Antibodies to guinea pig lymphokines. II. Suppression of delayed hypersensitivity reactions by a "second generation" goat antibody against guinea pig lymphokines. A "second generation" antibody to a highly purified lymphocyte product was raised in a goat against material eluted from a rabbit anti-guinea pig lymphokine immunoadsorbent column. This anti-lymphokine serum, in constrast to anti-lymphocyte serum (ALS) did not appear to contain cytotoxic antibodies directed against membrane antigens on guinea pig lymph node lymphocytes. Furthermore, the anti-lymphokine serum did not inhibit the formation of spontaneous T rosettes nor significantly depress lymphocyte response to mitogens. The anti-lymphokine serum totally suppressed the delayed skin reactivity to PPD and contact sensitivity to DNCB when injected intradermally around the site of antigen challenge. By contrast, intradermally injected ALS did not appear to suppress the PPD response in sensitized guinea pigs. Intravenously and i.p. administered anti-lymphokine serum was somewhat less effective in suppressing the delayed skin response to PPD. The intradermal injection of the antiserum had no effect on nonspecific inflammation evoked by turpentine-olive oil or on the extravasation of circulating Evans blue evoked by intradermally injected histamine. Histologic examination of 24-hr DNCB-induced skin lesions from sensitized guinea pigs treated with intradermally injected anti-lymphokine serum showed marked reduction of mononuclear infiltration of the dermis and of epidermal lesions, as compared with skin sites taken from sensitized animals pretreated with normal goat serum. The anti-lymphokine serum injected i.v. also markedly reduced the perivascular infiltration of the dermis and subcutis in skin reaction sites from sensitized animals challenged with PPD. Intravenous treatment with ALS for 3 consecutive days caused extensive depletion of the paracortical areas of peripheral lymph nodes whereas treatment with normal serum and anti-lymphokine serum caused no such depletion. It is proposed that the anti-lymphokine serum is directed against activated lymphocyte products, one of them being MIF. These products are involved in the mediation of delayed hypersensitivity reactions. This is in marked contrast to ALS, the suppressive action of which appears to be central rather than peripheral.


Induction of T cell response to haptens coupled to mycobacteria. A new method for the induction of cellular immune response to commonly used haptens in the absence of detectable antibody response is described. Different haptens were convalently coupled to Mycobacteria and they were injected into guinea pigs in incomplete Freund's adjuvant. Humoral and cellular immune response to haptens were examined at weekly intervals for 5 weeks. Our results show that a significant anti-hapten cellular response was induced and subsequently elicited by both in vivo (skin test) and in vitro (Lymphocyte transformation and macrophage migration inhibition) assays.


Automated counting of T cell rosettes.

Automated counting of T cell rosettes. Human T cell rosettes were enumerated using an automated particle counter, the Bio/Physics Cytograf 6300A. An electronic oscilloscope representation of particle absorbance and scatter of a focused laser beam allows the separation and enumeration of both rosetted and non-rosetted lymphocytes. Repeated Cytograf sampling of a single rosette preparation gave highly reproducible results, and sampling from replicate tubes produced the same degree of variation as microscopic analysis. T cell rosettes prepared from 27 volunteers and compared by both methods of quantitation showed a high degree of correlation. This method can objectively measure at least 100 times as many cells for their rosette-forming capability as the tedious microscopic technique.


Some methodological studies on effector cells in the lymphocyte-dependent cytotoxic antibody assay. A method of direct freezing was found to be reliable for storage of the effectors for the LDA assay, though there is a considerable loss of cells. In order to get immunologically active K cells after thawing, an important step is to leave the cells to recuperate overnight in an appropriate medium before use. A short-term storage of fresh effectors is also possible. The use of a pool of effector cells from a minimum of 3 random blood donors obviates the selection of HL-A types furthermore permits a saving of the amount of serum used. Enrichment of a B cell population by removing the cells capable of forming spontaneous rosettes with SRBC was not found to enhance cytotoxicity. Pretreatment of cells with pronase, trypsin and neuraminidase did not significantly enhance their effector activity, while papain treated cells showed a systematically increased specific lysis.


Determination of DNA antibodies in normal and pathological sera by a new counterimmunoelectrophoresis method. A quantitative counter-immunoelectrophoresis technique has been applied to the evaluation of antibodies against native and single-stranded DNA. Anti-DNA antibodies have been found at high dilutions in patients with systematic lupus erythematosus, without correlation with the existence of renal lesions or with the degree of DNA binding assessed by Farr assay. Significant precipitates were also observed at significantly lower dilutions in other pathological situations and in normal subjects, posing the problem of the nature of the precipitates in these cases.


Lymphocyte effector molecules: an vitro production method for obtaining liter volumes of supernatants from mitogen-stimulated human lymphocytes. An in vitro method has been developed utilizing phytohemagglutinin (PHA) activated lymphocytes obtained from human tonsils and adenoids which permit the accumulation of multi-liter quantities of cell-free supernatants containing lymphotoxin and other lymphocyte effector molecules (LEM). An enriched media is employed which contains a large molecular weight, heat stable bovine serum fraction which supports lymphoid cell activation and levels of LEM secretion equal to that of cultures maintained in medium supplemented with whole serum. Elimination of whole serum from the media greatly reduces overall protein concentrations and facilitates concentration and purification studies. Various technical aspects of these cultures have been examined, i.e.: 1) cell concentration, 2) kinetics of LT production over a ten-day period, 3) mitogen dosage, and 4) types of media. Supernatants can be harvested repeatedly from a single culture over the ten day period, thus doubling the yield of LEM collected from a single culture.


Cellular basis of interferon formation and hyporeactivity after exposure to bacterial lipopolysaccharide. Endotoxin apparently induces interferon in only a few types of cell, yet it produces strong hyporesponsiveness to a large number of agents. After incubation for 24 hr with endotoxin in vitro, tissue cultures of thymus, spleen, mesenteric lymph nodes, and to a lesser extent, liver and lung produced interferon. Lymphoid tissues of bone marrow-derived (B-) cells (sacculus rotundus, appendix, and Peyer's patches) and kidney did not produce interferon. Adherent spleen cells produced more interferon than nonadherent cells. Purification of spleen cells on a bovine serum albumin gradient showed that light, DNA-synthesizing cells made interferon in response to endotoxin or polyriboinosinic-polyribocytidylic acid. Mouse spleen cells produced a "late" interferon 24-48 hr after exposure to endotoxin, which, in contrast to "early" interferon (produced at 0-24 hr) from spleen and other tissues, is stable at 56 C for 60 min. It is suggested that this late interferon represents a "B-cell" interferon. Hyporeactivity was produced in vitro by endotoxin only in tissues that make endotoxin-induced interferon, a fact consistent with the theory that the interferon-inducing mechanism must be initiated before hyporeactivity results. The fact that endotoxin has been found to act on a fairly large range of cells (i.e., macrophages, thymus-derived cells, and probably B-lymphocytes) explains its ability to produce broad hyporesponsiveness.


Enhanced expression of histocompatibility antigens of lymphoid cells in mice treated with interferon. Treatment of young and mature mice with potent preparations of mouse interferon results in a marked enhancement of the expression of histocompatibility antigens on the surface of thymocytes and splenic lymphocytes, as measured by an enhanced absorption of alloantiserum. These modifications in the expression of cell surface antigens may reflect an effect of interferon on lymphocyte naturation and may be relevant to theffect of interferon on lymphocyte function.


Leukocyte colony-stimulating factor and inhibitor activity. Native and density gradient separated rat peritoneal exudate cells were evaluated for both their capacity to stimulate granulocyte colony formation and their ability to inhibit colony growth in vitro. Granulocyte colony-stimulating factor (CSF) was primarily elaborated by monocytes and macrophages; neutrophils showed only minimal stimulatory activity. In contrast, freeze-thawed extracts of both monocyte-macrophage and granulocyte fractions were markedly inhibitory to colony growth using a standard L-cell-derived CSF. Characterization of the inhibitory material indicated it to be a low molecular weight, nonlipid, heat-stable substance. In addition to peritoneal leukocytes, other tissues including lymph node, thymic and splenic lymphocytes, liver, kidney, and skeletal muscle also contained inhibitory materials. These observations suggest that granulopoiesis, as assessed by in vitro culture techniques, is not influenced solely by a simple feedback loop; rather, leukocytic elements, as well as other tissues, appear to contain and release both stimulatory and inhibitory factors.


The influence of selective thrombocytopenia on nephrotoxic nephritis. Anticoagulation with agents that interfere with fibrin formation inhibit the development of the autologous phase of nephrotoxic nephritis (NTN). Platelet participation in the nephritic process has been suggested but not proved, therefore, the influence of selective thrombocytopenia on the autologous phase in rabbits was evaluated. NTN was produced with goat antirabbit glomerular basement membrane antiserum. Thrombocytopenia was induced with goat antirabbit platelet antiserum 24 hours prior to the onset of nephritis. Platelet accumulation within the nephritic kidney was quantitated using chromium labeled platelets. Thrombocytopenia has no inhibitory effect on the development of the autologous phase of NTN in rabbits. There was no platelet accumulation within the nephritic kidney in the presence of thrombocytopenia. Pharmacologic inhibition of platelet aggregation may be of no benefit in glomerulonephritis produced by a fixed antigen-antibody reaction within the glomerular capillary wall.


Determination of alpha1-antitrypsin phenotypes by isoelectric focusing in polyacrylamide gels. A method for alpha1-antitrypsin phenotyping is described that uses isoelectric focusing in a pH gradient 3.5 to 5 with polyacrylamide as supporting medium. The method is fast, reproducible, and reliable and offers some advantages over the currently used starch-gel electrophoresis.


Ly and Ia antigen phenotypes of T cells involved in delayed-type hypersensitivity and in suppression. The Ly and Ia phenotypes of T lymphocytes involved in different functions were characterized by the use of specific antisera. T cells responsible for delayed-type hypersensitivity (DTH) and for helper functions were found to be Ly-1+,2- in contrast to cytotoxic T cells and T cells responsible for suppression of antibody responses which were Ly-1-,2+. Unlike some primed helper cells, T cells involved in DTH were Ia-. Suppressor cells in the system were Ia+.


Inhibition of antibody-dependent cellular cytotoxicity and immunoglobulin synthesis by an antiserum prepared against a human B-cell Ia-like molecule. Rabbit antisera to the human B-cell-specific antigen complex, p23,30, was used to define further the functional heterogeneity of isolated human lymphocyte subpopulations. Specific depletion of p23,30-bearing cells from Ig-negative cell populations and Ig-negative, E rosette-negative (Null) populations by either complement-mediated lysis or by physical separation on goat antirabbit Fab immunoabsorbent columns, eliminates the antibody-dependent cellular cytotoxic (ADCC) function. Furthermore, binding of anti-p23,30 serum to the effector cell surface inhibits ADCC but does not interfere with EA rosette formation. Apparently p23,30 represents a cell surface site which is distinct from the Fc receptor but which is important in the triggering of ADCC. In addition, depletion of p23,30-bearing cells from unfractionated cell populations, Ig-positive B-cell populations and Ig-negative, E rosette-negative (Null) populations eliminates the capacity of these populations to secrete immunoglobulin during subsequent culturing. Thus both the Ig-secreting cells and the ADCC effector cells within the Ig-negative, E rosette-negative (Null) population reside in the same population of cells which bears the p23,30 antigen.


Antibody response of C3H in equilibrium (CKB X CWB)F1 tetraparental mice to poly-L(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys immunization. To test whether the antigen-specific stimulation of low responder-genotype B cells in tetraparental mice is due to a histoincompatibility reaction (allogeneic effect) against these B cells, tetraparental mice were constructed (a) between an Ir-1A low responder to the antigen poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys. [(T,G)-A--L] and an Ir-1A F1 high responder and (b) between two histoincompatible Ir-lA low responders. In the first case the F1 high responder embryo shares the whole of the H-2 complex, including Ir, with the low responder embryo.


The modulation of lymphocyte functions by molecules secreted by macrophages. II. Conditions leading to increased secretion. Cultures of peritoneal exudate cells rich in macrophages were studied for the secretion of lymphostimulatory molecules. Two conditions produced increased secretion: (a) addition to the cultures of various agents that readily interacted with macrophages, such as latex particles, antibody-coated red cells, endotoxin, Listeria organisms, or Be salt; or (b) addition of activated lymphocytes. In the first case the increased activity was found during the first 24 or 48 h after uptake of the stimuli. Increased activity was found in normal or peptone-stimulated macrophages but not in macrophages after injection of endotoxin or thioglycollate. The addition of T lymphocytes from Listeria-infected mice to macrophage cultures increased greatly the activities. This increase was also produced by addition to antigen-primed T cells together with antigen. The lymphocytes by themselves did not secrete active factors. The lymphostimulatory activities were tested on thymocyte DNA synthesis and on antibody formation in vitro. The latter assay was done on spleen cells from immunized mice where one striking effect was the stimulation of differentiation to antibody-secreting cells. Some dissociation of both activities (thymocyte DNA synthesis and B-cell differentiation) was observed with selected culture fluids.


Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. III. Dual gene control of the T-cell-mediated suppression of the antibody response. The antigen-specific suppressive T-cell factor of mice, which had previously been shown to be an I region gene product, could effectively suppress the in vitro secondary antibody response of spleen cells from syngeneic or H-2 compatible mouse strains but not that of H-2 incompatible strains. The identities among genes in the left side half (K, I-A, and I-B) of the H-2 complex between the donor and recipient strains were found to be both necessary and sufficient for the induction of suppression. This suggests that the acceptor site for the suppressive T-cell factor is also determined by the gene present in the left side half of the H-2 complex. The cell type which expresses the acceptor site was found to be a subset of T cell. In general, the suppressive T-cell factor obtained from F1 mice could suppress the responses of both parental strains, and the parental factors could suppress the response of F1 mice. The results indicate that both suppressor and acceptor molecules are codominantly expressed on F1 T cells. There were found two types of defects in the expression of suppressor and acceptor molecules among mouse strains: A/J mice could not produce the suppressive T-cell factor despite that they could accept the factor produced by other H-2 compatible mouse strains. In contrast, all the B10 congeneic lines could produce the T-cell factor, but could not accept the factor produced by syngeneic and H-2 compatible non-B10 congeneic lines. The F1 hybrid of A/J and B10. A could both produce and accept the T-cell factor, and thus the expressions of suppressor and acceptor molecules were found to be dominant traits. These results indicate that the antigen-specific T-cell-mediated suppression is regulated by at least two genes both present in the H-2 complex, and that the complementation of these two genes is required for the induction of suppression.


Histocompatibility antigens and genetic control of the immune response in guinea pigs. III. Specific inhibition of antigen-induced lymphocyte proliferation by strain-specific anti-idiotypic antibodies. The in vitro T-cell proliferation induced by penicilloylated bovine IgG (BPO-BGG) in sensitized strain 2 and strain 13 guinea pigs could be specifically blocked by strain-specific antisera presumably directed against cell membrane-associated immunoglobulin idiotypes. The anti-idiotypic antisera were prepared in strain 2 and strain 13 guinea pigs against immunoadsorbent purified anti-BPO-BGG antibodies which had been raised in strain 2 and strain 13 animals. Strain 13 antistrain 13 anti-BPO-BGG (a strain 13 BPO-BGG) suppressed the in vitro BPO-BGG response of cells from immunized strain 13 animals but did not inhibit the response of cells from immune strain 2 animals. Conversely, the corresponding antiserum raised in a strain 2 combination (a strain 2 BPO-BGG) only inhibited the in vitro BPO-BGG response of strain 2 cells. Furthermore, the inhibitory activity of the antisera could only be absorbed by immune cells from the syngeneic strain. The activity of the a strain 13 BPO-BGG serum was highly specific; the inhibitory activity could only be absorbed by BPO-BGG-sensitive strain 13 cells. The inhibitory activity of the anti-idiotypic sera was predominantly associated with the 19S fraction. The data suggest that immune cells and in particular T lymphocytes from strain 2 and strain 13 guinea pigs possess strain-specific recognition structures from BPO-BGG with the same idiotypes as the corresponding strain-specific immunoglobulins. Furthermore, the production of such inhibitory anti-idiotypic sera was restricted to syngeneic combinations, which suggests a potential role of autoanti-idiotypic antibodies in the regulation of the immune response. The anti-idiotypic antisera used here are apparently directed against gene products not associated with the strain 2 or strain 13 major histocompatibility complex.


Requirement for non-T cells in the generation of cytotoxic T lymphocytes in vitro. I. Use of nude mice as source of non-T cells. The ability of small numbers of LN cells to produce cytotoxic lymphocytes on in vitro culture with allogeneic stimulator cells is greatly augmented by the addition of spleen cells from athymic nude mice. The possibility that the synergism is a result of improved culture conditions or a "feeder effect" is excluded. All cytotoxic cells found in these cultures are shown to be T cells and to arise from precursors contained in the LN-cell component. The nude spleen cell component appears to be providing a required non-T cell which has been lost from the LN component through dilution. Synergism between the two components can occur whether they are syngeneic or allogeneic provided that both can recognize the same alloantigens in the stimulator population.


Genetic regulation of the antibody response to H-2Db alloantigens in mice. II. Tolerance to non-H-2 determinants abolishes the antibody response to H-2Db in B10.A(5R) mice. B10.A(5R) mice (H-2i5), immunized with spleen cells from congenic B10 mice (H-2b), responded to alloantigens of the H-2Db region by producing antibodies of only IgM type. In contrast, they produced both IgM and IgG antibodies when immunized with noncongenic H-2b cells that carry other foreign cell surface antigens (non-H-2) in addition to H-2Db. A hypothesis was proposed comparing the H-2Db antigen on a congenic cell to a hapten on a nonimmunogenic carrier which fails to induce T-cell helper function responsible for the switch from IgM to IgG secretion in B cells. Data presented here confirmed this hypothesis. 5R mice rendered tolerant to the relevant non-H-2 antigens were unable to mount the anti-H-2Db IgG response in a noncongenic immunization. Tolerance induction did not lead to abrogation of the T-cell mediated cytotoxicity.


Genetic control of specific immune suppression. IV. Responsiveness to the random copolymer L-glutamic acid50-L-tyrosine50 induced in BALB/c mice by cyclophosphamide. Previous reports from our laboratory have demonstrated the stimulation of specific suppressor T cells in genetic nonresponder mice after immunization with the terpolymer of L- glutamic acid, L-alanine, and L-tyrosine (GAT) (1,2) and with the copolymer of L-glutamic acid and L-tyrosine (GT) (3-5). These findings raise two important questions: (a) do the specific suppressor T cells inhibit an antibody response which would otherwise develop in nonresponder mice; and, (b) can specific helper T cells inhibit an antibody response which would otherwise develop in nonresponder mice; and, (b) can specific helper T-cell activity be detected in these animals. Responsiveness appears to be completely dominant over suppression in (responder x suppressor)F(1) hybrids, therefore, we have been unable to detect suppressor cells in these hybrids after conventional immunization with GAT (2). However , using special conditions of antigen administration, GAT helper activity could be demonstrated in nonresponder DBA/1 ("suppressor") mice. Thus, GAT-specific helper activity was not detected in these nonresponder animals after immunization with GAT irrespective of the adjuvant used, but could be stimulated by macrophage-bound GAT or by GAT complexed with methylated bovine serum albumin GAT-MBSA (6). In the current report we have taken advantage of the fact that suppressor T-cell activity is more sensitive to cyclophosphamide treatment than T-cell helper activity (7) to demonstrate the presence of GT-specific helper activity in "nonresponder" BALB/c mice. We describe: (a) the dose of cyclophosphamide and conditions of treatment which inhibits the well-documented stimulation of specific suppressor T cells in BALB/c mice injected with GT previous to immunization with GT-MBSA, and (b) the ability of cyclophosphamide to permit the development of primary PFC responses to GT in these "nonresponder" mice. These cyclophosphamide-induced responses are not characterized by the high levels of antibody detected in genetic responder animals.


Association between Ia antigens and the Fc receptors of certain T lymphocytes. The Fc receptors of thymic and splenic T lymphocytes were detected using indirect immunofluorescence and soluble antigen-antibody complexes. 10-20% of thymocytes and 40-50% of Thy-1-positive splenic lymphocytes bound antigen-complexed Ig. The binding to thymocytes was partially inhibited (45-74%) by antibodies against antigens determined by the I region of the H-2 complex, but not by antibodies against K- or D-region antigens or Thy-1 antigen. The inhibition did not require the Fc portion of the inhibiting antibody. These results provide evidence that Ia antigens and the Fc receptors of some T lymphocytes are associated, and that the populations of T cells which bear these moieties at least partially overlap.


Differential susceptibility of neonatal and adult murine spleen cells to in vitro induction of B-cell tolerance. The relative susceptibility of neonatal and adult murine splenocytes to induction of B-cell tolerance was studied in vitro. Adult cells required approximately 1,000-fold more trinitrophenyl-human gamma globulin to be rendered tolerant than did cells from 9- to 12-day-old neonates. The potential effects of suppressor T cells were excluded by pretreating the cultured B cells with anti-Thy-1 and C' and the helper T cells with anti-Ly-2.2 and C'. The possible role of cell surface immunoglobulin isotypes in contributing to this observed difference is discussed.


Antifluorescein affinity columns. Isolation and immunocompetence of lymphocytes that bind fluoresceinated antigens in vivo or in vitro. A new method for the isolation of specific immunocompetent lymphocytes has been described in which lymphocyte populations are exposed to fluoresceinated antigens (FLAGs) in vivo or in vitro, and the FLAG-binding cells retained on antifluorescein affinity columns. Specific cells are then eluted with an unrelated FL-labeled protein and shown to be fully immunocompetent. This methodology has been applied successfully in diverse antigenic systems including polymerized flagellin and TNP-specific B cells and alloantigen-reactive cytotoxic T lymphocytes. The method is rapid, inexpensive (requiring only antifluorescein beads), and can be applied to any antigens (or antibodies) in which a fluorescein group can be introduced.


Ontogeny of B cells in the chicken. I. Sequential development of clonal diversity in the bursa. The initial development and distribution of lymphocytes expressing surface IgM (sIgM) and of specific antigen-binding cells (ABC) were studied in the chicken in an attempt to gain information on the process by which B-cell diversity is generated. The antigens used were sheep erythrocytes (SE), keyhole limpet hemocyanin (KLH), and poly-L(Tyr, Glu)poly-D,L-Ala-poly-L-Lys (TGAL). The results indicate that generation of the total sIgM-positive population begins in the bursa and that specific clones of ABC develop in a fixed sequential pattern which is not influenced by either deprivation of or deliberate exposure to exogenous antigens. Cells bearing sIgM by immunofluorescence (IgM-positive cells) were detected first in the bursa on the 12th day of incubation, KLH-ABC and TGAL-ABC by the 16th day, and SE-ABC on the 18th day. The doubling time of the sIgM-positive population of bursal cells was determined to be approximately 10 h before significant antigen-independent seeding to the spleen began a few days before hatching. Clonal expansion of SE-ABC in the bursa also appeared to be antigen independent as was the initial development of SE-ABC in the blood and spleen which ceased abruptly after bursectomy at hatching. Specific ABC were observed to develop in multiple bursal follicles as small foci of ABC among the much larger total population of sIgM-positive cells within an individual follicle. Intravenously infused SE-ABC homed to the embryonic spleen but not to the bursa. The results are interpreted as favoring a hypothetical model in which individual stem cells give rise to multiple clones of B cells by a predetermined pattern of sequential expression of variable region genes.


[Cytogenetic and statistical study of a group of patients treated with butazolidine (phenylbutazone)]. The authors studied a group of 16 patients suffering from rheumatic diseases, who were being treated with Butazolidine (Phenylbutazone). The control cases were divided into two groups: one consisted of six patients who were suffering from the same chronic rheumatic diseases, but who were being treated with other drugs; the other group consisted of 15 normal persons whose age and sex corresponded, more or less, with those of the group of patients treated with Butazolidine. A chromosomal examination of the lymphocytes of the peripheral blood was carried out on the 16 patients and the 21 persons not being treated with Butazolidine. A comparison of the karyotypes of all the individuals studied showed no significant difference in the number of breakages between the three groups. Statistical analysis confirmed that the differences in the percentages of chromosomal damage were not significant.


Computerized tomography (the EMI Scanner): a comparison with pneumoencephalography and ventriculography. Computerized tomography, using the EMI Scanner, allows the diagnosis of cerebral atrophy or hydrocephalus to be made with the same degree of accuracy as conventional neuroradiological methods. Ventricular measurements made on EMI scans have been compared with those from pneumoencephalograms and ventriculograms. A range of normal ventricular measurements for the EMI scan is suggested.


Systemic candidiasis and endophthalmitis in neurosurgical patients. Report of three cases. Three cases of systemic candidiasis in neurosurgical patients are presented. Two of the three patients also had endophthalmitis. All of the cases were treated with broad-spectrum antibiotics and glucocorticoids prior to the appearance of candidiasis. The authors stress the high susceptibility of neurosurgical patients to opportunistic infections of this type.


Tubuloreticular structures and antinuclear antibodies in autoimmune and non-autoimmune diseases. Tissues obtained at random from patients suffering from autoimmune and non-autoimmune diseases were studied for the presence of tubuloreticular structures (TRS). It could be demonstrated that the occurrence of TRS in renal tissue is not a specific characteristic of systemic lupus erythematosus whereas the presence of such structures in skin tissue might be suggestive for this disease. The serum of some of the patients could be studied for the presence of antinuclear antibodies (ANA). A statistically significant correlation was found between TRS and ANA in the group of patients with autoimmune diseases. The possibility is discussed that this correlation might favour the theory that viruses may be involved in the aetiology of autoimmune diseases, particularly of systemic lupus erythematosus.


Possible effect of maternal promethazine therapy on neonatal immunologic functions. The effect of the administration of promethazine in the treatment of erythroblastosis fetalis was studied in four maternal-fetal pairs. The three infants exposed for a prolonged period of time had decreased neonatal number and function of T cells, and abnormal specific humoral immune responses. The possible role of promethazine in the induction of fetal immunoincompetence is discussed.


Gingival hemorrhage related to aspirin ingestion. A case report. A case report illustrating the clinical manifestations of platelet defects induced by ingestion of two aspirin tablets has been presented. The specific effects on platelets produced by aspirin ingestion have been summarized and the resultant hemostatic defect explained.


Brain and peripheral metabolism of 5-hydroxytryptophan-14C following peripheral decarboxylase inhibition. Following selective peripheral decarboxylase inhibition, a greater fraction of peripherally measured monoamine metabolites should derive from central nervous system monoamine metabolism. In rats pretreated with the peripheral decarboxylase inhibitor L-alpha-(3,4-dihydroxybenzyl)-alpha-hydrazinopropionic acid (MK-486) (50 mg/kg i.p. or i.v.), the peripheral formation of 5-hydroxytryptamine-14C (5-HT-14C) from the precursor DL-5-hydroxytryptophan-14C (5-HTP-14C) was reduced by 82 to 100% over a 4-hour interval. There was a marked increase in the penetration of 5-HTP-14C into brain and in the appearance in brain of 5-HT-14C and 5-hydroxyindoleacetic acid-14C (5-HIAA-14C). The cerebral metabolism of 5-HTP-14C in vehicle-pretreated animals appeared to occur mainly in the brain vascular compartment. Following MK-486 pretreatment, the in vivo metabolism of 14C-5-hydroxyindoles in the extracerebral compartment obeys linear kinetics as does the uptake and decarboxylation of 5-HTP-14C in brains. The cerebral turnover of 5-HT-14C appeared to increase as a function of the dose of 5-HTP injected. This phenomenon may be a result of either saturation of brain 5-HT storage sites or nonspecific metabolism of 5-HTP in brain catecholamine neurons. A highly signigificant correlation was found between the brain and blood 5-HIAA-14C levels following MK-486. The adrenal formation of 5-HT, which was not inhibited by MK-486, did not appear to contribute significantly to the blood 5-HIAA-14c levels. These results suggest the possibility that following peripheral decarboxylase inhibition a larger fraction of peripherally measured 5-HIAA may derive from central nervous system 5-HT metabolism.


Temperature-induced interconversion of alpha-and beta-adrenoceptors in the frog heart. 1. The effect of ambient temperature on the properties of adrenoceptors mediating inotropic responses was assessed in isolated frog hearts on the basis of the effects and tissue uptake of alpha- and beta-adrenoceptor antagonists. 2. At temperatures of 23degree C and above inotropic responses to adrenaline were antagonized by propranolol (0-4-4-0muM), but were unaffected by phentolamine (26-5muM) and were potentiated by phenoxybenzamine (POB) (0-7-29-5muM). Below 17degree C the activity of propranolol was reduced at least tenfold, and the alpha-adrenoceptor antagonists inhibited responses to both adrenaline and isoprenaline, but not those to CaCL2. 3. The responses of hearts exposed to POB at 14degree C and then tested, after thorough washing, at both 14 and 24degree C were similarly inhibited at both temperatures, i.e. the usual beta-adrenoceptor response did not appear at the higher temperature. Conversely, exposure to POB at 24degree C produced only potentiation at both test temperatures. 4. Parallel to the reciprocal changes in their blocking actions, significantly more (14C)propranolol was retained by hearts exposed at high temperatures and significantly more (3H)POB was bound to the myocardium at low temperatures. Changes in binding and in the pharmaco logical effects of both blocking agents occurred entirely within a relatively narrow temperature range (17-22degree C) Parallel to the change from alpha- to beta-adrenoceptor characteristics with increasing temperature, the sensitivity of the hearts to adrenaline increased about tenfold. 5. Phentolamine (26-5muM) effectively protected hearts from block by (3H)POB at 14degree C, unmasked a potentiation of responses to adrenaline equivalent to that produced by POB at 24degree C, and reduced binding of the label to approximately the level found in unprotected hearts exposed at the higher temperature. At 24degree C, phentolamine did not alter the potentiation produced by (3H)POB, and reduced binding only slightly. There was no significant temperature differential in the amount of (3H)POB bound in the presence of phentolamine. 6. The results presented indicate a close functional and, probably, morphological association of alpha- and beta-adrenoceptors in the frog heart. It is suggested that the two classes of adrenoceptors may represent allosterie conformations of the same structure.


X-linked recessive type of pure spastic paraplegia in a large pedigree: absence of detectable linkage with Xg. A family with 24 males affected by an X-linked type of spastic paraplegia is reported. Twelve affected members were personally examined showing the pure form of the disease. Half of the affected males had many descendants, all normal. Linkage studies strongly suggest that this X-linked form of spastic paraplegia and Xg loci are not at a measurable distance on the X chromosome.


Tryptophan metabolism and the occurrence of amino acids and serotonin in the leech (Hirudo medicinalis) nervous system. The occurrence and distribution of serotonin (5-HT) and amino acids along the central nerve chain of the leech, Hirudo medicinalis, was analyzed using dansyl-chloride in order to obtain information on the functional roles of amines and amino acids. There was no statistical variation in the occurrence of most of the amino acids or serotonin in the different parts of the dorsal nerve chain of the leech. A variation in the serotonin content was found during the year with the highest level occurring in winter. Leech ganglia also accumulated 3H-tryptophan and metabolized part of it to form 5-HTP, 5-HT, and 5-HIAA. The results are discussed from the point of view of 5-HT being a transmitter substance.


Changes in occupation after aortocoronary vein-bypass operation. The effect of aortocoronary vein-bypass operation on changes in occupational status was investigated in a cohort of 893 men. The median period of time between the operation and follow-up evaluation of postoperative occupational status was 14 months. The patients were divided into two age groups, with 55 years as the dividing point. The results showed that 11% of the younger men and 26% of the older group who were employed before the operation retired following the operation. In addition, 30% of the patients changed their occupational status following the operation. When occupational changes also resulted in changes in physical demands, 49% of the patients took new jobs that were less demanding physically, while 40% took jobs that were more demanding. Close to 9% of the patients were retired prior to the operation; about one fifth of them came out of retirement following the operation.


Cerebral ventricular enlargement. Chronic alcoholics examined by computerized tomography. Computerized tomography was used to measure cerebral ventricular size in hospitalized alcoholic patients, all of whom had evidence of liver disease. Twelve alcoholic patients with neurologic symptoms such as withdrawal seizures, neuropathy, and drug overdose were included. All these patients had normal results from the mental status examinations by the time of discharge. Alcoholic patients had a much higher mean ventricular size compared to 60 control patients. One third of the alcoholics had markedly enlarged ventricles as opposed to only one of the 60 controls.


Retrograde aortic dissection occurring during cardiopulmonary bypass. Successful repair and concominant subclavian-to-coronary artery vein bypass. A retrograde aortic dissection that occurred during cardiopulmonary bypass was successfully repaired. The cause of dissection was related to the jet of retrograde perfusion. The use of subclavian-to-coronary artery vein bypass when the ascending aorta is not suitable for vein anastomosis because of dissection or aneurysms appears to be a satisfactory alternative to aorta-coronary bypass.


Effects of L-glutamine on acetylsalicylic acid-induced gastric lesions in normal and cirrhotic rats. Cirrhosis of the liver in rats was induced by the administration of carbon tetrachloride (0.1 ml/100 g of body weight, s.c.) biweekly for 13 weeks. In the pylorus ligation preparation, acetylsalicylic acid (ASA) 100 mg/kg p.o. induced much more serious gastric damage in CC14-induced cirrhotic rats as compared with rats with a normal liver. L-glutamine 750 mg/kg p.o. prevented the ASA-induced gastric lesions in both normal and cirrhotic rats, even though the degree of the inhibition was weaker in cirrhotic rats. Gastric analysis indicated that L-glutamine 750 mg/kg p.o. markedly inhibited the gastric ionic changes (acid back diffusion) in response to ASA in both cirrhotic and normal rats.


Estimation of cell surface associated protease activity and its application to lymphocytes. A new method has been developed to estimate proteolytic activity available at the cell surface. Radioiodinated protein substrates are covalently linked to modified polystyrene-divinylbenzene beads with various diameters. These beads are presented to viable cells. Secreted enzyme activity is estimated when no contact occurs between beads and cells. Surface associated proteolytic activity is estimated by the increased rate of iodinated peptide release due to a contact between beads and cells. This method was applied to various lymphocyte preparations. In the absence of serum, mouse spleen lymphocytes produce three- to fourfold higher proteolytic activity than lymph node cells. This activity is completely inhibited by serum diluted 1:10. Since the proteolysis is so marked in the case of spleen cells, one must conclude that lymphocytes removed from the serum and treated in buffered mediums at 37 degrees C have enzymatically altered surface properties. Cell surface associated enzyme activity was measured using rat lymph node lymphocytes with less than 0.1% contamination by granulocytes. This predominantly thymus derived, T cell population had 30% increase in proteolysis due to contact between cells and solid-phase localized substrate of casein. The released enzymatic activity was inhibited by diisopropylfluorophosphate, but its effect on the surface associated enzyme activity remains questionable since it perturbs several membrane functions.


Light-induced tetracycline accumulation by Rhodopseudomonas sphaeroides. Light has been used as a primary energy source in studies of tetracycline transport by Rhodopseudomonas sphaeroides. Accumulation of the antibiotic occurs in light, while efflux occurs in dark. Both fluorescence enhancement and radioisotopic tracing have been used to monitor transport. Km's obtained from both techniques are similar. Light-induced accumulation of tetracyclines is inhibited by a variety of inhibitors, including antimycin A, N-ethylmaleimide, carbonylcyanide m-chlorophenylhydrazone, and 2,4-dinitrophenol. A rapid efflux is observed after loading when cells are placed in the dark or treated with inhibitors.


Support of the myocardium with intra-aortic balloon counterpulsation following cardiopulmonary bypass. Intra-aortic balloon counterpulsation (IABC) was instituted in 27 patients in cardiogenic shock who had undergone cardiopulmonary bypass (CPB). Patients who required IABC either prior to CPB or else to be weaned from CPB had a survival rate of 22 per cent (2/9). In contrast, the survival rate for those patients requiring IABC after CPB had been discontinued was 72 per cent (13/18). The composition of these two groups was different. The first group contained primarily patients with either severe coronary artery disease or aortic valve stenosis, whereas the latter group contained patients with either less severe coronary artery disease or mitral valve disease. Most patients had an initial satisfactory response to IABC. The over-all survival rate was 55 per cent (15/27). IABC was particularly beneficial for those patients in cardiogenic shock following CPB who had not had massive and irreveraible myocardial injury.


Aneurysm of the sinus of Valsalva producing obstruction of the left main coronary artery. An aneurysm of the left sinus of Valsalva compressed the left main coronary artery and the patient experienced anginal pain. Surgical correction consisted of obliteration of the orifice of the aneurysm, aortic valve replacement, and a saphenous vein bypass from the ascending aorta to the distal left anterior descending coronary artery. Postoperative studies revealed excellent function of the prosthetic valve, no recurrence of the aneurysm and retrograde filling of the left anterior descending and circumflex coronary arteries. Three years after the operation, the patient is asymptomatic.


Aspirin and prophylaxis of thromboembolic complications in patients with substitute heart valves. Anticoagulation therapy with acenocoumarin or with anticoagulants plus aspirin was given to 65 and 57 patients, respectively, with cardiac valve replacement. The follow-up was 1,462 months (22.5 months per patient) for the first group and 1,411 months (24.7 months per patient) for the second group. The frequency of embolic accidents was significantly lower in the group taking aspirin: Thirteen thromboembolic accidents were detected in patients receiving the anticoagulant and 3 in the group receiving the anticoagulant plus aspirin. These figures represent a 20.3 per cent incidence (one each 9.3 years of treatment) for the anticoagulant group and a 5.2 per cent incidence (one accident each 39.1 years of treatment) for the other group. The statistical significance between groups is p less than 0.005. There was no difference in the hemorrhagic risk between the two groups. We conclude that the use of an anticoagulant plus aspirin is a good and safe therapy for the prevention of thromboembolism in these patients.


The effect of hemodilution on plasma levels of cortisol and free cortisol. The effect of hemodilution on plasma levels of total cortisol and free cortisol was studied in 12 patients undergoing open-heart surgery. In each case, at the onset of extracorporeal circulation (ECC) the hematocrit value was rapidly reduced to 25 to 30 per cent and was maintained around this level during perfusion. Total plasma cortisol levels fell significantly with the hemodilution (p less than 0.0001), but the plasma concentration of free, biologically active cortisol was maintained at its pre-dilution level because of an increase in the percentage of plasma cortisol existing in the free form. There was a highly significant correlation between the degree of hemodilution and the percentage rise in the free cortisol fraction (r = 0.79; p less than 0.001). These results indicate the presence of a compensatory mechanism associated with cortisol binding which maintains the plasma level of free, biologically active cortisol when hemodilution has reduced the plasma level of total cortisol.


Left ventricular function and coronary obstruction as predictors of survival following aorta-coronary bypass. A retrospective analysis was undertaken of clinical data and catheterization studies of 151 consecutive unselected patients who underwent aorta-coronary bypass at the University of Kansas Medical Center between 1971 and 1973. The purpose was to determine the effect of preoperative left ventricular function and extent and severity of coronary artery obstruction on operative mortality rate and long-term survival. The postoperative follow-up period ranged from 10 to 49 months and averaged 26 months. Left ventricular function was assessed by qualitative analysis of left ventricular angiograms. Severity of coronary obstruction was quantified by scoring coronary arteriograms according to the system of Friesinger and associates. Patients with normal or near normal ventriculograms were considered to have good left ventricular function. Patients showing moderate or severe impairment of contraction were considered to have poor left ventricular function. Obstruction scores ranging from 2 to 7 points were classified as low scores, and scores from 8 to 15 points were classified as high scores. Four groups of patients were identified based upon preoperative left ventricular function and obstruction severity: Group I, 29 patients with good left ventricular function and low scores; Group II, 22 patients with poor left ventricular function and low scores. Group III, 28 patients with good left ventricular function and high scores. Elective aorta-coronary bypass in these three groups was accompanied by no operative or late deaths. Group IV comprised 72 patients with poor left ventricular function and high scores. In this group there was a 10 per cent operative mortality rate (7 of 72 patients) and a 5 per cent year late mortality rate. Relief of angina occurred equally in all groups. Thus operative risk can be prospectively determined by analysis of left ventricular function and severity of coronary obstruction. Surgical treatment resulted in negligible operative and late mortality rates (0 per cent) in all patients except those in whom poor ventricular function was accompanied by severe and diffuse coronary artery obstruction. Operation should be offered to this latter group (Group IV) despite the higher operative and postoperative risk because of salutary postoperative results.


On a model for ontogenic development.

On a model for ontogenic development. A theory to explain both the endogenous control of differentiation and programmed organismal aging as the result of one fundamental regulatory mechanism is advanced. It is postulated that these phenomena are linked to cell division, which is presumed to be the primary unit of measurement for the organism's maturation and aging. The hypothesis developed here holds that a genetic locus (DSI), modulating both cell division and enzyme induction, is first activated and then inactivated with each cycle. The number of DSIs in the genome of each cell is finite, cellular sensescence occurring when the genome is depleted of functional DSIs. Protein inducers are linked to specific DSIs, which are only transcribed at appropriate times during ontogeny, this in turn being a function of the number of DSIs previously inactivated during earlier mitoses. Experimental approaches which could test this model are discussed.


[Nasopharyngeal culture results in children with acute otitis media]. Nasopharyngeal cultures in 463 children, suffering from otitis media were examined in 1968-1970. In 45% of cases H. influenzae, D. pneumoniae, S. aureus and beta hemolytic streptococci were found. These are thought to be the causative organisms for acute otitis media, however their dominance may vary. In our findings H. influenzae came first. 102 of 463 children, that is, 21.9% showed this organism. D. pneumoniae was second with 10.7%, which is generally considered as the primary cause of bacterial otitis media in children.


Age-related changes in ConA- and LPS-induced lymphocyte transformation. I. Effect of culture conditions on mitogen responses of blood and spleen lymphocytes from young and aged rats. Age-related changes in LPS- and ConA-responsiveness of rat spleen lymphocytes as judged by 14C-TdR incorporation were studied. It was found that responses to both mitogens decreased with advancing age. This report shows that the reduced 14C-TdR incorporation could not be attributed to decreased cell survival or viability of spleen lymphocytes from old rats, to delayed proliferation of the old lymphocytes, or to differences in minimum mitogen doses required for optimal stimulation. The results suggest that the observed decrease is due to a decrease in the number of mitogen responsive cells. The response to LPS was even more depressed than was the response to ConA. The response to ConA in whole blood is also shown to decline with ageing at multiple mitogen doses.


Medical decision profiles derived from a symptom questionnaire. The introduction of formalized systems for data acquisition provide a basis for the investigation of medical decision making. Patients admitted to a general medical ward completed a comprehensive, medical history. Decisions relating to their subsequent diagnosis, investigation and management were made after complete investigation and were recorded with their questionnaire responses. A computer programme was developed to compare questionnaire responses from patients who did, and patients who did not have each particular decision made, and to assign a value to each question depending on the significance of its association with the decision. The set of values, one for each question, was termed a decision profile and was characteristic of that decision.


Detection of cytotoxic lymphoid spleen cells from STU-mice with Moloney sarcoma by a 3H-proline microcytotoxicity assay. A microcytoxicity assay with 3H-proline prelabeled target cells was used for the detection of sensitized lymphoid spleen cells from STU inbred mice inoculated with Moloney sarcoma virus (MSV-M) or ascitic MSV-M tumor cells. The target cell line was derived from ascitic MSV-M tumor cells. With regard to the specificity of the assay nonimmune slpeen cells displayed no or only a weak cytotoxicity against these cells, and this was also the case when 3H-proline-labeled secondary cultures of syngeneic mouse embryo cells were exposed to both sensitized and nonimmune spleen cells. The time-course pattern of the development of cytotoxic lymphoid spleen cells in STU mice inoculated intramuscularly either with MSV-M or ascitic MSV-M tumor cells was studied. At the stages of tumor development, peak tumor size, and tumor regression the lymphoid spleen cell preparations were found to have relatively strong cytotoxic activity independent of whether the tumor was induced by MSV-M inoculation or tumor cell transplantation. However, in the latter case effector cells appeared earlier and were demonstrable for a longer period than in MSV-M-inoculated mice. Anti-theta serum treatment of lymphoid spleen cells taken at the stage of peak tumor size abrogated the cytotoxic activity or diminished it considerably indicating a T-lymphocyte response.


The effect of a lymphotoxic factor from patients with multiple sclerosis on acute lymphosarcoma cell leukemia and acute lymphoblastic leukemia. Eight patients with acute lymphosarcoma cell leukemia or acute lymphoblastic leukemia received infusions of plasma containing a lymphotoxic factor. The lymphotoxic factor induced a transient fall in the number of "blast" cell forms in the peripheral blood in six of the eight patients but did not produce sustained remissions. Previous investigations have demonstrated that this lymphotoxic factor, found in the plasma of patients with active multiple sclerosis, is of low molecular weight and does not have the properties normally associated with an antibody. This factor appears to selectively interfere with ribonucleic acid synthesis in the thymus-derived lymphocyte. Lymphotoxic factor activity was demonstrated in the serum of one patient during a remission in leukemia induced by a viral illness.


Complement consumption in fresh blood sera by double culture of Paramecium caudatum and Aerobacter cloacae compared with survival and stage of disease in some malignant tumors in man. Using the complement consumption test by double culture of Paramecium caudatum and Aerobacter cloacae (DPA) as antigen we examined blood sera and compared survival rates and stage of disease in 124 patients with carcinoma of cervix uteri, corpus uteri, ovaries and breast. The evidence suggests that bacteria Aerobacter cloacae constitute the proper antigenically effective substances of DPA. The intensity of reaction and therapy the relative titres of antibodies detected by the test were expressed by the amount of complement consumed in the reaction and designated by the abbreviation "NMHD", i. e. number of minimum haemolytic doses of complement fixed by antigen in the reaction. Patients with NMHD above 8 (i. e. with an intensive reaction corresponding to a high level of antibodies) exhibited partly higher three-year survival rates -- starting from the time of diagnosis, partly more often the clinical stages of disease I or II as compared with patients with NMHD below 4. The best survival rates were found in patients with NMHD above 8 and clinical stage I or II. NMHD values in patients with the initial period of disease and in healthy women did not differ substantially.


Scintigraphy in lymphomas and leukemia of the brain. Scintigraphy with 99mTc-pertechnetate made it possible to detect focal brain lesions in 4 patients with primary malignant lymphomas of the brain, one patient with CNS involvement with lymphatic immunoblastoma, one patient with Sézary syndrome (mycosis fungoides and T cell leukemia) and one child with a space occupying infiltration of myeloblastic leukemia. The scintigraphic results were verified by morphological data from biopsy or autopsy.


[Artery-nerve conflict. Involvement of the acoustic-facial group]. Six cases of "Conflit Artère-Nerf" concerning acoustico-facial nerves discovered by surgical exploration of cerebello-pontine angle. This conflit is due to an encircling middle cerebellar artery constricting the nerve or by a large Internal Auditory Artery lying upon it. Dissection of the surroundings arachnoidal tracts had given in these cases good results.


Computerized tomography: abnormal intracerebral collections of blood in children. Three children with unusual abnormal intracerebral collections of blood were examined by computerized tomography. These cases demonstrate the complementary relationship of this technique with other neuroradiological diagnostic methods. An intracerebral aneurysm and an arteriovenous malformation of the vein of Galen are demonstrated on computerized tomograms.


Computerized axial transverse tomography in normal pressure hydrocephalus. Twenty patients with normal pressure hydrocephalus were examined by computerized axial transverse tomographic (CT) scanning and the results were compared with pneumoencephalographic findings and clinical responses to ventricular shunting. The CT scan revealed significant cortical atrophy, not demonstrated by pneumoencephalogram in seven patients. The cortical atrophy was confirmed by autopsy in one case. This examination also revealed greatly enlarged ventricles (25 to 40 per cent of intracranial volume) in eight patients up to 4 years after ventricular shunting. There was no relationship between the presence or absence of cortical atrophy, or the postoperative ventricular size, and the clinical responses to ventricular shunting. Current concepts of normal pressure hydrocephalus must be revised in view of these findings.


Correlation between computerized transaxial tomography and radionuclide cisternography in dementia. A study of the findings on cisternograms and computerized transaxial tomography (CTT) of 144 patients showed good correlation between the two tests. Patients with a cisternographic pattern of communicating hydrocephalus tended to show more severe degrees of lateral ventricular dilation, with involvement of the third and fourth ventricles and relative sparing of the cerebral sulci. Patients with a cisternographic pattern of cerebral atrophy showed lesser degrees of lateral ventricular dilatation and more severe degrees of dilatation of the cerebral sulci. The statistical significance of the individual CTT findings in these patients is presented, and a cheme for interpretation is proposed. The study shows that CTT can replace pneumoencephalography in evaluating patients with dementia, while cisternography contributes complementary information.


Cerebrospinal fluid T and B lymphocyte kinetics related to exacerbations of multiple sclerosis. Cerebrospinal fluid T and B lymphocyte populations were identified in 21 patients with relapsing and 10 patients with stable multiple sclerosis. The results indicate that the percentage of T cell is largest in the acute stage of a relapse (65 percent) and diminishes by the second week (41 percent). Conversely, the stable patients had a lower percentage of T cells (30 percent) and a relatively high percentage of nonreacting cells (66 percent). The proportion of T cells in the cerebrospinal fluid varies directly with the clinical activity of the disorder, further implicating cellular immune mechanisms in the pathogenesis of multiple sclerosis.


Significance of Purkinje cell density in seizure suppresion by chronic cerebellar stimulation. Cerebellar biopsy specimens were obtained at the time of cerebellar electrode installation in three epileptic patients. Cerebellar autopsy specimens also were examined from four epileptic patients and from five patients without epilepsy or neurologic disease. All specimens from seizure patients showed isomorphic gliosis of the cerebellar cortices. Significantly lower Purkinje cell densities were found in epileptic patients as compared with nonepileptic control patients. Our two epileptic patients showing marked Purkinje cell loss before cerebellar stimualtaion appeared to have better seizure control during stimulation than the patient who had only mild reduction in Purkinje cell density. These data suggest that augmentation of Purkinje cell inhibitory discharges in not the dominant mechanism for seizure suppression during cerebellar stimulation. Comparison of cerebellar specimens obtained during electrode installation with those obtained later during electrode revisions may have been prognostic significance.


Myoclonus after 5-hydroxytryptophan in rats with lesions of indoleamine neurons in the central nervous system. A myoclonic syndrome consisting of tremor, myoclonus, and seizures was produced following the systemic administration of 5-hydroxytryptophan to adult rats previously given intracisternal injections of 5,7-dihydroxytryptamine and systemic desmethylimipramine, but not in their controls. This behavioral response was blocked by pretreatment with the putative serotonin receptor blocking agents methysergide, lysergic acid diethylamide, and bromolysergic and diethylamide, as well as centrally effective doses of the aromatic amino acid decarboxylase inhibitor Ro4-4602. Blockers of receptors of other neurotransmitters had little effect. This neurologic response in the adult rat may be relevant to some forms of clinical myoclonus and may be useful in testing potential agonists and antagonists of serotonin receptors in the mammalian central nervous system.


Immunologic characterization of cerebrospinal fluid lymphocytes: preliminary report. Cellular immunocompetence of cerebrospinal fluid lymphocytes was investigated in several neurologic diseases. Microtechniques were developed to enable determination of E-rosetting capacity and phytohemagglutinin responsiveness of scant numbers of cells present in the cerebrospinal fluid specimens studied. Although most individuals had phytohemagglutinin-responsive cells in their CSF, reactivity was somewhat less than that found simultaneously in their blood. Three of eight patients had comparable percentages of E rosettes in their blood and CSF. Int the remainder, the values differed significantly. Although preliminary, these result illustrate a new approach to immunologic characterization of CSF lymphocytes in diseases.


[Progress of clinical pharmacology in essential headaches]. By testing venomotor receptors (venous-constriction test), it was possible to show a potentiation of the venous constriction effect of serotonin by methysergide and ergotamine. This 5-HT potentiation was observed only when these drugs were sampled in concentrations similar to those in therapeutic use. When ergotamine and methysergide are sampled in concentrations higher than those used in clinical practice, the expected 5-HT antagonist effect is clearly evident. We could therefore conclude that methysergide and ergotamine can be considered pro-serotonin and not anti-serotonin drugs. The pro-serotonin effect of methysergide and ergotamine might take place peripherally on vasomotor or sensitive receptors and/or at a CNS level, making up for the lack of serotonin which, according to the central theory of essential headache, provokes the painful cephalic syndrome.


[Case of reduced platelet adhesion with a slight P.T.A. plasma deficit]. A case of vascular deficit associated with P.T.A. plasma deficit of hereditary-familiar character has been studied hand described.


[Importance of chemical mediators for the pathogenesis and treatment of hemicrania]. The vascular mechanism of migraine attacks--intracranial vasoconstriction during the prodromal stage and passive vasodilatation of extracranial arteries during the painful phase--has been confirmed by modern methods. In addition, number of humoral factors--plasmakinin, serotonin, histamine--intervene in the chain of events that culminates in migraine headache. In addition to these three humoral mediators, the part played by tyramine in migraine of alimentary origin, the precipitating effect of oestrogen decrease in menstrual migraine and the hypothetical role of prostaglandins and prolactin are discussed. The multifactorial mechanism of migraine accounts for the very variable profiles of effective anti-migraine drugs.


[Transcutaneous nervous stimulation in the treatment of hemicrania and other forms of headache]. Transcutaneous administration of a slightly painful electrical stimulus was employed in the management of migraine and other forms of headache in 35 patients with various pictures of pain. Stimulation during crisis led to its total disappearance in 6 subjects with migraine. A relatively high percentage of successes was noted in the remaining patients, with persistence up to 8 months. The theory of "gate control" is cited to explain this effect. Stress is laid on the particular suitability of the method in the management of chronic headache, since it is not associated with either dependence or toxic medicamentous effects.


Localization of E and EAC binding lymphocytes in human tonsils. The localization of T and B lymphocytes in frozen sections of human tonsils was determined using E and EAC binding techniques. It was revealed that there were thymus-dependent areas with E binding lymphocytes in peri- and interfollicular zones. EAC binding lymphocytes were found mainly in the follicles. This suggests that B cells are produced in germinal centres. The present experiment confirmed that human tonsils contain two different kinds of lymphocytes demonstrating selective localizations in the tissues as similar to the lymph nodes.


[Blood and cerebrospinal fluid B and T lymphocytes in mumps-meningitis (author's transl)]. 20 children, 12 boys and 8 girls, with mumps-meningitis have been investigated during the acute stage of illness. Immunoglobulin-concentration, B and T cell ratios were determined in venous blood and cerebrospinal fluid. In the blood no correlation between the percentage of B cells and immunoglobulin-levels, or the course of illness could be observed. Total protein level as well as cell count, the concentration of glucose and chloride were determined in the cerebrospinal fluid at the same time. No correlation between the percentage of B cells and immunoglobulin-levels could be observed in cerebrospinal fluid. No difference in the number of B and T cells was observed between blood and cerebrospinal fluid. These results demonstrate, that the lymphocytes in cerebrospinal fluid in meningitis possess the same surface markers and show about the same B to T cell ratio as it is found on the lymphocytes of blood.


Effects of Newcastle disease virus (NDV) on infection of adult mice with the Thogoto-like Ar-126 arbovirus. Inoculation of mice with Newcastle disease virus (NDV) alters the course of infection with the Thogoto-like arbovirus Tho-Ar-126. The Tho-Ar-126 content of liver, spleen, and lymph nodes was approximately 10 times greater in mice treated with NDV 24 h before infection; the mortality was somewhat increased, but liver damage (as indicated by serum transaminase levels) did not seem to be potentiated. Lymphocytopenia was observed in NDV-inoculated mice, and in the spleen and lymph nodes the proportion of lymphocytes susceptible to lysis by anti-theta (a marker for thymus-derived lymphocytes) was markedly decreased in these animals. This suggests that NDV potentiates infection by Tho-Ar-126 through its action on thymus-derived lymphocytes.


Transcutaneous electrical nerve stimulation to relieve pain. As a therapeutic technique, transcutaneous electrical nerve stimulation is in its infancy, but the instrumentation is rapidly becoming more sophisticated. Mindful of precautions and of the practical limitations of the technique, the practicing physician may find it worthy of serious consideration, particularly in relieving pain on a short-term basis.


Perinatal infection: diagnosis, treatment, and prevention. The majority of clinically recognizable acute infections in the neonate are bacterial. Such infections may be acquired from the mother prior to or at birth or from environmental sources. Because of the limited ability of neonates--especially those born prematurely--to express symptoms, even minor deviations from normal behavior should suggest bacterial disease. Chronic congenital and perinatal infections, unlike acute bacterial disease, are generally asymptomatic in mother and neonate and may remain latent or subclinically active in host tissue for prolonged periods, possibly causing insidious injury to the central nervous and perceptual systems. When overt, these infections almost invariably cause mental or perceptual handicaps or both. In view of the significant mortality and morbidity associated with either acute or chronic infections, diagnosis and treatment should be aggressive.


Plasma natriuretic activity in oedematous states. Accumulating evidence suggests that extracellular volume (ECV) may be governed in part by a natriuretic hormone. To study its possible role in oedema formation plasma fractions IV from patients with the nephrotic syndrome, with cirrhosis of the liver, and with idiopathic oedema were studied for their effects on frog skin Na-transport and on rat renal Na-excretion. Plasma fractions IV from ECV-expanded healthy subjects and patients with aldosteronoma significantly inhibited PD and SCC and in the rat increased urinary flow, CH29, and UNaV. Neither antinatriferic nor natriuretic activities were observed in patients with the nephrotic syndrome or liver cirrhosis. In patients with idiopathic oedema recurrent episodes of fluid retention up to 9 percent of b.wt. followed by spontaneous natriuresis were well correlated with antinatriferic plasma activity. The results suggest that ECV in healthy subjects may be governed in part by a natriuretic hormone which is absent in ECV-expansion due to oedema. However, this mechanism may operate appropriately, though at an elevated threshold, in patients with idiopathic oedema.


Occult blood loss and iron balance in chronic renal failure. In 38 patients with chronic renal failure total daily blood loss and intestinal iron absorption were determined by means of a whole-body counter and radioiron. Bone marrow iron content was measured histochemically. Mean daily blood loss (corrected for laboratory blood sampling) and iron absorption were significantly higher than in normal controls. Bone marrow iron content was reduced in 46% of the patients. The results prove that gastrointestinal blood loss in patients with chronic renal failure is of such magnitude that negative iron balance results.


Ontogeny of murine B lymphocytes: sequence of B-cell differentiation from surface-immunoglobulin-negative precursors to plasma cells. Among bone-marrow-derived (B) lymphocytes exist subpopulations of cells that can be induced to express the markers: surface immunoglobulin (Ig), the antigen associated with the immune response gene (Ia), and the receptor for the third complement component (CR). Inducible cells for the first two markers are found in bone marrow, and inducible cells for all three are in spleen. Experiments were designed to determine whether induction involves a single precursor cell population that on triggering with lipopolysaccharide expresses all three surface markers, or three separate precursor cell populations each of which expresses a single marker. Specific B cell subpopulations were eliminated by treatment with anti-Ig or anti-Ia and complement, or by rosette formation with erythrocytes-antibody-complement followed by differential centrifugation, and surviving cells were subsequently tested for inducibility of the three B cell markers. After anti-Ig cytolysis only Ig, but not Ia and CR, could be induced, implying that the Ia- and the CR-inducible cells are Ig+. Similarly, after anti-Ia cytolysis Ig and Ia but not CR could be induced. Thus, CR-inducible cells must have the Ig+Ia+ phenotype. Elimination of CR+ cells did not affect the induction of Ig, Ia, or CR from their precursors. None of the three elimination experiments affected the conversion of prothymocytes (Thy-1-) to thymocytes (Thy-1+). From these results we propose the hypothesis that the differentiation of B lymphocytes proceeds through at least four distinct stages characterized by the following phenotypes: Ig-Ia-CR- leads to Ig+Ia-CR- leads to Ig+Ia+CR- leads to Ig+Ia+CR+.


Adjuvant arthritis in T lymphocyte depleted rats. Markedly T lymphocyte depleted rats were prepared by thymectomy, irradiation, and repopulation by bone marrow hematopoietic and lymphoid cells. Such rats had persistent T lymphopenia of about 20% of normal. When T depleted and normal rats were injected with adjuvant, all animals developed arthritis but with slightly less severity in the T depleted animals. Such experiments, and other observations, suggest a complex immunological mechanism in the pathogenesis of adjuvant arthritis in the rat.


Fate of intraintestinal thymocytes labeled with 125iododeoxyuridine or tritiated thymidine. A suspension of thymocytes labeled with 125UIdR or 3HTdR was injected into the jejunum of mice. The bulk of the radioactivity disappeared within few hours from the intestine and was recovered principally in the urine. This indicated a very rapid breakdown of labeled thymic cells, reabsorption and subsequent elimination of the tracer in the kidney. In mice injected with cells labeled with 3HTdR, the initial rapid loss of radioactivity was of shorter duration, and slower during the second phase, presumably due to more extensive reutilization and/or prolonged persistence of acid-soluble radioactivity. Pretreatment of the recipients with antibiotics did not significantly reduce the rate of radioactivity loss.


Biological bases for the integration of appetitive and consummatory grooming behaviors in the cat: a review. Cats with pontile lesions, frontal neocortical lesions, and thyroidectomized cats display a dissociation of the appetitive and consummatory components of grooming behavior following tactile stimulation of the body surface, an abnormal behavior which waxes and wanes with the seasons of the year. Tryptophan hydroxylase activity and serotonin levels were significantly decreased in the superior colliculi (but not other brain regions) in cats with pontile lesions or frontal neocortical lesions, but not in thyroidectomized cats. Systemic administration of 5-hydroxytryptophan or monoamine oxidase inhibition plus tryptophan administration abolishes the abnormal grooming behavior in each group of cats, and microinjections of 5-hydroxytryptophan or serotonin into the superior colliculi has the same effect, indicating that the change in a serotonergic system is a critical aspect of the abnormal behavior in cats with lesions and that a serotonergic system may also be involved in the genesis of the abnormal grooming behavior in thyroidectomized cats. Functional inactivation of the serotonergic system by p-chlorophenylalanine, LSD, or serotonin receptor blockade does not induce the abnormal grooming behavior in normal cats, indicating that other factors are involved. Cats with lesions and thyroidectomized cats display a rhythmic dysfunction in the excretion of glucocorticoids and glucocorticoid administration abolishes the abnormal grooming behavior, suggesting that glucocorticoids are the other critical factor. Adrenalectomized cats do not display the abnormal grooming behavior, but when adrenalectomized cats are treated with p-chlorophenylalanine, the abnormal behavior appears. Thus, a serotonergic system in the superior colliculi, operating at some level of glucocorticoid function, is involved in the integration of appetitive and consummatory grooming behaviors.


Pharmacological studies of N,N-dimethylaminoethyl chloroacetate and N,N-dimethylaminoethyl acrylate as inhibitors of choline acetyltransferase in isolated skeletal and smooth muscle preparations. Two tertiary amine esters, N,N-dimethylaminoethyl chloroacetate (Cl-DMA) and N,N-dimethylaminoethyl acrylate (acryl-DMA), which have recently been shown to be inhibitors of choline acetyltransferase (ChAc) were investigated to determine their actions in isolated skeletal and smooth muscle preparations. Both compounds caused neuromuscular blockade in indirectly stimulated nerve-muscle preparations (ED50 values of Cl-DMA were 6.9 -42.0 X 10(-4) M and those of acryl-DMA were 1.2-5.8 X 10(-4) M). The blockade was completely or partially reversible after drug washout. A comparison of the ED50 values for neuromuscular blockade with the ID50 values for ChAc inhibition suggested that the acryl-DMA compound might not cause neuromuscular blockade via ChAc inhibition because the potency ratios (ED50/ID50) of Cl-DMA were higher than 1, whereas those of acryl-DMA were equal to or lower than 1. This was borne out by further experiments on isolated neuromuscular preparations which showed that the site of action for acryl-DMA was post-junctional, whereas that for Cl-DMA was prejunctional. In addition, the weak stimulating properties of Cl-DMA and acryl-DMA were investigated in isolated skeletal and smooth muscle. Cl-DMA was shown to be a partial cholinergic agonist, whereas acryl-DMA was a nonspecific stimulant not involving cholinergic receptors. Although both Cl-DMA and acryl-DMA are inhibitors of ChAc, only Cl-DMA appears to have sufficient specificity for use as a possible ChAc inhibitor in vivo.


Principles of therapy in cirrhosis.

Principles of therapy in cirrhosis. Since progression of certain types of cirrhosis can be prevented by withdrawal of the offending agent or administration of anti-inflammatory drugs, optimal therapy depends on accurate diagnosis of the specific cause. Anticipation and appropriate treatement of complications will allow a more favorable prognosis.


[Echoencephalographic determination of normal values of the width of the third ventricle in children]. The maximum diameter of the third ventricle was ultrasonically determined on 769 children aged 3 to 10, of whom 401 were boys and 368, girls. The empirical range included values between 2.1 and 5.5 mm, the average value being 3.8 mm and the standard deviation, 0.57 mm. Limiting ranges bordering on pathological values are, for the time being, considered to be as follows: 4.5 mm in the third year of life; 5.0 mm in the fourth to fifth years of life; 5.5 mm in the sixth to seventh years of life; and 6.0 mm in the eighth to tenth years of life.


Computed tomography: evaluation of the posterior third ventricle. The normal computed tomography (CT) appearances of the posterior third ventricle and related structures are presented. Seventy-six patients with lesions directly involving this ventricle were studied by CT, and results of other neuroradiological procedures evaluated. Primary tumors, metastases, hematomas, infarcts, and cysts may be reliably distinguished by CT, particularly if contrast enhancement is utilized. Size and density resolution limit the direct visualization of the aqueduct of Sylvius; stenosis however may be inferred. Small infarcts may be difficult to demonstrate by the use of CT scans without contrast enhancement, yet be shown by isotope scans.


Enterolith causing bleeding in a patient with Meckel's diverticulum. Angiographic demonstration. Angiography demonstrated a bleeding Meckel's diverticulum supplied by tortuous, presumably embryonic branches of the superior mesenteric artery. A large enterolith, partially impacted into a constriction near the center of the diverticulum, caused a bleeding ulcer. The diverticulum contained no gastric mucosa.


Migration into pseudo-follicles of draining lymph nodes of medullary small thymocytes injected in the mediastinal cavity. After an intramediastinal injection of labelled thymic cells, few cells were found in the pseudo-follicles of the draining nodes while the extrafollicular zone of their cortex contained abundant labelled cells (Sainte-Marie and Peng, in press). We proposed that the cells having migrated into the pseudo-follicles were small lymphocytes of the thymic medulla, or medullary small thymocytes, which accounts for about 5% of the thymocyte population. The purpose of the present study was to test the validity of the proposal. Rats received corticosterone injections to destroy, their cortical thymocytes and, thereafter, a dose of 3H-cytidine in order to label the surviving medullary small thymocytes. One hour later, these cells were suspended and injected in the mediastinal cavity of recipients which were killed 3 and 24 hours after the injection. The radio-autographs of the draining, and of the remaining, nodes revealed that most labelled cells, present in the nodes at the 24-hour interval, were situated mostly in the pseudo-follicles. The finding indicates, that, unlike the cortical small thymocytes, the medullary small thymocytes can migrate into pseudo-follicles. This is probably due to the greater motility of the medullary small thymocytes and possibly, to their involvement in the function(s) carried out in the pseudo-follicles.


[Cold lymphocytotoxins in various pathological situations]. Cold lymphocytotoxins have been described extensively in many situations. In the present work, this kind of antibody has been found less frequently than previously in some diseases like infectious mononucleosis, rheumatoïd arthritis, or kidney transplanted patients. These discrepancies may be due to technical considerations. In contrast, cold lymphocytotoxins, in the present work, have been frequently detected in auto-immune hemolytic anemias with cold agglutinins, and in patients having immuno-deficiencies.


[Application of free flow preparative methods for the separation of blood cells]. Human blood cells can be separated using an apparatus described by Hanning and co-workers (Model FF4 Desaga Heidelberg). The method of free flow preparative electrophoresis uses a specific property of blood cells when subjected to an electric field: their electrophoretic mobility. Three regions of migration can be defined: --a high mobility region (HMR); --a low mobility region (LMR) and --an intermediate mobility region (IMR). After the electrophoretic migration, the various cell fractions are identified. If human leucocytes are subjected to an electric field (40 volts/cm) it is possible to isolate several populations which differ by their membranes electric charge. The repartition of the neutrophiles granulocytes is twofold: --one fraction of high mobility (HMR) and --one fraction of low mobility (LMR). The meaning of these two populations is being discussed. Between these teo fractions is located the lymphocyte fraction which is represented by a single peak of intermediate mobility (IMR). Eosinophiles and monocytes are concentrated in low mobility fraction (LMR). With appropriate migration parameters (80 volts/cm, various component buffers) it is possible to obtain from lymphocytes, purified by density gradient, an electrophoretic separation of T and B lymphocytes population. Histograms obtained from quantitative measures (on collected cell fractions) show an unimodal distribution. When separated cells are characterized by three membranes markers (E. Rosettes, EAC Rosettes and surface immunoglobulins) the electrophoretic heterogeneity of B and T cells is then demonstrated. With E Rosettes (T cells) the majority of T lymphocytes is distributed in HMR and IMR. With EAC Rosettes and membrane immunofluorescence (B cells markers) the majority of B lymphocytes is found in the LMR. Thus an important enrichment of T and B sub-population is obtained, but contamination from one another still remains too important. More selective methods should lead to an improvement of this cell separation.


Suppression and stimulation of immunoglobulin synthesis by agents present in rheumatoid synovial effusions. Synovial effusions from 14 patients with rheumatoid arthritis contain factors capable of enhancing and suppressing the production of immunoglobulin when added to normal peripheral lymphocyte cultures in vitro. Utilizing a radioactive immune coprecipitation technique it could be demonstrated that enhancement was observed upon addition of relatively small amounts of synovial fluid, while addition of higher amounts resulted in suppression of immunoglobulin synthesis. Nine of ten non-rheumatoid joint effusions showed neither enhancing nor suppressing activities. The possible relationship of these events to lymphokine production in the joint is discussed.


Estimation of B- and T-lymphocytes in lymphoid tissue by means of photometry and 51Cr labelled marker erythrocytes. Some new techniques for estimating B- and T-lymphocytes in lymphoid tissue are introduced. The density of marker erythrocytes on closed chamber incubated sections was estimated by the light transmission in relation to the number of the respective lymphocyte subpopulation, measured on suspensions of eluted lymphocytes. Using 51Cr labelled marker erythrocytes, the number of adsorbed marker erythrocytes per lymphocyte could be estimated from the gamma-irradiation of the section. The number of lymphocytes in the section was determined by the amount of protein in the section compared with the protein amount of a tissue specimen of known wet weight and known lymphocyte content. Furthermore, the number of adsorbed marker erythrocytes per rosette in suspensions of eluted lymphocytes was estimated by means of radioactively labelled marker erythrocytes.


[Motor complications during Herpes zoster of the ophtalmic branch of the trigeminal nerve. Electromyographic study of 7 cases (author's transl)]. It has been recently shown that in addition to ganglia the nerve is involved during Herpes Zoster. Electromyographic investigations of the masseter muscle, were carried out on the side of the skin lesions in 7 cases of Herpes Zoster of the first trigeminal branch. In 4 cases there was a partial denervation, possibly due to a mononeuritis of the motor branch of the trigeminal nerve. It is probable that systematic electromyographic examinations may demonstrate a higher proportion of motor complications during Herpes Zoster than previously accepted.


Extracorporeal irradiation of thoracic duct lymph as immunosuppressive treatment in rheumatoid arthritis. Thoracic duct drainage and re-infusion of the irradiated lymph was carried out as immunosuppressive treatment in 2 patients with progressive, therapy-resistant rheumatoid arthritis. In both patients, a marked clinical improvement was achieved even during the first days of treatment. A reduced number of T cells in the blood was seen 3 days after onset of drainage, whereas no significant change in the number of B cells was observed. No recirculation of the infused cells could be detected, nor was the radiation removal of T cells accompanied by rapid proliferation of "new" T cells. As clinical improvement and reduction in T cells occurred simultaneously, there is probably a connection between these two events. The beneficial clinical response and the achievement of T cell suppression by thoracic duct drainage--the result of irradiation and re-infusion of irradiated lymph--encourage further clinical trials with this type of treatment in severe therapy-resistant rheumatoid arthritis.


Granulocyte reactive antinuclear factors in juvenile rheumatoid arthritis. The prevalence of mouse liver reactive antinuclear factors (L-ANF) and human granulocyte reactive antinuclear factors (G-ANF) was determined in sera from 34 age- and sex-matched pairs of patients with juvenile rheumatoid arthritis (JRA) and controls. Neither type of antinuclear factor was found in any of the control sera, whereas of the patient sera, 35% were L-ANF positive and 59% were G-ANF positive. 90% of the G-ANF positive sera were of the IgG class and 50% were able to fix complement. L-ANF was most frequent in female patients. Several types of ANF were associated with the polyarticular form of the disease. Such varying prevalences of ANF with disease types might indicate that JRA is a syndrome rather than a disease. In particular, the complement fixing G-ANF titre was positively correlated with parameters related to disease activity. The great variation in prevalence figures of different ANF types previously reported and the possible clinical significance of these auto-antibodies are discussed.


A human syndrome caused by immotile cilia. Four subjects who produced immotile sperm were studied. In three of the subjects, who had frequent bronchitis and sinusitis, there was no mucociliary transport, as measured by tracheobronchial clearance. Electron microscopy indicated that cilia from cells of these patients lack dynein arms.


Myocardial infarction in patients less than 45 years old: acute course, angiographic findings, and long-term follow-up. The clinical courses of 57 patients who had an acute myocardial infarction when less than 45 years of age were reviewed to identify descriptors which might be useful in selecting candidates for coronary artery surgery. Follow-up for the subgroup of 45 patients seen initially with acute myocardial infarction was 98% (44/45) complete. Those patients referred to the medical center because of complications for specifically for coronary artery surgery following recent infarction were not followed. Average duration of follow-up for survivors without coronary surgery was 45 months and ranged from 10 to 105 months. The hospital mortality for the above group was 16% (7/45). During the follow-up period, 11% (4/37) died, 51% (19/37) had angina, 19% (7/37) had congestive heart failure, 51% (19/37) returned to work, and only 43% (16/37) remained asymptomatic. Angiographic assessment of coronary artery lesions by the Friesinger method indicated moderately severe disease in these young patients. Multiple regression analysis did not reveal a reliable predictor of hospital or late death or subsequent morbidity.


Bilateral renal cortical necrosis: a report of 2 cases. Two cases of renal cortical necrosis, one of which occurred after an obstetric complication (abruptio placentae) and the other after postpartum haemorrhage, are described. The diagnosis was made by percutaneous renal biopsy, intravenous pyelography and selective nephro-angiography. Immunofluorescence studies of the kidney showed no abnormality in one patient, but showed the presence of IgM in the glomerular basement membrane in the second patient. Hypotension was not observed when anuria occurred. Both patients survived. The importance of prolonged haemodialysis is stressed, since one patient was oliguric for 57 days and required intermittent haemodialysis for 5 months, while the second patient was oliguric for 17 days, required haemodialysis for 5 months and now has established hypertension.


[Observations in two cases of primary fibrosarcoma of the lung (author's transl)]. Two cases of primary fibrosarcoma of the lung are reported. The different clinical findings as well as the different courses in both patients reveal problems in diagnosis and treatment of this rare pulmonary lesion. The diagnostic aspects are given and discussed with regards to bronchial carcinoma. It is believed that lobectomy is the rational treatment of primary fibrosarcoma although pneumonectomy must be considered in the indifferentiated typ. The doubtful prognosis requires an exact postoperative follow up in order to have the change of early surgical treatment or irradiation if metastasis or recurrence of the tumor occurs.


[Bronchial carcinoids (author's transl)]. Of 35 patients with bronchial carcinoids seen at the Kantonsspital Zürich during 16 years, 33 underwent an operative resection. The endoscopic resection is not recommended because of the risk of hemorrhage recurrence, and that this operation results in only partial removal of carcinoids which develop extrabronchially. It is concluded that bronchial carcinoids are potentially malignant tumours and that resection should be most radical if they show recurrence, invasive growth or metastases. Controls are necessary for a long period of time because even in presence of metastases the growth is very slow.


[Leiomyoma of the esophagus (author's transl)]. Benign neoplasms of the esophagus are rare. According to Linder and Grözinger (1968) they come up to about 0,5-2% of all esophageal tumors. Among new growths of mesenchymal origin leiomyomas are dominant in 75-85%. In nearly the half of the concerned patients symptoms occur, indicating operative intervention. At the Surgical Department of the RWTH Aachen besides 58 patients with esophageal cancer only 4 patients suffering from benign tumors have been operated on between 1967 and 1975. Histologically three times the diagnosis of a leiomyoma could be established. In one female, a preoperatively simulated leiomyoma was verified as an intramural cyst of bronchogenic origin. Thoracotomy and enucleation or extirpation are the preferable methods of treatment. Postoperatively no essential complications were seen. A clinically silent fistula healed up spontaneously.


[Surgery for coarctation of the aorta in the first year of life (author's transl)]. A new surgical repair of coarcation of the aorta is reported on 7 infants in the first year of life. Hereby the subclavian artery is used as a modified patch for the coarctation and utilised for re-establishing aortic continuity. The results and advantages are presented and discussed.


[Penetrating shot injury of the intern carotid artery (author's transl)]. The case of a young male patient with gun-shot-trauma of the internal right carotid artery is reported. The primary arterial reconstruction in the hemiparetic and unconscious man was successfully done. The problems of the carotid shot trauma - especially indication, time of reparation, kind of operation and the intraluminary shunt - are discussed.


A new cannulation method for isolated mitral valve surgery--"apicoaortic-pa" cannulation. The present paper describes experimental and clinical studies of a new method "Apicoaortic-PA" cannulation for mitral valve surgery. Our experimental study showed that this method was more rapid and more physiological for cardiopulmonary bypass. We used this technique in 55 cases of isolated mitral valve surgery with successful results. Our general philosophy of surgical approach to the mitral valve diseases is also discussed. We advocate the utilization of the "Apicoaortic Pulmonary Artery" cannulation method for clinical use in isolated mitral valve surgery through the left thoracotomy.


[Cor triatriatum: total correction in an infant using normothermic inflow occlusion (author's transl)]. Successful correction of cor triatiatum in a 3-month-old infant is presented. The diagnosis was established preoperatively by separate angiocardiographic visualization of the two left atrial compartments. To our knowledge all successful total corrections were done under cardiopulmonary bypass. In this case, the abnormal diaphragm in the left atrium was resected under normothermic inflow occlusion. We believe that the technically very simple resection of the diaphragm does not necessitate the use of extracorporeal circulation in an infant, provided the diagnosis can be made beyond any doubt before the operation.


[Clinical experiences with cardioplegic injection in open heart surgery (author's transl)]. Two groups of 50 patients each who had undergone valve replacement with extracorporeal circulation, were examined. In the first group surgery had been performed only under coronary ischemia, whereas in the second group cardiac arrest was induced pharmacologically. IC CLUMP OCCURE MORE OFTEN. Also the amount of necessary defibrillation at occurrence of ventricular fibrillation was significantly lower. Besides it was extraordinary that after the cardiopulmonary bypass the consumption of positive inotropic drugs (Catecholamine) fsults injection-cardioplegia with its simple handling seemed evidently superior to coronary ischemia. But it remains to be seen, if injection-cardioplegia is equal to coronary perfusion.


[On myocardial abscess (author's transl)]. Authors describe an abscess in the area of a myocardial infarction. The possibility of surgical treatment is discussed.


The influence of x-rays, vitamin A and protease inhibitor on the hydroproteolytic activity and serotonin content in pancreas and intestine of rats. Activity of MAO, hydroproteolytic enzymes including some lysosomal markers as well as serotonin content were examined in pancreas and intestinal tissue of rats 24 hours after irradiation with the dose of 800R. It was stated that postirradiation disturbances of enzymatic activity in intestinal tract were accompanied by changes of serotonin content. Administration of vitamin A into rats caused in some parts of the intestine slight increase of acid phosphatase activity-and evident changes in serotonin content. Inhibitor of proteases (Trasylol) evidently prevented the disturbances of serotonin content both in rats exposed to X-rays or vitamin A administration- when simultaneously its influence on changes in hydroproteolytic activity (except of pancreas and colon) was of smaller degree.


Pneumocystis and Histoplasma infections in wild animals from the Amazon region of Brazil. Routine examination of tissues from wild forest rodents from Amapá, north Brazil, revealed Pneumocystis carinii in lung smears from a newly captured Oryzomys capito (Cricetidae). Acute, fatal infections with this parasite are also recorded in a number of captive "coatimundis", Nasua narica (Carnivora: Procyonidae) and a sloth, Bradypus tridactylus (Edentata). Pneumocystis was also encountered in lung smears from a newly captured and apparently healthy sloth, Choloepus didactylus. The presence of infection in newly captured animals leads us to believe that the fatal, fulminating pneumocystosis seen in the captive Nasua and Bradypus was due to exacerbation of pre-existant infections acquired in their natural forest environment. Pneumocystis carinii is a well known cause of fatal, interstitial plasma-cell pneumonia in human infants and sometimes the weakened adult: the keeping of exotic pets such as the coatimundi is, therefore, not without some hazard in this respect. Histoplasma, another well known pathogen for man, was isolated from 4 rodents, Proechimys guyanensis (Echimyidae), all from virgin forest along the newly opened Trans Amazon Highway, Pará State, and from a single sloth, Choloepus didactylus, from near Belém, Pará. All these animals showed no symptoms of infection: isolation of the parasite was made by the inoculation of laboratory hamsters with saline suspensions of triturated liver and spleen.