparation of cat jejunum was used to measure changes in tissue volume and capillary filtration coefficient (CFC), simultaneously with measurements of arterial and venous pressures, and total blood flow. 2 Secretin was infused and injected intravenously and also infused intra-arterially in relatively small doses. Probable resulting blood concentrations were compared with those determined under physiological conditions in other investigations. 3 By intravenous or intra-arterial infusion, secretin caused increases in CFC, indicating an increased functional exchange vessel area, and increases in jejunal volume, indicating increased vascular capacitance. The jejunal blood flow increased whilst the blood pressure remained essentially unchanged. 4 By intravenous injection, secretin caused rises in jejunal volume and reductions in calculated jejunal vascular resistance over the same dose range. Effects were statistically significant at 500 mu/kg and higher doses caused reductions in systemic arterial pressure. 5 The calculated peak blood concentrations of secretin resulting from the lower doses used in this investigation were of the same order of magnitude as those determined under physiological conditions in man. 6 It is possible that at physiological concentrations secretin causes an increased functional exchange vessel area in the small intestine, and may also increase the total blood flow through this tissue.


Labelled decamethonium in cat muscle.

Labelled decamethonium in cat muscle. 1 Tritium-labelled decamethonium was infused intravenously in 12 cats at final rates of 1.3-4.2 nmol kg-1 min-1 to produce a steady plasma concentration which ranged between 0.21-1.3 mumol/l in different experiments. Muscle contractions were elicited by nerve stimulation and the potential at the end-plate regions of superficial fibres was recorded by extracellular electrodes. 2 Under these conditions, it was not possible to obtain a steady degree of neuromuscular block. The initial decrease in muscle contractions was followed by recovery towards the original value although the concentration of decamethonium in the plasma remained constant, or in some cases rose. The initial depolarization of the end-plate region also waned during the constant infusion of the drug. 3 Once the twitch tension had returned to control values during infusion of the drug, prolongation of the infusion for a total of four hours did not produce a secondary neuromuscular block. 4 Scintillation counting showed that during infusion of labelled decamethonium the radioactivity of the muscles increased progressively with time. The uptake was less in the soleus muscle than in the fast-contracting flexor longus digitorum and extensor longus digitorum muscles. Muscles which had been denervated 12-13 days previously showed a greater uptake of labelled drug than control muscles from the contralateral limb. 5 The labelled drug was localized by autoradiography of frozen sections of leg muscles following intra-arterial injection of decamethonium. Grain counts in individual fibres showed that small amounts of decamethonium had entered the muscle fibres along their entire length, and there was increased uptake of the drug into the cell in the region of the end-plate. 6 The mechanisms underlying the waning of the pharmacological response during constant application of depolarizing drugs are discussed.


Action of surugatoxin on nicotinic receptors in the superior cervical ganglion of the rat. Surugatoxin (SGTX, 0.1-2 muM) reversibly depressed orthodromic transmission and antagonized the depolarizing action of carbachol on the isolated superior cervical ganglion of the rat. The apparent dissociation equilibrium constant against carbachol-induced depolarization (measured in the presence of hyoscine) was 58 and 76 nM determined at 0.2 and 2 muM respectively. SGTX (2muM) did not reduce the depolarizing effects of (+/-)-muscarine, gamma-aminobutyric acid or angiotensin, but did reduce that to 5-hydroxytryptamine. Release of [3H]-acetylcholine following repetitive (10 Hz) preganglionic sympathetic stimulation was maintained in the presence of 2 muM SGTX. It is concluded that SGTX has a high and selective affinity for ganglionic nicotinic receptors.


Further studies on the mode of action of isoprenaline on gastric secretion in the conscious rat. 1 The effect of isoprenaline on gastric secretion evoked by various means has been studied in conscious rats provided with Pavlov and Heidenhain pouches. 2 Interdigestive acid secretion in the Pavlov pouch was reduced by isoprenaline, whereas pepsin secretion was unaltered. 3 Central vagal stimulation effected by 2-deoxy-D-glucose injection evoked a gastric secretory response that was substantially reduced by isoprenaline. 4 2-Deoxy-D-glucose increased the mobilization of gastric mucosal histamine, an effect that was prevented by isoprenaline. 5 Isoprenaline infusion alone induced a slight increase in histamine mobilization and also a considerable elevation of immunoreactive serum gastrin concentration. 6 The secretory response to food in the Pavlov pouch was almost abolished by isoprenaline. 7 Although the acid response to histamine in the Heidenhain pouch was susceptible to isoprenaline inhibition, that to methacholine was not. 8 Pepsin secretion in the Heidenhain pouch preparation stimulated by histamine or methacholine seemed to be enhanced by isoprenaline.


A comparison of D and L-tryptophan on the cerebral metabolism of 5-hydroxytryptamine and dopamine in the dog. 1 After D and L-tryptophan (50 mg/kg) were given intravenously in the dog, the concentration of the amino acid was increased in ventricular cerebrospinal fluid (CSF) during the subsequent 4 h or sampling, although the concentrations were significantly lower following the administration of the D-isomer. 2 There was no evidence that D-tryptophan increased the synthesis of 5-hydroxytryptamine (5-HT) in dog brain as judged by the failure to cause a change in 5-hydroxyindoleacetic acid (5-HIAA) concentrations in ventricular CSF different from that seen with controls. 3 There was no appreciable conversion of D-tryptophan to L-tryptophan in the dog. 4 D-tryptophan was cleared more rapidly from plasma than L-tryptophan. 5 No difference in plasma binding between D and L-tryptophan was detected.


Circulatory effects of oral and subcutaneous administration in normal subjects of a new bronchodilator, ibuterol, a pro-drug to terbutaline. 1 The di-isobutyryl ester of terbutaline, ibuterol, was given subcutaneously and orally to healthy volunteers and its effects on heart rate, arterial blood pressure, and ECG were compared with those of terbutaline itself. The effects of the two substances were qualitatively identical, but quantitatively different. 2 By mouth, ibuterol acted more rapidly, and was 2-3 times more active. After intramuscular injection, ibuterol caused less increase in local blood flow than terbutaline. 3 Ibuterol can be regarded as a pro-drug, which in itself has little activity, but which can be made active in the body.


The action of tetraethyl-ammonium chloride on the response of the rat anococcygeus muscle to motor and inhibitory nerve stimulation and to some drugs. 1 Tetraethylammonium chloride (TEA) 0.125 mM to 20 mM potentiates the response of the anococcygeus muscle to field stimulation of the motor adrenergic nerves without affecting the response to noradrenaline suggesting a pre-synaptic origin of potentiation. The potentiation is greatest at low, submaximal, frequencies (2 Hz) of stimulation and only slight at the higher frequency of 20 Hz. This difference is due to the restraint imposed on the demonstration of potentiation by maximal or near maximal motor responses since reduction of the mechanical response at 20 Hz by either phentolamine (post-synaptic block) or guanethidine (pre-synaptic block) resulted in a great increase in potentiation of the response at this frequency. 2 TEA in concentrations up to 1 mM similarly potentites the response to inhibitory nerve stimulation and again the greatest effect is at low frequencies. Higher concentrations (5-20 mM) progressively depress the inhibitory response. It is suggested that TEA may specifically antagonize the post-synaptic action of the inhibitory transmitter and that at higher concentrations of TEA this effect dominates the pre-synaptic action in increasing transmitter release. 3 TEA has no effect on the motor response to tyramine. 4 TEA (5-20 mM) causes a maintained rise in muscle tone. Part of this is abolished by phentolamine but part is resistant. A similar muscle stimulant action of TEA is observed in muscles from rats previously treated with 6-hydroxydopamine in which indirect sympathomimetic drugs and field stimulation could no longer produce a motor response. These results suggest that part of the motor effect of TEA is due to an increased spontaneous release of noradrenaline and part to a direct action on the muscle. 5 TEA 0.125 mM to 20 mM antagonize the stimulant action of carbachol. Dose-response curves show a parallel shift to the right with no change in the maximum response suggesting a competitive atropine-like action. Such an effect has previously been reported in amphibian tissue but not so far as we can determine in mammalian preparations. 6 The possible mode of action of TEA is discussed.


The kinetics of competitive antagonists on guinea-pig ileum. 1 The kinetics of action of some competitive muscarinic and histamine antagonists were examined on guinea-pig isolated ileum and their behaviour compared with the predictions of the interaction-limited model described by Paton (1961). 2 The kinetics of antagonism were not consistent with the predictions of this model: (1) The apparent dissociation rate constant calculated from the decrease in occupancy on washout was not independent of the concentration of antagonist. (2) The dissociation rate constant of a 'slow' antagonist calculated from the change in occupancy when a 'fast' antagonist was superimposed varied with the concentration of fast antagonist. (3) If the concentration of slow antagonist was increased when the fast antagonist was superimposed so that the equilibrium occupancy of the 'slow' was the same as before, a transitional phase was observed. 3 The kinetics of antagonism were observed in longitudinal muscle strips and intact pieces of ileum, bathed in Tyrode or Krebs solution, and with isometric and isotonic recording. No evidence was found that the discrepancies between the interaction-limited model and the observed kinetics could be accounted for by the experimental method used. 4 It is therefore concluded that either access is rate-limiting in these circumstances or, if interaction is rate-limiting, some alternative interaction-limited model is required to describe the kinetics of antagonism. In either case it would seem unwise at this time to calculate antagonist-receptor rate constants from the observed kinetics of antagonism.


The effect of high rates of vasopressin administration on renal potassium and sodium excretion during potassium loading in the sheep. 1 The influence of potassium loading on the renal excretion of sodium, potassium and solute during high rate vasopressin administration has been investigated in sheep. 2 Adrenalectomized sheep were infused with 0.43 M KCl at 2 ml/min for 2-2.5 hours. Coincident with the rise in plasma potassium concentration, the urinary excretion of sodium, potassium, solute and water was increased as was the reabsorption of solute-free water. The rates of urinary excretion of sodium and potassium, osmolal clearance (COsm) and solute-free water reabsorption (TcH2O) for the first 50 min of potassium infusion were each found to be linearly related to the plasma potassium concentration. 3 After 50 min an infusion of vasopressin at 1 or 4 mu/min was superimposed on the potassium infusion for a period of 30 minutes. The administration of vasopressin was consistently associated with further augmentation of potassium excretion and clearance, of osmolal clearance and of solute-free water reabsorption to values above those anticipated from the pre-vasopressin regression lines for these parameters. Urinary sodium showed a coincident depression in the rate of excretion and clearance during the same period. 4 Thirty to fifty minutes after the cessation of vasopressin infusion the potassium and sodium excretions had returnied to values which approximated the pre-vasopressin relations between plasma potassium and the urinary excretions of these ions. 5 Both rates of vasopressin infusion were equally effective in increasing the potassium clearance. Any differences in clearance between the two rates of vasopressin administration were not statistically significant. 6 The large increments in potassium excretion (averaging greater than 40%) were interpreted as indicating that, when vasopressin is present at high concentrations, the distal tubule is one site of action of the hormone in the nephron of sheep.


The release of a coronary vasodilator metabolite from the guinea-pig isolated perfused heart stimulated by catecholamines, histamine and electrical pacing and by exposure to anoxia. 1 A procedure involving two guinea-pig isolated hearts perfused in series is described for detecting in the recipient heart the release of a possible coronary vasodilator metabolite from the donor heart. 2 Adrenaline and isoprenaline stimulated the rate and force of contraction and produced a multiphasic coronary vascular response, the predominant phase of which was vasodilatation. When the beta-adrenoceptors of the recipient heart were blocked, stimulation of the donor heart by the catecholamines was associated with a coronary vasodilatation of the recipient heart. 3 Histamine stimulated rate and force of contraction and was predominantly coronary vasodilator. After blockade of histamine H1- and H2-receptors in the recipient heart, coronary vasodilatation followed increases in activity of the donor heart in response to histamine. 4 These vasodilator responses of the recipient heart were attributed to the release from the donor heart of a vasodilator metabolite by the increased activity. This is the proposed mechanism for the predominant coronary vasodilator response to catecholamines and histamine. 5 Periods of electrically-paced tachycardia and anoxia of the donor heart also led to the release of vasodilator activity. 6 The possible identity of the metabolite is discussed.


Myocardial digoxin uptake: dissociation between digitalis-induced inotropism and myocardial loss of potassium. The time course of myocardial uptake of digoxin, of increase in inotropic effect and of changes in myocardial potassium content were studied following a single intravenous dose of digoxin. Nineteen dogs with intact circulation were investigated by the use of a biopsy technique which allowed samplings before and 10, 30, 60, and 90 min after administration of digoxin. The myocardial concentration of digoxin was 196 X 10(-9) mol/kg 10 min after administration of digoxin. Uptake continued at a slower rate, maximum concentration being 293 X 10(-9) mol/kg at 60 minutes. The inotropic effect increased parallel with the uptake of digoxin; 10 min after digoxin, contractility was 127% of the control value and this increased to 139% at 90 minutes. Myocardial potassium content was slightly increased 10 min after digoxin, suggesting an initial stimulation of membrane Na+-K+ ATPase. A subsequent significant fall in the myocardial potassium content probably reflects ATPase inhibition. The temporal dissociation between the early onset of the positive inotropic effect and the delayed inhibition of membrane Na+-K+ ATPase indicates that inotropism of digitalis glycosides is not mediated by the same binding site as that responsible for inhibition of Na+-K+ ATPase.


On the decrease of myocardial oxygen consumption induced by chloracyzine. The effects of chloracyzine (2-chloro-10-(3-diethylaminopropionyl)-phenothiazine hydrochloride; antianginal drug) on myocardial oxygen consumption were studied in open-chest cats and cat isolated hearts using oximetry and polarography respectively. It was found that chloracyzine produced a decrease in myocardial oxygen consumption accompanied by a reduction in coronary blood flow preceded by transient coronary dilatation. Chloracyzine produced an insignificant increase in arterial pressure; heart rate increased slightly in the open-chest experiments but not in the isolated heart. It is suggested that reduced oxygen uptake after chloracyzine is realized through improved efficiency in the use of oxygen.


Bradykinin and functional vasodilatation in the salivary gland. Blood flow through the submandibular gland of the dog was measured and the venous effluent monitored for potential mediators of the functional vasodilatation by passing it over a series of assay tissues. On chorda lingual nerve stimulation there was salivation, an increased blood flow and the release of a bradykinin-like substance (kinin) into the venous effluent. In about half of the preparations, increasing the frequency of stimulation from 2 to 10 Hz led to an increased output of kinin, whereas in the others successive stimulations led to a decreasing output of kinin in the face of normal secretory and vascular responses. Following the administration of atropine, the vasodilatation persisted, salivation was abolished and after several stimulations kinin release could no longer be detected. Release of prostaglandin did not appear to be responsible for the vasodilatation. It is concluded that neither kallikrein nor kinin is the main mediator of parasympathetic vasodilatation in the salivary gland.


Effect of indomethacin and prostaglandin on the smooth muscle contracting activity of angiotensin and other agonists. Indomethacin had an equal inhibitory effect on the response of the guinea-pig isolated ileum to angiotensin II (angiotensin), bradykinin, histamine and acetylcholine. This effect did not seem to result from inhibition of prostaglandin synthesis, as it did not depend on the time of treatment with indomethacin. Prostaglandin E2 (prostaglandin) potentiated the responses of the guinea-pig ileum to angiotensin, bradykinin, histamine and acetylcholine without significant differences in the effects observed. In the rabbit isolated mesenteric and coeliac arteries, indomethacin had an equal potentiating effect on the responses to angiotensin and to adrenaline. In these organs pre-incubation with indomethacin was necessary for the effect to be observed, and this effect lasted for 2 h or more after that drug was removed from the medium. No cross-tachyphylaxis between angiotensin and adrenaline was observed in the rabbit mesenteric and coeliac arteries. It is concluded that the effects of indomethacin and prostaglandin on the response of the guinea-pig ileum to the four agonists result from an action on the smooth muscle contractile mechanism per se rather than from an inhibitory action on the release of endogenous prostaglandin produced by the four agonists. The results with the rabbit isolated arteries indicate that tachyphylaxis to angiotensin in these organs is not caused by prostaglandin release.


The denervated cremaster muscle of the guinea-pig as a pharmacological preparation. The pharmacological responses of both denervated and innervated cremaster muscle preparations from the guinea-pig have been investigated and compared. Acetylcholine (ACh) dose-response curves were obtained in both preparations. The affinity constants for (+)-tubocurarine and for atropine were calculated and indicated that the ACh receptors in both preparations were nicotinic. Histamine dose-response curves could be obtained only in the denervated preparation. The response was unaltered by metiamide, and the affinity constant for mepyramine fitted in with those previously obtained by others on ileum and trachea, indicating that the histamine receptors are H1 in type. Sustained contractions were obtained to adrenaline and noradrenaline but not isoprenaline, with the denervated preparations. Schultz-Dale responses were obtained with denervated muscle in sensitized guinea-pigs. This preparation did not respond to 5-hydroxytryptamine, bradykinin, or the slow-reacting substance of anaphylaxis.


The action of microelectrophoretically applied L-3,4-dihydroxyphenylalanine (DOPA) on single cortical neurones. The technique of microelectrophoresis was used in order to compare the actions of L-3,4-dihydroxyphenylalanine (DOPA) and noradrenaline on single neurones in the cerebral cortices of cats and rats. DOPA could both excite and depress cortical neurones. Cells excited by DOPA were also excited by noradrenaline and cells depressed by DOPA were also depressed by noradrenaline. In the case of both excitatory and depressant responses, DOPA appeared to be less potent than noradrenaline. Responses to DOPA and noradrenaline could be antagonized by phentolamine and propranolol. Responses to acetylcholine were not affected. Responses to acetylcholine, but not responses to DOPA, were antagonized by atropine. The results indicate that locally applied DOPA may mimic the actions of noradrenaline on cortical neurones. Possible mechanisms for these effects of DOPA are discussed.


Effects of ketamine on the peripheral autonomic nervous system of the rat. The effects of ketamine (2-(o-chlorophenyl) 2-methylaminocyclohexanone) (2-50 mg/kg) on the responses of the pithed rat arterial pressure, anococcygeus muscle and colon to selective stimulation of the spinal autonomic outflows were examined. Ketamine depressed the vasopressor response produced by stimulation of the lumbar sympathetic outflow in a dose-dependent manner but did not significantly affect the pressor response to intravenous noradrenaline (NA) administration. Ketamine depressed the motor responses of the anococcygeus to stimulation of the pre-ganglionic lumbar sympathetic outflow or to stimulation of post-ganglionic fibres in the sacral region in a dose-dependent manner, the response to preganglionic stimulation being relatively more sensitive to such depression. The anococcygeus response to NA was significantly potentiated with doses of ketamine of 20 mg/kg and 50 mg/kg. Ketamine depressed the motor response of the smooth muscle of the colon to stimulation of the sacral parasympathetic outflow in a dose-dependent manner and at lower doses than were required to produce an equivalent depression of the sympathetic responses in the other tissues. A comparison was made of the effects of ketamine and cocaine on the motor responses of the anococcygeus muscle in vitro to NA, carbachol and field stimulation. Both ketamine and cocaine produced a non-specific depression of all responses at high doses whereas cocaine but not ketamine produced a large potentiation of NA and motor nerve responses at lower doses. The results are discussed in relation to the hypothesis that ketamine might elevate blood pressure in conscious animals and man by potentiating vascular adrenergic responses.


Renal function and renal venous prostaglandin concentrations during different stages of experimental renal hypertension in the rat. Renal hypertension was produced in rats and the changes in renal function, renal venous prostaglandin E2 and F2alpha concentrations and secretion rates were studied at various times. Renal plasma flow transiently fell in the ischaemic kidney 2 weeks after clamping, whilst that of the other kidney did not change. Glomerular filtration rate remained constant in both kidneys throughout the entire study. Prostaglandins E2 and F2alpha concentrations rose in the venous plasma from the ischaemic kidney, but did not change in the other kidney and appeared to be inversely related to renal plasma flow. Calculated secretion rate of both prostaglandins fell in the ischaemic kidney and did not change in the other kidney. Clamping the second kidney, two weeks after the first, caused a further elevation in blood pressure, a fall in renal plasma flow and a fall in prostaglandin secretion rate in both kidneys. The implications of these prostaglandin changes are discussed.


The lack of effect of oxytetracycline on responses to sympathetic nerve stimulation and catecholamines in vascular tissue. The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined. Oxytetracycline (0.1 mM) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5-10 Hz) or noradrenaline (0.5-50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline. Oxytetracycline (0.1 mM) did not alter the position or shape of the concentration-response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips. It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue.


Study of disease associations from linked records. Comparisons are made between the principal diagnosis on discharge from hospital in successive periods of inpatient care for persons in the Oxford Record Linkage Study area admitted over a period of years. The observed numbers of pairs of diagnoses are compared with expected numbers computed to take account of the discharge rates in the population by age and sex and the number of man years of exposure. Three topics have been selected to display some of the types of analysis possible with the very extensive material: mental disorder and diseases of the central nervous system, hospital discharges preceding those for neoplasm, and discharges following those for tuberculosis. The details of the method of calculation of the observed and expected numbers and the assumptions and approximations involved are given in an Appendix.


Cancer mortality and saccharin consumption in diabetics. The mortality experience of 5971 members of the British Diabetic Association (BDA) was followed-up for between five and eight years to mid-1973. Overall, 1207 deaths occurred compared with 778 expected from the mortality of the population of England and Wales in 1972. This excess of deaths was due almost entirely to diabetes mellitus and ischaemic heart disease. Deaths from cancer (128) were significantly fewer than expected (168), mainly because of a deficit in the number of deaths from cancers related to smoking (cancers of the buccal cavity and pharynx, oesophagus, respiratory system, and bladder). There was also a lower than expected mortality from chronic bronchitis and emphysema. Data on saccharin consumption by BDA members showed that more than half of them used saccharin tablets daily, with an overall daily intake of three to six tablets, depending on age and sex. Information on a small sample of survivors from the mortality study suggested that about 23% of them would have taken saccharin daily for 10 years or more and 10% for 25 years or more by the end of the follow-up. It was concluded that these relatively high levels of saccharin intake had not increased the risk of cancer in general among BDA members.


The relationship between blood pressure and biochemical risk factors in a general population. The relationship between blood pressure, ponderal index, sex, blood glucose, haemoglobin, serum uric acid, calcium cholesterol and creatinine, and albumin has been examined in 698 subjects aged between 44 and 49 years from the register of a group general practice. Sixty per cent of the variation in systolic pressure could be explained by statistically significant associations with diastolic pressure, sex, blood glucose, serum calcium, and cholesterol. The diastolic blood pressure (not corrected for systolic pressure) was significantly related only to ponderal index, haemoglobin in men, and cholesterol in women. Pulse pressure was also positively related to the risk factors blood glucose, serum cholesterol, and calcium. The possibility is discussed that one or more of these variables reduce aortic compliance and that the serum calcium contributes to this end. Diastolic, but not systolic pressure, had a prime association with relative weight, obesity being only basically associated with an increase in diastolic pressure.


Mental capability of children exposed to lead pollution. 'Eleven-plus' school examination scores were obtained for 851 Birmingham children residing since birth in a lead-polluted area and 1642 children residing in two similar but unpolluted areas. It was found that the children in the lead-polluted area actually scored higher on the average than children in the control areas. Within the area of lead contamination, children living closest to the source of pollution did not have significantly lower scores than children living further away. The results indicate that lead pollution of the magnitude reported in this investigation did not have a demonstrable effect on the mental capabilities of children in the affected community.


A study of the validity of the Hospital Activity Analysis information. For a number of years the medical profession and its administrators have been using statistical tabulations from the Hospital Activity Analysis returns. The quality of this information has often been criticized and no attempt has been made to quantify the levels of 'errors' in England and Wales. This paper reports the findings of such a study in Nottingham, and concludes that the Hospital Activity Analysis system in that area is almost as good as the clinical notes from which it is derived.


Epidemiology of twin births from a climatic point of view. The twinning rate was analysed using figures taken from statistics for Japan. During the years 1955 to 1959 there were 58 570 twin deliveries out of a total of 9 088 233, a frequency of 6-44 per 1000. Using Winberg's differential method for zygosity estimation, the monozygotic twinning rate was 4-04 per 1000 and the dizygotic was 2-40. Twinning rates in 46 prefectures were also estimated and their correlations with meteorological parameters as well as with the mortality from cerebrovascular disease were examined. The twinning rates increased from a low level in the south west to a high level in the north east of Japan. The tendency was more obvious for the dizygotic than the monozygotic twinning rate. A negative correlation was observed between incidence rates of dizygotic twins and mean air-temperatures throughout the year, and a positive one between incidences of dizygotic twins and mortality rates for vascular lesions affecting the central nervous system in 46 prefectures. A seasonal variation of twinning rates was also observed in Niigata City for statistics of births during the periods 1948-55 and 1963-70. This took the form of a bimodal curve, with high conception rates for twin births in intermediate mild seasons, the spring and autumn and, low rates in the more stressful hot and cold seasons. These relationships between climate and twin births within a single race-group are discussed.


Accuracy of cancer registration.

Accuracy of cancer registration. In South Wales cancer registration is done principally by means of the Hospital Activity Analysis. Altogether 1460 hospital records of cancer patients (19% of the 1972 registrations received by May 1973) were studied and the principal items of information required for cancer registrations by the Office of Population Censuses and Surveys were copied and subsequently compared with the corresponding registrations at the Welsh Hospital Board's cancer bureau. Differences between these 're-registrations' and the original registrations were analysed item by item. There were 234 registrations with errors in the diagnostic summary (although 110 of these would cause misclassification only under the fourth digit of the ICD code), 164 with errors in date of birth (36 of which would cause classification in the wrong WHO age group) and 198 with errors in the date of registration (112 of which were wrongly ascribed to the year 1972). Error and omission rates were particularly high for NHS number, occupation, place of birth, and histology.


Personality and symptom pattern in depression. This paper reports relationships between symptoms and premorbid personality in a varied sample of depressed patients. Symptoms were rated by a psychiatrist at clinical interview; personality was rated by patients on a self-report after clinical improvement, using the Maudsley Personality Inventory and an inventory of obsessive, hysterical and oral personality. Additional ratings on the latter were obtained at interview with a relative. The most prominent finding was that patients with premorbid neuroticism also showed a neurotic rather than an endogenous symptom pattern. Additional relationships were relatively weak but consistent with previous studies. Depressives with neurotic rather than endogenous symptom pattern showed more evidence of oral dependent personality and less obsessionality. Patients with hysterical personalities tended to be less severely ill and to show a pattern characterized by mixed depression and hostility with less evidence of anxiety.


Cardiac effects of different tricyclic antidepressant drugs. The effects of tricyclic antidepressants on the heart are reviewed. Statistically significant increases in heart rate and in atrioventricular conduction times were found following the administration of tricyclic drugs to 32 depressed patients. The method of His bundle electrocardiography was used to study atrioventricular conduction in ambulant patients and in patients admitted after an overdose of tricyclic antidepressant drugs. Distal conduction defects were frequently found in patients following tricyclic overdosage, but these were not seen with doxepin overdosage. Impaired distal conduction was also found in occasional patients on therapeutic doses of tricyclic drugs. Some animal experiments giving similar results to the above clinical findings are also described. The clinical implications of these findings are discussed.


Mianserin hydrochloride: a novel antidepressant. The antidepressant activities of mianserin hydrochloride were investigated and compared with those of amitriptyline. The therapeutic efficacy of the two drugs appeared similar, but the incidence of side-effects was significantly higher with amitriptyline. Plasma levels of mianserin were determined during the trial and were not related to the therapeutic activity of the drug.


Circadian body temperature in chronic schizophrenia. The 24-hour oral temperatures of 51 chronic schizophrenic patients, 19 non-schizophrenic chronic psychiatric patients and 14 non-patients have been measured and compared. The chronic schizophrenias have an ealier peak temperature and differ significantly from the other groups. Compared with the non-schizophrenic patients their hourly mean temperatures reach significantly higher levels in the morning. Compared with the non-patients their mean temperatures fall to significantly lower levels in the evening after 5:00 pm.


Mental disorder and season of birth--a southern hemisphere study. Studies on the relationship between season of birth and mental disorder have been substantially confined to northern hemisphere regions. Such studies have generally found an excess of winter births of schizophrenics, and variably an excess of winter births of manic-depressive and mentally retarded patients. In the present study information on sex, diagnosis and date of birth was obtained on all 20,358 patients first admitted to psychiatric facilities in New South Wales between July 1970 and June 1974 and born in New South Wales. The collective 1962-71 monthly live-births for New South Wales were used as a control. A significant winter excess was found for the female schizophrenic group, while a significant spring excess was found for neurotic patients, most marked in those with anxiety neurosis. It is hypothesized that the relationship between schizophrenia and winter birth is consequent upon a greater sensitivity of schizophrenics to those physiological factors which determine conception in the general population.


Predicting success in the treatment of psychopaths. Factors from the social history of male psychopaths were examined in relation to their success or failure as measured by re-convictions of psychiatric hospital re-admissions 2-3 years after treatment at Henderson Hospital. From these data a weighted prediction formula was calculated and was tested out on a further cohort of patients. As a prediction instrument it was found to be reliable to a degree of significance just above the 1 per cent level. Other aspects of the subsequent career of treated patients are noted, in particular a tendency to early but often short-lived relapse and then longer standing success.


The effects of stimulus attributes upon latency of word recognition. This experiment investigated the properties affecting the time taken to read individual words and to discriminate between words and non-words. The number of letters in a word was found to affect the time taken to read it aloud, but not the time taken to discriminate it from non-words. The frequency of a word affected the time for discrimination, but not that for reading. Non-words which obeyed the rules of English orthography and phonology were more difficult to discriminate from words than those which violated those rules. Imageability, concreteness, and the number of syllables in a word were found not to affect performance, nor were derived nouns more difficult to process than simple nouns. It is suggested that reading aloud employs grapheme-phoneme translation based upon a letter-by-letter analysis of the stimulus: that discriminating words from non-words obeying the rules of English orthography and phonology employs a search of the lexicon based upon a holistic analysis of the stimulus; and that discriminating words from non-words violating those rules employs a direct test of the regularity of the stimulus based upon the combinatory rules of English orthography.


A failure to explain the effects of false heart-rate feedback on affect by induced changes in physiological response. An experiment was performed to validate and extend the self-persuasion hypothesis of Valins by using slide stimuli reported to create strong unpleasant feelings. The hypothesis suggests that in situations where there is no immediate explanation of induced arousal in terms of a cue of false heart-rate feedback then reported affect is dependent on a cognitive interpretation. Evidence is presented in the present study which not only supports such an interpretation but finds no support for a previous study that reported changes in affect to be a consequence of induced changes in actual physiological responses. The implication of this discrepancy from the previous reported findings are related to the possible efficiency of techniques of systematic desensitization.


The electrodermal component of the orienting response in blind and deaf individuals. Skin conductance response (SCR) was monitored as an index of the orienting response (OR) to a series of 20 tones presented to blind and sighted schoolchildren. Blind children showed fewer criterion SCRs than sighted children, and significantly more of the blind sample exhibited SCR habituation. The blind group also demonstrated fewer non-specific SCRs than sighted control subjects, but demonstrated a higher average skin conductance level (SCL). A second experiment found similar effects for deaf versus hearing children presented with simple visual stimulation, save that no significant difference was observed between these groups in SCL. These results can be explained by assuming that loss of modality results in more efficient development of a neuronal model of the salient features of stimuli impinging on the remaining intact modalities. An explanation in terms of the assessed significance of the stimulus situation can also be entertained. The atypical skin conductance activity of three of the blind group was given separate consideration.


Qualitative analysis of the performance of introverts and extraverts on Standard Progressive Matrices. The present study was designed to bring out the differences between extraverts and introverts on Standard Progressive Matrices. A group of 100 subjects of equal number of sexes were given a qualitative analysis of their performance on SPM. The study brought out the initial superiority of extraverts over introverts. But with passage of time and increase in difficulty level the introverts did significantly better as shown both by the t-ratios and the F-ratios. Personality interacted with sex to yield differences in performance of wrong scores only. These findings were discussed in terms of arousal, cortical excitation and reactive inhibition.


Cognitive strategies and multidimensional scaling. The problems involved in equating multidimensional scaling solutions with cognitive strategies are considered. Empirical evidence is presented to suggest that scaling solutions are relatively insensitive to the combination rule used by subjects, and thus may be used as an indication of the basic variables, but not their method of combination, that underlie a cognitive strategy.


Right- and left-handed counting of braille dots in subjects unaccustomed to braille. Previous work has shown that children acquainted with Braille can usually read better with their left than with their right hand. It is also known that, at least in right-handed people, the right cerebral hemisphere is dominant for counting dots. The present paper compares, in right-handed subjects unacquainted with Braille, the comparative skill of right and left middle (M) and index (I) fingers in counting Braille dots. In one experiment with 30 subjects no significant difference was found between LI and RI fingers. Another experiment failed to reveal any R/L differences although it detected a superiority of I over M fingers at P less than 0-025. When the task was split between the two I fingers working simultaneously they performed significantly (P less than 0-001) better than when working alone. This latter finding is thought to have a bearing on the failure to detect R/L differences; other possible explanations of the findings are also discussed.


Selective renal occlusion phlebography with a balloon catheter. Technique of selective renal occlusion phlebography is described. For the temporary occlusion of the renal vein a Swan-Ganz or Dotter-Lucas balloon catheter are used. The balloon catheter is directed into the renal vein using a Desilets-Hoffmann or EDSLAB introducer. Occlusion of the renal vein is achieved by insufflation of 2-3 ml. air into the balloon of the catheter. Selective renal occlusion phlebography leads to optimal retrograde opacification of the renal venous system.


Radiological manifestations of oesophageal involvement in acanthosis nigricans. Radiologic features of two cases of acanthosis nigricans with oesophageal involvement are reported. The first case demonstrated diffuse, granular shadows throughout the oesophagus which were difficult to differentiate from oesophageal moniliasis. Another case showed many discrete and tiny elevations resembling pseudopolyposis of the colon. Emphasis is placed on radiological differential diagnosis from moniliasis and leukoplakia of the oesophagus.


Pineal gland calcification (PGC) in Ugandans. A radiological study of 200 isolated pineal glands. Two hundred formalin-fixed pineal glands from consecutive unselected post-mortems on Ugandan Africans have been X-rayed. The degree of pineal gland calcification has been divided into four stages and it is shown that 43 per cent of all pineal glands after the age of ten years are likely to be detected in an ordinary skull X ray. This high percentage of calcification contrasts with the previously reported low figure from races other than whites. The pineal glands from females were more often calcified and heavier than those from males; however, the stalks of pineal glands from males were calcified more frequently than those of females. The average weight per decade was almost constant. In Ugandan Africans the pineal glands were significantly lighter than in Caucasians, and a possible reason for this is briefly discussed.


"Vascular" cerebral infarctions demonstrated by serial gamma-camera scinti photography. The apparently paradoxical appearance of increased vascularity appearing in the radionuclide angiographic studies of a patient with cerebral infarction has recently been described and attributed to the "luxury perfusion syndrome". It is suggested that this phenomenon occurs more frequently than previously thought and in fact has been observed in nine patients presenting for a cerebral scan during a ten-month period. These cases are reviewed and an alternative explanation for the occurrence of increased vascularity on the dynamic study is submitted.


Computerized axial tomography: estimation of spatial and density resolution capability. The spatial and density resolution capability of the EMI-Scanner device for computerized axial tomography has been determined in vitro. For density differences greater than +/-1 per cent the spatial resolution is 6 X 6 mm. For density differences of 3 per cent and greater the resolution is 3 X 3 mm. Density resolution is at least +/-1 per cent for objects greater than 1 cm. Preliminary data on in vitro measurement of X-ray linear attenuation coefficients in tissue biopsies and standard solutions are given, together with the early results of enhancement of tissue density differences in vivo. Implications of this new technique for an in vivo neuropathology are suggested.


A comparison of clinical results in brain scanning using germanium semiconductor detectors and sodium iodide detectors. A comparison is presented of the image quality obtained with a 70 mm Ge(Li) detector scanner and with routine techniques based on NaI (Tl) detectors. One hundred and sixty-five pairs of brain scans have been examined for which the patients have been scanned with both Ge(Li) and NaI (Tl) detectors. It is concluded that no major difficulties exist in introducing Ge(Li) scanners and that while a comparison of scans from different instruments is difficult there is evidence that improved diagnostic information may be obtained from scanners with Ge(Li) detectors.


Scanning electron microscopy of mouse intestinal mucosa after cobalt 60 and D-T neutron irradiation. The stem-cell population of the intestinal crypt is an important model system in experimental radiobiology. Standardized techniques have been developed to allow quantitation of the response of crypt cells to radiation injury following doses of 0-2 krad of D-T neutrons or 60Co gamma rays. These techniques rely on the identification of regenerating crypt cells three-and-a-half days after irradiation. The results are expressed as the number of regenerating crypts per circumference of small intestine, as determined by conventional histological examination; the more profound the injury, the smaller the crypt count. The practical relevance of crypt-counting techniques to clinical radiotherapy is limited by their relative insensitivity; the dose levels commonly used in fractionated radiotherapy produce no detectable response. Scanning electron microscopy of the mucosal surface provides a more sensitive measure of radiation injury. The earliest detectable changes occur at the level of 300 rad of gamma radiation, well below the threshold of the crypt-counting technique. At around 1,000 rad, where the first drop in crypt counts occurs, there are well-marked morphological changes which become more severe with increasing dose levels. Some differences have been observed between the morphological effects of gamma and neutron irradiation at points of radiobiological equivalence in terms of crypt counts (using an RBE value of about 2). The changes observed may reflect more than the disruption of epithelial cell kinetics. Mucosal morphology is the total expression of many different biological parameters of which the regenerative ability of the crypt cells is only one. The surface microanatomy of the gut may be the most sensitive indicator of radiation injury which is conveniently available for study.


Measurements of neutron spectra at depths in tissue equivalent material for fast neutron beams generated by deuterons on beryllium. The threshold foil technique has been used to investigate the behaviour in tissue of the spectra of neutron beams produced by the bombardment of thick Be targets with 13-0 and 20-5 MeV deuterons. The results indicate a gradual "softening" with depth in tissue of the spectrum generated by 20-5 MeV deutrons which contrasts with a gradual hardening as reported by other authors. This is discussed in terms of the significance of field size and the methods used for data collection and analysis.


Grey-scale ultrasonic imaging of the kidney. The ultrasonic appearances of the kidney in images which contain grey shades corresponding to the detected echo-pulse heights have been examined. These "greyscale" images were obtained using a standard Nuclear Enterprises Diasonograph 4102B and a Varian 620/L digital computer interfaced to this Diasonograph. The computer was used to analyse and display the ultrasonograms with 16 grey shades. Both kidneys of 36 subjects were examined and compared with IVU findings. This group included patients with normal kidneys, polycystic kidneys, hydronephrosis, glomerulonephritis and neoplastic tumours. It was found possible to make sharp, grey-shaded ultrasonograms which were very useful to the diagnostician. In particular, the grey shade of the renal parenchyma was used as a standard to compare other grey-shaded structures. Also the grey shading was useful in defining the renal pelvis in transverse scans and the renal poles in axial scan.