Differential response of serum LH in hypogonadotropic hypogonadism and delayed puberty to LH-RH stimulation before and after clomiphene citrate administration. The differential diagnosis between hypogonadotropic hypogonadism and delayed puberty is facilitated by comparing the response of gonadotropins to LH-RH stimulation before and after administration of clomiphene citrate 200 mg daily during 7 days. Premedication of clomiphene citrate depresses peak values of LH and FSH on LH-RH in delayed puberty. In hypogonadotropic hypogonadism clomiphene citrate raises LH-RH induced peak LH while FSH does not change.


Immunohistochemical changes in morphologically involved and uninvolved colonic mucosa of patients with idiopathic proctitis. Alterations in secretory component, IgA, IgG, and IgM were studied by immunofluorescent techniques in mucosal biopsy specimens obtained at colonoscopy from inflamed and grossly uninvolved colonic mucosa from 12 patients with idiopathic proctitis. Parotid-salivary secretory component and IgA and serum immunoglobulins were also investigated. Decreased secretory IgA was observed in the epithelium of all grossly involved rectal mucosa and in 40% of proximal normal mucosa. Salivary secretory IgA was not diminished. These observations suggest that a local immune defect may be pathogenetically related to idiopathic proctitis.


The electrophysiologic effects of quinidine in the transplanted human heart. Using His bundle recording techniques, we examined direct and autonomically mediated conduction system effects of quinidine in five cardiac transplant recipients who have anatomically denervated hearts. We made control conduction interval and refractory period measurements, and then infused 10 mg/kg quinidine gluconate over a 20-min period. At 30 min, we determined the electrophysiologic changes induced by quinidine. Quinidine significantly increased the atrial-His (AH) interval (from 97+/-9 [SEM] to 108+/-7 ms, P less than 0.001), the His-ventricular (HV) inteval (from 43.9 +/- 1 to 52.8 +/- 3 ms, P less than 0.01), the donor heart sinus cycle length (from 599 +/- 38 to 630 +/- 56 ms, P less than 0.08), and the atrial effective refractory period (from 214 +/- 14 to 241 +/- 11 ms, P less than 0.01). Quinidine significantly decreased the innervated, remnant atrial sinus cycle length (from 847 +/- 104 to 660 +/- 96 ms, P less than 0.01) and the blood pressure. The mean plasma concentration of quinidine at the time that electrophysiologic measurements were repeated was 4.37 +/- 0.449 micrograms/ml. We conclude that quinidine's predominant sinus nodal and atrioventricular nodal effects in man are autonomically mediated and opposite to its direct actions upon these structures. On the other hand, quinidine's prevailing effect on atrial refractoriness and His-Purkinje conduction in man is direct.


Role of in vitro and in vivo tests of hypersensitivity in beryllium workers. The value of the beryllium macrophage migration inhibition (Be MIF) and Mantoux tests in the diagnosis of chronic beryllium disease and in the detection of hypersensitivity in healthy beryllium workers is demonstrated. In the absence of steroid treatment the Be MIF test is positive in chronic beryllium disease patients. Seven of 50 (14%) helathy beryllium workers were Be MIF positive, while all the control subjects, normal and sarcoidosis patients, were negative. Healthy beryllium workers tend to be more often Mantoux negative than a comparable group of non-exposed workers, and although not conclusive this finding correlates with a positive Be MIF test. Although the detection of hypersensitivity is not diagnostic of disease, the Be MIF test can be used as an additional method for monitoring the health of beryllium workers. The full significance of our results should be assessed by a long-term study.


Complementary use of aesculin hydrolysis and inositol fermentation in the characterisation of Klebsielleae. Rates of aesculin hydrolysis and inositol fermentation adequately differentiate Klebsielleae from other Enterobacteriaceae. In combination with tests for motility and growth in potassium cyanide medium, presumptive differentiation between Klebsielleae, and confirmation of Klebsiella pneumoniae, is obtained.


Twice weekly prophylactic therapy in haemophilia A. Factor VIII-containing materials were administered to four severely affected haemophiliacs twice weekly in doses calculated to raise the factor VIII level to either 15% or 30% of average normal. The pooled results from those patients with statistically similar baseline bleeding frequencies showed a significant reduction in bleeding frequency on both doses in the first 48 hours. The 30% dose produced a more significant reduction than the 15% dose in the first 24 hours, but there was no significant difference between the two doses in the second 24 hours. It appears that to reduce the bleeding frequency of severely affected haemophiliacs by 60% would require a two-and-a-half-fold increase in therapeutic materials. A 90% reduction would need nine times the amount of material currently in use.


Colony-forming ability of marrow from patients receiving immunotherapy during chemotherapy-induced remission in acute myeloid leukaemia. An in vivo culture system, the agar diffusion chamber technique, has been used to measure the population of colony-forming precursor cells in the bone marrow of patients receiving immunotherapy during acute myeloid leukaemia in remission. The results of these assays indicate that (1) the level of committed granulocytic stem cells usually remains below the range found in normal marrow throughout remission, and (2) the maintenance of adequate cell counts in the blood may be due to increased cell production by these early granulocytic precursor cells. The relevance of these findings to the possible protective effect of immunotherapy against cytotoxic chemotherapy is discussed.


The 15 g D-xylose absorption test: its application to the study of coeliac disease. The absorption of xylose following an oral load of 15 g D-xylose has been studied by serial blood levels in 17 untreated adult coeliac patients, 21 treated coeliac patients, and 30 non-coeliac patients. A statistically significant difference in xylose blood levels was found between untreated coeliac and non-coeliac patients at all the times studied, but a complete separation between these two groups occurred only at the 75 minute stage. The reproducibility of absorption was assessed by repeating the test in 16 subjects. The 95% confidence limits of the standard error of estimate are narrowest at 75 and 90 minutes.


Scanning electron microscopy of the subarachnoid space in the dog. V. Macrophages challenged by bacillus Calmette-Guerin. Mongrel dogs were anesthetized intraperitoneally with pentobarbitol. One cc of cerebrospinal fluid was drawn through a needle inserted into the cisterna magna and mixed with 1 cc (4-9 million viable BCG organisms) of freeze-dried bacillus Calmette-Guerin. One minute later this mixture was injected by the same needle into the cisterna magna. At 1 and 12 days postinjection, experimental animals were perfused with buffered aldehydes. Samples of the leptomeninges were post-fixed in OsO4 and routinely prepared for scanning and transmission electron microscopy. Leptomeningeal samples of untreated, control animals were similarly prepared. Scanning and transmission microscopy confirm that free cells resting on the subarachnoid linings and within the subpial connective tissue space of control animals possess the morphology of macrophages (Malloy and Low, '76). Viable BCG in the subarachnoid space produces a 3-fold increase in the free cell population of the leptomeninges in 24 hours and a 10-fold increase in 12 days. These cells tend to form associations varying from loose aggregates to tight clusters. Approximately 80% of these free cells express macrophage morphology, with abundant plasma-lemmal microappendages and cytoplasmic vacuoles. Transmission electron microscopy of the free cell population of BCG-stimulated animals reveals at least two other members of the leukocyte series on the leptomeningeal linings.


Gluconeogenesis in cattle: significance and methodology. Gluconeogenesis is a continual process that is of great importance in ruminants because almost all dietary carbohydrates are fermented to volatile fatty acids in the rumen. In turn, propionate is the only major volatile fatty acid that contributes to gluconeogenesis. Many different techniques and analytical procedures are involved in studying ruminant gluconeogenesis. Glucose kinetics can be examined by single-injection or continuous-infusion isotope dilution techniques with a variety of glucose labels. Correcting for recycling of label is an important consideration. Absorption of glucose from the gut can be measured by combining arterial-venous differences and flow rates of portal blood or can be estimated by determining the amount of glucose plus alpha-glucose polymers passing into the small intestine. Production of propionate in the ruminoreticulum can be measured by isotope dilution techniques. Quantitating the conversion of propionate to glucose requires the use of [carbon-14]propionate with careful corrections for propionate carbon entering the citric acid cycle before incorporation into glucose; The same fundamental techniques used with propionate are required to quantitate the contributions of amino acids and other precursors to glucose. In vitro studies of gluconeogenic enzymes, and cellular, tissue, or organ preparations provide valuable insights into the gluconeogenic processes and controls but must be validated by in vivo experiments. Progress has been considerable in understanding some aspects of ruminant gluconeogenesis, but many more studies will be required to obtain a complete understanding.


Parasitism and calfhood diseases.

Parasitism and calfhood diseases. That animals can and do acquire an effective immunity against helminth parasites has been demonstrated extensively experimentally, and the fact that domestic animals such as cattle, sheep, and horses become adults while maintaining good health in spite of constant exposure to reinfection long has suggested that immunity must be important to such survival. Although our attempts to date to vaccinate calves against helminth parasites have either failed or been unsatisfactory because of the pathosis induced by the experimental vaccines, the results are not surprising or discouraging. In contrast to the long history of immunization research on bacterial and viral diseases, only within a relatively short time have serious efforts been directed at exploiting hostal immunity for prevention and control of helminthic diseases. Unlike the comparatively simple structures of viruses and bacteria, helminths are complex multicellular animals with vast arrays of antigens and complicated physiological and immunological interactions with their hosts. Much more fundamental information on helminth-bovine interactions, on helminth antigens, and on cattle antibody systems must be developed before progress on control of cattle helminths by vaccination can be meaningful.


Influence of the topical application of fluoride on the in vitro adhesion of fissure sealants. The adhesion of four polymeric sealant materials to enamel treated with a topical application of fluoride has been assessed by tensile bond strength tests. The ultraviolet light-activated resin, Nuva Seal, was found to bond adequately to stannous fluoride-treated teeth. The tensile bond strength of Espe 71730, Alpha Seal, and Epoxylite 9075 to enamel was reduced by treatment of the enamel with stannous fluoride. Treatment of the etched enamel with acidulated phosphate fluoride reduced the bond strength of all four fissure sealants.


Immune responses of the bovine fetus.

Immune responses of the bovine fetus. The bovine fetus is capable of mounting an antibody response when a bacterial antigen (killed Escherichia coli) or viral antigen (live reovirus) is deposited into the amniotic fluid. Time required for the fetus to respond to bacterial antigen given orally (amniotic fluid) is approximately 10 to 14 days and 8 to 10 days for viral antigen. Calves vaccinated prenatally with E. coli from 9 to 102 days before birth and deprived of colostrum survived oral challenge doses of viable E. coli which killed calves not vaccinated prenatally. One mechanism of protection was the local production of antibody in the gastrointestinal mucosa where immunofluorescent techniques showed immunoglobulins IgG, IgM, and anti-E. coli antibody in the duodenum, jejunum, and ileum as well as in the jejunal lymph node. Prenatal vaccination has been used in the field for prevention of colibacillosis. However, the occurrence of some stillbirths and premature births indicates the need for further research before there can be widespread field application of the technique.


Comparison of gingival health and gingival crevicular fluid flow in children with and without diabetes. GCF flow measurements and a clinical scoring of gingival health were both recorded for a group of 56 children with diabetes and 41 children without diabets. The children with diabetes  had significantly more  gingival disease than the children without diabetes when compared with either measure. A small but significant correlation was found between the GCF flow and the clinical scores with the children with diabetes but not with the children without diabetes.


High incidence of horse serum protein allergy in various autoimmune disorders. In 186 persons (68 patients suffering from different so-called autoimmune diseases, 30 kidney recipients, 38 control patients from a surgical ward, and 50 healthy volunteers) the immune response to horse IgG was examined. The lowest rate of sensitization was found in kidney transplant recipients (3%) and the highest in autoimmune patients (33%). After excluding 39 patient who had received horse serum treatment prior to the examination, it was found that without previous injection of horse serum, 27% of the patients with autoimmune disease were sensitized to horse IgG. Compared to the other groups (kidney transplant recipients, 4%: surgical controls, 0%; healthy volunteers, 3%), this difference was statistically significant (p is less than 0.01).


Job enrichment in job design.

Job enrichment in job design. For optimal operation in labor-intensive industries, such as foodservice, not only scientific management principles but also behavioral aspects (the people) must be considered in designing job content. Three psychologic states--work that is meaningful, responsibility for outcomes, and knowledge of outcomes--are critical in motivating people. These, in turn encompass the core dimensions of skill variety, task identity, task significance, autonomy, and feedback. Job enrichment and job enlargement--related but not identical means of expanding job content--when combined, offer the likelihood of redesigned jobs in the core dimensions. Effective implementation of a job enrichment program hinges on diagnosing problems in the work system, actual changes in the work, and systematic evaluation of the changes. The importance of the contribution of the behavioral sciences to management cannot be neglected.


Geriatric profile of Thomas Jefferson (1743-1826). This geriatric profile specifically reflects the impressive achievements of Thomas Jefferson during the years of his retirement (ages 66-83) following a distinguished political career culminating in the Presidency. President Monroe sought his advice even after the age of 80, and Jefferson's reasoning was instrumental in the formulation of the Monroe Doctrine. Education was a foremost priority in retirement. He was responsible for the establishment of the University of Virginia, in which his versatility was manifested as architect, builder, and fund raiser. Jefferson was a man of breadth and extraordinary vision for his time, and has come to be known as the "Father of American Democracy." The basic concepts of his philosophy, including the realm of aging, remain valid today-150 years after his passing.


Lloyd Morgan's theory of instinct: from Darwinism to neo-Darwinism. Darwin's proposal of two sources of instinct--natural selection and inherited habit--fostered among late nineteenth century evolutionists a variety of conflicting notions concerning the mechanisms of evolution. The British comparative psychologist C. Lloyd Morgan was a cardinal figure in restructuring the orthodox Darwinian conception to relieve the confusion besetting it and to meet the demands of the new biology of Weismann. This paper traces the development of Morgan's ideas about instinct against the background of his philosophic assumptions and the views of instinct theorists from Darwin and Romanes to McDougall and Lorenz.


Contemporary historiography of psychology: Italy. In the context of a world-wide coverage of contemporary historiography of psychology, a descriptive account is presented of major recent events and of publications, grouped into five categories: original works, new editions, editions of the classics of science, readings, and translations. The younger generation tends to combine historical analysis with critical assessment (studio storico-critico), taking into account significance for psychological theory and implications for human affairs.


History of psychology: a review of the last decade. A review of the Journal of the History of the Behavioral Sciences revealed that all of the author's opinions on historiography have been well represented. Warning against the development of the history of psychology as a parochial superspecialty, the author proposes an interactional conceptualization of historical work which explicates the historian's presuppositions and deals with issues relevant to contemporary psychology.


Hermann von Helmholtz and the empiricist vision. The philosophical convictions of Hermann von Helmholtz and the empiricist psychology he developed have been extensively discussed in historical literature. This literature has not usually emphasized the tacti assumptions about human physiology that underlaid these convictions nor the way in which Helmholtz's epistemology served as a methodological directive in his research. Helmholtz assumed nerve transmission between sense organs and the mind to be a passive process. Distortion in stimulus patterns occurs physically in the sense organs, which can therefore be treated through mechanical analogies. Stimuli become converted to the perceptions of consciousness through mental processes that are essentially analogous to conscious, inductive inference and that are therefore susceptible, in principle, to introspective investigation. This view of mental function reflected Helmholtz's intellectual debt to German idealism, especially to the philosophical views of J.G. Fichte.


The case records of the Psychological Clinic at the University of Pennsylvania (1896-1961). The case records of the Psychological Clinic of the University of Pennsylvania the first established in this country, have been transferred to microfilm to save them from desctruction. A survey of the records indicate that they may be valuable in both historical and follow-up research. The microfilms can be made available to qualified investigators with worthy projects.


Cytochemical localization of NADH oxidase in Candida albicans. The application of a recently published technique to localize reduced nicotinamide adenine dinucleotide oxidase activity is described in glutaraldehyde-fixed Candida albicans. The reaction product appears as a finely granular precipitate on the mitochondrial cristae and on the central vacuolar membrane, and, if present, on the vacuolar contents. Fixation should be kept to a minimum and prolonged incubation times up to 2 hr are necessary to show these reactive sites. The reaction appears to be strongly substrate-dependent and not affected by cyanide. Exposure of C. albicans cells to the antimycotic miconazole resulted in a strong increase in reduced nicotinamide, adenine dinucleotide and oxidase activity. The hypothesis is put forward that this enzyme, together with peroxidative and catalatic enzymes, may be implicated in the mechanism by which miconazole exerts its lethal effect on C. albicans.


Catabolism and biologic properties of two species of rat IgG2a Fc fragments. Prolonged papain digestion of rat IgG2a has recently been shown to yield two species of Fc fragments, termed Fc(I) AND Fc(II). The results of structural studies indicated that Fc(II) fragment was 15 to 20% smaller than Fc(I), probably secondary to loss of a carboxy-terminal peptide. The effects of these structural laterations on the catabolism and biologic properties of the Fc fragments were determined. The results of catabolic experiments indicated that after injection into normal rats Fc(I) fragments were retained in the circulation and slowly catabolized whereas Fc(II) fragments rapidly underwent filtration in the kidneys. In nephrectomized rats, however, both Fc(I) and Fc(II) fragments possessed identical slow rates of catabolism, as determined by serum disappearance and whole body catabolic experiments. Fragment pFc, corresponding to Cgamma3 domain, was different from either of the Fc fragments in exhibiting rapid rates of catabolism in both normal and nephrectomized rats. Fc(I) was more active in complement fixation and in adherence to the Fc receptor on monocytes in comparison with Fc(II). These results support the conclusion that catabolism of Fc and maintenance in circulation are separate processes influenced by different structures in the Fc fragment. The catabolism of Fc is controlled by structures in the Cgamma2 domain. This process probably is not related either to complement fixation or to adherence to the Fc receptor on monocytes. Some correlations between the structure and biologic properties of these Fc fragments are discussed.


Identification and purification of immunosuppressive activity in the urine of rats and a human patient treated with niridazole. Administration of the antischistosomal compound niridazole to mice, guinea pigs, and humans results in the suppression of several manifestations of cell-mediated immunity. Sera from animals treated with niridazole blocked the in vitro production of migration inhibitory factor (MIF) while niridazole itself was inactive, suggesting that these effects are caused by water soluble mediators. We now report that crude extracts prepared from the urine of rats and a patient receiving nirdazole, but not from pretreatment control urine, similarly suppress antigen-induced inhibition of migration of peritoneal exudate cells from sensitized guinea pigs. With immunosuppressive activity monitored by the direct MIF assay, combined solvent extraction and chromatographic techniques were used to fractionate immunosuppressive activity from the urine of niridazole-treated rats and the patient; the most active fractions, purified about 100-to 1000-fold as compared to methanol-water extracts of dried voided urine, inhibited MIF production at 0.1 to 0.01 ng/ml of assay mixture. These purified fractions also showed immunosuppressive activity by an in vivo assay wherein doses as low as 1 mug/kg injected intravenously (i.v.) into mice suppressed cell-mediated granuloma formation around Schistosoma manisoni eggs. Identically purified fractions prepared from urine of rats and the patient before they received niridazole showed no immunosuppressive activity either in the MIF or in the granuloma assay systems.


A new histogenetic method for minor histocompatability antigen typing. A new method for typing minor H antigens is described. The method is based on the observation that effector T cells, sensitized in vivo to minor H mitigens and then rechallenged in vitro, will lyse labeled target cells in the CML assay, provided that the target, the sensitizing, and the responding cells share the same allele at H-2K or H-2D loci. In this method, two congenic lines differing at a minor H locus are cross-immunized (by skin grafting, injection of lymphoid cells, or, preferably, by a combination of both treatments), rechallenged in vitro, and tested against a panel of strains carrying the same H-2 haplotype as the two lines. Target cells of the panel carrying the same minor H antigens as the strain against which the effector cells were sensitized are lysed; target cells not carrying these antigens are unaffected. The feasibility of the method was demonstrated by testing for H-3 antigens of a panel fo H-2b-bearing strains. The new method is faster and more economical than the classicial F1 method which has been used until recently.


Inhibition of C1s-induced vascular leakage in guinea pigs by substituted benzamidine and pyridinium compounds. A variety of benzamidine and pyridinium compounds were examined for their ability to inhibit irreversibly C1s-induced vascular leakage in guinea pig skin. Vascular leakage was compared with esterolysis of N-Z-L-Tyr-Np and catalysis of EAC42 formation by C1s. Vascular leakage correlated significantly better with esterolytic activity than with EAC42 formation. The presence of a sulfonyl fluoride moiety in the compounds is important in the inhibition of C1s-induced vascular leakage.


Immunologic characteristics in relation to high and low leukemogenic activity of radiation leukemia virus variants. I. Cellular analysis of immunosuppression. Infection of adult C57BL/6 mice with variants of the radiation leukemia virus resulted in variable leukemia incidence. One variant, designated D-RadLV, induced lymphatic leukemia in 0 to 25% of mice after virus inoculation directly into the thymus of young adult mice. The leukemia incidence could be increased to 80 to 100% by host exposure to x-rays. The second variant, A-RadLV, induced lymphatic leukemia in 80 to 100% of similarly inoculated mice without the need for additional radiation treatment. Adult mice were inoculated with D-radLV or A-RadLV. Both variants reduced the immune response to sheep erythrocytes whereas only D-RadLV had an immunosuppressive effect after immunization with a thymus-independent immunogen polyvinyl-pyrrolidone (PVP). Results of transfer experiments indicated that the immunosuppressive effects were expressed at the immunocompetent cell level. Thymus-derived cells were affected by A-RadLV since their immunocompetent function was impaired, whereas D-RadLV affected the marrow cell population of immunocytes. Exposure of D-RadLV-inoculated mice to x-rays induced functional impairment of both thymus and marrow cells. Since the radiation leukemia virus induces "T" lymphatic leukemia it could be proposed that the initial tropism of the virus to thymocytes would lead to high leukemia induction potential, whereas virus tropism to bone marrow cells would yield a low leukemia incidence. The coleukemogenic effect of x-rays could perhaps be related with its capacity to alter and introduce a change in virus-lymphoid cells interaction.


Ontogeny of the antibody-forming cell line in mice. IV. Appearance of cells bearing Fc receptors, complement receptors, and surface immunoglobulin. The ontogeny of Ig, FcR, and CR-bearing cells in liver and spleen has been followed by using rosetting procedures. These studies demonstrated a sequential appearance of surface receptors during development. Two types of Ig+ cells could be distinguished according to their rosette morphology and adherence to carbonyl iron: 1) an adherent cell which bound few erythrocytes was found predominantly in fetal liver from 13 days gestation and 2) a nonadherent cell which bound larger numbers of erythrocytes appeared in small numbers in fetal liver from day-16 gestation but represented the major Ig+ cell type after birth. Changes in the proportions of receptor-bearing populations occurred at two particular periods during ontogeny. The first was at birth, where an increase in the proportion of FcR+ cells occurred and the proportion of type 2 Ig+ cells rose rapidly. This probably represented the first appearance of FcR+ B lymphocytes even though cells bearing FcR were detected in fetal liver of all ages (days 12 to 18). The second period was around 10 days after birth when the proportion of Ig+ cells again increased concomitant with the appearance of CR+ nonadherent cells.


Identification of human peripheral T cell antigens. A new type of differentiation antigens on human T cells was demonstrated by using a heterologous anti-human T cell serum (ATS). This type of antigen, referred to as human peripheral T cell antigen (HPTA), was found on peripheral T cells and medullary thymocytes, but not on cortical thymocytes and B cells. The percentage of ATS-reactive lymphocytes in human peripheral lymphoid organs was correlated with that of cells rosetting with sheep erythrocytes, but contrasted with the number of B cells defined by the presence of a complement (C) receptor or by rabbit anti-human B cell serum (ABS). ATS also reacted with T cells purified by nylon fiber column filtration but ABS did not. Chronic lymphocytic leukemia cells rosetted with either sheep erythrocytes or erythrocyte-antibody-complement complexes were lysed by ATS and ABS, respectively. Mitogenic responses of blood lymphocytes to phytohemagglutinin (PHA) and concanavalin-A (Con A) were abrogated by treating them with ATS and C, whereas ABS suppressed only their response to Con A. Although numerous thymus cells rosetted with SRBC, only 14% were reactive with ATS. Quantitative absorption studies demonstrated that HPTA content of the thymus cells was much lower than that of lymph node cells. Anatomical localization of ATS-reactive lymphocytes in human lymphoid organs studied by immunofluorescence indicated that they were present in the thymus-dependent paracortical areas of lymph node and in the medullary region of thymus. ABS, on the other hand, did not stain thymocytes but reacted selectively with the cells located in the lymphoid follicles of lymph node. These data, together with that from cell suspension studies, confirmed that HPTA were shared between medullary thymocytes and peripheral T cells.


Radioimmunoassay of class-specific antibodies (RIACA): chicken antibodies to DNP. A radioimmunological method for the quantitation of class-specific antibodies has been developed. The method allows the quantitation of nanogram per ml concentrations of IgG- and IgM-anti-DNP antibodies without any physical or chemicadioimmunoassay of class-specific antibodies (RIACA) against BSA (Viljanen et al., 1975) developed recently by us. DNP was coupled covalently to a cyanogen bromide activated paper disk with the augmentation of lysine molecule. Anti-DNP antibodies were allowed to react with the coupled DNP and then quantitated by their capacity to bind 125I-labeled anti-chicken-mu or anti-chicken-gamma. The inter-assay variation coefficients ranged from 8.1 to 14.7% and the mean standard deviations of duplicate determinations were about 11%. The combination of this method with the exact immunoradiometric quantitation of the total serum IgM and IgG, and with an immunoabsorption technique, makes possible to quantitate class-specific antibodies in weight units.


A simple method for the production of migration inhibitory factor by concanavalin A - stimulated lymphocytes. A simple method for preparing culture supernatants containing macrophage migration inhibitory factor (MIF) by pulse exposure to guinea pig lymphocytes to concanavalin A (ConA), is described. The method is based on the property of originally nonadherent lymphocytes to attach to the flask surface in the presence of Con A. The Con A-induced lymphocyte 'monolayer' can be easily rinsed, allowing the removal of free Con A without repeated, cell damaging centrifugation. The Con A-pulsed lymphocytes are cultured for 24 h in medium and supernatants containing MIF but free of undesired Con A are regularly obtained.


Application of the soluble antigen fluorescent antibody (SAFA) test to the serodiagnosis of rabies. The adaptation and evaluation of the Soluble Antigen Fluorescent Antibody (SAFA) test for the serologic diagnosis of rabies is described. Evaluation of the SAFA test was based on a comparison between serum titers obtained in the SAFA test, the mouse Serum Neutralization (SN) test and in the Indirect Fluorescent Antibody (IFAT) test. Dog, fox, raccoon and skunk sera were used for the comparison with mouse SN titers. Human serum was used for the comparison with the IFAT titer. The purity and concentration of the test antigen is a crucial factor in determining the efficiency of the SAFA test for rabies serodiagnosis. Viral antigen obtained by the AIPO4 gel method for rabies virus purification and concentration was found to be sufficiently purified and concentrated for use in the SAFA test. Conjugate dilution decreased the level of non-specific staining. Although specific activity was also decreased, there was a statistically significant difference (P less than or equal to 0.05; Student's t test) between the rabies positive and the rabies negative serum samples at all conjugate dilutions for all species studied. In three cases (fox, raccoon, skunk) SAFA titers were greater than mouse SN titers. In one case (dog) the SAFA titer was less than the mouse SN titer. The IFAT titer of the human serum sample was greater than the SAFA titer. Comparison of Fluorometer Dial Readings (FDR) of sera obtained in separate protocols demonstrated satisfactory reproducibility of the SAFA test for rabies serodiagnosis.


A microfluorometric assay for immunoglobulin class and subclass levels in murine serum. The IgG fractions of rabbit antisera specific for the Fc part of mouse IgA, IgM, and the four subclasses of IgG (1, 2a, 2b, and 3) were coupled covalently to Sepharose beads by the cyanogen bromide method. The beads were then incubated with different dilutions of mouse serum. The mouse immunoglobulins (Ig) binding to the beads were demonstrated by the use of a fluorescent goat anti-mouse/Ig conjugate. Incubations were done in flat bottom of the plates with an inverted microfluorometer. The logarithm of the fluorescence was linearly related to the logarithm of the serum dilution for serum dilutions between 10(3) and 10(5). Ig levels of individual samples can be determined with as little as 1 mul of serum. The sensitivity of the method for IgM was estimated with MOPC 104E plasmacytoma IgM. Five ng of IgM per sample was easily detected. The method offers an attractive alternative to radioimmunoassay techniques.


A radioimmunoassay for human antibody specific for microbial antigens. A simple and sensitive method for detecting and quantitating antibody specific for microbial antigens is described. Bacterial, fungal, parasitic or viral antigens attached to bromoacetyl cellulose or the intact cells themselves were added to a series of two-fold dilutions of human serum. After a short incubation period, which allowed human antibody to attach to the antigens, the complex was thoroughly washed and carbon-14 labeled anti-human light chain antibody was added to each dilution. The resulting complex was washed, collected on a filter pad, placed in a scintillation vial and radioassayed. The relationship between radioactivity bound and --log2 of the serum dilution was linear. The endpoint for each assay and a confidence interval was calculated by doing inverse prediction from simple linear regression. Results obtained using this assay indicated the presence of antibody in a pool of normal human sera specific for herpes virus and for both cell surface and intracellular antigens of Streptococcus mutans, Naegleria fowleri, and Cryptococcus neoformans. In general the dominant response was against the intracellular antigens rather than cell surface antigens.


Methods for producing T- and B-lymphocyte receptor-specific antisera. Spent tissue culture medium from two continuous lymphoblastoid cell lines, FL-74 and CT45-S, expressing the T-lymphocyte receptor for guinea pig E and the B-lymphocyte receptor for EAC respectively were used to produce receptor-specific antisera. Anti-E receptor sera blocked E rosette formation on FL-74 cells, canine and feline lymphocytes and canine and feline thymocytes but not EAC rosette formation by CT45-S cells or canine and feline lymphocytes. Anti-EAC receptor sera blocked EAC rosette formation on CT45-S cells and canine or feline lymphocytes. Absorption of antisera will the appropriate lymphoblastoid cell line removed E or EAC-blocking activity. The results of this study suggest that similar methods may be used to produce lymphocyte subpopulation-specific antisera in other species including man.


Quantification of in vitro antibody secretion by immune spleen cells. A simple method to study 19S anti-SRBC antibody production is described. This technique, performed by incubation of immune spleen cells, SRBC and C in the fluid phase, utilises photomeric estimation of antibody mediated haemoglobin release. The test is quicker and more accurate than the two-step haemolytic plaque assay (Jerne technique). In combination with the Jerne technique this method gives information about haemolysin production per PFC. This was maximal on day 2 and on day 6 after immunisation, and least on day 4. The steady state value was reached again at day 9. In principle this method is suitable for the estimation of IgG production.


Specific separation of cytotoxic T lymphocytes on immunoadsorptive films. A method for the specific separation of cytotoxic T lymphocytes (CTL) on immunoadsorptive films is described. The films were prepared by polymerizing a mixture of gelatine and polyethyleneimine with glutaraldehyde on the bottom of plastic tissue culture flasks. By using an excess of glutaraldehyde unsaturated aldehyde groups on the film surface can react with other chemical groups predominantly with aliphatic amino groups. In this study detergent solubilized H-2 antigens were conjugated covalently to the films CTL, prepared by filtering spleen cells from alloimmunized mice through nylon wool columns, were incubated on immunoadsorptive films and the adsorbed cells were quantitatively recovered by mechanical detachment. The cells were functionally intact and tested in a microcytotoxicity assay using embryonic fibroblasts as target cells. Specificity adsorbed cells were enriched in specific cytotoxic cells up to 100 fold compared to the original fraction. Depending on the cell density per film area the non-adsorbed cells could be quantitatively depleted of CTL. The immunoadsorptive films are stabile at 37 degrees C and can be reused.


Role of Candida albicans in granulomatous tissue reactions. I. In vitro degradation of C. albicans and immunospecificity of split products. Several mannan-containing fractions were obtained from whole cells, cell walls, and cytoplasm of Candida albicans by means of treatment with hot formamide or precipitation with (NH4)2SO4. The immunological and chemical characteristics of the fractions were compared with those of C. albicans mannan prepared by standard procedures. Antisera to C. albicans from rabbits immunized with whole cells of the organism were found to be primarily directed against the mannan content. With use of such antisera, mannan was localized in both the inner and outer layers of the cell wall, whereas the middle layer was found in all likelihood to represent the glucan polymer. Stepwise removal of mannan from whole cells or cell walls resulted in increasing loss of periodic acid-Schiff staining, immunofluorescence, and peroxidase reactivity. Thus, it appears that mannan is responsible for the ability of cell walls of C. albicans to be stained by periodic acid-Schiff or labeled with fluorescent antibody. The component of the pathogen most resistant to physical or chemical treatment was the glucan, which lacked all immunological reactivity.


Role of Candida albicans in granulomatous tissue reactions. II. In vivo degradation of C. albicans in hepatic macrophages of mice. Hepatic granulomas were induced in mice by injection of blastospores, cell walls, and glucan of Candida albicans. Granulomatous reactions in liver tissue initially multiplied but later decreased. A dose-response relationship was apparent with up to 3 mg of inoculum. Shortly after injection of C. albicans spores, fungal elements appeared in liver macrophages and were detectable in granuloma and Kupffer cells for 20 days. Gram-stain, periodic acid-Schiff (PAS), and immunofluorescence reactions soon vanished, and the organisms could no longer be seen. Glucan of C. albicans, which lacked PAS and immunofluorescence reactivity, proved active in initiation of granulomas. Degradation of phagocytized spores of C. albicans, reductions of cytoplasm, and cell wall deformation and collapse support the premise that loss of PAS and immunofluorescence reactivity was caused by enzymatic breakdown of candida cell wall mannan in macrophages. We conclude that C. albicans can induce granulomatous reactions in mouse liver when the glucan that forms the cell wall matrix in Candida persists in identifiable residues.


Postnatal development of binding of streptococci and lipoteichoic acid by oral mucosal cells of humans. The colonization of mucosal cells in the oral cavity of newborn infants was studied at various intervals after birth in an attempt to define the nature of the epithelial binding sites for group A streptococci and their lipoteichoic acid (LTA). Stained smears of buccal mucosal cells showed that the average number of naturally acquired bacteria/cell was zero to one in infants less than one day old, one to four in infants one day old, and 11-19 in infants two days old. Samples of the same mucosal cells were incubated with group A streptococci, and the average number of streptococci bound per cell was 10-31 in infants less than one day old, 33-62 in one-day-old infants, and 75-100 in two-day-old infants. Experiments that were repeated with group B streptococci type III produced similar results. LTA, the substance that mediates the binding of streptococci to epithelial cells, was similarly bound by fewer buccal mucosal cells obtained within 6 hr of birth than cells obtained during the next 48 hr. Streptococcal and LTA binding reached adult levels between 48 and 72 hr after birth. No difference was shown in the streptococcal binding capacity of oral epithelial cell obtained from mothers at term and cells obtained from other normal adults. Preincubation of adult buccal cells with amniotic fluid did not decrease streptococcal binding. These studies demonstrated a scant capacity of the oral mucosal cells of neonates to bind LTA and streptococci and suggest that LTA-binding sites are developed or unmasked during the first few days after birth.


Enterotoxigenic Escherichia coli isolated from patients at a hospital in Dacca. Enterotoxigenic strains of Escherichia coli, a significant cause of acute, watery, cholera-like diarrhea, were isolated from 23 of 65 patients with diarrhea in whom no other enteric pathogens were found during one week (November 1974) at the Cholera Research Hospital, Dacca, Bangladesh. Diarrhea associated with enterotoxigenic strains of E. coli occurred primarily in adults but affected persons of all age groups and could not be distinguished from cholera or from other cholera-like diarrhea on clinical grounds. Routine bacteriologic methods were inadequate for identification of enterotoxigenic E. coli as the etiologic agent of the diarrhea. The enterotoxigenic E. coli, producing heat-stable and/or heat-labile enterotoxin, were detected by use of assays in the Y1 adrenal cell, the Chinese hamster ovary cell, the rabbit ileal loop, and the infant mouse. The two tissue culture assays yielded comparable results in tests with 640 (193 positive, 447 negative) of 643 isolates of E. coli. The results of this study support the idea that enterotoxigenic E. coli play a significant role as pathogens in the etiology of acute watery diarrhea.


Experimental hematogenous endophthalmitis due to Candida: species variation in ocular pathogenicity. The ocular pathogenicity of species of Candida other than albicans was studied in the rabbit model of hematogenous candida endophthalmitis by injection of 10(5)-10(8) colony-forming units of Candida krusei, Candida parapsilosis, Candida guilliermondii, Candida tropicalis, Candida stellateoidea, and Candida albicans (control). At one and three weeks after infection, rabbits were examined by indirect ophthalmoscopy and were sacrificed for culture of eyes and kidneys. With an inoculum of 10(8) organisms, C. tropicalis and C. stellatoidea infected the kidneys but only occasionally infected the chorioretina and never infected the vitreous. Organisms were cultured only rarely from the kidneys of rabbits infected with C. krusei, C. guilliermondii, and C. parapsilosis; these species were never isolated from eyes. The C. albicans control consistently infected the kidney, chorioretina, and vitreous; approximately equal numbers of C. albicans were isolated from these organs. These data suggest a relative resistance of ocular tissues to hematogenous candida infections with species other than C. albicans.


Rectal colonization with group B streptococcus: relation to vaginal colonization of pregnant women. Anorectal carriage as a possible primary source of vaginal colonization by group B Streptococcus was investigated. The study was performed during two separate periods and included 789 pregnant women and 422 neonates. Specimens from multiple sites were obtained for culture from all women and infants and were streaked onto blood agar plates containing 8 mug of gentamicin sulfate/ml and 15 mug of nalidixic acid/ml, which allow selective growth of streptococci. Cultures positive for group B streptococci were obtained from 162 (20.5%) of the pregnant women and from 50 (11.8%) of the neonates. Rectal cultures were positive for streptococci in 142 (17.9%) of the women, and vaginal cultures gave positive results in 81 (10.2%). The higher incidence of positive results in rectal as opposed to vaginal cultures (ratio of 2:1) was encountered during all phases of the study. This finding suggests that the gastrointestinal tract may be the primary site of colonization by group B Streptococcus and that vaginal colonization may represent contamination from this source.


Enterotoxigenic Escherichia coli isolated from food. Approximately 8% of 240 isolates of Escherichia coli obtained from food of animal origin in the United States were found to be enterotoxigenic, as determined in adrenal cells, rabbit ileal loops, and assays in infant mice. These organisms were of diverse serotypes that are not included among the so-called enteropathogenic serotypes and would not have been identified by usual laboratory methods. These enterotoxigenic E. coli are of potential importance to public health.


Studies on the effects of C. coli endotoxin on canalicular bile formation in the isolated perfused rat liver. The impairment of biliary excretory function induced by E. coli endotoxin  in the isolated perfused rat liver was studied by investigating its effects on canalicular bile formation. In experiments where no bile salt was infused, endotoxin administration resulted in significant decreases in bile salt-independent bile flow (BSIF) and sulfobromophthalein (BSP) excretion. It also caused dose-dependent decreases in the transport maximum of BSP but did not alter the ability of the liver to concentrate BSP in the bile. At 2 mg./100 ml. it decreased the hepatic removal rate but increased the hepatic storage of the dye. Measurement of 14 C-erythritol clearance and bile salt secretion also revealed that endotoxin significantly reduced the BSIF fraction of bile. The results indicated that the primary effects of endotoxin were on BSIF and BSP excretion.


Infectious pneumonias: a review.

Infectious pneumonias: a review. Diplococcus pneumoniae remains the most frequent cause of community-acquired bacterial pneumonia. Other frequently isolated bacterial pathogens are Hemophilus influenzae, Klebsiella organisms, and Staphylococcus aureus. The etiologic agents most commonly implicated in hopsital-acquired pneumonias are gram-negative bacilli including E. coli, proteus organisms, and species of Klebsiella-Enterobacter, pseudomonas, and Serratia. Among older children and young-adults, Myocoplasma pneumoniae is a common cause of penumonia. Influenza is the most important cause of viral pneumonia in adults, but there is increasing concern about pulmonary infection due to adenoviruses. In those with a history of travel to endemic areas, the diagnosis of fungal pneumonia due to Histoplasma capsulatrum, Blastomyces dermatitides, or Coccidioides immitis, should be considered. Penumonias due to opportunistic fungi (including species of Candida, Aspergillus, and Phycomycetes) and higher bacteria such as Nocardia asteroides are also on the increase, and these arise mostly in compromised hosts. Treatment of pneumonia almost always must be started before culture results are known and in the overwhelming majority of cases, appropriate regimens can be selected after taking an adquate history, doing a careful physical examination, evaluating expectorated sputum for cells and organisms, and examining the chest x-ray. Although anti-infective agents are the mainstay of treatment for most infectious pneumonias, supportive therapy, including adequate tracheobronchial toilet, drainage of abscesses, oxygen inhalation, maintenance of adequate nutrition, and monitoring for super-infection and anti-infective side effects may be life-saving in certain situations.


The kinetics of rosette-forming cell response against sheep erythrocytes in the lizard. The immune response of the lizard Calotes versicolor to sheep erythrocytes (SRBC) has been studied in terms of the appearance of rosette-forming cells (RFC) and plaque-forming cells (PFC). Two distinct RFC peaks were observed in the spleen, one within three days and the other, between six and ten days after immunization with 0.1 ml of 2.5%, 0.25% or 0.025% SRBC. Lower doses of antigen induced greater and quicker first RFC peaks, whereas higher doses stimulated increasing numbers of PFC as well as quicker appearance of second RFC peak. The early increase in RFC response is suggested to be due to "helper" activity and the second peak to the proliferation of precursors of antibody producing cells. Formalinised SRBC induced the formation of the first RFC peak but not the second, thus supporting the above suggestion. The interesting possibilities with regard to the dissociation of various cellular events during the development of antibody response in the lizard immune system are discussed.


A review of directionality trends in the horizontal dimension as a function of innate and environmental factors. This report reviews research on directionality trends in the horizontal dimension. The literature reviewed shows that such trends are predominantly a function of handedness and acquired reading-writing habits and that innate directional tendencies of left-handers are more influenced by acquired habits than those of right-handers. It is suggested that these trends may reflect some aspect of lateralization of cerebral function and that in mature adults the mixed-dominance left-handers are more influenced by environmental factors than are right-handers. Suggestions for future research include utilization of larger samples of left-handers and employment of longitudinal studies which systematically vary handedness and reading and writing habits. It is also suggested that controls for lateral dominance should be established. In addition it is suggested that reading and writing habits can be broken down into component parts and that their influence on directionality should be examined.


Genetic and other factors in schizophrenic, manic-depressive, and schizo-affective psychoses. The major psychoses have been investigated for genetic and environmental etiological factors for over two centuries. Recent emphasis has been placed on a genetic (diathesis) environmental stress model. For schizophrenia, manic-depressive, and schizo-affective psychoses, research evidence from psycho-biological studies, family, pedigree, twin, and adoptee studies has provided sufficient data from diagnostic and follow-up studies and new psychopharmacological research that for these three major psychoses a strong necessary but not sufficient basis for genetic causation exists. This review attempts to summarize existing data into a hypothesis that suggests that two separate gene pools of polygenic nature relate to the development of schizophrenia and manic-depressive illness and that schizo-affective illness may result from genetic transmission from each of these separate gene pools. The hypothetical model for each psychosis proposes that polygenetic inheritance affects different central nervous system neuroanatomical sites in the human which are in homeostasis as to catecholamine neurotransmitter regulation of the psyche. With sufficient environmental stress, an "imbalance" occurs in the neural integrative systems which produces phenotypically the three separate psychotic behavioral syndromes of schizophrenia, manic-depressive psychosis, and schizo-affective psychosis.


Art and recovery style from psychosis.

Art and recovery style from psychosis. The concepts of integration and sealing-over as recover styles from acute psychosis are common clinical parlance. Our experience with acute schizophrenic patients has led to specific operational definitions and a scale which can reliably assign patients to these two categories. All acutely schizophrenic patients on an NIH Clinical Center research ward participated in individual art sessions during drug-free periods at admission, at discharge, and at 1-year follow-up. In each session, the patient drew: a) a picture of his choice; b) a self-portrat; and c) a picture of his psychiatric illness. We hypothesized that integrators would pictorially represent themselves and their illness with greater expression, ideational fullness, and affective force than patients who sealed-over. Twenty-four patients were divided equally into integrator and sealing-over groups (based upon ratings at follow-up) and matched for age, sex, and race. Their art productions were presented randomly to two independent raters unfamiliar with the patients. They scored pictures quantitatively for color, motion, detail, empty space, and global expressiveness. Inter-rater reliability was satisfactory. A mean rating was obtained for all pictures from each patient on each of the five art variables. Paired t-tests (two-tailed) were applied to contrast the two groups on each of the five art variables. The results were that the integrators used more color (p less than .05), drew with greater detail (p less than .01), and more globally more expressive (p less than .05). Integrators also tended to depict more motion (p less than .10), but were not different from the sealing-over patients in amount of space left empty. These results support the validity of integration and sealing-over as defined and support the use of art as a medium through which differences in individual styles of coping with the psychosis can be discriminated. Slides of the patients' artwork illustrate the findings.


Lithium carbonate in personality disorders: a case of hysteria. A growing literature--most uncontrolled--suggests that lithium may be useful in the treatment of some non-manic-depressive personality disorders. The diabolical behavior, conversion symptoms, and diffuse violence and cruelty of a young woman responded remarkably to treatment with lithium. Blind substitution of a placebo confirmed a lithium effect. Patients with the DSM-II diagnosis of explosive, antisocial, and hysterical personalities would appear to be the best candidates for a trial of lithium.


Preprosthetic bone graft augmentation with allogeneic bone: a preliminary report. Allogeneic bone biologically interacts with host tissues at a graft site. Addition of autogenous cancellous bone and marrow to allogeneic bone enhances the osteogenic activity of the graft. These observations have been confirmed by noninvasive, quantitative radionuclide methods. The process of freeze-drying greatly reduces and, from the standpoint of clinical significance, essentially eliminates the antigenicity of allogeneic bone. Judged by the results of 14 cases that are under continuous follow-up, allogeneic bone graft augmentation of the denture-bearing area is a possible alternative to autogenous grafting. The process of obtaining and preparing the blanked bone for surgery is reasonable although some questions remain, such as the desirable length of time for tissue reconstitution and the need for culturing or adding antibiotics to the reconstitution solution, or both. It appears that the addition of autogenous cancellous bone and marrow is desirable in most instances unless the dimension of the area to be augmented is quite small or an iliac osteotomy is precluded for medical reasons. The occurrence of complications such as infection and dehiscence during the postoperative course is similar to that in patients with autogenous grafts. Dehiscence can be expected although it appears that if the graft has been supplemented with autogenous cancellous marrow the incidence and extent are dminished. It should be emphasized that dehiscence does not signify failure of the graft-allogeneic bone is not sloughed in toto after being exposed to the oral cavity. Secondary soft tissue procedures can be used in patients with allogeneic grafts; additional cases with long-term follow-up are still needed to establish this method.


Bone grafts with surface decalcified allogeneic and particulate autologous bone: report of cases. A method for mandibular bone grafting that uses a combination of SDAB and particulate autologous cancellous bone and marrow is presented. The results of this treatment in four patients are described. Two additional maxillary bone grafts that use only SDAB are also reported. Grafts that are a combination of SDAB and cancellous autologous bone and marrow are biocompatible, anatomically contoured, easily adapted at surgery, and the allogeneic component is biodegradable. They do not require elaborate internal metallic devices for structural support.


Scarlet fever and group A streptococcal surgical wound infection traced to an anal carrier. Four patients developed group A streptococcal wound infections shortly following orthopedic surgery. Two of these patients developed scarlet fever which provided an early indication of the presence of a streptococcal epidemic. A single antigenically characteristic strain of group A streptococci was recovered from the wounds of all four patients and from the anus of one surgeon who had participated in the surgery on three of the patients.


Further characterization of brain actin by electron microscopy. The physical state of actin in nerve ending preparations and its relationship to the membranes was studied at the ultrastructural level by negative staining with uranyl acetate before and after treatment with muscle heaving meromyosin (HMM). Actin prepared from synaptosomal or synaptic membrane preparations did not polymerize to fiber formation as readily as striated muscle actin under the same conditions. Treatment of these brain actin preparations with HMM, however, resulted in formation of fibers characteristically decorated with arrowheads which were quite similar to those formed with muscle actin. Treatment of the synaptosomal or synaptic membrane fractions themselves with HMM caused the formation of numerous decorated fibers although fibers were not evident before HMM treatment. This did not occur with the presynaptic vesicle fraction. The studies suggest that at least part of the actin is associated with synaptic membranes and is in a partially polymerized or non-polymerized state; polymerization can be induced by HMM.


Abnormalities of the immune system in children with neuroblastoma related to the neoplasm and chemotherapy. Children with localized and metastatic neuroblastoma were studies to determine their immune status at the time of diagnosis and while they were receiving intensive intermittent chemotherapy; Investigations included leukocyte and differential counts, delayed hypersensitivity response, quantitative serum immunoglobulins, percentages of T and Fc receptor lymphocytes, PHA-induced mitogenesis, and antibody-and PHA-dependent cellular cytoxicity. Abnormalities related to the neoplasm at diagnosis were limited to depressed leukocyte and lymphocyte counts and increased concentrations of serum IgM in patients with metastases to bone marrow and other sites. No abnormalities were observed in those with localized tumors. Intermittent chemotherapy of metastatic neuroblastoma caused immunosuppression. Effects were most marked during five-day courses of chemotherapy; they included abrogation of DH and decreased leukocyte and lymphocyte counts and percentages of Fc receptor lymphocytes. Recovery of DH with partial recovery of leukocyte and lymphocyte counts was observed three weeks, later, prior to the next course, We conclude that both metastatic tumor and chemotherapy cause abnormalities of the immune system in children with neuroblastoma.


Sepsis and congenital asplenia.

Sepsis and congenital asplenia. Fifty-nine children with congenital asplenia were reviewed for episodes of severe infection. Seven children had isolated asplenia and 52 had asplenia associated with complex congenital heart disease (asplenia syndrome). A control group of eusplenic children with comparable cardiac lesions were assembled and used for comparative statistical analysis. There were 16 instances of documented sepsis among 59 children (27%). In those less than six months of age, the invading organism was usually gram-negative (Escherichia coli or Klebsiella). In children six months of age or older, the infecting organism was usually a pneumococcus or H. influenzae. When those with asplenia syndrome were compared to the control population, the former group had a significantly greater incidence of sepsis. Children with asplenia syndrome who survived the first month of life were at greater risk of dying from sepsis than from their heart disease. It is recommended that prophylactic antibiotics be administered to children with congenital absence of the spleen, commencing at three months of age, to be continued indefinitely.


A comparison of tooth accumulated materials from quadrants treated surgically or nonsurgically. The objective of this study was to test the validity of the clinical concept that periodontal surgery is beneficial in aiding the patient to reduce the amount of tooth accumulated materials in moderate to advanced cases of periodontal disease. Twelve arches in eight patients with moderate to severe bone loss were selected for this investigation. Using a split-mouth technique, 12 quadrants were subjected to pocket elimination by the use of osseous and soft tissue recontouring, and 12 quadrants received thorough deep scaling, root planing, and polishing. These patients were seen at 1,2, and 4 weeks after surgery for root planing and more oral hygiene instructions. At 6 weeks they received a prophylaxis, including root planing if indicated, throughout the mouth. The patients returned in 2 weeks, at which time plaque accumulations were then removed and collected by quadrant to be subjected to analysis using wet weights, dry weights and ash weights. The quantity of tooth accumulated debris on the surgically-treated quadrants was significantly greater than on those treated nonsurgically, as determined by the wet weight (P less than 0.01) and dry weight (P less than 0.05). There was, however, no significant difference with ash weight comparisons. The dry weight was the more accurate indicator of tooth accumulated materials. The mean ash weight on the surgically-treated mandibular quadrants (2.21 mg) was significantly greater (P less than 0.05) than from those treated nonsurgically (1.35 mg). The investigators' hypothesis that there would be more accretions on the side not involved in osseous surgery and pocket eradication was not supported in this study. Several possible reasons for this were elucidated and discussed.


The sharpening of scaling instruments: I. An examination of principles. The theory and practice of sharpening with particular emphasis upon dental scalers and periodontal curettes have been discussed in Part I of this series. Various cutting modes and edge characteristics are described together with the special requirements they present in sharpening. Different approaches to sharpening are examined. Stressed are the advantages of using powered rotary stones on the sides of the blade instead of the blade face in sharpening scalers and curettes. Part II will describe the sharpening procedure--materials and technique--used and preferred by the authors.


The sharpening of scaling instruments: II. A preferred technique. The authors' preferred procedure for sharpening scalers and curettes is described in detail; powered rotary stones are used in grinding the sides of the blade. Selected sharpening materials are discussed and evaluated and the control and removal of edge burrs are described. A regular sharpening schedule is recommended, both to simplify sharpening and to extend the useful life of the armamentarium.


Acid and pepsin secretion of separated gastric pouches during perfusion of antral pouches with cholinergic stimulating and blocking agents and lignocaine. 1. Secretion of HCl and pepsin from abomasal fundic pouches was studied in sheep during perfusion of antral pouches with cholinergic blocking and stimulating agents and lignocaine. 2. Resting secretion was reduced to about 50% of control levels and secretory responses to feeding were largely or completely blocked during antral pouch perfusions with atropine (0-01-0-16%) and hexamethonium (1%). 3. Antral pouch perfusions with lignocaine (2%) reduced fundic pouch resting secretion to about 60% of control values but did not block secretory responses to feeding. 4. Perfusions of acetylcholine (0-1%) and carbachol (0-0037 and 0-005%) through antral pouches characteristically stimulated increases in the concentration of acid, outputs of acid and pepsin, but not concentration of pepsin. 5. The mechanisms involved in the release of gastrin in the sheep are discussed. 6. It is concluded that antral secretion of gastrin contributes both to the maintenance of resting secretion of acid and the secretory responses of fundic pouches of sheep when they eat freshly provided food.


Quantitative evaluation of the loss of human platelet dense bodies following stimulation by thrombin or A23187. 1. Distributions of dense bodies per platelet were evaluated in unstimulated human platelets and in platelets stimulated to secrete by the addition of varying amounts of thrombin or the ionophore A23187. Since distributions were not Gaussian, they were compared by non-parametric methods. 2. Most distribution obtained following varying levels of dense-body release differed significantly from the control (unstimulated) distribution. In general, distribution from points widely separated in terms of per cent release of total dense-body content also differed significantly. Distributions obtained at points where the total number of dense bodies lost was approximately the same did not differ significantly, regardless of the drug and incubation conditions used to produce the dense-body loss. 3. Dense bodies were lose from platelets during the secretory process (measured as the release of either calcium or ATP), and the number of dense bodies lost correlated at a significant level with the amounts of both substances secreted. 4. Following maximal secretion produced by either thrombin or A23187, a population of dense bodies (refractory dense bodies) remained in platelets. The refractory dense bodies could not have been distributed uniformly among the control populations of either platelets or dense bodies. The distribution of refractory dense bodies could, however, be described by a model in which platelets containing large numbers of dense bodies had a greater proportion of their dense-body complement refractory than did platelets containing fewer dense bodies.


Effects of the calcium ionophore A23187 on pancreatic acinar cell membrane potentials and amylase release. 1. The effects of the Ca2+-ionophore A23187 and the non-metabolizable cholinergic agonist bethanechol on acinar cell membrane potentials and amylase release from the superfused mouse pancreas were studied. 2. In the presence of extracellular Ca2+ (2.56 mM), A23187 (10(-5)M) and bethanechol (3 X 10(-5)M) caused an equal increase in the release of amylase. Both stimulants depolarized theacinar cells, A23187 by 6-0 mV and bethanechol by 12-3 mV. 3. When Ca2+ and Mg2+ were removed from the superfusate, the ability of A23187 to increase the rate of amylase release was virtually abolished, while the effect of bethanechol remained unaltered. Similarly, in the absence of these divalent cations, A23187 did not cause depolarization of the acinar cells, while depolarization in response to bethanechol was largely normal. Consequently it is unlikely that cholinergic agonists initiate secretion by activating a Ca2+-ionophore-like mechanism in the cell membrane. 4. When the concentration of Ca2+ in the medium was raised to 10 mM was the only extracellular divalent cation present, the depolarization in response to A23187 was increased to 11-8 mV. When Mg2+ in a concentration of 10 mM was the only extracellular divalent cation, the depolarization was only 2-1 mV. 5. The Ca2+ dependent, A23187-induced depolarization was abolished in the absence of Na+ (Tris substitution). Addition of Na+ to the superfusate caused an immediate depolarization. 6. It is concluded that the Ca2+ dependent depolarization of pancreatic acinar cells induced by A23187 is not directly due to an increased divalent cation conductance. Our findings are consistent with the view that the depolarization is due to an increased influx of Na+ resulting from a Ca2+ mediated increase in Na+ permeability.


An overdenture survey: preliminary report. The preliminary conclusions from this survey are listed: 1. The exceedingly high incidence of periodontal pathology seems to be the major problem in the long-term use of overdentures. 2. The incidence of caries is fairly low, but it remains a potential problem. 3. Subjective evaluations by the patients are favorable. 4. The overdenture technique as described by Lord and Teel seems to be practical and advantageous. 5. Additional research to find the most effective agent for inhibiting caries in overdenture support roots should be initiated. 6. Need exists for more surveys by other schools, institutions, or prosthodontists. 7. The overdenture is a valid alternative to complete denture therapy.


Behavioral factors and denture status.

Behavioral factors and denture status. The experiences and impressions for most of the 64 patients who entered the project in 1968 reveal that the opportunity to obtain new dentures, prepared according to the best available technology by highly skilled dentists and dental laboratory technicians, has had an identifiable impact on each of the several behavioral variables for which changes were predicted before the study began. There has been general improvement in self-image, confidence, and relaxation, and these changes often were associated with perceived improvement in fit of dentures, ability to eat, ability to talk, and general health. Although some patients experienced serious health problems during the 6 year study period, neither were these attributed to nor did they appear associated in any way with denture status. The patient population, in general, was very cooperative. Fifty-three patients stayed with the study for 6 years. Most kept their appointments and followed the instructions and advice of their dentists on all matters but one--that of removing their dentures at night. In explaining why they did not remove their dentures at night, most of the patients gave evidence of a high degree of sexual symbolism associated with teeth and denture status.


Prosthodontic techniques and the timing of complete denture procedures--a survey. This survey has attempted to show some of the differences in techniques and materials used by three groups of dentists involved in prosthodontic work in the United States. Some contrasting features between dentistry performed by the NHS and that in the United States have been illustrated, but fair comparisons between the two systems could not be made because of the basic difference in the number of patients and completed treatments and the fee schedules.


The role of coronal contour in gingival health. 1. Total clinical crown contour is related to gingival health. 2. The subgingival convexity of a tooth or a restoration should extend facially or lingually no more than one half of the thickness of the gingiva. This protects the gingival crevice and promotes a knifelike free gingival margin, important in plaque control. 3. The facial and lingual surface contours should have gradual curvatures in all directions to facilitate the rubbing and cleaning function of the lips, cheeks, and tongue. 4. The interproximal contour of adjacent teeth, of the tooth contact areas, and of the teeth in relation to the gingival papilla must be such that moving tissues can rub or the patient can perform oral hygiene easily. The requirements may vary depending on the degree of gingival recession and cosmetic needs. 5. Undercontour is better than overcontour where clinical judgment is vague.


Bond strength studies of precious, semiprecious, and nonprecious ceramic-metal alloys with two porcelains. One-hundred cylindrical pull-through ceramic-metal test specimens were subjected to shear loading forces. Two porcelain systems were treated in association with five ceramic alloys--one precious, one semiprecious, and three nonprecious alloys. 1. There was no significant difference in bond strength between Ceramco and Vita porcelains. 2. The various alloys tested demonstrated significantly different bond strengths. 3. Differential statistical tests suggested that nonprecious alloys performed better with Ceramco porcelain than with Vita porcelain. 4. The bond strength of Ceramco porcelain fused to nonprecious alloy N-C2 was significantly greater than that of Ceramic and traditional gold-based alloys. 5. Nonprecious alloy N-C1 produced significantly less bond strength than the traditional gold-based alloys. 6. Semiprecious alloy W produced high bond strengths with both Ceramco and Vita porcelains. 7. The cylindrical pull-through test was a reliable, reproducible method of testing ceramic-metal bond shear strength. 8. The surface roughness appears to be the one common factor in nonprecious alloys that relates to large differences in bond strength. Additional tests must be made to verify this hypothesis.


The comparison of denture-base processing techniques. Part I. Material characteristics. Some of the physical properties for three techniques for processing acrylic resin were tested. Tests included: (1) thickness changes from a standard die which simulated the palatal and flange regions of a denture, (2) relative Rockwell surface hardness, (3) color stability, and (4) surface detail. The three processing techniques under investigation were: (1) an all-stone investing technique, (2) a silicone-gypsum investing technique, and (3) a fluid-resin technique.


Proplast-coated high-strength magnets as potential denture stabilization devices. This study was designed to determine if a samarium-cobalt magnet could be effectively sealed from the in vivo environment and be physically stablized in bone under similated functional stress. The following conclusions can be made from this study. (1) It is possible to effectively seal a samarium-cobalt magnet from the in vivo environment. Clinical observation, radiographs, and photomicrographs on all samples showed good healing and dense tissue over the surgical sites. The samples showed that connective tissue penetrated the Proplast, and clinically, the magnets appeared to be well stabilized in bone. (2) It follows that if magnets are properly coated and good surgical techniques are used, Proplast can be an effective sealant. Samarium or cobalt appeared in the surrounding tissues only where the coating was faulty. Further studies are being conducted which will cover a 2 year period as opposed to the original 5 month study. It is hoped that with specific tests, we will be able to demonstrate absolute fixation and no migration of the magnets.


Making complete dentures for research purposes. A method for construction of complete dentures for research purposes has been described. According to this method, a baseplate is fabricated of hard acrylic resin in combination with resilient denture liner. These dentures can be repeatedly used by interchanging denture teeth of the same mold.


Communication systems for deaf people: a review of possibilities. This article reviews the possibilities for communication in deaf people. The various types of deafness are categorised and their associated problems briefly discussed. Communication aids are then described in greater detail in terms of the three possible modes of transmission and reception: speech, the written word and coded signals.


Epidemiology of group-B streptococcal carriage in pregnant women and newborn infants. In a population of pregnant women, the prevalence of group-B streptococcal carriage was relatively low. During the 3rd trimester of pregnancy 5-6% of women haboured group-B streptococci and 8-3% were positive at the onset of labour. Some 42% of women who gave positive cultures in labour had given negative cultures during the 3rd trimester and 19% of women who were positive during late pregnancy were culture-negative in labour. The conversion of culture status observed in these women suggests that carriage may be intermittent or that new acquisition of genital-tract streptococci may occur in late pregnancy. The unpredictability of conversion diminishes the reliability of a single culture taken during the 3rd trimester of pregnancy.


Transfer of R factors from Escherichia coli to salmonellas in the rumen of sheep. Adult sheep were given into the rumen c. 10(8) cells each of donor strains of E. coli containing an R factor and prospective salmonella-recipient organisms and were maintained on a diet of lucerne chaff; the animals excreted the organisms, remained healthy, and no transfer of the R factor was detected. When the animals were starved for 48 h before inoculation, the ruminal environment was altered so that, on resumption of feeding, small numbers (c. 10(2)-10(4) cells--less than one cell per ml of rumen fluid) of the introduced organisms were able to multiply and reach sufficient numbers for the transfer of R factors to occur within the rumen. One animal, given 7-8 X 10(3) cells of recipient S. lomita after starvation for 48 h, became a carrier of this organism. A second animal, given 4-4 X 10(2) cells of S. typhimurium after starvation for 48 h, developed acute, fatal salmonellosis 5 days later; at the time of death, large numbers of salmonella organisms (c. 10(9) cells per g) were present in the faeces; these included many (c. 10(6) cells per g) that had received the R factor by transfer in vivo. These results indicate that short periods of starvation may enhance the transfer of R factors and possibly other plasmids between suitable micro-organisms in vivo, and may increase the susceptibility of animals to pathogenic micro-organisms.


The anaerobic culture of clinical specimens: a 14-month study. This paper presents the results of the examination of routine clinical specimens for anaerobes and gives details of the revised anaerobic cultures techniques recently introduced into this laboratory. The species of anaerobic bacteria isolated from lesions in different sites of the body are described and recommendations are made concerning methods of identification and culture.


Airborne infection with Mycobacterium leprae in mice. Although the portal of entry and mode of spread of M. leprae in human leprosy are still uncertain, it is widely held that direct person-to-person skin contact is important. This assumption has ignored the fact that patients with highly bacilliferous leprosy have nasal as well as dermal infection and that, since M. leprae is shed predominantly from the nose, leprosy might be an airborne infection. The present study was designed to investigate this possibility with mice exposed to airborne infection with M. leprae. The conditions are described in which thymectomised-irradiated CBA strain mice exposed to M. leprae aerosols sustained an immediate lung retention of 1 X 10(5) bacteria. Fourteen to 24 months later, 33% (10 of 30) of the mice had countable numbers of acid-fast bacilli (greater than 2 X 10(4)) with the characteristics of M. leprae in one or more homogenates prepared from ears, foot pads, nose or lungs. Evidence is presented from the distribution of M. leprae that the infection had arisen from systemic spresd of bacilli initially entering the lungs rather than from multiplication of organisms locally retained there, or in the nose, at the time of airborne infection. The relevance of these results to the possible route of infection of leprosy in man is discussed.


The isolation of Streptococcus pyogenes from throat swabs. Simulated throat swabs were prepared with known numbers of Streptococcus pyogenes; some were suspended in pasteurised human saliva and an equal number in saline. Two types of commercially available swabs were tested; these were composed of (1) plain, buffered, cotton wool, and (2) albumen-coated cotton wool. The mean recovery rates of first platings on solid media from albumen-coated and plain cotton-wool swabs were similar (8-2% and 8-3%) and the mean recovery rates from platings 1-4 were also similar (6-6% and 6-5%). The greater the delay in plating, the less were the chances of recovery of streptococci, although the viability of these was significantly prolonged on swabs held at 4 degrees C. Similar results were again produced by both types of swabs; processing swabs in saliva, however, produced by both types of swabs; processing swabs in saliva, however, produced a recovery rate that was 1-2% greater than the rate for the saline series. Swabs were also agitated or squeezed by forceps in nutrient broth to release any organisms they contained, and standard samples of the broth were then plated on solid media. Counts thus obtained indicated that about 50% of the original inoculum was still viable and could be recovered from the broth; in comparison, recoveries from initial direct plating of the swabs were low. No demonstrable toxic effect was produced by the cotton wool in these experiments.


Typing of Proteus strains by proticine production and sensitivity. A simple, reliable and highly discriminating scheme for the bacteriocine typing of Proteus has been developed. Strains are typed on MacConkey's agar according to their ability to produce a proticine active against one of 14 indicator strains having a single and specific proticine sensitivity and also according to their sensitivity to the different proticines of 13 proticine-producing strains. This new scheme of combined production and sensitivity typing was formulated after 250 strains of Proteus from clinical material had been examined for the production of proticines active against the 24 indicator strains of Cradock-Watson's proticine typing scheme and for proticine activity and sensitivity towards each other. Three new types of proticinogenic strains were discovered and defined. Strains producing proticines of types 1, 2 and 3 were isolated frequently. These common proticines could be subtyped by their different actions on newly characterised indicator strains. By means of this production/sensitivity (P/S) typing scheme, 250 Proteus strains were differentiated into 90 distinct types, whereas typing by sensitivity alone distinguished only 40 types and typing by production alone distinguished only 20 types (including subtypes).


Immunosuppression studies in foreign body tumorigenesis: no evidence for tumor-specific antigenicity. Sarcomas were induced in CBA/H mice by sc implantation of 15 X 22 X 0.2-mm polyvinyl chloride vinyl acetate copolymer films. The animals were immunosuppressed with azathoprine, antilymphocyte globulin, or thymectomy. Sarcoma development was not accelerated in comparison to nonimmunosuppressed demonstrated in sarcomas of immunosuppressed mice. It was concluded that foreign body tumorigenesis in mice in neither associated with nor dependent on the emergence of tumor-specific transplantation antigens.


Responses of tumors induced in inbred guinea pig strain JY=1 and strain Hartley/F to BCG. A transplantable fibrosarcoma induced in inbred JY-1 guinea pig strain by 3-methylcholanthrene (MCA) and designated J4, an allotransplantable subline of J4 (JH4) which was obtained by the transplantation of J4 into the inbred Hartley/F guinea pig strain and maintained by passages in this strain, and a syngeneic liposarcoma H10 induced in a Hartley/F guinea pig by MCA were tested for their immunotherapeutic response with BCG. The growth of J4 and H10 tumors was suppressed in most of the animals when tumor cells were mixed with BCG before being injected sc into BCG-immune or BCG-nonimmune recipients. The growth of the JH4 tumor was suppressed at the sites of injection with a mixture of tumor cells and BCG in BCG-immune recipients but not in nonimmune animals. All guinea pigs surviving the injection of a tumor cell-BCG mixture resisted a second tumor cell challenge. When subcutaneous sarcomas grew to about 8-15 mm in diameter, BCG was injected into the tumors. The growth of JH4 tumor was not influenced by the injection in either BCG-immune or BCG-nonimmune animals, while the regression of the established J4 transplants was produced in 2 of 3 nonimmune recipients. The growth of the H10 tumor was not inhibited with an intratumor injection into nonimmune guinea pigs, while the H10 tumor regressed in BCG-immune animals for 4-5 weeks after intratumor injection and thereafter grew progressively. Skin reactions in animals that received repeated intradermal injections of the tumor cells and BCG were tested with 10(6) viable tumor cells as eliciting antigens. Typical delayed-type hypersensitivity reactions that were specific to the homologous antigens were observed. The possible reasons for the different responses to BCG among the guinea pig tumors, including line-10 hepatocarcinoma in strain-2 guinea pigs, were discussed.


Xanthogranulomatous pyelonephritis in children. Xanthogranulomatous pyelonephritis in children, contrary to adult onset, rarely is associated with non-function or calcification. The lesion is predominantly on the left side in children. There appears to be a normal humoral but temporarily impaired cellular immune response in addition to sustained depression of polymorphonuclear chemotaxis. The etiology of this is uncertain but may be attributed partially to hyperosmolarity of serum and urine, and to leukocyte specific antinuclear antibodies. The presence of leukocyte specific antinuclear antibody or cold agglutining may interfere with normal phagocyte chemotaxis requiring tissue macrophages to produce a xanthogranulomatous reaction to bacterial invasion.


Chyluria: a case report and brief literature review. A case of chyluria presumably caused by Filaria bancrofti is presented. The radiographic and urologic presentation as well as a brief review of the natural history, diagnosis and treatment is included.


Renal transplantation in patients with insulin-dependent diabetes mellitus. Forty patients  (including 37 juvenile diabetic patients) with insulin-dependent diabetes mellitus and end-stage renal failure received 42 renal allografts during the interval from June 1970 to December 1975. Of the 30 patients who are alive (between six and 72 months after transplantation; average, 29 months), 19 have been fully rehabilitated. Gangrene of peripheral extremities occurred in 30% of the survivors. The use of "pretreated" cadaveric kidneys in the diabetic patient may become an attractive alternative to grafts from living related donors. Renal transplantation with living related and pretreated cadaveric donor kidneys is the treatment of choice and is superior to dialysis in the insulin-dependent diabetic patient with end-stage renal disease.


[Clinical evaluation of clindamycin-2-phosphate in infectious diseases (author's transl)]. Clindamycin-2-phosphate (7(S)-chloro-7-deoxylincomycin-2-phosphate) is a new semi-synthetic antibiotic. It is recognized that the drug itself is inactive against bacteria in vitro but it is hydrolyzed rapidly to active clindamycin, drug intramuscular or intravenous administration. Clindamycin-2-phosphate was administrated intravenously to seven patients with infections, except one intramuscularly, 300 approximately 600 mg, every 8 or 12 hours a day, for 2 approximately 12 days. Three patients (1 bacterial pneumonia, 1 chronic bronchitis and 1 urinary tract infection due to E. coli) recovered from their infection; one patient (bacterial infection in bronchiectasis) partially responded; and three patients (1 urinary tract infection due to E. coli, 1 pneumonia due to Mycoplasma pneumoniae and 1 patient with mycoplasmal pneumonia and acute biliary tract infection) failed to respond to the drug. No remarkable side effect was noted except pain at intramuscular injection site in one patient.


[Clindamycin-2-phosphate and surgical infections (author's transl)]. Blood levels of clindamycin-2-phosphate in dog at dosis of 10 mg/kg body weight showed the maximum of 21 mug/ml 30 seconds after one-shot i.v. administration. Continuous infusion of the antibiotic at the infusion speed of 150 and 300 ml/hour/10 kg b.w. with 6 mg/ml solution maintained blood levels of 30 and 170 mug/ml respectively. It may be recommended clinically to use lower concentration than 6 mg/ml to avoid cardiocirculatory disturbances. Four cases of surgical mixed infections with gram-positive cocci, gram-negative bacilli and anaerobes were treated with clindamycin-2-phosphate at a daily dosis of 1,200 mg intravenously and 2 of 4 cases revealed good clinical response. There was none of the haematological, hepatic, nephrontic, cardiocirculatory and allergic side effects.


Application of the free vascularized bone graft in the treatment of malignant or aggressive bone tumors. Although recent advances in clinical microsurgery have made free tissue transfer a clinical reality, the value of free bone transfers in the reconstructive tumor surgery of long bones has not been reported to our knowledge. Two patients with malignant or aggressive bone tumors who underwent en bloc resection of their tumors and reconstruction with free vascularized bone grafts are presented. In the first case, a giant cell tumor of the distal radius was resected, and a 10 cm free vascularized fibular graft was performed as a reconstructive procedure; in the second case a chondrosarcoma of the femur was excised and replaced by a 20 cm segment of free vascularized fibula. Postoperatively, these patients were followed with arteriograms and sequential bone scans. The indications for the procedure and the operative technique are discussed. A comparison of the merits of free rib versus free fibular transfers is presented with emphasis on bony architecture, vessel characteristics, dissection required and the options available for reconstructive surgery. The advantages and disadvantages of free vascularized bone grafts with respect to conventional methods and the potential applicability of this technique are discussed.


[Treatment of aplastic anemia in children by bone marrow transplantation (author's transl)]. The course of a successful bone marrow transplantation in a 8 year old boy with severe aplastic anemia is presented. The boy lives now 22 months after bone marrow transplantation with normal bone marrow function and an essentially undisturbed performance; The indication for bone marrow transplantation for severe aplastic anemia in children is discussed. Despite improved intensive supportive care (antibiotics, infectious prophylaxis, substitution of blood components) and the treatment with corticosteroids and/or androgens the mortality of sever aplastic anemia in childhood is still high. The advantages of early bone marrow transplantation in severe cases are stressed.


[Bone marrow transplantation in a case of acute lymphoblastic leukemia (author's transl)]. In a 6-year-old girl with acute lymphoblastic leukemia, pericardial effusion and mediastinal mass remission lasted for 7 wks. only in spite of intensive chemotherapy. Bone marrow transplantation for a HL-A-identical, MLC-negative sister was attempted after antipleukemic therapy (Cytosin-arabinoside, BCNU, Cyclophosphamide) and total body irradiation, After uneventful course of engraftment complete remission was achieved for 5 1/2 months.


[Classiciation of non-Hodgkin's lymphomas of childhood (author's transl)]. The malignant non-Hodgkin's lymphomas of childhood are of highgrade malignancy only. There are lymphoblastic and immunoblastic forms. The lymphoblastic lymphomas can be of the Burkitt type (B-cell-derived) or of the "convoluted" or acid phosphatase type (T-cell-derived). A larger number of the lymphoblastic lymphomas are "unclassified" and usually do not belong to either the B-or the T-cell system (stem-cell-derived?). Most of the immunoblastic lymphomas (previously called "reticulosarcomas") are derived from the B-cell series. Besides the lymphomas in the actual sense, there are also true histiocytic reticulosarcomas of childhood. Hodgkin's disease is probably more common in childhood than all of the non-Hodgkin's lymphomas combined.


[Bone marrow transplantation (author's transl)]. Bone marrow transplantation is an experimental therapy, which has been used with success in patients with aplastic anemia, severe combined immunodeficiency and leukemia. We report here on the procedure of transplantation and the possible difficulties which can be encountered.


[The west-berlin therapy study of acute lymphoblastic leukemia in childhood--report after 6 years (author's transl)]. During the last 6 years 73 previously untreated children and adolescents with acute lymphoblastic leukemia were enrolled on a non-randomized therapy protocol. In this longitudinal sutdy the specific accent was put on the intensified induction treatment of 8 weeks' duration which was thought to achieve a higher remission quality. In this phase 8 effective drugs were applied up to the patient's tolerance limits; in addition prophylactic irradiation to the central nervous system was given in two modifications. After 4 weeks all patients were in complete remission. During the first 4 months 6 children died due to complications for which therapy must be at least partially responsible. 17 out of 67 patients relapsed between 4 and 59 months after diagnosis, which corresponds to a remission rate according to the life table analysis of 62% (50 out of 67 patients in first remission). The majority of patients with relapse is characterized at diagnosis by a specific pattern of clinical findings. 2 therapy groups, differently treated in respect to central nervous system irradaiation and duration of continuation therapy, do not at present statistically differ from each other. According to statistics 8 more children may be expected to suffer from relapse. The improved results are due to a lower incidence of bone marrow relapses; it seems that there is a direct relation between intensity of treatment during the induction phase and the occurrence of bone marrow relapses. The specific problems of the presented study take place during the induction phase, which, due to toxicity, regularly results in a number of side effects and severe complications. In order to realize the induction therapy, the use of prophylactic and supportive procedures is of utmost importance. Profound knowledge of possible side effects and complications is most essential as well as the knowledge of how to cope with these problems. It is the authors' opinion that the induction phase can only be performed in specialized institutions, because only at these places enough information may be obtained from an adequate number of patients and only there pediatric oncologists may share in the decisions and responsibilities. Only by using every kind of medical service this method of therapy may be justified at present, according to the results of this study, for the benefit of children with leukemia.


[Lipid-protein-interactions of human apolipoproteins-structural aspects and models of lipoproteins (author's transl)]. The plasma lipoproteins are complex macromolecular structures which play an essential role in fat transport and in energy and membrane metabolism of higher organized organisms. Much has been learned in the last decade about the structural and functional interrelationships of the different lipoprotein classes. Their protein moieties, the so-called apolipoproteins, have been purified and characterized, the primary structure of four of them is known. Initial recombination experiments showed a considerable potential of the (unfractionated) lipoprotein protein to bind to lipids and to form particles similar to native lipoproteins. Further binding experiments performed in several laboratories with the purified A-  and C-apolipoproteins and different physico-chemically well defined lipids have lead to the identification of lipid binding sites within the protein molecules and the formation of amphipathic helices upon and during lipid binding. This possible common mechanism of lipid-protein fractions forms the basis of a recently proposed model of one lipoprotein class, namely the high density lipoproteins (HDL). The significance of protein-protein-interactions in the formation and maintenance of these lipoprotein particles is still unknown. Whether disturbed lipid protein interactions lead to structural and/or functional alterations of the corresponding lipoproteins is a topic of discussion. The pertinent literature is listed in this paper and the physiological relevance of these studies and their clinical aspects will be presented.


Measles virus meningoencephalitis. Immunofluorescence study of brains infected with virus mutants. The localization of measles virus antigens in hamster brains inoculated with a temperature-sensitive mutant of measles virus r its revertant was studied by immunofluorescence. We found significantly less virus antigen in mutant-inoculated than in revertant-inoculated brains. In mutant-inoculated brains the virus antigens were very often found in the meninges. Possible mechanisms for the development of experimental hydrocephalus and meningoencephalitis are discussed.