Historical background and aspects of the mechanism of leukocyte adherence inhibition. The development of leukocyte adherence inhibition is traced from early experiments with murine tumors to recent applications in human cancer and in cell-mediated immunity in general. Arbitrary experimental conditions (serum in culture medium, preincubation, and tumor extracts at a single concentration) were initially set up and permitted detection of specific inhibition of adherence of sensitized leukocytes reacting with antigen of the tumor extracts. Blocking serum completely or partially restored adherence. It was readily demonstrated that leukocyte adherence inhibition was mediated by a soluble lymphokine-like factor [leukocyte adherence inhibition factor (LAIF)]. Recent studies suggest that serum is important in enabling detection of LAIF;  this may explain the inability of some other workers to confirm our findings. Serum appears to protect LAIF from enzymatic destruction in mixtures containing tumor extracts. Complex cell interactions are involved in LAIF production. With mouse cells in vitro, macrophages are required for production by both T- and B-lymphocytes, and there is evidence for suppressor cells also.


Evaluation of the microplate leukocyte adherence inhibition test and its reproducibility, sensitivity, and relationship to other tests of cellular immunity. The microplate version of the leukocyte adherence inhibition (LAI) test was evaluated in murine and human studies. It was used in parallel with the microcytotoxicity assay, lymphotoxin assay, leukocyte migration inhibition, and lymphocyte stimulation tests in a transplantable murine tumor model, and it compared favorably with these established techniques for the detection of cellular immunity. The LAI test detected both primary and secondary anamnestic responses in Bacillus Calmette-Guérin-primed mice, and it displayed sensitivity to host humoral factors comparable to that seen with other tests. The LAI phenomenon was shown to be mediated by a soluble supernatant factor liberated by antigen-exposed immune leukocytes in the mouse and by concanavalin A-stimulated human leukocytes. In the mouse, deliberate depletion of T-cells ablates LAI reactivity in cells taken at the peak of a primary response; however, immune serum "arms" non-thymus-dependent cells taken from unimmunized hosts. In the mouse, the results of LAI tests correlate with other established techniques, when purified protein derivative reactivity was assessed in spleen cells from Bacillus Calmette-Guérin-immunized mice. Comparable correlation is not found when reactivity to this antigen is assessed in human peripheral blood samples from unimmunized donors.


Correlations between the leukocyte adherence inhibition microassay and in vivo tests of transplantation resistance. The leukocyte adherence inhibition (LAI) microassay detects tumor-associated antigen(s). Extracts of colon carcinoma (MCA-38 and B16 melanoma tumors, both syngeneic to the C57BL/6J mice) are recognized only by peritoneal cells from mice bearing the corresponding tumor. To ascertain whether this in vitro antigenic recognition correlates with the ability of the host to recognize and reject a tumor in vivo, serial LAI microassays were performed synchronously with experiments designed to test the ability of mice bearing tumors to reject live secondary tumor challenges. Concomitant tumor immunity was present in the MCA-38 tumor-bearing mice on 3 occasions from 5 to 15 days from primary inoculation. In the B16 system, concomitant immunity was present on one occasion 10 days after primary inoculation. These results in turn were paralleled with the specific in vitro recognition of tumor antigens as detected by the LAI microassays. Loss of immunity in the "eclipse" phase of tumor development, as detected by concomitant tumor immunity, was paralleled by nonreactivity of the indicator cells in the LAI microassay.


Cellular and humoral factors involved in the mechanism of the micro-leukocyte adherence inhibition reaction. To study the cellular basis for specific antigen-induced leukocyte adherence inhibition, enriched populations of B-cells, T-cells, and monocytes were prepared by a two-stage adherence separation procedure from spleen cells of normal C57BL/6J mice and mice bearing progressively growing MCA-38 tumors. The reactor cell undergoing specific antigen-induced adherence inhibition was identified as a monocyte (esterase positive, did not respond to mitogens, and did not bear Thy 1.2 antigen or surface immunoglobulin). Furthermore, an enriched population of MCA-38-sensitized B-cells could program normal monocytes to undergo specific antigen-induced adherence inhibition. In contrast, enriched populations of MCA-38-sensitized T-cells could not program normal nylon wool-adherent cells to undergo antigen-specific adherence inhibition. Programming of normal monocytes by MCA-38-sensitized B-cells occurs through a soluble mediator and not by direct cell contact. The soluble mediator appears to be immunoglobulin in nature and induced both adherence inhibition and the inhibition of adherence. Thus, in this murine tumor model, leukocyte adherence inhibition appears to be due to programming of monocytes by a secretory product of specifically sensitized B-cells.


Assessment of the mechanism of the leukocyte adherence inhibition test. This study was designed to elucidate the mechanism of the leukocyte adherence inhibition (LAI) test in man. To identify the reactive cell types, enriched leukocyte populations (dextran-separated leukocytes and Hypaque-Ficoll-isolated mononuclear cells and neutrophils, as well as rosette-isolated B- and T-lymphocytes) were tested for leukocyte adherence in the absence of serum to tumor-specific antigens. LAI reactivity was not restricted to any of the enriched populations, suggesting the involvement of multiple cell types. Attempts to demonstrate soluble lymphocyte factors in the LAI mechanism have been uniformly negative. In contrast, factors in serum of immune donors were able to arm naive cells to be specifically responsive. This suggests a role for serum factors in the mechanism of LAI reactivity and partially explains the participation of multiple cell types in the responses observed. In additional studies, we could not document a correlation between the magnitude of the dermal test (delayed cutaneous hypersensitivity) and the magnitude of the LAI response in patients with squamous cell carcinoma of the head and neck. In 34 of 54 of these patients, there was agreement between the two tests (both positive, 27 of 54; both negative, 7 of 54). In the remaining 20 patients, the dermal test was greater than 5 mm while the LAI test was negative (less than 30% inhibition).


Demonstration of the microtest version of the leukocyte adherence inhibition assay. This paper gives a detailed description of the microtest leukocyte adherence inhibition technique, as well as the results obtained with blood specimens coded by impartial observers. Three coded blood specimens from patients with colon cancer, pancreatic cancer, and melanoma were tested against crude membrane preparations of pancreatic and colon adenocarcinoma tumors. No tissue type-specific reactivity was observed. The inability to demonstrate specific reactivity was due to extensive variability observed within each test. The extensive variability resulted from time constraints of the workshop that necessitated deviations from the normal procedure.


Malignant pleural effusions.

Malignant pleural effusions. Recurrent malignant pleural effusion is a relatively common problem that often occurs many months before the terminal stages of a patient's malignant disease. Despite careful evaluation, it is often impossible to identify the exact physiologic cause of an effusion and difficult to identify a pragmatic course of therapy. Aggressive management including chest tube drainage, with or without instillation of inflammation-inducing drugs, and radiotherapy or surgery in selected cases is indicated for palliative treatment and probably for increased survival. In formulating a treatment plan, attention should be given to a variety of factors including pathogenic forces in the formation of malignant pleural effusion, tissue type of the metastatic malignancy, general clinical status of the patient, the presence of pleural loculations and adhesions, and the exclusion of other non-malignant causes of pleural effusion.


The management of adult acute lymphoblastic leukaemia. The important advances made in recent years in the therapy of adult ALL have been reviewed. The definition of bad-prognosis patients has been improved and includes those with T-ALL, ABLL, and Ph1+ALL, in addition to those presenting with evidence of extensive disease. In contrast to childhood ALL, induction chemotherapy should include another drug (or drugs) in addition to VCR and prednisolone, and one of the anthracycline drugs (ADR or DNR) has been employed most frequently in this context. Such therapy should result in a CR rate of 70 to 75%. Similar to the experience in childhood ALL, the improvement in haematological response rate has led to an apparent increase in CNS leukaemia, and the need for adequate CNS prophylaxis is stressed. Despite these improvements, the outlook for adults with ALL is not yet as good as it is for childhood ALL. Controlled studies involving large numbers of patients are urgently needed to provide answers to a number of questions. In induction therapy, the use of higher drug dosage, the use of more and other drugs, and the use of an individual patient's risk factors to determine drug dosage, must be assessed. The benefits of consolidation therapy and the optimal duration and intensity of maintenance therapy have yet to be established. Methods of CNS prophylaxis other than cranial irradiation and IT MTX must be carefully studied. These important questions require that adult patients with ALL should be concentrated in centres capable of providing optimal overall care and, at the same time, able to conduct the necessary clinical trials.


Coronary capillary permeability and tissue volumes for sucrose and water in dogs: a comparison of bolus and constant infusion multiple-indicator methods. This study was undertaken to determine the accuracy with which heart interstitial and water volumes could be determined from multiple-indicator dilution experiments on the coronary circulation in open-chest dog preparations. Sucrose permeability by extraction calculations was found to average 0.26 +/- 0.02 cm3 . (min . g tissue)-1. The extravascular sucrose volume averaged 0.15 cm3 . g-1 tissue by both multiple-indicator and post-mortem methods. Indicator-dilution tritiated water curves labelled 85% of the post-mortem water content.


Ultrastructure of the extracutaneous pigment cells in the plaice (Pleuronectes platessa, L., Teleostei). The extracutaneous pigment cell system of the plaice (Pleuronectes platessa L.) was examined by light and electron microscopy in selected regions, including two cutaneous regions for comparison. The extracutaneous pigmentation consists of guanocytes and melanocytes with differing distributions within the body. The eyeless side lacks melanocytes. The pigment cells are differentiated as very flat elements with long processes. They display an affinity for loose connective tissue at boundary layers such as the peritoneal epithelium, organ capsules or blood vessels, to which they are parallelly arranged at a very constant distance. In some locations guanocytes are intimately associated with melanocytes forming "reduced chromatophore units". Extracutaneous pigment cells are poor in mitochondria, endoplasmic reticulum, microfilaments, caveolae intracellulares, ribosomes and glycogen granules, all of which are more abundant in cutaneous pigment cells and pigment cells of the eye. In extracutaneous guanocytes the crystals are loosely arranged parallel to the cell surface, in cutaneous guanocytes perpendicular. Cells with rod-like vesicular cisternae are described as "guanoblasts". No single pigment cell was found exhibiting different types of pigment granules. The varying colors of extracutaneous pigmentation arise from varying combinations of guanocytes and melanocytes in addition to the color of the tissue itself.


An inexpensive computer-aided system for  quantitative echocardiography. A comprehensive system has been developed to quantitatively analyze standard M-mode pediatric echocardiograms. It utilizes relatively inexpensive hardware together with a telephone coupling to a time-sharing computer. A complete patient report on the study is printed out upon completion, and all the data are digitally stored for future research computations. Initial and operating costs for this system are significantly less than for any comparable one available.


Computer analysis of oximetry data in cardiac catheterization. An on-line computer technique is described for the detection and quantitation of left-to-right shunts. The computer used Student's t test to evaluate the probability that variations in right heart oxygen saturations were due to left-to-right shunts. The computer method was found to compare favorably to the present step-up method of detecting left-to-right shunts. The computer also calculated pulmonary blood flow, systemic blood flow, their ratio, and shunt blood flow as accurately as standard methods, as evidenced by correlation coefficients of 0.98, 0.94, 0.95, and 0.71 between the computer and hand calculations.


[Goodpasture's syndrome].

[Goodpasture's syndrome]. 1. The paper summarizes the clinical course, histopathological examinations and immunohistological examinations of 4 personal cases [2 males aged 20 and 26 years, 2 females aged 65 and 18 years] of Goodpasture's pulmorenal syndrome. 2. The characteristic histopathological findings included pulmonary haemorrhage with a focal acute alveolitis and renal lesions that were classed as acute or subacute glomerulonephritis with the finding of scarce multinucleated cells. Such cells are regarded as being of diagnostic value and they are thought to indicate interaction of antibodies with the basement membranes. 3. Immunohistologically, all the cases showed a linear fluorescence following the basement membrane of the interalveolar septa. In 3 of the cases there was linear fluorescence in the glomerular capillary walls. In one case [observation No. 2] who had been hypertensive before death and had had necrotizing arteriitis at postmortem, there was fluorescence of granular type in the kidney believed to indicate the participation of immune complexes in the development of the pathological condition.


The hemodynamic effects of prostaglandins in the rat. Evidence for important species variation in renovascular responses. The hemodynamic effects of prostaglandins E2, F2alpha, D2, and I2, and of indomethacin and arachidonic acid were studied in Sprague-Dawley rats, by means of the radioactive microsphere technique. In contrast to effects in other species, PGE2, PGD2, and arachidonic acid were renal vasoconstrictors in the rat, although PGE2 and arachidonic acid reduced total vascular resistance. PGF2alpha and indomethacin had no effect on the renal vasculature, but PGI2 produced renal and systemic vasodilation. These data indicate that if prostaglandin-mediated renal vasodilation occurs in the rat, PGI2 may be the substance responsible. In view of the species differences in renal vascular responses to the prostaglandins, the rat may not be an appropriate model for study of the prostaglandin system as it relates to other species.


Neurogenic skeletal myopathy in patients with primary cardiomyopathy. Eleven patients with hypertrophic obstructive cardiomyopathy and eight patients with idiopathic congestive cardiomyopathy underwent extensive neuromuscular studies to determine if a skeletal myopathy is associated with uncomplicated primary cardiomyopathy. The clinical examination revealed peripheral neuropathies in six patients, but no evidence of muscle weakness or atrophy. Nerve conduction studies demonstrated a neuropathy in five of these six and in one other patient: three were in the hypertrophic group and three in the congestive group. Seven patients had abnormal electromyography, but none had characteristic myopathic changes. Of these seven patients, muscle biopsies showed denervation in two patients in the congestive group and type II atrophy in two patients in the hypertrophic group. We found no evidence of primary skeletal muscle involvement; however, neuropathic features and biopsy changes of denervation were present in both groups.


Monitoring diazepam and desmethyldiazepam concentrations in plasma by gas-liquid chromatography, with use of a nitrogen-sensitive detector. We describe a modified [from Anal. Chem. 36, 2099 (1964)] procedure for determining diazepam and its pharmacologically active metabolite, desmethyldiazepam, in plasma, with use of a nitrogen-sensitive detector in the gas-liquid chromatography. We used medazepam as the internal reference standard. Diazepam and desmethyldiazepam are converted to their respective benzophenones by mineral acid hydrolysis. With this procedure, as little as 100 muL of plasma can be used to determine the drug in concentrations as low as 10 microgram/L, accurately, reproducibly, and quickly. Within-run and between-run CVs for 100 microgram/L concentrations of the two compounds were 5 and 7%, respectively.


Homogeneous enzyme immunoassay of serum digoxin with use of a bichromatic analyzer. We applied the Enzyme Multiplied Immunoassay Technique (EMIT; Syva Corp., Palo Alto, CA) for determination of serum digoxin to the ABA-100 bichromatic analyzer. Assay conditions were almost exactly as prescribed for the manual procedure, but the ABA-100 offers high automation, smaller reagent volumes, and shorter reaction time. Precision studies gave CV's of less than 10%. Sixty patients' samples, analyzed for digoxin by radioimmunoassay and this enzyme immunoassay, gave a correlation (r) of 0.941. Results obtained with the ABA-100 were apparently slightly higher. One kit provides reagents for 250 assays, as compared to 70 assays with the manual procedure. In an emergency situation a result will be available about 60 min after the patient's sample is received; one operator can analyze about 120 samples in 8 h.


Evaluation of a commercial enzyme immunoassay for insulin in human serum, and its clinical application. We applied a "sandwich" method, with use of beads coated with anti-insulin serum and of peroxidase-labeled anti-insulin serum, to an enzyme immunoassay of insulin in human serum. 5-Aminosalicylic acid was used as the substrate for the enzymic reaction. As little as 5 milli-int. units of insulin per liter of serum insulin was detectable. Reproducibility was satisfactory, but extraordinarily high concentrations of proinsulin and of hydrogen donors such as reduced glutathione affect results of the assay. Values determined by our enzyme immunoassay and by double-antibody radioimmunoassay correlated highly (r = 0.938, p less than 0.001, n = 216). We recommend this method for use in the clinical laboratory.


Immunoradiometric assay of endotoxin in serum. We describe an immunoradiometric assay for the specific detection and quantitation of endotoxin from Escherichia coli 026, with use of 125I-labeled antibody. The sensitivty of this assay is 1 microgram/L.E. coli 026 endotoxin was detected in serum of rats for as long as 24 h after intraperitoneal injection of 0.1 mg of endotoxin per 100 g body weight. The assay is specific for the O-polysaccharide portion of this endotoxin, as confirmed by results after protein digestion and oxidation of the endotoxin, as well as by failure to detect endotoxin in serum after similar injections of E. coli 0127 and Salmonella typhosa 0901 endotoxins.


Enzyme-immunoassay of human placental lactogen. An enzyme-immunoassay (EIA) for estimation of human placental lactogen (HPL) in plasma or serum was developed using HPL labelled with horseradish peroxidase (HRP) and anti-HPL sera raised in rabbits. The separation between antiserum-bound and free labelled hormone was accomplished with a double antibody solid phase technique. Interference of substances from the sample with the immunoassay was prevented by dilution of the sample with at least a factor of 20 and measurement of the labelled hormone attached to the solid phase. The peroxidase activity was colorimetrically measured using o-phenyl-enediamine and urea peroxide as substrate. The standard curve of the assay ranged from 3 to 40 ng HPL/ml allowing estimations of HPL in serum or plasma starting from about the 10th week of pregnancy. Normal values were established. Intra- and inter-assay variation coefficients of 6 and 7.5% respectively were found. The EIA showed no cross-reaction with human serum proteins or HCG. The low cross-reaction noted with human growth hormone did not interfere with the assay. An excellent agreement was found with the results of radioimmunoassay (RAI).


Adam Politzer.

Adam Politzer. Adam Politzer (1835--1920) received his degree as Doctor of Medicine in 1859. His method of tubal inflation of the middle car with the Politzer bag was published in 1863. Together with J. Gruber, he was appointed director of the newly-founded Clinic for Otology of the University of Vienna, the first clinic of its kind in the world. Thousands of doctors from all over the world came to Vienna to attend his advanced training courses. He was aided in his teaching by his textbook, Lehrbuch der Ohrenheilkunde, which was translated into several languages. Under Politzer, Vienna became a Mecca for otologists. In 1893, Politzer demonstrated focal alterations of the otic capsule as being the cause of otosclerosis for the first time. He published 103 scientific papers. During his 46 years of teaching, Politzer transformed otology from a "sterile, hopeless discipline" into an academically recognized specialty.


Tympanic epithelial migration.

Tympanic epithelial migration. The literature on tympanic epidermal migration is reviewed. From isotope experiments and whole-mount autoradiographs the tympanic mitotic activity appeared to be confined to an area close to the annulus typmpanicus. A very slow migratory activity was observed of labelled cells, situated in the basal cell layer. Perforation of the tympanic membrane showed no effect on the position of the labels. This slow migration is considered to differ from the rapid epithelial migration described by several authors. The latter migration is suggested to occur in the upper layers of the stratum corneum, and to represent a physiological mechanism taking care of the removal of keratin from the tympanic membrane. The extrusion and displacement of ear grommets might be at least partly attributable to this phenomenon.


Tympanoplasty with preformed autologous ossicles. A method of creating a preformed new bone graft from the patient's temporal region using a titanium mould is described. The preliminary work which was performed on animals demonstrated the ability to generate healthy bone in this way. Subsequent application of this technique to the problems of ossicular reconstruction in human ears has proved encouraging in selected cases.


A simple method to detect linkage for rare recessive diseases: an application to juvenile diabetes. A simple procedure designed specifically to detect linkage for rare recessive diseases is described. The method uses information on identity by descent scores for a pair of sibs at a marker locus conditioned on the number of affected sibs in the pair. A procedure for estimating the recombination fraction is described, and a table facilitating the likelihood ratio test of linkage is provided. The method, when applied to a collection of multiplex families segregating for juvenile diabetes mellitus, suggests the possibility that this disease is linked to the HLA complex. The method is found to compare favorably to the maximum likelihood approach, for which the computer program LIPED gives a maximum lod score of 2.48 at a male and female recombination fraction of theta = 0.20.


Idiopathic paraproteinaemia. I. Studies in an animal model--the ageing C57BL/KaLwRij mouse. A search for a suitable animal model for studies on idiopathic paraproteinaemia showed that an age-dependent increase in the appearance of homogeneous immunoglobulins in serum was common to all of the seven mouse strains investigated to date. The highest frequency was found in C57Bl/KaLwRij mice. Further investigations in this strain demonstrated that, except for some quantitative differences, most of the features of human and C57BL Mouse idiopathic paraproteinaemia were essentially the same. No clear-cut correlation was found between the idiopathic paraproteinaemia and, in the old C57B1 mice, a rather frequently occurring reticulum cell sarcoma B and amyloidosis. The mouse idiopathic paraproteinaemia can be regarded as an analogue of the human idiopathic paraproteinaemia and therefore as a suitable model for further experimental studies.


Magnetic enzyme immunoassay of anti-grass pollen specific-IgE in human sera. This paper reports a magnetic solid-phase sandwich enzyme immunoassay for specific IgE antibodies in human sera. Crude extracts of grass pollen bound to magnetic polyacrylamide agarose beads were mixed with human serum to be tested. After washing in a magnetic rack, the beads were incubated with the glucose-oxidase-labelled sheep anti-IgE. The enzyme activity associated with the beads was measured by colorimetric assay. Results obtained from sixty-one human sera, as measured by the magnetic enzyme immunoassay, gave a linear correlation coefficient of 0.98 with the values as determined by radio-immunoassay. This procedure, which allows the grass pollen specific IgE in human sera, to be measured, is easy to perform, reproducible and may avoid the use of radioactive compounds.


Autoimmune glomerulotubular nephropathy in mice. We produced an autoimmune glomerulotubular nephropathy in Swiss-Webster mice using human glomerular antigen in Freund's complete adjuvant. The disease is associated with circulating antibody to both mouse and human glomerular basement membranes (GBM) and tubular basement membranes (TBM). All mouse IgG subgroups are deposited initially in a linear pattern along the GBM and TBM. IgG deposition remains linear, while that of the other subgroups assumes a granular GBM pattern with continued linear TBM deposits. Despite tissue deposition of antibody capable of C-3 fixation, no C-3 is found in vivo along the GMB or TBM, nor is there C-3 fixation in vitro. This appears to be related to spatial limitations of IgG molecule attachment to basement membranes. A unique ultrastructural lesion of the GMB developed, characterized by periodic expansions of the lamina rara externa to form a beaded pattern. Eluate of nephritic kidneys contained all subgroups of IgG, but mainly IgG1 fixed in vitro to mouse kidney and in vivo when injected intravenously into normal mice. Fixation of other IgG subgroups in vivo may have resulted from antibody formation to abnormally formed GBM, thereby accounting for the peculiar ultrastructural findings and tissue fixation characteristics of the eluted immunoglobulin. Abnormal proteinuria without glycosuria or lysozymuria developed in test animals as compared to controls. Our model is similar in certain aspects to previously described models of Stebley nephritis, but differs because of the total involvement of TBMs, unique ultrastructural lesions, and dissimilarity to other reports of this model in mice.


Requirement of functional T-cells in the production of autoimmune glomerulotubular nephropathy in mice. In order to study T-cell function related to the production of autoimmune nephropathy, we immunized random-bred mice, homozygous athymic nude (nu/nu) mice and heterozygous hairy (nu/+) mice with human glomeruli contained in Freund's complete adjuvant. The random-bred and heterozygous hairy mice developed circulating antibodies to mouse and human kidney and an autoimmune glomerulotubular nephropathy, while the nude mice, even after prolonged immunization, developed neither antibodies nor nephropathy. We therefore concluded that the development of autoimmune glomerulotubular nephropathy in mice requires the presence of functioning T-cells.


Macrophage secretion and the complement cleavage product C3a in the pathogenesis of infections by mycoplasmas and L-forms of bacteria and in immunity to these organisms. Mouse peritoneal macrophages in culture exposed to Mycoplasma pulmonis show marked biochemical changes. This micro-organism induces the release of hydrolytic enzymes from macrophages. The release is time- and dose-dependent and is not associated with loss of the cytoplasmic enzyme lactate dehydrogenase or any other sign of cell death. Secretory products of macrophages may play a role in the pathogenesis of chronic inflammatory responses elicited by mycoplasma infections. One of the products of activated macrophages is the complement cleavage product C3a. Purified C3a was incubated with M. hominis, M. pulmonis, Proteus mirabilis and an L-phase variant of this organism. All mycoplasmas and the L-phase variant were lysed by low concentrations of C3a, whereas the bacterial form of Pr. mirabilis was resistant.


Lymphocyte response of leprosy patients to human-derived and purified armadillo-derived Mycobacterium leprae, BCG and PPD. The lymphocyte transformation test was applied to compare in vitro lymphocyte responses of tuberculoid (high resistant) and lepromatous (low resistant) leprosy patients to purified Mycobacterium leprae derived from experimentally infected armadillos and crude M. leprae derived from man, as well as to bacille Calmette-Guérin (BCG) and purified protein derivative (PPD). It was found that the purification procedure using enzymic digestion did not affect the immunogenicity of armadillo-derived M. leprae as compared with the crude human-derived preparation, although 2.5-5-fold higher doses of the purified organisms were required to elicitate equivalent lymphocyte responses. The result indicated the suitability of purified armadillo-derived M. leprae as the standard antigen for lymphocytes transformation tests in leprosy. The cross-reactivity studies show a close relationship between PPD and BCG, but not between M. leprae and PPD or BCG.


Severe combined immunodeficiency disease: a model of T-cell dysfunction. Studies in three patients with severe combined immunodeficiency disease (SCID) and normal adenosine deaminase demonstrated that the combined defect of both T- and B-lymphocyte function may reflect the lack of normal maturation of thymic epithelial cells. This results in the failure of initiation of T-cell differentiation and consequent failure of T-cell dependent maturation of B-lymphocytes to an antibody-secreting stage. SCID B lymphocytes were shown to be capable of generating a specific IgM-antibody response to two T-cell-dependent antigens in vitro under either of the following conditions: (a) provision of autologous T-helper cells which were induced following incubation of precursor cells on monolayers of cultured human thymic epithelium or (b) in the presence of allogeneic T-helper cells. Specific IgM anti-ovalbumin (OA) responses were also generated in the absence of provided T-helper cells when the antigen was insolubilized (Sepharose-OA). The antibody-secreting cells and their circulating precursors carried surface IgM, HLA and Ia-like determinants and proliferated in response to antigen. Identification of this form of SCID may be important when considering therapy and provides an excellent model for the study of the T-cell-dependent acquisition and expression of B-cell immunity.


The mechanism of imipramine in enuresis nocturna. 1. To evaluate the mechanism of action of imipramine in enuresis nocturna, we compared the effects of imipramine with those of scopolamine butylbromide in fourteen children suffering from this condition. A double-blind, cross-over design was used. 2. Imipramine, 10--20 mg, was superior to scopolamine butylbromide (10--20 mg), in eleven of the fourteen subjects (P less than 0.01), and the latter drug was no better than the placebo. 3. As scopolamine butylbromide does not cross the blood-brain barrier, it is concluded that peripheral antimuscarinic effects are not important in the beneficial effects of imipramine in enuresis nocturna. 4. The therapeutic effects of imipramine in depression frequently take 3 to 4 weeks to develop. Such a delay was not seen in our enuretic patients. Thus the mechanism of the drug in the two conditions is probably different.


Tumor detection with 67Ga-citrate: a literature survey (1970--1978). Gallium scan detection of various neoplasms is tabulated by anatomic and histologic categories. The experience with many neoplasms is sufficient to accurately predict the likelihood of detection with gallium. This tabulation helps to point out other areas where the cumulative experience is insufficient to accurately predict sensitivity rates.


Measles in Africa: a deadly disease. Some personal comments. Measles dominate childhood illnesses in tropical Africa with a variety and severity of complications virtually unknown in the West. There is no apparent continental variation in measles virus but environmental factors vary widely. The frequent association of severe measles with malnutrition and recent studies indicating impaired humoral, cellular, and mucocutaneous immunologic function in the malnourished may explain this perplexing disease. Prevention of early malnutrition combined with lasting and economic early immunization with heat-stable vaccine, currently unavailable, are needed to halt this frequent costly, and often fatal African scourge.


Atenolol and chlorthalidone on blood pressure, heart rate, and plasma renin activity in hypertension. The antihypertensive effect of atenolol, with and without chlorthalidone, on hypertension was assessed in an outpatient as well as in an inpatient study. In the outpatient study atenolol alone induced decreases in systolic and diastolic BP amounting to 20 and 15 mm Hg. Maximal response of BP and HR developed within a week at the lowest dose used (100 mg twice daily). Combined atenolol-chlorthalidone treatment decreased lying and standing systolic BP by 7 and 14 mm Hg more than atenolol alone, but diastolic BP was decreased little more. In the inpatient study the addition of atenolol to chlorthalidone therapy in a dose of 100 mg twice daily resulted in a maximal decrease in BP within 3 days. At this dose PRA was lowered only slightly. Larger doses did not lead to any significant further decrease in BP, whereas PRA fell progressively. Our results indicate that, in contrast to nonselective blockade, specific beta-1-adrenoceptor blockade by atenolol is capable of inducing a distinct antihypertensive effect, unrelated to suppression of PRA. The decrease in PRA after larger doses of atenolol was not accompanied by a further decrease in BP. Because diuretic-induced renin release plays a role in the maintenance of the BP, our findings suggest that at higher dosages a hypertensive effect of the beta blocker compensated for the hypotensive effect of the decrease in PRA.


Comparative trial of large and small fractions in the radiotherapy of head and neck cancer. A random controlled trial was performed to compare long and short fractionation of radiotherapy in patients with head and neck cancer with a poor prognosis. Ninety-eight matched pairs were treated, one member of each pair received 10 fractions in 22 days, the other 30 fractions in 42 days. The same nominal standard dosages were used in each arm of the trial. Mucosal reactions were more severe with 10 fractions, skin reactions more severe with 30 fractions. No difference in survival, local tumour control rates or late normal tissue effects could be demonstrated. It is suggested that any possible therapeutic advantage of prolonged fractionation is minimal and that it is justified to use a small number of large fractions in clinical trials involving hyperbaric oxygen or electron-affinic sensitizers.


Use of the uricase-inhibited rat as an animal model in toxicology. An accessible, reproducible, and inexpensive animal model for toxicologic evaluation of hyperuricemic conditions has been required for some time. A number of authors have tried to develop such a model by administering high doses of uric acid to various animal species (dog, rabbit, rat) but the potent liver uricase in these species prevented development of sustained hyperuricemia. Johnson et al. [4], Stavric et al. [5], and a number of other investigators [72, 75] successfully used potassium oxonate [63] to block the effect of hepatic uricase and to produce hyperuricemia in rats [4, 5, 68, 69, 72, 74, 76, 80], rabbits [66], mongrel dogs [67], mice [65], and pigs [64]. The oxonate-treated rat can serve as a useful animal model not only in investigation of the uric acid nephropathy, but also in a number of other toxicologic evaluations connected with uric acid. This model has been used to evaluate drugs that affect uric acid excretion, to determine which dietary factors affect serum urates, or to evaluate possible therapeutic agents in certain disorders associated with uric acid. The same model could also be used by behavioral scientists, for whom research on uric acid has become increasingly popular in recent years [33, 137]. The ideal uricase inhibitor for induction of hyperuricemia would be one which is irreversible, noncompetitive, and relatively nontoxic, so that its activity would be independent of high levels of uric acid, and effective inhibition could be attained at low dosage levels. Oxonic acid is not an ideal uricase inhibitor, because it is competitive and is eliminated from the body relatively rapidly. Although relatively nontoxic, oxonic acid and its salts are foreign substances that could interfere with some other metabolic systems. The possibility exists that an ideal, or at least a better inhibitor, could be developed by appropriate substitutions on the molecule of oxonic acid or by introducing different types of compounds such as derivatives of diazohypoxanthines, barbiturates, or similar substances. Until such improvements on the uricase-inhibited rat models are available, potassium oxonate, which is easily obtainable, can be used as an effective inhibitor of uricase in vivo.


Toxicologic assessments in acute heroin fatalities. The recent improvements in analytic methods enable routine morphine detection in blood in microgram or nanogram quantities. It is now possible to assess acute death from heroin use by toxicologic analyses. A review of available data indicates a rapid distribution of morphine even in sudden fatalities, to the various organs of the body. Blood morphine levels in most acute heroin-involved deaths range from 0.1 to 1.0 microgram/ml, while morphine concentration in liver ranges from 0.1 to 10.0 microgram/gm. In rapid death, the blood to liver ratio is approximately 1:5. Blood and liver appear to be the specimens of choice in determining fatality due to heroin; however a distribution study that included other tissues such as brain, bile, and urine would afford a more meaningful evaluation in forensic investigation. The correlation of the survival periods of decedents to concentrations of morphine in tissues is discussed. Since morphine concentration decreases precipitously in antemortem blood immediately after administration of heroin, the assurance of detecting and determining morphine is greater in blood specimens from decedents who died within 1 hr after drug taking than from those who survived for a longer period. Blood levels of morphine also appear to be regulated by dosage. The role of ethanol and other drugs, including excipients in illicit heroin preparations, in acute narcotism is still poorly understood. Morphine is produced in the antemortem metabolism of codeine. A close evaluation of toxicologic data is necessary to determine whether the morphine detected, if a metabolite, is a conversion product of codeine, heroin, or both. In any event, the cause of death involving heroin is determined only after information from history and pathology, as well as toxicology, are carefully correlated.


Toxicologic properties of fluorescent whitening agents. From the collection of toxicologic data, it is seen that the fluorescent whitening agents are a well-investigated class of compounds. Only in one of the groups of compounds investigated did it appear advisable to discontinue the use of a particular product on the basis of the toxicologic findings. In the large number of the other cases, the findings indicate that there is a considerable degree of toxicologic safety in the use of the FWAs in soap and detergent products.


Co-ordination of the school and general dental services in Rochdale, England. The administrative process in the implementation of a scheme of co-operation between the school and general dental practitioner services to screen and treat children aged 14 years and above in an Area Health Authority is described. 84% of the target group were screened in periods amounting to 12 months. The uptake of treatment as assessed by return of notices of referral was only 1.5%. Interview of a sample of those referred revealed that 49% had been to a dentist within 6 months and of these 34% would not have otherwise attended. 13% had taken referral forms to practitioners. The implications of these findings are discussed and a more effective means of evaluating treatment uptake is proposed.


A programmable calculator program for rapid logarithmic extrapolation, and calculation of mean transit time from an indicator-dilution curve. Reconstruction of the primary indicator-dilution curve is accomplished by exponential curve-fit from a set of points obtained on the downslope of the curve. Curve-fit is simplified by requiring entry of indicator concentrations (Yi) only, where time increments (Xi) are made self-generating in the program. Similarly, calculation of mean transit time requires only the entries of Yi. Stored values supply the needed quantities for calculations of cardiac output and the central blood volume as defined by the injection and the sampling sites. The Texas Instrument TR 52 model hand-held programmable calculator is utilized in this program but it should be adaptable to other programmable calculators. The present program provides a procedure for rapid reconstruction of the primary indicator-dilution curve, and hence calculations of cardiac output, mean transit time and central blood volume.


PEEP: its use in young patients with apparently normal lungs. PEEP has been advocated for use in patients with the acute respiratory distress syndrome characterized by a marked reduction in FRC. It has not been advocated for patients with apparently normal lungs requiring prolonged mechanical ventilation. We have done inert gas washouts on five young patients comparing no PEEP to 10 cm H2O PEEP. Four of the five showed a significant improvement in PaO2, a decrease in AaDO2 and Qs/Qt, the fifth a slight improvement on PEEP. Arterial washouts were significantly faster on  PEEP in all patients suggesting a decrease in intrapulmonary shunting. Airway washouts in the initial phase were faster off PEEP suggesting an increase in lung volume and FRC with PEEP. Later portions of the curve were faster on PEEP suggesting improved distribution of ventilation. These findings suggest that PEEP might be of significant value in treatment of patients requiring prolonged mechanical ventilation for reasons other than lung abnormalities.


Comparison of assisted and controlled mechanical ventilation in anesthetized swine. We compared assisted mechanical ventilation with controlled mechanical ventilation with and without PEEP in 10 anesthetized swine. Catheters were placed to measure airway, intrapleural, and blood pressure; PaO2 and PaCO2; arterial pH; total minute ventilation; and mixed exhaled oxygen and carbon dioxide tensions. We calculated the ratio of physiological dead space to tidal volume, alveolar minute ventilation, CO2 production, VO2, and RQ. We found no clinically or statistically significant difference between assisted and controlled ventilation.


Comparison of hemodynamic, pulmonary, and renal effects of use of three types of fluids after major surgical procedures on the abdominal aorta. Hemodynamic, pulmonary, and renal variables were measured in 24 patients scheduled for major abdominal aortic operations. Control values were obtained before preoperative medications were given. All patients received 5% dextrose in Lactated Ringer's solution intraoperatively. Postoperatively, group 1 patients received 5% dextrose in water plus albumin, group 2 received 5% dextrose in 0.45 sodium chloride solution, and group 3 received 5% dextrose in lactated Ringer's solution. There were significant increases in Qs/Qt and AaDO2, 48 hours after operation in group 3. Oxygen consumption and cardiac output increased in all groups 24 hours after operation. Twenty-four hours later, these two variables returned to control values in group 1 but continued to rise in the other two groups. Significant diuresis occurred in group 1, 48 hours postoperatively, whereas the other two groups continued to retain water. Use of albumin and 5% dextrose in water in the postoperative period seemed to produce less deviations from control values of most measured variables, than the other two groups.


A randomized crossover comparison of acebutolol and methyldopa in the treatment of mild to moderate essential hypertension. In a randomized crossover comparison between acebutolol and methyldopa for the treatment of mild to moderate essential hypertension in 30 patients, acebutolol, a cardioselective beta-one-adrenergic blocker, at 400 to 800 mg daily was found to be significantly better (p less than 0.002) than 500 to 1000 mg methyldopa daily in reducing both systolic and diastolic blood pressures and pulse rate. Patient compliance with therapy was excellent, and there were no side-effects on acebutolol, whereas patients on methyl-dopa reported a significant number of side-effects (p less than 0.002). The potassium-sparing effect due to acebutolol was significant (p less than 0.005) and this has not been reported before. This may be beneficial in diuretic-induced hypokalaemia in the hypertensive patient.


Fenbufen compared with indomethacin in osteoarthrosis. A double-blind, crossover clinical trial was carried out with a new propionic acid derivative, fenbufen, versus indomethacin and placebo in 20 patients with osteoarthrosis. Active drug dosages of 75 mg indomethacin daily and 600 mg fenbufen daily were used. Fenbufen scored significantly better than placebo with respect to two and indomethacin better than placebo with respect to five of the assessment indices used. Indomethacin was significantly better than fenbufen with respect to two indices and, overall, appeared more effective in the dosages tested. Biochemical abnormalities of liver function (serum alkaline phosphatase and/or SGOT) were noted in 5 patients after fenbufen therapy (in 3 patients after 4-weeks' treatment and in 2 after 6 weeks) but in none after indomethacin therapy. The significance of these findings is discussed. It is concluded that fenbufen should be withdrawn from further clinical use until the true incidence and significance of hepatotoxicity has been evaluated.


A comparative clinical investigation of the therapeutic effect of levodopa alone and in combination with a decarboxylase inhibitor (carbidopa) in cases of Parkinson's disease. The therapeutic effect of the combination of levodopa and carbidopa ("Sinemet") was compared with that of levodopa alone in 21 patients with Parkinson's disease. Eighteen parameters of the clinical condition and of functional impairment were determined quantitatively and the results satistically evaluated. Changing over from levodopa to the combination preparation resulted in an average improvement of 51.9% within 2 weeks. No relationship was found to exist between the degree of improvement and the severity or the progression of the disease. By the use of the combination preparation, the daily dosage of levodopa could be reduced by 77%. Side-effects connected with the gastro-intestinal tract occurred much less frequently, while hyperkinesia increased. No arrhythmogenic effect was found with the combination product. From the clinical standpoint, combination therapy appeared to be qualitatively superior. By selective maintenance of freshly formed dopamine, it should be possible to assure a directed influence on the disturbed equilibrium of the functional systems of the brain.


A controlled study of short-term treatment of tension headache. A double-blind trial was carried out in 12 patients with chronic recurring tension headache to compare the effectiveness of treatment with an analgesic combination ("Syndol") and placebo. Treatment was confined to the period of an attack and the response in the 46 attacks studied showed that, in those of mild to moderate severity, significantly more patients had initial relief within 15 minutes after active treatment than after placebo, and significantly fewer tablets were required to produce complete remission of symptoms for more than 48 hours. The interval between attacks, however, was not significantly affected by active drug or placebo. Severe attacks, which occurred only in the periods assigned to active treatment, required significantly more tablets and a day longer for complete remission.


A controlled comparative study of the use of porcine xenograft in the treatment of partial thickness skin loss in an occupational health centre. Twenty-eight patients with partial thickness skin loss of the limbs, mainly due to burns, were treated on an out-patient basis in an occupational health centre. Thirteen patients were treated with porcine skin graft and the other 15 by the conventional method with paraffin gauze. The results showed that the median healing time was 13 days in the porcine skin graft group and 28 days in the control group. Other than healing time, the effects of porcine xenograft in reducing pain, infection and sickenss absence were far greater than those with conventional treatment. From a comparison of total dressing costs, it was estimated that for lesions of comparable size the cost of treatment with porcine xenograft was approximately one-third of that using paraffin gauze.


Bromocriptine in the treatment of secondary amenorrhoea and ovarian dysfunction in hyper- and normo-prolactinaemic patients. The clinical use of bromocriptine (2.5 mg twice daily) was investigated in 40 women attending an infertility clinic and presenting with secondary amenorrhoea (18) or with ovarian dysfunction (22) which had failed to respond to anti-oestrogen therapy. Patients in each group were sub-divided into those with raised and those with normal prolactin levels, and re-examined at 3 and 12 months after the start of treatment. The results confirmed that bromocriptine is effective in the treatment of hyperprolactinaemic states whether there is amenorrhoea or not. Moreover, in cases of ovarian dysfunction as well as of amenorrhoea where the prolactin levels were within the normal range, there was evidence to suggest that bromocriptine can be associated with a return of ovulation, although the mechanism by which it might do so still needs evaluation.


Positive end-expiratory pressure in the management of lobar atelectasis. Positive end-expiratory pressure (PEEP) has been extensively utilized in the treatment of severe hypoxemia from noncardiogenic pulmonary edema. The usefulness of therapy with PEEP in the management of lobar atelectasis has not been previously stressed. Recently, we observed four patients with lobar atelectasis who failed to respond to the usual conservative measures of endotracheal suctioning and thoracic physiotherapy. Atelectasis was confirmed by physical examination and chest x-ray films, and three of the four patients subsequently underwent fiberoptic bronchoscopic examination. Endobronchial obstruction was not found, and despite extensive irrigation and suctioning, the atelectasis failed to resolve. Therapy with PEEP was then added, with pressures of 5 to 15 cm H2O. Serial chest x-ray films disclosed resolution of the atelectasis within 4 1/2 hours in two patients, within 14 hours in one patient, and within 24 hours in the remaining patient.


Criteria for selective positive end-expiratory pressure and independent synchronized ventilation of each lung. Respiratory failure of different origins often requires therapy with mechanical ventilation and positive end-expiratory pressure (PEEP). These supports are occasionally inadequate if the damage to one lung is significantly more pronounced than that to the other lung. Technical means exist to ventilate each lung independently or to provide a different PEEP to each lung. The findings from nine patients in whom one of these techniques was applied are presented, and advantages and disadvantages are discussed.


Severe hypoxemia secondary to pulmonary embolization treated successfully with the use of a CPAP (continuous positive airway pressure) mask. We describe a patient who was admitted with acute onset of dyspnea and pleuritic chest pain. The patient was in acute hypoxic respiratory failure documented by arterial blood gas levels. The severe hypoxemia was refractory to 100 percent O2 administration. The cause of the patient's sudden deterioration was a pulmonary embolus documented by angiography. The patient was managed successfully with heparin therapy. A continuous positive airway pressure (CPAP) mask corrected the severe hypoxemia, which otherwise would have required a more invasive method of respiratory support.


Effects of S-carboxymethylcysteine on tracheal mucus velocity. The effects of S-carboxymethylcysteine on tracheal mucus velocity were assessed in a double blind crossover study between 2 grams S-carboxymethylcysteine and placebo. Subjects included six healthy non-smokers, eight smokers with small airway disease and chronic simple bronchitis, and eight subjects with chronic obstructive bronchitis. Tracheal mucus velocity was measured prior to and two and three hours after each subject had ingested S-carboxymethylcysteine or placebo. No significant change in tracheal mucus velocity occurred after placebo or S-carboxymethylcysteine in any of the groups, indicating that the drug has no acute effect on mucus transport.


Repeated massive hemoptysis: successful control using multiple balloon-tipped catheters for endobronchial tamponade. Endobronchial tamponade with a balloon-tipped catheter (Fogarty catheter) is used to control massive hemoptysis. This case documents that recurrent massive hemoptysis can be successfully controlled with repeated use of this procedure and that the simultaneous placement of more than one catheter can be safe and effective therapy that is well tolerated by patients.


Health supervision of children in foster care. The 1971--74 survey of the health needs and services provided to New York City children in foster care indicates a failure of the Medicaid program to ensure adequate routine care and treatment.


[25 years of curative cancer-therapy stagnation--a change in a sight?]. Two measures are urgently needed to improve curative therapy results in cancer treatment. 1. Improvements in the early recognition of specific types of tumor and in appropriate modes of preventitive treatment.--2. The introduction of a metastasis prophylaxis before each diagnostic and therapeutic operation for cancer; several possibilities are proposed. The stagnation of cancer therapy results can only be overcome by an alteration in the current concept of treatment, which in cases of early cancer is as yet directed exclusively at the primary tumor.


Meiotic effects of DNA-defective cell division cycle mutations of Saccharomyces cerevisiae. The meiotic effects of several cell division cycle (cdc) mutations of Saccharomyces cerevisiae have been investigated by electron microscopy and by genetic and biochemical methods. Diploid strains homozygous for cdc mutations known to confer defects on vegetative DNA synthesis were subjected to restrictive conditions during meiosis. Electron microscopy revealed that all four mutants were conditionally arrested in meiosis after duplication of the spindle pole bodies but before spindle formation for the first meiotic division. None of these mutants became committed to a recombination or contained synaptonemal complex at the meiotic arrest.--The mutants differed in their ability to undergo premeiotic DNA synthesis under restrictive conditions. Both cdc8 and cdc21, which are defective in the propagation of vegetative DNA synthesis, also failed to undergo premeiotic DNA synthesis. The arrest of these mutants at the stage before meiosis I spindle formation could be attributed to the failure of DNA synthesis because inhibition of synthesis by hydroxyurea also caused arrest at this stage.--Premeiotic DNA synthesis occurred before the arrest of cdc7, which is defective in the initiation of vegetative DNA synthesis, and of cdc2, which synthesizes vegetative DNA but does so defectively. The meiotic arrest of cdc7 homozygotes was partially reversible. Even if further semiconservative DNA replication was inhibited by the addition of hydroxyurea, released cells rapidly underwent commitment to recombination and formation of synaptonemal complexes. The cdc7 homozygote is therefore reversibly arrested in meiosis after DNA replication, whereas vegetative cultures have previously been shown to be defective only in the initation of DNA synthesis.


[Tertian malaria in children and adults from an epidemic region in southern Turkey (author's transl)]. Since 1974 an epidemic of tertian malaria has been spreading around the Adana and Tarsus townships in southern Turkey, with a peak incidence of 115 500 cases in 1977. A further increase is to be expected because the insect vectors have become resistant to insecticides. Since 1975 eleven children and three adults have been treated for P. vivax malaria. They had all stayed in the epidemic area during the transmission season which lasts from July to October. Because of a long primary latent period seven patients only developed first manifestations of the disease six to nine months after leaving Turkey. The classical malarial paroxysms were missing during the first weeks of the primary attack. Several children had a febrile illness over weeks with headache, vomiting, abdominal pain, hepatosplenomegaly, high blood-sedimentation rate and severe haemolytic anaemia, so that appendicitis or septicaemia had been suspected. Tetracyclines and trimethroprimsulphamethoxazole were able to suppress the disease without preventing relapses.


[Innovative trends in dentistry: background, bases and outlook]. This article briefly analyzes the present situation in dental practice with emphasis on its inherent discrepancies, and describes the background, theoretic and methodologic bases, and prospects of the PAHO/WHO Program of Innovation in Dental Education and Care. An account is given of the conceptual framework of the Program, which is based on the hypothesis that changes in oral health in a country depend partly on the national socioeconomic situation at any given point in its history. At the same time, it is recognized that there is leeway in the general political setting for the trial and application of plans for curricula and care that can work quantitative and qualitative changes in the educational and service sectors. There follows a description of the operational arrangement and the subprograms and prpkects going forward in 16 dental schools of Latin America.


[Problems of bacteriologic diagnosis and aimed antibiotic therapy in pyogenic maxillofacial infections]. Bacteriologic analysis of pathogens from pyogenic infections of the jaw in 71 patients revealed that bacteria normally found in the buccal cavity predominated in 86% of the specimens. Considering the fact that no pathogens could be identified in 7% of the specimens, this then means that pathogens were only found in 7% of the specimens. Six to 12 strains were usually isolated in the mixed bacteria population of the buccal cavity. A total of 430 strains of bacteria were cultured and tested for their response to 20 common antibiotic preparations. We were able to confirm the high effectiveness of penicillin and/or broad spectrum penicillin 92% of the cases (8600 determinations of resistance). Tetracycline was effective in 89% of the cases; trimethoprim sulfamethoxazole, in 83%. The effectiveness of newer, more expensive, antibiotic preparations was not significantly better than that of pencillin. Administration of such antibiotic preparations therefore should be limited to problematic pathogens.


[Bacteriology of odontogenic abscesses]. The primary bacteria strains and their sensitivity to antibiotic drugs were examined in 329 patients with extraoral split abscess who were treated on an in-patient basis. Combination therapy using various antibiotics together with gentamycin was recommended. An antibiogram however should be completed if antibiotic therapy is to be purposeful.


[Indications for surgical treatment of mandibular osteomyelitis]. A plan of treatment was worked out based on the current classification of osteomyelitis of the mandible. On the basis of clinical follow-up examinations between 1973 and 1977 and the use of improved diagnostic tools, it was shown that active surgical procedures have become more and more accepted in our hospital.


[Surgical technic in the treatment of mandibular osteomyelitis]. Our experience with operative treatment of 70 patients with osteomyelitis of the mandible showed that the incision and drainage of soft-tissue abcesses combined with antibiotic therapy led to healing in 22 patients. More extensive measures, such as sequestectomy, decortication, resection of whole areas of the mandible, and transplantation of autologous cancellous bone, however were necessary with 48 of the patients. A detailed description of the various operative techniques was presented; the respective indications were mentioned.


[Delayed infections after foreign body inclusion in the maxillofacial region]. Nine cases of so-called late infections following foreign body inclusions due to trauma as well as possible developmental mechanisms were discussed. The question arises as to whether a nonirritating incorporated foreign body should be surgically removed as early as possible to eliminate the possibility of late infection.


Excretion of valproic acid into semen of rabbits and man. Dipropylacetic acid (VPA, valproic acid) has been quantified in plasma and semen from rabbits and man using a new gas-liquid chromatographic assay. The drug assay is rapid, sensitive and free from interference by VPA metabolites. The beta phase half-life of VPA in rabbits after an i.v. dose (50 mg/kg) was 56 +/- 6 min. The concentration of VPA in rabbit plasma was 17 to 30 times the concentration in rabbit semen. In man, 500 mg doses of the free acid, p.o., resulted in VPA concentrations in plasma that were 11 to 17 times the concurrent levels in semen. VPA, in concentrations up to 10(-3) M, did not influence the motility of rabbit spermatozoa in vitro.


A controlled study of the effect of sodium valproate on photosensitive epilepsy and its prognosis. The effect of sodium valproate on photosensitive epilepsy was studied. The range of flash rates of intermittent photic stimulation to which patients were sensitive (photosensitive range) was tested prior to treatment, and the reliability of this measure established by repeated tests on 70 patients. The photosensitive range was measured on 50 patients prior to and during treatment with sodium valproate. In 27 patients photosensitivity was abolished and in a further 12 patients photosensitivity was significantly reduced. A group of 167 patients followed without treatment did not show significant improvement over a 7 year period. Sixteen patients had drug treatment withdrawn, and in 7 months their photosensitive range had returned to its predrug level.


Energy-related pollutants in the environment: use of short-term tests for mutagenicity in the isolation and identification of biohazards. In an effort to gather information on the potential genetic hazards of existing or proposed energy-generating or -conversion systems, we have begun a correlated analytical and genetic analysis of a number of technologies. The work is divided into two phases: one deals with known compounds expected to occur in the environment through energy production, conversion, or use; the other deals with actual samples from existing or experimental processes. To approach the problems of coping with and testing large numbers of compounds, we set up a form of the "tier system." Operating units utilizing Salmonella, Escherichia coli, yeast, human leukocytes, mammalian cells, and Drosophila have been initiated. Various liquid-liquid extraction methods and column chromatographic separations have been applied to crude products and effluents from oil-shale, coal-liquefaction, and coal-gasification processes. Mutagenicity of the various fractions is assayed by means of reversion of histidine-requiring auxotrophs of Salmonella typhimurium; comparative studies are carried out with the other genetic systems. In order to incorporate metabolic activation of these fractions and compounds, rat liver homogenates (S-9) are used in the various assays. Results implicate chemicals occurring in the basic (ether-soluble) and the neutral fractions as potential genetic hazards. Chemical constituents of these fractions (identified or predicted) were tested individually for their mutagenic activity.


Comparative aspects of pesticide metabolism in plants and animals. Pesticide chemicals are an important component of modern agriculture. Through their use, plants and animals are exposed to pesticides directly and indirectly from transport through soil, water, and other environmental components. Pesticide chemicals which are absorbed by plants and animals undergo extensive biotransformation. Lipophilic compounds are converted to polar metabolites through a variety of microsomal and extramicrosomal reactions in plants and animals. Generally, biotransformations are qualitatively similar in both systems. However, there are important quantitative rate differences in metabolism which often determine the balance between activation and deactivation of a pesticide. Furthermore, there are qualitative differences in conjugative mechanisms in plants and animals. Animals through an efficient excretory system eliminate transformation products via the urine and feces. Since efficient excretory systems are absent in plants, terminal degradation products are stored as conjugates and/or derivatives which may be incorporated into the plants themselves. Metabolic transformations of selected pesticides illustrating various types of reactions in plants and animals are discussed.


Overview of potential mutagenic problems posed by some pesticides and their trace impurities. This review principally addresses a number of aspects of usage of pesticides as well as populations at potential risk and attempts to highlight categories of pesticides whose structures or those of their metabolites and/or trace impurities, degradation and transformation products suggest an a priori mutagenic and/or carcinogenic risk. The pesticides considered include: DDT, hexachlorobenzene (HCB), 2,4,5-T, pentachlorophenol, and various herbicidal precursors (e.g., carbamates, triazines) of nitrosamines and nitroso derivatives. Structural features of a number of halo-unsaturated pesticides (e.g., dichloropropenes) were also reviewed from a viewpoint of contrasting their potential mutagenicity with that of vinyl chloride and vinylidene chloride. Additionally the mutagenicity of the organophosphorus pesticide Trichlorophon is contrasted with that of its degradation products.


Sorption of pollutants by plant detritus: a review. Detritus particles derived from the decomposition of vascular plants appear to have a high sorptive capability for a wide range of pollutants. Evidence is presented and reviewed which shows detrital concentration of heavy metals, radionuclides, and organochlorine insecticides. A study of a roadside marsh indicates that lead originating from automobile exhausts may reach concentrations as high as 1415 ppm on marshgrass detritus. We suggest that these elevated concentrations may, in turn, be passed on to detritivores which ingest the contaminated particles and experience desorption and assimilation of the pollutant within the digestive tract. Finally, potential mechanisms are listed which might explain detrital sorption; these include; microbial uptake (adsorption and metabolic absorption), association with detrital and microbial lipids, electrostatic adsorption in response to charges on the detritus particles, and formation of complexes and chelates at active sites on the organic molecules of the decomposing detritus.


Soil and plant factors influencing the accumulation of heavy metals by plants. The use of plants to monitor heavy metal pollution in the terrestrial environment must be based on a cognizance of the complicated, integrated effects of pollutant source and soil-plant variables. To be detectable in plants, pollutant sources must significantly increase the plant available metal concentration in soil. The major factor governing metal availability to plants in soils is the solubility of the metal associated with the solid phase, since in order for root uptake to occur, a soluble species must exist adjacent to the root membrane for some finite period. The rate of release and form of this soluble species will have a strong influence on the rate and extent of uptake and, perhaps, mobility and toxicity in the plant and consuming animals. The factors influencing solubility and form of available metal species in soil vary widely geographically and include the concentration and chemical form of the element entering soil, soil properties (endogenous metal concentration, mineralogy, particle size distribution), and soil processes (e.g., mineral weathering, microbial activity), as these influence the kinetics of sorption reactions, metal concentration in solution and the form of soluble and insoluble chemical species. The plant root represents the first barrier to the selective accumulation of ions present in soil solution. Uptake and kinetic data for nutrient ions and chemically related nonnutrient analogs suggest that metabolic processes associated with root absorption of nutrients regulate both the affinity and rate of absorption of specific nonnutrient ions. Detailed kinetic studies of Ni, Cd, and Tl uptake by intact plants demonstrate multiphasic root absorption processes over a broad concentration range, and the use of transport mechanisms in place for the nutrient ions Cu, Zn, and K. Advantages and limitations of higher plants as indicators of increased levels of metal pollution are discussed in terms of these soil and plant phenomena.


Accumulation of radionuclides by plants as a monitor system. The accumulation of radionuclides by plants acting as a monitoring system in the environment may occur by two modes; foliar absorption by the leaves and shoot of the plant, or by root uptake from the soil. Data on plant accumulation of radionuclides may be obtained from studies of fission product radionuclides deposited as worldwide fallout, and from tracer studies of plant physiology. The epidermal features of plant foliage may exert an effect upon particle retention by leaves, and subsequent uptake of radionuclides from the surface. The transport of radionuclides across the cuticle and epidermis of plant leaves is determined in part by the anatomy of the leaf, and by physiological factors. The foliar uptake of fallout radionuclides, 99Sr, 131I, and 137Cs, is described with examples from the scientific literature. The environmental half-life of 131I, for example, is considerably shorter than its physical half-life because of physical and biological factors which may produce a half-life as short as 0.23/day. 99Sr and 137Cs are readily taken up by the leaf, but 137Cs undergoes more translocation into fruit and seeds than 99Sr which tends to remain in the plant part in which it was initially absorbed. Soil-root uptake is conditioned primarily by soil chemical and physical factors which may selectively retain a radionuclide, such as 137Cs. The presence of organic matter, inorganic colloids (clay), and competing elements will strongly affect the uptake of 99Sr and 137Cs by plants from the soil. The role of plants as monitors of radionuclides is twofold: as monitors of recent atmospheric releases of radionuclides; and as indicators of the long-term behavior of aged deposits of radionuclides in the soil.


Effects from past solid waste disposal practices. This paper reviews documented environmental effects experience from the disposal of solid waste materials in the U.S. Selected case histories are discussed that illustrate waste migration and its actual or potential effects on human or environmental health. Principal conclusions resulting from this review were: solid waste materials do migrate beyond the geometric confines of the initial placement location; environmental effects have been experienced from disposal of municipal, agricultural, and toxic chemical wastes; and utilization of presently known science and engineering principles in sitting and operating solid waste disposal facilities would make a significant improvement in the containment capability of shallow land disposal facilities.


Potential of plant genetic systems for monitoring and screening mutagens. Plants have too long been ignored as useful screening and monitoring systems of environmental mutagens. However, there are about a dozen reliable, some even unique, plant genetic systems that can increase the scope and effectiveness of chemical and physical mutagen screening and monitoring procedures. Some of these should be included in the Tier II tests. Moreover, plants are the only systems now in use as monitors of genetic effects caused by polluted atmosphere and water and by pesticides. There are several major advantages of the plant test systems which relate to their reproductive nature, easy culture and growth habits that should be considered in mutagen screening and monitoring. In addition to these advantages, the major plant test systems exhibit numerous genetic and chromosome changes for determining the effects of mutagens. Some of these have not yet been detected in other nonmammalian and mammalian test systems, but probably occur in the human organism. Plants have played major roles in various aspects of mutagenesis research, primarily in mutagen screening (detection and verification of mutagenic activity), mutagen monitoring, and determining mutagen effects and mechanisms of mutagen action. They have played lesser roles in quantification of mutagenic activity and understanding the nature of induced mutations.Mutagen monitoring with plants, especially in situ on land or in water, will help determine potential genetic hazards of air and water pollutants and protect the genetic purity of crop plants and the purity of the food supply. The Tradescantia stamen-hair system is used in a mobile laboratory for determining the genetic effects of industrial and automobile pollution in a number of sites in the U.S.A. The fern is employed for monitoring genetic effects of water pollution in the Eastern states. The maize pollen system and certain weeds have monitored genetic effects of pesticides. Several other systems that have considerable value and should be developed and more widely used in mutagen monitoring and screening, especially for in situ monitoring, are discussed. Emphasis is placed on pollen systems in which changes in pollen structure, chemistry, and chromosomes can be scored for monitoring; and screening systems which can record low levels of genetic effects as well as provide information on the nature of induced mutations. THE VALUE OF PLANT SYSTEMS FOR MONITORING AND SCREENING MUTAGENS CAN BE IMPROVED BY: greater knowledge of plant cell processes at the molecular and ultrastructural levels; relating these processes to mutagen effects and plant cell responses; improving current systems for increased sensitivity, ease of detecting genetic and chromosome changes, recording of data (including automation), and for extending the range of genetic and chromosome end points; and designing and developing new systems with the aid of previous and current botanical and genetic knowledge.


Hazardous solid waste from agriculture.

Hazardous solid waste from agriculture. Large quantities of food processing, crop, forestry, and animal solid wastes are generated in the United States each year. The major components of these wastes are biodegradable. However, they also contain components such as nitrogen, human and animal pathogens, medicinals, feed additives, salts, and certain metals, that under uncontrolled conditions can be detrimental to aquatic, plant, animal, or human life. The most common method of disposal of these wastes is application to the land. Thus the major pathways for transmission of hazards are from and through the soil. Use of these wastes as animal feed also can be a pathway. While at this time there are no crises associated with hazardous materials in agricultural solid wastes, the potential for problems should not be underestimated. Manpower and financial support should be provided to obtain more detailed information in this area, esepcially to better delineate transport and dispersal and to determine and evaluate risks.


Somatic mosaicism in plants with special reference to somatic crossing over. Plant systems in use for the detection of environmental mutagens appear capable of detecting all types of genetic effects which can be studied in animals. The study of somatic mosaicism, however, is better developed in plants than in higher animals. A case is presented here which shows the ability of plant systems in analyzing a host of genetic end points, including chromosome aberrations like deletions, somatic crossing over, numerical inequality, gene conversion, paramutations and point mutations. The systems in general use utilize certain varieties of Tradescantia, Glycine max, Nicotiana tabacum, Antirrhinum majus, Petunia hybrida, and Arabidopsis thaliana. Heterozygous plants or their homozygous counterparts with gene markers affecting chlorophyll development or anthocyanin in floral parts are exploited in these studies. Mutagens produce different frequencies of different types of spots typical of the mode of action of the agent. Analysis of these parameters may be used to predict, at least qualitatively, the kind of genetic damage that might be produced in man. Besides, one can test the validity of interpretation by traditional progeny tests of plants raised from tissue culture from sectors as in Nicotiana and/or by precursor analysis as done in Antirrhinum. The study of mosaicism in plants offers quite inexpensive, rapid, and reliable tests of mutagenicity at least as a preliminary eukaryotic test system.


Transport and transportation pathways of hazardous chemicals from solid waste disposal. To evaluate the impact of hazardous chemicals in solid wastes on man and other organisms, it is necessary to have information about amounts of chemical present, extent of exposure, and chemical toxicity. This paper addresses the question of organism exposure by considering the major physical and biological transport pathways and the physicochemical and biochemical transformations that may occur in sediments, soils, and water. Disposal of solid wastes in both terrestrial and oceanic environments is considered. Atmospheric transport is considered for emissions from incineration of solid wastes and for wind resuspension of particulates from surface waste deposits. Solid wastes deposited in terrestrial environments are subject to leaching by surface and ground waters. Leachates may then be transported to other surface waters and drinking water aquifers through hydrologic transport. Leachates also interact with natural organic matter, clays, and microorganisms in soils and sediments. These interactions may render chemical constituents in leachates more or less mobile, possibly change chemical and physical forms, and alter their biological activity. Oceanic waste disposal practices result in migration through diffusion and ocean currents. Surface area-to-volume ratios play a major role in the initial distributions of chemicals in the aquatic environment. Sediments serve as major sources and sinks of chemical contaminants. Food chain transport in both aquatic and terrestrial environments results in the movement of hazardous chemicals from lower to higher positions in the food web. Bioconcentration is observed in both terrestrial and aquatic food chains with certain elements and synthetic organics. Bioconcentration factors tend to be higher for synthetic organics, and higher in aquatic than in terrestrial systems. Biodilution is not atypical in terrestrial environments. Synergistic and antagonistic actions are common occurrences among chemical contaminants and can be particularly important toxicity considerations in aquatic environments receiving runoff from several terrestrial sources.


Chromosome aberrations in plants as a monitoring system. The potential of higher plants as a first-tier assay system for detecting chemical mutagens is evaluated. The use of plant tissue (primarily root tips and pollen mother cells) for studying the induction of chromosomal aberrations is one of the oldest, simplest, most reliable, and inexpensive methods available. Specific types of abnormalities have been induced by different classes of pesticides. Chromosome clumping, contraction, stickiness, paling, fragmentation, dissolution, chromosome and chromatid bridges, C-mitosis, and endoploidy have been reported in the literature. Examples of cytogenetic studies with pesticides demonstrating the usefulness of higher plants as a monitoring system are reviewed. Pesticides which cause chromosome aberrations in plant cells also produce chromosome aberrations in cultured animal cells. Frequently, the aberrations are identical. For example, studies have shown that compounds which have a C-mitotic effect on plant cells have the same effect on animal cells. It is recommended that plant systems be accepted as a first-tier assay system for the detection of possible genetic damage by environmental chemicals.


Activation of chemicals into mutagens by green plants: a preliminary discussion. This paper is a review of recent studies that demonstrate the activation of chemicals (especially pesticides into mutagens by green plants. Such activation of pesticides may be hazardous to the public health because of their widespread use in agriculture and the current lack of information that exists about such processes. The mutagenic properties of the s-triazine herbicides (atrazine, simazine, and cyanazine) as exhibited in various assay systems are discussed. In vivo, in vitro, and in situ plant assays are presented, and the maize wx locus assay is discussed.


Testing the environment for dispersed mutagens: use of plant bioconcentrators coupled with microbial mutagen assays. Mutagens dispersed in ecosystems are usually in low concentration and episodic in occurrence. The possibility of detecting such dispersed mutagens by utilizing indigenous bioconcentrator organisms coupled with a microbial mutagen assay offer a useful screening protocol. There are numerous examples of plant and animal species which concentrate toxic substances from the environment. Body extracts of these bioconcentrators can be suitably fractioned and tested for mutagens with various microbial mutagen assays. The fractions may be tested with a broad range of microbial assays covering numerous genetic end points as well as both with and without mammalian microsomal activation. This kind of environmental screening has an advantage over physicochemical techniques, in that sampling techniques are simpler and a wider chemical spectrum can be screened. There are problems inherent with testing a complex biological extract, however. If a reversion assay is used, the metabolite necessary for growth may be present. Toxins may be introduced, either concentrated from the environment in the same way as the mutagen, or produced by the concentrator itself. Finally, the concentrator may also produce an endogenous mutagen which will give spuriously active extracts. Methods for minimizing some of these difficulties are discussed.


Utility of specific locus systems in higher plants to monitor for mutagens. Plants possess biological and operational attributes that have encouraged geneticists to use them extensively in the development of fundamental genetic concepts. Attributes such as regenerative plasticity, high fecundity, cultural adaptability, range of ploidy, economics of culture and maintenance of specific populations, and versatility make plant genetic systems prime candidates with which to monitor the environment for mutagens. A specific locus (equivalent to a classical Mendelian gene) controls the development of a phenotypic characteristic. It can also mutate to a new allelic form with a consequentially altered phenotypic characteristic and can be separated by crossing over from adjacent loci that govern other specific phenotypic characteristics. Since various plant species have numerous specific loci, one has a rich array of potential systems from which to select. Specific locus systems in higher plants could be used to assess the mutagenicity of single chemical compounds or combinations of chemical compounds. Depending on the circumstances, seeds and/or seedlings could be used; plants could be grown in situ in either containers or plots to assess the immediate environment for one or more mutagens over an extended period. Since plants are eucaryotes, data from such experiments could serve as one more source of information along with that obtained from a battery of other tests used in the tier system.


Self-incompatibility systems as bioassays for mutagens. Many flowering plants are unable to set seeds with their own pollen because a system known as gametophytic self-incompatibility is operating. The basis of this system is a single multiallelic locus S, and if the S allele carried by a pollen grain matches one of the two S alleles carried in the style, as it is certain to do upon self-pollination, then pollen tube growth is inhibited. Should one of the self-pollen grains carry a mutated S allele, however, it would not match either of those carried in the style and would therefore, not be inhibited. Gametophytic self-incompatibility thus provides a mechanism for discriminating between such mutant and nonmutant pollen grains. Knowing the numbers of pollen grains available to the stigma, and also the numbers of seeds produced, it becomes possible to estimate the frequency with which mutations occur at the S locus. Assay systems of mutagenesis which employ gametophytic self incompatibility will allow very large numbers of pollen grains to be screened for S allele mutants, which should indicate the mutagenicity of the environment. These systems have the added benefit that screening is done by the stylar tissues, rather than technicians. Finally, they may be used to construct largely autonomous assay systems which would provide continuous monitoring of the environment.


Maize Adh1 as a monitor of environmental mutagens. The maize Adh1 gene is introduced, with citations. The use of this gene as a mutagen monitor is discussed, with emphasis on differentiating quantitative and qualitative parameters. A proper assessment of hazard from environmental pollutants requires data on possible mutagen specificities for different kinds of DNA.


Processing in vitro of precursor periplasmic proteins from Escherichia coli. Precursors of two secreted periplasmic proteins in Escherichia coli, arabinose-binding protein and maltose-binding protein, were synthesized in vitro on membrane-bound polysomes. Addition of Triton X-100 to the system resulted in processing of the precursors to mature forms.


Mutants (ompA) affecting a major outer membrane protein of Escherichia coli K12. Seventy independent mutants have been analyzed affecting a major protein, polypeptide II, of the outer cell envelope membrane from Escherichia coli K12. They were classified as nonsense mutants of the amber type (20%), mutants most likely of the missense type possessing the protein at normal concentrations (9%), and mutants either missing the protein or harboring it at much reduced concentrations for unknown reasons (71%). Forty of the mutants were analyzed genetically and all were found to map at or near ompA, the structural gene for protein II. Two-dimensional electrophoretic analyses of envelopes from such mutants revealed an unusual heterogeneity of the protein which on such patterns appeared as at least 12 well separated spots, and the majority of these is due to artifacts of the method but apparently specific for this protein. In no case was a polypeptide fragment found in envelopes from the nonsense mutants. The results are discussed regarding two different phages which use the protein as a receptor and concerning the biosynthetic incorporation of the protein into the outer membrane.


Studies on polypeptide-chain-elongation factors from an extreme thermophile, Thermus thermophilus HB8. 2. Catalytic properties. Catalytic properties of the elongation factors from Thermus thermophilus HB8 have been studied and compared with those of the factors from Escherichia coli. 1. The formation of a ternary guanine-nucleotide . EF-Tu . EF-Ts complex was demonstrated by gel filtration of the T. thermophilus EF-Tu . EF-Ts complex on a Sephadex G-150 column equilibrated with guanine nucleotide. The occurrence of this type of complex has not yet been proved with the factors from E. coli. 2. The dissociation constants for the complexes of T. thermophilus EF-Tu . EF-Ts with GDP and GTP were 6.1 x 10(-7) M and 1.9 x 10(-6) M respectively. On the other hand, T. thermophilus  EF-Tu interacted with GDP and GTP with dissociation constants of 1.1 x 10(-9) M and 5.8 x 10(-8) M respectively. This suggests that the association of EF-Ts with EF-Tu lowered the affinity of EF-Tu for GDP by a factor of about 600 and facilitated the nucleotide exchange reaction. 3. Although the T. thermophilus EF-Tu . EF-Ts complex hardly dissociates into EF-Tu and EF-Ts, a rapid exchange was observed between free EF-Ts and the EF-Tu . EF-Ts complex using 3H-labelled EF-Ts. The exchange reaction was independent on the presence or absence of guanine nucleotides. 4. Based on the above findings, an improved reaction mechanism for the regeneration of EF-Tu . GTP from EF-Tu . GDP is proposed. 5. Studies on the functional interchangeability of EF-Tu and EF-Ts between T. thermophilus and E. coli has revealed that the factors function much more efficiently in the homologous than in the heterologous combination. 6. T. thermophilus EF-Ts could bind E. coli EF-Tu to form an EF-Tu (E. coli) . EF-Ts (T. thermophilus hybrid complex. The complex was found to exist in a dimeric form indicating that the property to form a dimer is attributable to T. thermophilus EF-Ts. On the other hand, no stable complex between E. coli EF-Ts and T. thermophilus EF-Tu has been isolated. 7. The uncoupled GTPase activity of T. thermophilus EF-G was much lower than that of E. coli EF-G. T. thermophilus EF-G formed a relatively stable binary EF-G . GDP complex, which could be isolated on a nitrocellulose membrane filter. The Kd values for EF-G . GDP and EF-G . GTP were 6.7 x 10(-7) M and 1.2 x 10(-5) M respectively. The ternary T. thermophilus EF-G . GDP . ribosome complex was again very stable and could be isolated in the absence of fusidic acid. The stability of the latter complex is probably the cause of the low uncoupled GTPase activity of T. thermophilus EF-G.


IgG versus albumin for measurement of plasma volume in normal and hypertensive men. Labeled IgG was evaluated versus labeled albumin for measurement of plasma volume, to see whether it would give a smaller initial dilution volume (indicating a smaller premixing extravascular loss of label) and a smaller difference between initial dilution volume and dilution volume at time 10 min (indicating a negligible extravascular loss in the first 10 min after mixing). IgG was found to have a lower transcapillary escape rate than albumin (P less than 0.01) in eight normal volunteers and in eight hypertensive subjects, hypertension being associated with an increased transcapillary escape of both proteins. Despite this, the dilution volumes obtained were indistinguishable and the need for a correction through a retropolation procedure was the same with both proteins. Albumin and IgG dilution volumes were highly correlated in 21 subjects (r=0.977) so that use of labeled IgG is a proper alternative to use of labeled albumin for plasma volume determination. However, since IgG brings no consistent advantage, labeled albumin remains the best available tracer for that purpose.


Fibrinolysis and trauma.

Fibrinolysis and trauma. Recent progress in animal and human research on the effect of trauma on the fibrinolytic system is reviewed. The normal balance between activating and inhibiting mechanisms is stressed. Some pathophysiological implications of trauma induced alterations in the fibrinolytic system are presented.


Survival of auxiliary rat liver grafts with decreased portal blood flow. After auxiliary liver transplantation in the rat, partial liver grafts (30% of the liver) were perfused with mesentericosplenic venous blood. This means a decrease in the total liver blood flow by approximately 34%. Recipient livers retained their arterial and pancreaticoduodenal inflow. Surgical interventions were carried out on the recipient's liver to evaluate the effect of the varying induced functional handicap on the fate of the graft in association with a decreased liver blood flow. Graft survival was obtained in all groups, but the conditions of the graft varied inversely with the severity of the functional handicap of the recipient's liver. Compared to previous experiments in which the auxiliary grafts were supplied with total portal blood inflow in the same experimental model, the grafts in this study showed a slightly impaired increase in weight. This impairment was attributed to the decreased blood flow. Recipient livers deteriorated or just maintained their size, even after 70% hepatectomy, despite the pancreaticoduodenal venous and arterial inflow. These results suggest that the total liver blood flow in combination with the functional state of the remaining recipient liver, rather than the quality of venous blood deriving from certain splanchnic areas and/or peculiar factor convoyed with it, determines the survival of a liver graft.


One-stage urethroplasty with free skin graft. The early results of 15 urethral strictures operated by one-stage urethroplasty with free skin graft are excellent. The technique is described.


Intrarenal arteriovenous fistula following renal allograft biopsy. Arteriovenous fistulae in renal allograft are rarely mentioned in papers dealing with vascular complications after renal transplantations. 2 cases of such central fistulae are reported. In our patients the fistulae remained asymptomatic and were incidentally detected, so that neither surgical nor medical measures had to be taken. Reviewing the rather scarce literature on this subject the etiology, symptomatology, prevention and therapy of these fistulae are discussed.


Adaptational factors in memory function in the aged. Memory function in the aged is described as due to the interaction of a number of variables in addition to physiology, including affective state and environmental conditions. Depression can cause a series of behavioral patterns ranging from exaggeration of memory complaint, to simulation of organic dysfunction, to "pseudodementia" in which there is production of an actual organic mental syndrome. Stress and noxious environmental conditions also contribute to cognitive dysfunction. Custodial care is singled out as especially harmful, producing a form of "excess disability" termed "unorientation" in which apparently impaired memory results from an apathetic, withdrawn reaction to the environment. All these adaptational patterns are subject to prevention, modification, and in some cases, reversal.


National Institute on Aging Mycoplasma Testing Service. The National Institute on Aging (NIA) has established a Mycoplasma Contamination Testing Service for NIA grantees studying cellular aging on cell-culture systems. The contractor is the Institute for Medical Research, Camden, New Jersey.


Beta-adrenergic blockade in stress protection. Limited effect of metoprolol in psychological stress reaction. In a model system the influence of mental stress on blood pressure and heart rate was studied in normal persons and in patients with hypertension (WHO grade III). Metoprolol was employed to investigate the preventive effect of beta-adrenergic blockade on the response to stress. In all groups blood pressure increased significantly during mental stress. The effect was not inhibited by metoprolol. The rise in heart rate, however, was depressed by beta-blockade. Reaction time, opticomotor coordination and concentration ability were studied as parameters of vigilance, but no significant difference between the metoprolol and control groups were observed. Thus, metoprolol only influenced the heart rate in mental stress and it did not affect vigilance.


Effect of acetylsalicylic acid, paracetamol, and placebo on pain and blood loss in dysmenorrhoeic women. The analgesic effect of paracetamol, acetylsalicylic acid, and placebo on dysmenorrhoea were compared in a double-blind crossover study of 30 women. There was a moderate placebo effect, but no significant difference was found between the three treatments. Blood loss was also measured and it did not vary with the type of drug ingested. It is concluded that paracetamol and acetylsalicylic acid in the doses used (0.5 g X 4 for 3 days) were not effective against heavy dysmenorrhoea, and that none of the drugs influenced the amount of blood lost.


[In vitro biosynthesis of octopamine by the nervous system and the heart of the mollusc gastropode Helix pomatia (author's transl)]. The tyrosine is decarboxylated in vitro by the central nervous tissue and by the intracardiac nervous tissue of Helix pomatia by aromatic amino-acid decarboxylase. The tyramine obtained is then partially transformed into octopamine by tyramine-beta-hydroxylase. The inhibition of monoamine oxidase favours apparition of the 2 amines. The monoamine oxidase seems able to regulate their synthese and to assure their inactivation.