The trigeminal system in the pigeon (Columba livia). I. Projections of the gasserian ganglion. The central projections of the Gasserian ganglion were investigated in the pigeon, Columba livia. Lesions were placed in the ganglion either by direct surgical exposure or stereotaxically, and following survival times of one to four days, the brains stained with the Fink-Heimer method. The main group of central axons bifurcate to form distinct ascending and descending branches, the tractus trigemini ascendens (TTA) and the tractus trigemini descendens (TTD). A smaller tract also courses caudally (ITTD) separate of TTD proper to terminate in the nucleus cuneatus externus. The TTA projects topographically upon the principal sensory nucleus of the trigeminus, ending in both the pars dorsalis and a smaller pars ventralis. The neurons at the point of bifurcation of the entering radix have been designated as the pars oralis of nTTD. The TTD distributes caudally to several distinct subnuclei at each level, and extends into the cervical spinal cord. Relatively discrete regions corresponding to the pars interpolaris and caudalis were recognized. The projections to the cervical cord terminate in laminae I-IV. There was no evidence of projections to the cerebellum, or contralateral PrV or TTD. There was a small projection to the contralateral cervical spinal cord. No clear evidence of a projection to the nucleus solitarius was found. The distribution of primary trigeminal axons is compared to that described in other vertebrates.


Determination of volume from computerized tomograms: finding the volume of fluid-filled brain cavities. The concept of characteristic computed density is introduced and used as the basis of a method for computing the volume of reconstructed objects. The interpretation of a computed tomographic (CT) scan as a picture is considered to be misleading for this purpose, and is replaced by the notion of a CT scan as a reconstructed slice, or slice array. A pattern recognition system for estimating the volume of fluid-filled brain cavities is described. Operational definitions for certain structures in the brain are given. Finding the volume of brain cavities is seen to hinge on an adequate estimation of the characteristic density of brain tissue bordering the cavities. Computer methods are discussed for producing a normalized (relative distance) map of a brain slice and for searching in three dimensions through a stack of slice arrays. An evaluation of the system, on mock brain tissue and ventricles in a human skull, yielded encouraging results.


The normal contrast-enhanced computed axial tomogram of the brain. Intravenous administration of iodinated contrast agents permits identification of the major cerebral arteries and veins; third, fourth, and lateral ventricular choroid plexuses; falx and tentorium on appropriate sections of contrast-enhanced computed axial tomographic (CECT) images. Combinations of these normal vascular structures into conglomerate densities may produce confusing contrast pseudotumors on CECT images.


Early detection of occlusal caries by measuring the electrical resistance of the tooth. The tooth resistance measuring instrument was compared to the traditional method of the explorer examination for the detection of occlusal carious lesions. The findings of the instrument were more sensitive as compared to the traditional method when verified by a histological examination.


Compounds which affect the adherence of Streptococcus sanguis and Streptococcus mutans to hydroxyapatite. Several compounds were evaluated in an in vitro assay system for their ability to block the adherence of Streptococcus sanguis to saliva-coated hydroxyapatite and Streptococcus mutans to dextran-coated hydroxyapatitite. Fatty acids, ranging from C-12 to C-20, the enzyme amylase, chlorhexidine, human sera, and several serum proteins blocked S sanguis adherence to saliva-coated hydroxyapatite. Chlorhexidine blocked S mutans adherence to dextran-coated hydroxyapatite, but human sera and serum proteins did not. The effects of these compounds on the adherence of these organisms to hydroxyapatite may help in the development of specific plaque control methods for use in human populations.


Triggering of cultured neoplastic mast cells by antibodies to the receptor for IgE. Cell surface receptors for IgE were isolated from detergent lysates of iodinated, IgE-saturated, rat basophilic leukemia cells by precipitation with anti-IgE antibodies followed by chromatography at acid pH. The isolated material showed a single 125I-band (m.w. approximately 58,000) on gel electrophoresis in sodium dodecyl sulfate and was used to immunize a rabbit. The resulting anti-serum was reacted with lysates of surface iodinated mouse or rat tumor mast cells. Analysis of the precipitates on (10%) gel electrophoresis revealed one major peak comprising greater than 80% of the detectable counts and having an estimated m.w. of approximately 58,000. The antiserum reacted with detergent-solubilized and cell-bound receptors in the presence or absence of excess IgE; it also inhibited the binding of 125I-IgE. Cultured mouse mastocytoma cells never exposed to IgE released 3H-serotonin when incubated with F(ab')2, but not Fab' fragments of the antiserum, which had been rigorously freed of IgE and anti-IgE. The release was inhibited in the presence of excess IgE, was Ca++ dependent, and equaled 80% of the maximum obtained with IgE and anti-IgE. We conclude that aggregation of the receptors for IgE provides the critical signals for cell activation.


Mechanism of allosuppression: evidence for direct suppression of responding B cells. The mechanism of allosuppression has been investigated. As previously described, negative allogeneic effects result when T cells recognize MHC-encoded alloantigens on responding lymphocytes, preventing the generation of a secondary anti-PFC response in vitro. Several experiments suggested that this suppression was not due to the generation of cytotoxic effectors. First, effective suppression occurred only when T cells, either unprimed or alloantigen activated, were added during the first 24 hr of the responding culture. Even previously generated cytotoxic effectors were relatively ineffective when added late in the response. Furthermore, no detectable cytotoxic effectors were found in suppressed cultures. The major target of suppression was the responding B cell. Only B cells carrying alloantigens (thus recognized by the T cells) were suppressed; bystander B cells were little affected. Thus allosuppression appears to involve the recognition by T cells of alloantigens on responding B cells and direct suppression of some early event in the development of these B cells into PFC. The responses of primed B cells were found to be preferentially sensitive to the suppressive effects of allo- T cells, whereas the response of unprimed B cells was influenced preferentially by the helper effects of alloantigen-activated T cells. It is possible that the state of differentiation of the B cell may determine the outcome of the interaction with regulatory T cells.


Differential endotoxin sensitivity of lymphocytes and macrophages from mice with an X-linked defect in B cell maturation. The in vitro sensitivity of B lymphocytes and macrophages derived from (CBA/N X DBA/2N) F1 male mice, which carry an X-linked recessive gene that produces defective B cell maturation, was compared to phenotypically normal F1 female mice. B lymphocytes of F1 males exhibit an abnormal mitogenic response to LPS in serum-free culture conditions, which is partially reversed in the presence of serum. In contrast, both resident and thioglycollate-induced peritoneal macrophages of F1 male mice respond normally to LPS. In response to LPS in vitro, F1 male macrophages produce the monokine, lymphocyte-activating factor (LAF) and release prostaglandins. Furthermore, F1 male macrophages are sensitive to the lethal effects of LPS. Therefore, the defective CBA/N gene appears to be expressed only in B lymphocytes and not in macrophages. Since F1 male mice are normally sensitive to the lethal and adjuvant effects of LPS in vivo, these findings suggest that a mature B lymphocyte population is not required for these effects and support the role of the macrophage in the mediation of LPS-induced lethality and adjuvanticity.


Persistent activity of suppressor cells in T cell-mediated immune response. Tolerance to dinitrochlorobenzene contact sensitivity induced i.v. injection of dinitrobenzenesulfonic acid in guinea pigs is a long-lasting phenomenon (up to 1 year). The tolerogen, however, was traceable in the circulation only up to 3 months after its application. In spite of that, tolerance was adoptively transferred by parabiosis 6 months after being induced. Moreover, active suppressor cells eliminated by cyclophosphamide treatment are able to regenerate in those adoptively tolerized animals. These results indicate that the tolerogenic injection stimulates precursors of suppressor cells to generate active suppressor cells and memory cells of suppression. The further formation of active suppressor cells from memory cells seems to be tolerogen independent, but the existence of specific stimulator cells for suppression may be considered. These cells may bind undetectable small amounts of tolerogen. The recovery of suppression might, however, be also due to recovery of suppressor cells which were temporarily inactivated but not destroyed by cyclophosphamide treatment.


Fc-receptors for IgG and IgM immunoglobulins on human T lymphocytes: mode of re-expression after proteolysis or interaction with immune complexes. The susceptibility to proteolysis and the mode of re-expression of receptors for IgM or IgG present on two different subpopulations of human T lymphocytes (T.M and T.G cells, respectively) have been investigated. The IgM receptor was highly susceptible to both trypsin and pronase, whereas the IgG receptor was resistant to trypsin and sensitive only to high concentrations of pronase. The receptors have been removed by treating purified human T cells with pronase and their reappearance on the cell surface has been followed in vitro. The IgM receptors on the cell surface were detectable within 2 hr and the resynthesis was completed in 6 hr. IgG receptors were detectable in 4 to 6 hr and the resynthesis completed within 12 hr. When protein synthesis was inhibited by culturing the cells in the presence of cycloheximide for up to 12 hr, only the IgM receptor (which had a higher turnover rate) failed to be expressed. Whereas interaction of IgG immune complex with the IgG receptors was previously shown to induce a modulation of the receptors, contact with antigen-IgM antibody complexes did not alter the mode of expression of IgM receptors.


Activation of a human T cell subpopulation bearing receptors for autologous erythrocytes by concanavalin A. Human lymphocytes from different lymphoid organs were examined for rosette formation with autologous erythrocytes. The autorosette-forming cells (A-RFC) were shown to belong to a T cell subset including less mature lymphocytes. When normal human peripheral blood lymphocytes were stimulated with low doses of the plant lectin concanavalin A (Con A), in the presence of autologous plasma, the A-RFC levels were strongly enhanced. This response gave rise to two peaks: the first one coincided with the peak of thymidine incorporation but the maximum increase occurred 5 or 6 days later when the proliferative response was impaired. Depletion of A-RFC before stimulation with Con A led to a clear-cut decrease in autorosette levels at both peaks of the response. It is concluded that Con A, generally used for polyclonal activation against heteroantigens, may also result, in terms of A-RFC marker, in expansion of an autoreactive T cell population.


Identification of T and B lymphocytes in pigs by combined E-rosette test and surface Ig labelling. A procedure for combining labelling of B lymphocytes with [125I]anti-Ig-antibodies and E-rosetting is described which permits simultaneous detection of B lymphocytes and T lymphocytes. Pig lymphocytes were incubated with iodinated anti-Ig antibodies and the E-rosette test with SRBC was performed. E-rosettes appeared stable after methanol fixation of cell smears on agarose-coated slides and treatment for autoradiography on stripping films. The percentage of cells classified as B or T lymphocytes in pig peripheral blood closely resembles that in man. No doubly marked cells were demonstrated provided cells were classified as E-rosettes only when 5 or more red cells were attached.


Potentiometric investigations of antigen-antibody and enzyme-enzyme inhibitor reactions using chemically modified metal electrodes. The electrical potential between an immunoreactive electrode and a reference electrode in a buffer solution was studied. The immunoelectrode was made of titanium wire, on which an antigen or an antibody was chemically fixed. The electric potential of the electrode sensitized with anti-hCG gamma-globulin shifted in the positive direction in the presence of a small amount of hCG in the solution. On the other hand, the potential of the hCG-sensitized electrode ran in the negative direction upon addition of anti-hCG to the buffer solution. Similar changes in potential were observed between trypsin and its inhibitor, aprotinin. Kinetic analysis was made for the reactions between these species and the change in potential was explained by a simple charge transfer model.


Genetic polymorphism of serum alpha-1-protease inhibitor (alpha-1-antitrypsin): Pi i, a deficient allele of the Pi system. The microheterogeneity of the I allele of the Pi system of APi (alpha-1-antitrypsin) was studied in 43 individuals with the new PAGIF technique. The unique aspect of the I allele product (unequal distribution of bands 4 and 6), previously demonstrated with acid-starch gel, was confirmed. In addition, two subtypes of the  Pi I allele--I1 and I2--were clearly distinguished. Serum concentrations of APi associated with the expression of the I allele were significantly decreased (68% of normal values) and thus very similar to those associated with the expression of the S allele. This indicates that the I allele can be considered as a "deficient" allele of the Pi system.


Requirement for hexose, unrelated to energy provision, in T-cell-mediated cytolysis at the lethal hit stage. The requirement for D-glucose in T-cell-mediated cytolysis was studied using mouse spleen cells sensitized against alloantigens in vitro. Glucose was required for cytolysis: (a) cytolysis proceeded in a simple buffered salt solution containing Ca++ and Mg++ (low phosphate-buffered saline, LPBS) in the presence but not in the absence of added glucose; (b) 2-deoxy-D-glucose blocked cytolysis. The block by this agent was overcome by excess glucose added as late as 40 min after the inhibitor. This block was not due to inhibition of NADP reduction, since 2-deoxy-D-glucose failed to interfere with the rate of CO2 production by the pentose cycle which we found to be of significant activity in sensitized spleen cells; (c) dialyzed fetal bovine serum (DFBS) in LPBS supported cytolysis in the absence of added glucose. However, 2-deoxy-D-glucose was also inhibitory under these conditions, suggesting that carbohydrate was required here as well. Further results supported the conclusion that DFBS was not acting as a direct source of the required carbohydrate. The relationship between cytolysis, glucose requirement, and provision of energy was studied. As little as 0.1 mM D-glucose in LPBS supported cytolysis. At this glucose concentration, there was no measurable accumulation of lactate in sensitized spleen cells, but Krebs cycle activity was detectable. In 3 mM glucose or above, the range covered by standard tissue culture media, anaerobic glycolysis became a major source of energy in sensitized spleen cells. Consequently, it appears that in standard tissue culture medium, effector cells can generate sufficient energy for cytolysis either by aerobic or anaerobic metabolism. However, the addition of an energy source alone in the absence of glucose was insufficient to support cytolysis in LPBS. Pyruvate in LPBS did not support cytolysis but was shown to be a good substrate for aerobic metabolism in sensitized spleen cells. Glycogenic amino acids and glycerol also failed to support cytolysis. The stage of cytolysis at which glucose is required was investigated. Glucose was necessary for the calcium-dependent lethal hit phase, but not for the cytochalasin A-blockable recognition stage, nor for 51Cr release from injured target cells. Models for the lethal hit process are discussed, which are compatible with the observed requirement for certain hexoses unrelated to their capacity to serve as sources of energy.


Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. NZB/NZW F1 mice of both sexes were castrated at 2 wk of age and implanted subcutaneously with silastic tubes containing either 5-alpha-dihydrotestosterone or estradiol-17-beta. Mice receiving androgen showed improved survival, reduced anti-nucleic acid antibodies, or less evidence of glomerulonephritis as determined by light, immunofluorescent, and electron microscopy. By contrast, opposite effects were observed in castrated mice receiving estrogen. Intact male NZB/NZW F1 mice received androgen implants at 8 mo, an age when they develop an accelerated autoimmune disease associated with a decline in serum testosterone concentration. Such treated mice had improved survival and reduced concentrations of antibodies to DNA and to polyadenylic acid (Poly A). Prepubertal castration of male NZB/NZW F1 mice results in an earlier appearance of IgG antibodies to Poly A. This effect of castration was prevented if neonatal thymectomy was also performed.


In vitro induction of cytotoxic effector cells with spontaneous killer cell specificity. The present work shows that stimulation of peripheral blood lymphocytes with autologous or allogeneic B-cell lines leads to a strong induction of cytotoxic effector cells with spontaneous killer (SK) cell specificity, apart from the specific response directed against the particular stimulating cell. To demonstrate this we have determined a relative target cell specificity in the SK system, defined by the short-term 51Cr release assay, and established a relative specificity index (RSI). Using this approach we have been able to show that killer cells induced during a 5-day cocultivation period with B-cell lines have a similar PSI to that of unstimulated SK cells. In addition, we have shown that such killer cells can be induced from several different lymphocyte subpopulations and that they, in contrast to SK cells, do not express Fc receptors. The implications of these findings in relation to the nature, mechanism, and biological significance of the SK cell system is discussed.


The switch from IgM to IgG secretion in single mitogen-stimulated B-cell clones. The frequency of mitogen-reactive B cells yielding an IgG plaque-forming cell (PFC) response has been determined in vitro by limiting dilution analysis under culture conditions which allow every growth-induced B cell to grow and mature into a clone of Ig-secreting cells. The frequencies of lipopolysaccharide (LPS)-and lipoprotein-reactive precursors for IgG-secreting cells in the spleen of 6--8 wk old C3H/Tif and of C57BL/67 mice were found to be between 1 in 30 and 1 in 40 B cells and, therefore, only one tenth of the frequencies of mitogen-reactive precursors of clones secreting IgM. All IgG-secreting cells developed by switching in clones which previously contained IgM-secreting cells. This was shown in two experiments where the total number of mitogen-reactive precursor yielding IgM-secreting cell clones was limited such that 82 or 90% of all responding cultures originated from one precursor. Thus, of 480 cultures in the first and 720 cultures in the second experiment, 86 and 98 cultures were found positive, yielding IgM-secreting cells at day 5. When the same cultures were assayed at day 7 for IgG-secreting cells 9 and 10 cultures were found positive. All 19 cultures with IgG-secreting cells previously had contained IgM-secreting cells. The probability that IgG-secreting cells and IgM-secreting cells would have arisen from independent precursors can be calculated using Fisher's exact test of independence. For the two experiments those probabilities are 3.4 X 10(-7) and 4.0 X 10(-9). Since we have previously shown that each cell in a mitogen-stimulated, growing B-cell clone divides, and that each dividing cell secretes Ig, we conclude from these experiments that the large majority--in our experiments all--of the IgG-secreting cells in mitogen-stimulated B-cell clones develop by switch from IgM-secreting cells. IgG-secreting cells develop either early or late during growth of a single IgM-secreting cell clone. The switch to IgG secretion, therefore, is not fixed in the time of clonal growth after mitogenic stimulation.


Cellular and molecular requirements for X-linked, hapten-specific B-cell blockade in CBA/N mice. CBA/N mice, a mutant CBA subline, harbor an X-linked B-cell defect which prevents them from mounting immune responses to certain thymic-independent antigens such as pneumococcal polysaccharides and haptenated-Ficoll derivatives. These mice and the hybrid male progeny of CBA/N females are also exquisitely sensitive to a hapten-specific blockade of their otherwise adequate immune responses to thymic-dependent antigens such as N-2,4-dinitrophenylated-hemocyanin (DNP-KLH). As little as 10 ng of a DNP-Ficoll conjugate given 2 h before immunization with a 5,000-fold greater dosage of DNP-KLH, virtually abolishes the 4th-day direct plaque-forming cell (PFC) response specific for DNP. Responding hybrid (CBA/N x C3H/HeN) female mice are resistant to such blockade even at DNP-Ficoll dosages increased by three orders of magnitude. The DNP hapten and Ficoll must be chemically joined for this blocking effect to occur, and increasing the hapten derivatization of Ficoll increases its blockade-invoking capacity. Significant blockade can be produced by administering DNP-Ficoll as early as 4 days before or as late as 4 h after immunization with DNP-KLH. All currently available data point to the defective B cell as the target of this hapten-polysaccharide-mediated blockade. Mice bearing B memory cells, however, are refractory to such blockade. In addition, DNP-Ficoll injections which cause virtually total blockade of 4th-day primary direct PFC responses to DNP-KLH have little or no effect on the development of DNP-reactive B-cell memory measured at either 8 or 30 days. These findings suggest very different blockade susceptibilities for B cells or their precursors at various stages of differentiative development. Our findings also lead to the formulation of testable hypotheses regarding the mechanism of this selective B-cell blockade phenomenon.


Antigen requirements for induction of B-memory cells: studies with dinitrophenyl coupled to T-dependent and T-independent carriers. Mice were primed with dinitrophenyl (DNP) (trinitrophenyl, TNP) coupled to thymus-independent (TI) or thymus-dependent (TD) carriers. B cells from these mice were transferred to irradiated recipients with T cells from keyhole limpet hemocyanin (KLH)-primed mice. After secondary immunization with DNP-KLH a significant DNP-specific IgG memory response was produced only by mice which received B cells which had been primed with TD antigens. TI antigens were unable to induce differentiation of B-cell precursors to IgG producing memory B cells but they did not suppress the induction of B-memory cells by TD antigens. The results indicate that TI antigens fail to activate a cell type which is required for the induction of memory B cells.


Restricted helper function of F1 leads to parent bone marrow chimeras controlled by K-end of H-2 complex. F1 leads to parent bone marrow chimeras were prepared by transferring F1 hybrid marrow cells into heavily irradiated parental strain mice. When unprimed, donor-derived F1 T cells from the chimeras were activated to sheep erythrocytes (SRC) for 5 days in irradiated normal F1 mice, high IgM and IgG anti-SRC responses were observed with F1 B cells, and with B cells H-2-compatible with the strain in which the T cells were raised from stem cells. Significantly, however, responses with B cells of the opposite parental strain were either absent or very low. The restriction in T-helper function mapped to the K-end of the H-2 complex and could not be attributed to active suppression.


Hematopoietic thymocyte precursors: IV. Enrichment of the precursors and evidence for heterogeneity. A method has been developed for the enrichment of the hematopoietic precursors of thymocytes from spleen and bone marrow cells. Up to 40-fold enrichments were obtained resulting in preparations in which as few as 10(5) cells produced prompt repopulation of the thymus of an irradiated mouse. Precursor cells from bone marrow appear to contain the enzyme terminal deoxyribonucleotidyl transferase (Tdt), an agent suggested as a potential somatic mutator. This enzyme (Tdt) was not detectable in any spleen cell preparation examined, including one in which a 40-fold enrichment of thymocyte precursors had been produced. This is the first difference reported between the splenic and bone marrow precursors of thymocytes.


Wound healing in tadpole tailfin pieces in vitro. Explants of tail fins from R. catesbeiana tadpoles undergo reepithelialization of their cut surfaces (healing) when cultured in vitro in Hanks' balanced salt solution at 22 degrees C. Healing is initiated early and closure of the wound is complete by 12 to 24 hours. Morphogenesis continues for several days as further reorganization and migration of epidermal cells from the regions adjacent to the wound margins take place. The addition of serum to the culture media improves the general appearance of these tissues and promotes healing. The rate of healing is affected by temperature. Tail fins maintained at 10 degrees C do not heal while fins maintained at 30 degrees and 37 degrees, although healing more rapidly than at 22 degrees, undergo progressive degeneration in culture. Epidermal cell movements were also studied in explants consisting of a combination of intact tail fin plus tail fin deprived of its epithelium. Rapid and extensive migration of epidermal cells from the intact tail fin across the collagen lamella of the stripped fin is observed.


Contrast-enhanced lesions on computerised tomography in multiple sclerosis. Two patients are described in whom computerised tomography revealed contrast-enhanced lesions in the early stages of multiple sclerosis. Such lesions may be differentiated from tumours by their transient nature, lack of space-occupying effect, and localisation in the white matter. Contrast enhancement in demyelinating disease is probably related to local breakdown of the blood-brain barrier.


Determination of cerebrospinal fluid shunt function with water-soluble contrast medium. Determination of cerebrospinal fluid shunt patency with water-soluble contrast medium is a simple, rapid, reliable, and safe technique. Since September, 1974, the authors performed 113 examinations. With the Spitz-Holter valve, only the atrial catheter can be studied, but, with the Pudenz valve and with the shunting devices that have a double-dome reservoir, both the proximal and the distal catheter can be visualized. Through the ventricular catheter a full ventriculographic study can be made, demonstrating ventricular size, malposition of the catheter, and the lesion that caused the hydrocephalus, or its evolution. The problem of collapsed ventricules, in which clinical and "manual" evaluation of the flushing device can give misleading findings, is emphasized. The injection of the atrial or peritoneal catheter in the pathological cases demonstrated its blockage, level of disconnection, malposition, sleeve, or cyst formation. Computerized tomography has only slightly decreased the number of these studies: when the ventricles are large, the examination with water-soluble contrast medium is still needed to demonstrate the exact level of malfunction. This demonstration has decreased the number of the total revisions complete changes of shunting systems, eliminating some unnecessary changes of normally functioning catheters.


Evidence that serotonin mediates some behavioral effects of amphetamine. In the rat, d-amphetamine sulfate (15--80 mg/kg) causes numerous behavioral effects including simultaneous side-to-side head weaving or head tremor, forepaw padding and splayed hindlimbs. These signs are strikingly similar to a behavioral syndrome caused by intense serotonin (5-HT) receptor activation. Experiments were designed to determine whether some of the numerous effects of amphetamine on behavior can be ascribed to actions of the drug on 5-HT mechanisms. Catecholamine depletion with alpha-methyl-p-tyrosine did not prevent the amphetamine syndrome. However, 5-HT depletion with 5,7-dihydroxytryptamine or with p-chlorophenylalanine did prevent the syndrome. The degree of syndrome inhibition by p-chlorophenylalanine was correlated with the extent of 5-HT depletion. Normal responsiveness to amphetamine in p-chlorophenylalanine-treated rats was restored by 5-hydroxytryptophan, the precursor of 5-HT. Furthermore, methysergide, a 5-HT receptor blocker, prevented the amphetamine syndrome, whereas catecholamine blockers, phenoxybenzamine and pimozide, were ineffective. The results suggest that when amphetamine causes the signs of the syndrome it does so by activating 5-HT receptors in the brain, probably by displacement of endogenous 5-HT.


Distribution of T-lymphocytes and B-lymphocytes in peripheral blood and effusions of patients with cancer. The relative distribution of T- and B-lymphocytes in the blood and in pleural or abdominal effusions was compared among 24 patients with fluid accumulation due to metastatic cancer and 8 patients without evidence of cancer. The data obtained indicated that the mean percentage of T-lymphocytes in malignant effusions was significantly greater than that in the peripheral blood of the same patients. At the same time, the mean eprcentage of B-lymphocytes was decreased in malignant effusions when compared with peripheral blood. Neither of these differences was observed when effusions and blood of patients with nonmalignant effusions were compared. In addition, patients with both types of effusions had fewer total lymphocytes in their blood than did normal control patients, whereas those with cancer-associated effusions had an increased proportion of active T-lymphocytes in their blood.


Acute lymphocytic leukemia-associated cell membrane antigen. Antisera were raised in New Zealand White rabbits against non-B, non-T acute lymphocytic leukemia (ALL) cells coated with antilymphocyte serum. Following minimal absorption with chronic lymphocytic leukemia (CLL) cells, the antiserum reacted mainly with non-B, non-T ALL cells. The following numbers of patients had leukemia cells that reacted with the ALL antisera: 13 of 18 with ALL, 3 of 27 with acute myelocytic leukemia, 1 of 8 with chronic myelocytic leukemia (CML), and 0 of 12 with CLL. The positive CML was a patient in CML blast crisis. Normal peripheral blood B- and T-lymphocytes and normal bone marrow were negative. Reactions of the anti-ALL serum (136K) were compared with the reactions of a rabbit anti-B-cell antiserum (63K) that reacted with approximately 70% of leukemia cells. Cultured lymphoblastoid cell lines from normal donors were negative by both cytotoxicity and immunofluorescence tests. However, by immunofluorescence testing, 8 of 17 known malignant lines from a variety of lymphoproliferative disorders were positive; 4 of these lines were of T-cell origin. By immunoprecipitation and polyacrylamide gel electrophoresis, the ALL antigen appeared to consist of a single polypeptide chain of approximately 98,000 daltons. The anti-ALL antiserum was not cytotoxic for normal myeloid stem cells (colony-forming units).


Cellular and molecular toxicology of lead. II. Effect of lead on delta-aminolevulinic acid synthetase of cultured cells. The effect of lead nitrate on delta-aminolevulinic acid synthetase (ALA synthetase), the first and rate-limiting enzyme of the heme biosynthetic pathway, was studied by using an established rat liver cell line (RLC-GAI). Lead was shown to produce a time-dependent increase in ALA synthetase activity, with a maximum after incubation of the cells for 24 h with 10(-5) M lead nitrate. The effect of lead was not liver-specific in that increases in enzyme activity were produced in other tissue-derived cell lines. Cycloheximide but not actinomycin D, cordycepin, or hydroxyurea, at concentrations that inhibit the synthesis of protein, RNA, and DNA, prevented the lead-associated increase in ALA synthetase activity. Heme, added to the cells as hemin, also prevented the effect of lead. These results indicate that lead induced the synthesis of ALA synthetase secondary to an inhibition of the synthesis of heme.


Reappraisal of low-velocity gunshot wounds of the aorta and inferior vena cava in civilian practice. Eighteen low-velocity gunshot wounds of the abdominal aorta and inferior vena cava were analyzed. Injury to the aorta and inferior vena cava occurred in 9.2% of all penetrating abdominal injuries due to gunshot wounds in our series. The mortality rate was 33% for the suprarenal and 25% for the infrarenal inferior vena cava, 50% for the infrarenal aorta, 100% for the suprarenal aorta and for the combined injuries. Control of active bleeding is more closely related to survival than any other single factor.


Preoperative propranolol therapy and aortocoronary bypass operation. The relationship between long-term propranolol hydrochloride therapy and subsequent coronary bypass operation was prospectively investigated in 119 patients who were grouped three ways: propranolol therapy continued in full dosage to operation (group A), propranolol therapy discontinued or tapered 24 to 72 hours preoperatively (group B), and no preoperative propranolol therapy (control group). During preoperative hospitalization, one patient in each group A and the control group suffered an increase in anginal symptoms compared with 15 patients in group B, three of whom also had new ventricular arrhythmias. During anesthesia up to the period of cardiopulmonary bypass, 26% of group A patients showed signs of ischemia (eg, ST segment deviation or ventricular arrhythmias) as compared with 51% of the control group and 70% of group B. Hypotension and bradycardia were not more common in group A patients. No differences among groups were noted in case of emergence from bypass, need for cardiac stimulants, or mortality.


Specificity of anti-human IgG antibodies in antiglobulin (Coombs) sera. The agglutination test with latex particles coated with aggregated human IgG was introduced into the evaluation of Coombs serum as an additional test for anti-IgG antibody activity. In Coombs sera prepared by the conventional immunization method employing Freund's adjuvant, latex agglutination titers were found much lower than those of anti-D-coated red cell agglutination. On the other hand, in sera prepared by other immunization methods, such as the one according to Haynes and Chaplin (1971), anti-IgG antibody response was readily observed by IgG-coated latex agglutination. Specificity of anti-IgG antibodies in the latter sera seems to be predominantly directed to aggregated human IgG.


An improved cannulation technique for prolonged blood sampling of the American bullfrog. A T-cannula was used to collect serial blood samples from the sciatic artery of the American bullfrog (Rana catesbeiana). The horizontal arm of the cannula was implanted in the artery and the vertical arm employed to collect blood samples. The T-cannula allowed blood flow to continue in the cannulated artery and provided long-term, repetitive blood samples from conscious, caged, but otherwise unrestrained and undisturbed animals. The cannula functioned for at least 14 days, the maximum period investigated. Athough developed for studies on amphibians and reptiles, the technique appeared to be applicable, with appropriate modifications, to a variety of small animals.


Tissue localization of T-lymphocytes by the histochemical demonstration of acid alpha-naphthyl acetate esterase. Nonspecific acid alpha-naphthyl acetate esterase (ANAE) activity has previously been evaluated with the sheep erythrocyte (E) rosette assay and found to be a useful T-cell marker in cell suspension studies. T-lymphocytes display a solitary red brown nodule of reaction product (T-pattern) which can be readily distinguished from the diffuse, cytoplasmic staining of monocytes (M-pattern). Freshly obtained human tissue blocks were fixed with buffered formal sucrose and maintained in Holt's syrup; cryostat sections were cut and incubated under conditions appropriate for the histochemical demonstration of lymphocyte acid alpha-naphthyl acetate esterase activity. The results clearly demonstrate that T-pattern ANAE+ lymphocytes populate the paracortical and interfollicular regions of normal lymph nodes and tonsils and the periarteriolar sheaths of normal spleen, T-cell zones, while nearly every germinal center (B-cell area) lymphocyte is ANAE-. Macrophages and dendritic reticulum cells display diffuse cytoplasmic ANAE activity (M-pattern). Nodular malignant lymphomas (B-cell origin) are ANAE-; an E+ diffuse, cutaneous lymphoma was ANAE+. The histochemical demonstration of ANAE activity may represent the first reproducible, routine technique to localize T-lymphocytes in tissue sections.


Evaluation of lactate dehydrogenase isoenzyme patterns in serum of patients undergoing cardiac surgery. Serial determinations of serum lactate dehydrogenase (LD) isoenzymes were performed in 50 patients undergoing cardiac surgery for coronary artery bypass and heart valve replacement. A sequence of LD isoenzyme patterns was established in the patients with uncomplicated recovery. These patterns served as controls for the detection of abnormal patterns associated with clinical complications. Perioperative myocardial infarction was detected in seven patients by a characteristic reversal of the LD1:LD2 ratio. These studies established that accurate determination of LD isoenzymes improved their diagnostic specificity. These isoenzymes were determined by (1) using the same technique for tissues and for serum samples, (2) applying a volume of serum containing a standard amount of enzymatic activity, and (3) making a clear separation, which allows accurate quantitation. This test can provide useful information to the surgeon for the evaluation of operative procedures and to the clinician for the appropriate management of the patient undergoing cardiac surgery.


Aortic valve replacement in von Willebrand's disease. A patient with von Willebrand's disease having aortic valve replacement was managed with cryoprecipitate infusions and monitoring of factor VIII levels. This disorder is associated with low factor VIII levels and abnormal platelet function. There may be no history of bleeding, as the severity of the bleeding tendency varies greatly and fluctuates temporally. The partial thromboplastin time is frequently prolonged, but more detailed studies are necessary to establish a diagnosis (bleeding time, platelet adhesiveness to glass beads and ristocetin, von Willebrand's antigen, ristocetin-von Willebrand's factor, and factor VIII clotting activity). Elevation of factor VIII levels to 50 to 100% of normal allows adequate clotting and is best accomplished with cryoprecipitate or fresh frozen plasma rather than commercial concentrates of factor VIII, whose activity is unpredictable.


Changes in T cell population in patients with bronchogenic carcinoma. Absolute numbers of T cells were measured in a series of 84 patients with bronchogenic carcinoma and were compared with T cell percent with regard to clinical stage, course, and histologic type. Although T cell percent declined in accordance with the advancement of stage, the differences between the stages were not statistically significant. On the other hand, the absolute number of T cells decreased prominently in Stages III and IV as compared to Stages I and II (p less than 0.05 between Stages I and III, P less than 0.001 between Stages I and IV, and p less than 0.05 between Stages II and IV). Likewise in patients who were followed serially after resection, the absolute number of T cels correlated well with the postoperative course. These results lead us to the conclusion that it is more useful estimate the absolute T cell count rather than T cell percentage in lung cancer.


The rheumatologic manifestations of diabetes mellitus. The rheumatologic disorders associated with diabetes mellitus have been reviewed. From the evidence presented, it can be concluded that neuroarthropathy and osteolysis are definitely assoicated with diabetes. Ankylosing hyperostosis and periarthritis probably represent valid associations, and possible, but still unproven associations exist for gout, pseudogout, the carpal tunnel syndrome, osteoarthritis, Dupuytren's contracture and joint contractures. Despite the lack of a proven pathophysiologic basis these interrelationships may be clinically relevant. The discovery of one of these disorders may provide a clue to underlying glucose intolerance, and idabetics should be followed with the knowledge that they are at risk for the development of certain musculoskeletal problems.


Morphological reaction in transplanted small intestines using immunogenetically defined rat strain combinations. From the inbred rat stains F344, LEW and Brown-Norway (BN), the following combinations were formed: syngeneic (LEW--LEW), weakly allogeneic (F344--LEW) and strongly allogeneic (BN--LEW). A small intestine segment was transplanted using the by-pass technique; after 10 days the graft was removed and histologically investigated. The strongest rejection was found in the lymphatic tissue and the epithelium of the small intestinal transplant. The immunogenetical difference is significant for the survival of the graft: the greater the immunogenetical difference between donor and host, the more severe the morphologically demonstrable rejection reaction.


[The effect of bencyclane, flunarizine and naftidrofuryl on a calorically induced long time nystagmus (author's transl)]. The method of a calorically induced long time stimulation is shown. Appr. 15 minutes after begin fo stimulation a nystagmus plateau can be observed. We used this plateau to demonstrate the effects of three cerebral vasoactive drugs--Bencyclane, Flunarizine and Naftidrofuryl-Hydrogenoxalate in a randomized double blind study. All of them depressed the nystagmus significantly. Naftidrofuryl by 38.4 +/- 4.6%, Flunarizine by 31 +/- 4.5% and Bencyclane by 25.1 +/- 3.8%. The depressing mechanism of Flunarizine is partly due to sedation.


Degradation and clearance of methotrexate in children with osteosarcoma receiving high-dose infusion. Plasma methotrexate (MTX) concentrations were quantitated in 34 patients after 127 high-dose (35--350 mg/kg) infusions with citrovorum factor rescue. Significant linear correlations have been obtained between methotrexate dosage and concentrations in plasma at 6 and 24 hours after the initiation of the therapy. However, similar trends have not been observed when 48- and 72-hour samples were analyzed. Clinical toxicity was not serious when the methotrexate level in plasma was less than 4.5 X 10(-6) M at 48 hours after the start of a six-hour infusion in children. A minimal four-hour steady-state methotrexate plasma level can be maintained during a six-hour infusion. Children excrete methotrexate at a faster rate than adults; the half-life of MTX during the first phase of plasma clearance curve is one hour shorter in children. Urinary analyses have indicated that substantial methotrexate is metabolized. The chemical nature of these components has not been identified. Further, the urinary metabolic profiles varied among patients.


[The importance of echography in the differential diagnosis of renal insufficiency (author's transl)]. Experience with echographic investigation of the kidney and the urinary efferent system in the diagnosis of renal insufficiency is reported. Taking into account a number of criteria (size, differentiation from the surrounding tissues, position of the kidney in relation to neighboring organs and to the body surface, mobility or change of shape on respiration, on altehe evaluation of the nephroechographic findings an attempt is made to rationalize the applicatinon of further diagnostic measures. The method is recommended both for the initial diagnosis of renal insufficiency and for the supervision of patients with confirmed renal insufficiency.


Electrical brain stimulation for the control of chronic pain. An implanted brain stimulation system can be used for control of chronic intractable pain that is unresponsive to other forms of treatment. A trial period of temporary stimulation first determines whether a patient is likely to benefit from a permanent implant. Success has been achieved in the majority of patients, although technical problems have necessitated repairs.


[Measures for prevention of hospital-acquired infections of the urinary tract. Local antibiotics: yes or no? (author's transl)]. The most important measures for prevention of hospital-acquired urinary tract infections are: sterility when passing catheters, daily catheter care, careful disinfection of hands before manipulation of the catheter system, closed urine drainage systems. When using closed urine drainage systems whose continuity must never be interrupted, rinsing with local antibiotics is unnecessary.


[Short-term and long-term therapy with slow-release ISDN. Echographic, vector cardiographic and ergometric findings (author's transl)]. The effect of slow-release isosorbide dinitrate (Maycor retard) on the myocard was investigated in a short-term study (single dose of 20 mg slow-release ISDN) and in a long-term study (2 X 20 mg slow-release ISDN daily) in 10 patients with coronary heart disease. The parameters assessed were heart rate, blood pressure and skin temperature at rest, load ECG, orthogonal ECG and VCG by computer and UCG echocardiography. The reductions of diastolic and systolic ventricular diameter are statistically significant in the short-term and long-term trials. The ejection time decreases. The velocity of circumferential fiber shortening as a measure of myocardial contractility increases highly significantly. R peak and T wave amplitude in the Y lead change significantly. These findings can be interpreted as an expression of improved myocardial tension and a normalization of the contraction and relaxation.


[Studies on the antihypertensive effect of metoprolol in practice. Results of a cooperative study by 1296 general practitioners (author's transl)]. A study with the beta1-selective adrenergic receptor blocker metoprolol in general practice was carried out by 1296 practitioners and internists. The results in 10.088 hypertensive patients were analyzed with regard to 1.9 million separate data. 200 mg metoprolol lowered the blood pressure by 25/12 mm Hg, the pulse rate fell by an average of 8 beats per minute within 6 weeks. Metoprolol was well tolerated and the relatively rare side-effects decreased in the course of the 6 weeks' therapy.


[Orthopedics in infancy (author's transl)]. Early diagnosis and treatment is of decisive importance for the prognosis of many orthopedic diseases in infancy, especially of congenital skeletal lesions. Taking as examples deformities of the foot, hip dysplasia and luxation and infantile scoliosis, the principles of diagnosis and guide lines for therapy are indicated. Diseases of the locomotor apparatus can be considerably improved and late lesions to a great extent prevented by early recognition and treatment combined with good interdisciplinary cooperation.


[Epicondylitis of the humerus (author's transl)]. Principles of Treatment and Results after Hohmann's Operation: The method of clinical examination and rational conservative measures including physiotherapy are discussed in the light of the literature and the results of a cooperative study. To summarize briefly it may be said that conservative therapy should first of all be completely exhausted. Local injections of a corticosteroid should not exceed 3 and at most 6. If conservative therapy is unsuccessful after 4 months, operation is indicated and the extended Hohmann operation performed.


[Sport injuries due to squash. Epidemiology and prevention (author's transl)]. A statistical collection of squash injuries in 8000 players from 30 squash centers in the Federal Republic of Germany over a 12 months period is presented and evaluated. The comparison with other types of sport shows squash to be sooner likely to cause injuries than tennis, but to entail essentially less injuries than e.g. football or handball. With a view to prevention, certain demands must be made on the player as regards his manner of playing and equipment, but also as regards the ground conditions of squash halls.


[Vitamin D deficiency in femoral neck fractures (author's transl)]. In a therapeutic trial 20 patients with femoral neck fractures (FNF) were treated alternatively without supplemental vitamin D, calcium and phosphate or with 15 000 I.U. vitamin D2, 500 mg Ca++ and 560 mg of phosphate daily. Within two weeks, 25-OH-D in serum increased in patients with supplementary therapy. It is concluded that in the German Federal Republic, vitamin D deficiency is frequently found in the elderly during the winter months and that vitamin D deficiency could be important for the development of FNF.


[Hormonal contraception for adolescents? (author's transl)]. Pregnancy in adolescence is seldom planned. If an adolescent girl comes to the doctor with a pressing desire for hormonal contraception, the many risks must be weighed against each other. Endocrinologically the "post-pill amenorrhea" and later reduced fertility are quantitatively of little importance. Developmentally and psychologically the danger of delayed growth as a result of the steroids present in the ovulation inhibitors is small. It is particularly important to weight the perinatal risks of an unwanted pregnancy against the risks of a hormonal contraceptive. Among the psychosocial factors impaired development of personality is prominent. Altogether, an unwanted pregnancy carries considerably more risk for an adolescent girl than hormonal contraception.


[The effect of the female biological sexual rhythm on the time of the first cerebrovascular insult (author's transl)]. The relationship between the first cerebrovascular insult and estrogen production in the three sexual phases was investigated in 79 women treated in hospital. 46 women age about 14.7 years at the time of the menarche were affected at 69.5 years; 78 women who began the menopause at about 48.2 years fell ill at about 69.3 years on the average; the duration of fertility was determined at about 33.9 years in 45 women, their first illness due to cerebrovascular insult occurred at 69.3 years. No relationship could be established between the onset of menarche or menopause, or the duration of fertility and the age at the first cerebrovascular insult.


B-lymphocyte alloantigens associated with systemic lupus erythematosus. We examined B-lymphocyte alloantigens in 41 patients with systemic lupus erythematosus and 184 controls, using a panel of 47 pregnancy serums, and compared reaction frequencies of individual serums. One serum, la-715, reacted with B lymphocytes from 75.6 per cent of patients and 14.1 per cent of controls (Pc less than 0.005, relative risk 18.8). Twenty-eight of the patients were also typed with a panel of HLA-D-related serums from the Seventh International Histocompatibility Workshop, HLA-DRw types assigned, and compared to 490 Workshop controls. Both HLA-DRw2 (57.1 per cent vs. 26.4 per cent, Pc less than 0.004) and HLA-DRw3 (46.4 per cent vs. 22.2 per cent, Pc less than 0.03) were increased in systemic lupus erythematosus. This study demonstrates that select B-lymphocyte alloantigens, which are controlled by genes in the major histocompatibility complex, are present in increased frequency in systemic lupus erythematosus.


Cellular immunity in Guamanians with amyotrophic lateral sclerosis and Parkinsonism-dementia. To test the hypothesis that host resistance factors may be abnormal in Guamanians in whom amyotrophic lateral sclerosis and Parkinsonism-dementia develop, cellular immunity was evaluated in both diseases and compared to that of Guamanians with other nervous-system diseases, normal adult Guamanians and non-Guamanians with amyotrophic lateral sclerosis and Parkinsonism. Diminished responses to skin-test antigens, lymphopenia, diminished per cent and total T cells and, less frequently, decreased mitogen responses were seen in Guamanian patients with amytorophic lateral sclerosis and Parkinsonism-dementia but not in the other patient or normal groups. Guamanian patients with amyotrophic lateral sclerosis and diminished cellular immunity had an increased frequency of HLA-Bw35 (P less than 0.005) and shorter mean duration of disease (P less than 0.05) than those with normal cellular immunity. In Parkinsonism dementia diminished cellular immunity was less strongly associated with HLA-BW35 (P less than 0.05) and was not associated with differences in duration of disease. Normal Guamanians and those with other nervous-system diseases showed no association of diminished cellular immunity with HLA-Bw35. The association appeared disease-related, with onset concomitant with the neurologic expression of Guamanian amyotrophic lateral sclerosis and Parkinsonism-dementia.


Muscular fatigue investigated by phosphorus nuclear magnetic resonance. Muscular fatigue has been studied using 31PNMR to measure the levels and rates of utilisation of several key metabolites and the free-energy change for ATP hydrolysis. Force development is closely correlated with metabolite levels and is proportional to the rate at which ATP is hydrolysed.


Safety and clinical efficacy.

Safety and clinical efficacy. When applied under the circumstances of minimal patient risk documented in this paper, implanted neuroaugmentive spinal devices are a reasonable means of therapy for selected severe pain problems. With presently developed screening techniques, in 198 patients predominantly suffering from failed back surgery syndrome, a 50% good-to-excellent result was obtained. These figures represent a very significant improvement in the success of treatment for this group of patients when compared to other present modes of therapy. With continued optimization of the use of spinal neuroaugmentive devices, it is likely that clinical success can be further improved in the future.


Chronic stimulation via percutaneously inserted epidural electrodes. Thirty-one patients suffering from intractable pain associated with chronic low back syndrome, cancer, and other disorders have been studied after an average of 6 months of treatment by electrical stimulation of the spinal cord applied using electrodes inserted through a Touhy needle into the epidural space. As judged by three different subjective rating methods, epidrual stimulation successfully relieved otherwise intractable chronic pain in from 23 to 26 of the 31 patients. Reported improvements in the ability to perform various everyday activities, and elimination of drug usage by many patients, corroborated this finding.


Long term results of periventricular gray self-stimulation. Thirty patients were operated upon, with chronic implantation of self-stimulating devices for stimulation of the posterior periventricular gray matter for pain control. Three patients required removal of the electrodes because of failure of adequate pain control during the period of percutaneous testing, and five patients report on long term follow-up that they have had no pain relief with stimulation, and have discontinued it. Four patients describe minor relief of pain, and 18 patients report significant relief of pain with stimulation. Therefore, 18 patients, or 66% of the 27 patients having implantation, are considered to have had successful operations, and 12 of the patients are considered failures. Stimulation for brief periods of time, such as 5 to 30 minutes every 2 to 12 hours has been found adequate for control of chronic pain with minimal side effects and a low complication rate.


Safety and efficacy of chronic stimulation. It is our conclusion that chronic cerebellar stimulation is both efficacious and safe as a therapeutic measure for selected neurological disease. Improvements in patient selection, with patients chosen who are not as incapacitated as those of our first group, showed make this even more apparent. In order to be certain that calibration of the present stimulating equipment is accurate, each such apparatus should be calibrated by the group treating the patient. We no make this a routine aspect of our follow-up re-examinations.


Demyelinating, degenerative, and vascular disease. Fifty per cent of patients diagnosed as having multiple sclerosis, primary lateral sclerosis, or hereditary spinocerebellar disorders were observed to have enduring favorable changes in neurological function during the 15 to 27 months they have been followed. The patients who were the least severely disabled were benefitted the most by the stimulation and made the most rapid progress. For example, the patient having only an ataxic or a spastic gait typically was observed to improve faster than the patient having both an ataxic and a spastic gait. The long term effect of electrostimulation of the spinal cord on these patients is unknown. The purpose of the stimulation is to attempt to obtain an improvement in neurological function so that the patient may experience a better life style. It is not thought that the electrical current has any effect on the basic disease process. Electrostimulation over the posterior spinal roots and spinal cord, although not new, has not been used extensively for the treatment of patients with arterial disease. The patients who have responded the most dramatically to electrostimulation are those with vasospastic disorders. A larger percentage of patients showed a greater response to implanted stimulation than to transcutaneous stimulation. Electrostimulation of the nervous system is not designed to replace standard therapeutic measures of treatment of patients with vascular disease, but to supplement them.


Normal pressure hydrocephalus due to membranous obstruction of the sylvian aqueduct. In a patient presenting with the clinical features of normal pressure hydrocephalus, a membranous obstruction of the aqueduct of Sylvius was demonstrated by combined air encephalography and contrast ventriculography. Ventriculoatrial shunting resulted in clinical improvement without significant change in ventricular size.


Experience with implanted electrodes.

Experience with implanted electrodes. Implant units, manufactured by Medtronic, Inc., have been implanted in 31 patients for treatment of drop-foot. The principal problem encountered in this series was inflammatory reaction. This was observed in seven patients, and was serious enough in five to require removal of the implant. On the positive side, there have been no failures of the implanted equipment for periods of up to 7.3 years, although there is currently a question on one patient. There has also been no documented damage to the nerve from chronic stimulation. Fine wire elctrodes have been implanted intraneurally in a series of animals and in three patients. Preliminary results look encouraging, and this approach seems to hold considerable promise for a new generation of electrode design.


Diaphragm pacing as an adjunct in respiratory insufficiency. Most neurosurgical patients with permanent partial or complete respiratory insufficiency are managed with a mechanical ventilator and tracheostomy. This method presents many medical, technical, emotional, and social problems. A case is presented that illustrates the potential usefulness of electrical stimulation of the phrenic nerve ("diaphragm pacing") as an alternate method of therapy for respiratory insufficiency. This paper outlines the indications for, methods of, and problems with such a system and is intended to make its availability more widely appreciated among neurosurgeons.


[Acid-base metabolism in patients with hepatic cirrhosis treated with portacaval anastomosis at various intervals after the operation]. In a series of 68 cirrhotics subjected to portacaval anastomosis for digestive haemorrhage, alterations in the acid base balance, 3, 6, 12, 24 and 48 weeks after anastomosis, were examined. Following operation, an increase in the incidence of the usual acid base disturbances of liver cirrhosis is observed. Respiratory alkalosis increases with no direct relationship to teh postoperative increase in ammoniemia, the main stimulating agent of the resporatory centres. This is probably because the active fraction on the nerve cells is the non-ionized one only, freely diffusible through the haematoencephalic barrier, the plasma concentration of which is a function of blood pH. Postoperative metabolic alkalosis is secondary to the potassium and chloride depletion consequent on operative trauma, on the malnutrition syndrome and, in the case of potassium, on secondary hyperaldosteronism which, unlike what is observed in the other groups of cirrhotics, is uncorrected by anastomosis. After the shunt, metabolic acidosis may be the expression of an increase in lactates and pyruvates following on further liver function deterioration, and of a functional renal insufficiency which anastomosis makes more manifest.


The initial management of simple febrile seizures. One hundred consecutive cases of simple febrile seizures in childhood were studied. Seventeen of these children had had more than one seizure during the febrile episode, but none of the patients had a further seizure after treatment with simple antipyretic measures. Thus it appears unnecessary to give anticonvulsants to prevent early recurrence of simple febrile seizures.


Haemophilus influenzae amnionitis associated with prematurity and premature membrane rupture. Prematurity and premature rupture of the membranes present major obstetric problems. When associated with amnionitis, the result may be disastrous. A case of Haemophilus influenzae aminionitis in association with premature rupture of the membranes is presented. The rarity of this organism as a causative agent in amnionitis and its possible causative role in premature membrane rupture are considered in review of the scant relevant literature.


CT scan in intraventricular hemorrhage: correlation of clinical findings with computerized tomographic scans of the brain. Twenty-three adults who had evidence of intraventricular hemorrhage were identified, and their charts were reviewed. Thirteen patients died and 10 survived. Eleven of the 13 who died were hypertensive. All had severe neurological deficit and evidence of brain stem dysfunction at the time of admission and progressed rapidly to coma and death. Two of the survivors had periventricular arteriovenous malformations. They presented neurologically intact and remained so. The other eight survivors had a distinct clinical course. They presented with focal deficits and abnormalities of mental status. These persisted, and at follow-up 3 to 20 months later they all had profound deficits of recent memory and intellect, and none was capable of daily self-care. Computerized tomographic (CT) scans were not useful in predicting outcome. The presence of parenchymal clot, multiple chamber involvement, 3rd ventricular involvement, ventriculomegaly, and midline shift were seen in all groups. Illustrative examples are presented.


Lichen planus: immunologic and morphologic identification of the submucosal infiltrate. The purpose of this investigation was to specifically identify T cells, B cells, and histiocytes in the infiltrate typically seen in lichen planus. In frozen tissue sections, AET-treated sheep erythrocytes formed immunologic rosettes with the lymphocytes in the infiltrate, designating them as T cells. Rosette assays with reagent erythrocytes, IgGEA, IgMEA, IgMEAC, and E resulted in nonadherence, indicating a lack of B cells and macrophages, and indirectly implicating them as T cells. Scanning electron microscopy of the cellular infiltrate, in situ, showed that the cells had smooth, nonvillous surfaces. These observations were consistent with a T cell origin and were considered supportive of the immunologic data. The results of this investigation support the hypothesis that lichen planus is a disease mediated by thymus-dependent lymphocytes.


alpha 1-antitrypsin deficiency in early childhood. Among 200,000 infants screened for alpha 1-antitrypsin (alpha 1-AT) deficiency, 125 Pi Z, 48 Pi Z, 1Pi S-, and 2 Pi Z- children were followed up prospectively. Eleven percent of the Pi Z infants had neonatal cholestasis, and at 2 years of age three of them had cirrhosis. About 50% of the asymptomatic Pi Z and Pi Z- subjects occasionally had serum alanine aminotransferase (ALAT) levels above normal, and in 15% of them the levels were probably permanently increased during the first two years of life. Two previously healthy Pi Z children had transient symptoms of liver disease at age 2 years in connection with severe infections. The Pi SZ children had no significant clinical liver disease and only two had abnormal serum ALAT levels. Among Pi Z children up to 2 years of age the following diseases were also encountered: eight had recurrent bronchitis with wheezing, two had persistant cough (both had cirrhosis), one had severe pneumonia, one was mentally retarded, three had urinary tract infections, six had pronounced eczema, one had allergic shock, and three had congenital malformations. Among the Pi SZ children one had recurrent bronchitis, one had eczema, and one had juvenile rheumatoid arthritis. Three children, two Pi Z and one Pi SZ, have died. The Pi Z- and Pi S- subjects were healthy. In conclusion a variety of significant symptoms were observed in about 30% of the Pi Z children compared with 6% of the Pi SZ children during the first two years of life.


Study of foveal tritanopia.

Study of foveal tritanopia. This paper discusses the possibility there is a difference between men and women in foveal tritanopia. The discussion is based on a study carried out by Cobb and McCrossan in 1973 in which they measured the luminosity curves of the fovea in five women and five men. The instrument used was a Wright colorimeter which measured the luminosity curves with a 2 degree 12' field and a 0 degree 12.5' field. Comparison shows a loss of sensitivity to blue for the curve obtained with the 0 degrees 12.5 relative to the curve obtained with the 2 degree 12' field. Male subjects obtained two maxima with the 0 degree 12.5' field, usually at 555 nm and 595 nm, whereas for females on maximum, usually at 555 nm and from 555 nm to the long wavelength end of the spectrum, curves followed loosely the curve obtained with the 2 degree 12' field. Thus, a significant difference was found between the males and the females in their response to the longer wave-lengths when the 0 degree 12.5' (0 degree 12.5') field was used. In addition to this there were also large individual differences in the matching points obtained by the males while the differences among the females were much smaller.


Transient tension responses of voltage-clamped frog atrial muscle related to sudden changes in external Ca or Na. Frog atrial muscle strips were placed in a double sucrose gap chamber and perfusion of the central node was arranged as to allow rapid changes of external Ca or Na concentration during long-lasting (15 s) depolarizing clamps. When the superfusing fluid was suddenly switched, the intercellular space inside the fibre bundle equilibrated with a time constant in the order of 1 s. A fast change of perfusate during clamp was followed by a delayed change of tonic (sustained) contraction. When [Ca]0 was increased from 0.25 to 4 mM, tension rose in a sigmoid manner and the level reached at the end of the clamp was almost identical with the steady control in 4 mM-Ca-Ringer. A similar tension increase occurred upon a reduction of [Na]0 from 100 to 25% of normal. At a given depolarization time course and height of the tension responses followed the ratio of [Ca]0/[Na]20. Transient tension responses are interpreted in terms of a sudden perturbation of a transmembrane Ca-Na exchange system leading to a depression of Ca pumping activity.


Multichannel functional electrical stimulation--facts and expectations. Clinically applied multichannel stimulation was visualized in the very beginnings of FES. A short survey of existing multichannel systems was taken and compared to initial expectations. While much still remains to be done to get multichannel stimulation out of the research environment and into the clinical routine, the results obtained so far are encouraging enough to continue work in this area with increased effort.


Asymmetrical displacement currents in the membrane of frog myelinated nerve: early time course and effects of membrane potential. 1. Asymmetrical displacement currents were studied in myelinated nerve fibres from Rana esculenta with a voltage clamp technique. 2. For brief pulses symmetrical with respect to a holding potential of--97mV, the asymmetry current flowing during pulses (on-response) exhibited a rising phase to a peak followed by an approximately exponential decline. After the pulses the rising phase in the off-response could not be resolved; the time constant varied about 2-fold with either size or duration of the pulse. 3. For longer pulses a second slower component could be detected both in on- and off-responses. 4. The rapidly declining on- and off-responses associated with brief pulses carried about the same charges Qon and Qoff. Increasing the duration of the pulse reduced Qoff. For all pulses tested Qoff approached about one fifth of Qmax. The reduction of Qoff was roughly characterised by time constants ranging between 1.5 and 0.5 ms for potentials between--25 and + 23 mV. Analysis of individual membrane currents confirmed that the capacity current after depolarizing pulses decreased with pulse length. 5. The effects of membrane potential on asymmetry current were studied by varying the level from which pulses were applied during 46.9ms prepulses in the range from--97 to--29mV. The fast and slow components of asymmetry current were affected differently. For potentials more positive than--90mV the fast on-response was reduced and reversed its sign at a potential 25mV more negative than the potential estimated from the steady-state charge distribution measured from--97mV.


Rapid murine mixed lymphocyte cultures assessed by emergence of T cell insulin receptors. Murine T lymphocytes incubated in the mixed lymphocyte culture with allogeneic lymphocytes incompatible for the H-2 region or subregions thereof rapidly develop insulin receptors. In contrast, T cells cultured with syngeneic or H-2 and M-locus compatible cells do not develop insulin binding sites. The emergence of insulin receptors may allow rapid HLA-D typing in man.


Cole-Moore effect in the frog node.

Cole-Moore effect in the frog node. Potassium currents were recorded from the voltage-clamped frog node (Rana esculenta) during various test pulses that followed hyperpolarizing prepulses of different amplitudes and durations. Both the delay in potassium current onset and the shape of the current trace as a function of time were found to be a function of prepulse parameters. This finding is different from the current trace superposition described by Cole and Moore for a specific test pulse, sodium equilibrium potential in the squid giant axon. The Cole-Moore effect, which was found here only under a specific set of conditions, thus may be a special case rather than the general property of the membrane. The implication of these findings to the various excitable membrane potassium channel models, which are based on the Cole-Moore effect, is discussed.


Activated human T lymphocytes display new surface glycoproteins. We have analyzed the surface glycoproteins of resting and in vitro activated human T lymphocytes by the galactose oxidase/NaB3H4 and the periodate/NaB3H4 labeling techniques. The labeled glycoproteins were separated by polyacrylamide slab gel electrophoresis and visualized by fluorography. A "new" glycoprotein with an apparent molecular weight of 130,000 (GP130) was strongly labeled on alloantigen-activated T blasts but only weakly or not at all on mitogen-stimulated T blasts and resting T lymphocytes. These results demonstrate that human T cells, as earlier found in the mouse system, express different surface molecules in relation to the particular mode of activation and stage of differentiation.


Acute gastrointestinal hemorrhage: the changing role of barium examinations. The emergency evaluation of a patient with acute life-threatening gastrointestinal hemorrhage requires the coordinated efforts of medical, surgical, and radiologic personnel. In most patients with an acute upper gastrointestinal hemorrhage, endoscopy represents the primary diagnostic procedure. Arteriography may follow, depending on the identification of the lesion at endoscopy or the need for therapy through the vascular catheter. Arteriography should precede endoscopy when bleeding is massive or the clinical situation suggests that therapy by a catheter must be instituted on a more urgent basis. When personnel are available to perform endoscopy and arteriography, the barium examination of the upper gastrointestinal tract is best postponed for a few days until the patient can be stabilized completely. In the patient with massive red rectal bleeding and a negative nasogastric aspirate, the arteriogram is clearly the procedure of choice for the emergency diagnostic evaluation. Bleeding diverticular and vascular ectatic lesions can be diagnosed only by arteriography and treatment can usually begin immediately by a catheter infusion of vasopressin. Colonoscopic and barium enema examinations of the acutely bleeding patient are not reliable. In addition, the presence of barium in the colon interferes with arteriography for a number of hours. The barium examination of the colon should be performed at some time during the hospitalization to exclude other possible bleeding lesions and to provide a better overall anatomic assessment of the colon. Both the retrograde and antegrade small bowel enemas are useful in detecting obscure small bowel bleeding lesions that occasionally present as a massive lower gastrointestinal hemorrhage.


[Interstitial pneumonia in children with acute lymphoblastic leukemia. prophylaxis with pentamidine during induction chemotherapy (author's transl)]. The influence of pentamidine prophylaxis on incidence and degree of interstitial pneumonia (IP) during a standardized induction chemotherapy in 100 children with acute lymphoblastic leukemia has been investigated. For radiologic evaluation we established three stages of IP. With pentamidine prophylaxis the incidence of IP was reduced from 48% to 9%. In addition, there was a significant reduction of severe or lethal courses.


[Vertebral changes in histiocytosis x (author's transl)]. Manifestations of histiocytosis X in the vertebral column occurred in 3 of 15 children. Pathological alterations showed a marked variability. Especially a vertebra plana should be considered as eosinophilic granuloma, until another cause is proven. Bone scans were positive in all three cases. Even in most severe cases with vertebral destruction neurological abnormalities were absent.


[Meatocisternography with water-soluble contrast medium for diagnosis of cerebellopontine angle tumors (author's transl)]. First experiences with Metrizamide in Meatocisternography for evaluation of cerebellopontine angles tumors are reported. The diagnostic value of this method to demonstrate space occupying lesions in this area could be shown. Severe side effects had not been observed. Simultaneous monitoring of EEG, ENG and ECG showed no pathological alterations.


[Biorheologic study of pathological synovial fluids]. Rheometric studies of 34 synovial fluids done using a rheometer with a cone and stage (Shirley-Ferranti type) showed that arthrotic synovial fluids had pseudoplastic characteristics (non-Newtonian) but in inflammatory rheumatisms, the characteristics index rises, the consistency decreases and the fluid tends to loose its pseudoplastic properties and to become Newtonian. Radioisotope synoviorthosis seems capable of restoring to a certain extent and in certain cases the rheometric characteristics of the pseudoplastic properties.


[Study of cellular immunity in rheumatoid arthritis]. The responsiveness to mitogens of the in vitro cultural peripheral blood lymphocytes from 60 patients with rheumatoid arthritis (RA) and from controls was evaluated in terms of H3 TdR uptake. The size of the response was tested for a correlation with the percentages of T and B lymphocytes, determined by E and EAC rosette test, as well as with the various alterations of the clinical and biological parameters. In the RA cultures an elevated level of spontaneous H3 TdR uptake was found, which could be an in vitro carry-over of an activation in vivo. No significant statistical differences were found between rheumatic and control groups as regards: 1 degrees--the H3 TdR uptake induced both by PHA and SLO; 2 degrees--the proportion of the circulating T and B lymphocytes. The only positive correlation evidenced by this study in RA patients was that between the proportion of B lymphocytes and the gammaglobulin level in the plasma.


[Juvenile arthritis reevaluated in rheumatology in adult age. 30 cases]. The authors describe and comment on 30 observations of peripheral polyarthritis starting before puberty and reveluated in an adult rheumatologoy service at the average age of 29 and during an observation period of about 16 years. The actual classification of juvenile polyarthritis proves to be valid in this group since the clinical forms are still observed in adulthood. However, during the evolution, there is a shifting from one form to another. The systemic forms can reoccur in adulthood even after several years of quiescence, accompanied by visceral complications. The pauciarticular forms as a rule remain benign. As in childhood, they frequently show antinuclear factors. Some forms, initially peripheral, can show axial signs. The presence of HLA B27 antigens allow them to be linked up with ankylosing spondylarthritis. But this is not the case for all the forms with sacroiliac functions. The evolution since childhood is often characterized by long remissions which can still persist by the time of the visit, which is then motivated by resulting mechanical and local arthrotic problems. Despite often severe anatomical symptoms, the functional handicap is limited, allowing quite a remarkable adaptation. Most of the patients lead an active professional life. Yet despite this and despite an often satisfactory sex life, half of the patients have a psychological handicap which makes it necessary for them to be placed under special carl. No therapeutic conclusion, particularly about the efficiency of the basic therapy, can be drawn from this study.


[Circulating immune complexes and anti-IgG antibodies in rheumatoid arthritis]. Anti-IgG antibodies were studied in 222 patients hospitalized in a Rheumatology service using "radio-immuno-precipitation-PEG-assay" (RIPEGA), The presence of anti-IgG antibodies was observed in 94 per cent of sero-positive rheumatoid arthritis (RA+), 88 percent of seronegative rheumatoid arthritis (RA--), 50 percent miscellaneous chronic inflammatory rheumatisms (CIR) and 77 percent of no-classifiable chronic inflammatory rheumatisms. The study of circulating immune complexes (CIC) using the CIC-125 I linkage tests, carried out on 101 RA cases, demonstrated their presence in 80 per cent of RA+ and 85 per cent of RA--. The comparison of these two factors during RA showed a concordant relationship that was statistically significant. The presence of the rheumatoid factor (RF) in the form of complexes in the blood stream, is discussed.


alpha-1-antitrypsin (Pi) phenotypes in a Finnish population. alpha-1-antitrypsin (Pi) phenotypes of 548 normal Finnish blood donors were determined by isoelectric focusing in polyacrylamide gel. The frequencies obtained (M, 93.3%; FM, 0.4%, GM, 0.2%; MS, 3.5%; MZ, 2.7%) differed from those reported earlier for a more restricted Finnish population but agreed better with the frequencies reported for other Scandinavian populations. The disagreement with the earlier report was attributed to differences in sampling and laboratory techniques. The present study confirms an earlier finding of a sarcity of fast Pi variants in the Finnish population. One M variant was found. The isoelectric focusing technique used in this study has several advantages over the methods previously described for Pi typing.


Altered proportion of T mu-and T gamma-cell subpopulations in patients with Hodgkin's disease. The ability of peripheral blood lymphocytes from patients with Hodgkin's disease (HD) to form rosettes with ox red blood cells (ORBC) sensitized by anti-ORBC purified rabbit IgM and IgG was investigated. The mean percentage of cells capable of forming rosettes with ORBC coated with IgM (EAIgM-RFC) in the peripheral blood of either untreated or X-ray-treated patients with HD was significantly lower than that of normal individuals. In the same groups of patients with HD the mean percentage of T lymphocytes equipped with receptor for IgG (T gamma lymphocytes), evaluated by a mixed fluorescent rosette assay, was significantly higher than in normal controls. These data suggest that the altered proportion between T mu-and T gamma-cell subpopulations in patients with HD probably represents a disease-related phenomenon.


Lactate dehydrogenase isoenzyme pattern: marker for differentiation of lymphocytes. The lactate dehydrogenase isoenzyme pattern has been determined in different murine thymocyte cell populations. Enrichment of thymocytes with more mature cells through total irradiation results in a smaller percentage of LDH-1, LDH-2, LDH-3 and a greater percentage of LDH-4 and LDH-5. Fractionation of normal thymocytes by velocity sedimentation at unit gravity yields a fraction of cells with a high sedimentation rate. LDH-1 and LDH-2 formed a smaller percentage of the total enzyme activity in these cells. These findings indicate that the LDH isoenzyme distribution is a marker for differentiation of thymocytes.


beta-lactamases and R-plasmids of Haemophilus influenzae. The emergence of resistance to ampicillin and other antibiotics in Haemophilus influenzae has been a relatively recent event. In contrast, drug resistance has been rampant in the Enterobacteriaceae for many years. Ampicillin-resistance in H. influenzae is almost invariably attributable to possession of the TEM (Type III a)beta-lactamase. As is common in other bacteria the gene specifying this enzyme is plasmid-borne in Haemophilus. Some ampicillin-resistant strains of H. influenzae can transfer the TEM beta-lactamase gene to other strains of Haemophilus, to Escherichia coli and to Pseudomonas aeruginosa. The features of such transfer are unusual and lead for example, to the induction of adenine requirement in recipient strains of P. aeruginosa. Crypticity measurements of beta-lactamase activity show that in comparison to P. aeruginosa or E. coli, the outer membrane of H. influenzae affords only a weak penetration barrier to beta-lactam antibiotics. This may have consequences for the stability and distribution of beta-lactamase production in Haemophilus spp. which are discussed. A comparison of the molecular properties of R-plasmids determining a variety of resistances and carried by strains of H. influenzae isolated in diverse geographical locations has revealed unexpected homologies. A series of such plasmids of similar molecular weights (about 30 X 10(6)) differ substantially only in the transposable resistance genes that they carry. A model based on these findings is presented to explain the acquisition of ampicillin- and other resistances by Haemophilus.


Studies with cefuroxime and cefoxitin.

Studies with cefuroxime and cefoxitin. We have studied cefuroxime, a new beta-lactamase resistant cephalosporin, and cefoxitin, the first cephamycin antibiotic, which is also resistant to many beta-lactamases. Both of these antibiotics have been shown to be microbiologically superior to the "first generation" cephalosporins, cefuroxime having notable activity against Haemophilus influenzae, and cefoxitin against Bacteroides fragilis. Neither antibiotic is absorbed from the gut but, following parenteral administration, serum, urine and bile concentrations are high. Clinical trials have been conducted on both cefoxitin and cefuroxime. The results of these have been satisfactory and untoward side-effects minimal. We suggest that cefoxitin will be particularly valuable in the management of abdominal sepsis and cefuroxime in infections caused by H. influenzae.


Acoustic neuroma: results of brain stem evoked response audiometry. Brain stem evoked response (BER) audiometry presents abnormal findings in patients with acoustic neuromas. The test involves averaging of recordings at the vertex as sound-triggered nerve impulses travel from the cochlea to the brain stem. From the time the sound stimulus arrives at the cochlea until it reaches the first major brain stem synapse (within 10 milliseconds), five major waves have been identified as typical of normal averaged responses. Abnormality in the cochlea or eighth nerve causes specific changes in pattern, primarily in wave latency. These latency shifts can be used to predict the site of the lesion. In evaluating 17 lesions of the cerebellopontine angle, BER audiometry was accurate in the diagnosis of all of the tumors. This diagnostic tool should play a prominent role when acoustic tumor is suspected.


Observations on fifty distal splenorenal shunts. Fifty patients underwent conventional distal splenorenal shunts for bleeding esophageal varices. Five patient died within 30 days, giving an operative mortality of 10%. Three patients were lost of follow-up, but 47 patients were evaluated. Twelve patients died, 11 of liver failure, with more than half of the deaths occurring with 1 year, three fourths within 2 years, and all within 3 years after operation. Eleven patients rebled, and seven of these were among those who died. Sixteen patients had ascites prior to operation, but all responded to aggressive medical therapy. Twenty-two patients were available for study 2 or more years following operation. Eighteen (82%) are well with no encephalopathy, although the remaining four (18%) have had transient episodes of encephalopathy. Sixteen of the 18 patients judge their lifestyles to be productive. If the patient survived 24 months or longer, he had a four in five chance of living a normal life.


[Effect of olivomycin on denervation changes in the membrane of frog tonic muscle fibers]. Membrane properties of frog denervated tonic muscle fibers were investigated after the action of olivomycin, which is an inhibitor of protein synthesis. Olivomycin injected as a single dose (7.5 mg) during 1--2 days after the denervation of m. pyriformis decreases the regenerative action potentials. This action is decreased three weeks after denervation. After denervation, olivomycin failed to prevent the appearance of extrajunctional cholinoergic receptors, but blocked the increase of junctional ones. The data support the view that some neuronal factor may influence the synthesis of functional membrane proteins.


[Treatment of peyronie's disease with para-aminobenzoacidic potassium (POTOBA) (author's transl)]. A total of 214 urologists treated 2653 cases of Peyronie's Disease with para-aminobenzoacidic potassium (POTOBA). The treatment was successful in 57.3% and unsuccessful in 42.7% of the cases; 246 patients (9.3%) were 'cured. Particular prescriptions intended to increase gastric tolerance and thereby guarantee long-term use of the medication are pointed to as a prerequisite to successful therapy. Practical advice is presented on how to interest patients in carrying out long-term treatment themselves.


Rheumatoid granuloma of kidney.

Rheumatoid granuloma of kidney. A seventy-year-old black man with long-standing rheumatoid arthritis who had been treated with corticoids presented with painless hematuria originating from the kidney. The clinical findings were suggestive of a renal cell carcinoma. The resected kidney was markedly enlarged, scarred, and disclosed a necrotic rheumatoid granuloma surrounded by chronic inflammatory reaction. The mechanism of hematuria and the clinical significance of the rheumatoid granulomatous involvement of the kidney are discussed.


[Sulfanilimide acetylation and coenzyme A concentration in liver and heart muscle in experimental myocardial necrosis]. Sulfanilamide acetylation was inhibited and content of CoA was decreased in myocardium and liver tissue within the first day after occlusion of coronary arteries. Within 1-6 days after the occlusion the sulfanilamide acetylation and content of CoA were increased in the tissues studied; at the 12th day the reactions of acetylation were normalized in myocardium but remained at an increased level in the liver tissue. The content of CoA was similar to the values found in the normal state.


[Regional ventricular function at rest during exercise before and after bypass surgery (author's transl)]. In 9 patients with coronary heart disease isovolumetric contractility indices and ejection phase parameters were measured simultaneously, using an angiographic catheter with a manometer at the tip (Millar). Regional wall motion at rest, after leg raising and during physical exercise (bicycle ergometer) was analyzed applying the hemiaxis method. Five weeks after aortocoronary bypass surgery the same examinations were repeated. Preoperatively left ventricular enddiastolic pressure (LVEDP) increased from 21 to 37 mm Hg following leg raising. The velocity mean of fiber shortening (Vcf) and of regional fiber shortening in the anterior wall decreased significantly.--All patients discontinued physical exercise due to angina pectoris. LVEDP increased from 21 to 39 mm Hg. Large hypokinetic and akinetic areas developed especially in the anterior wall. Velocity of fiber shortening of the anterior wall decreased from 1.43 to 0.76/s. Enddiastolic volume remained unchanged while endsystolic volume increased significantly. In six patients with patent grafts surgery had a beneficial effect. Comparing angiograms at rest no significant changes were found. After leg raising and physical exercise, however, marked improvement in ventricular function occurred, compared to the preoperative performance. All 6 patients were exercised without complaints at a load of 100 watts for 8 minutes. Velocity of fiber shortening in the anterior wall increased significantly from 0.76 to 2.56/s, mean Vcf from 1.11 to 2.12 circ/s, max dP/dt from 2302 to 4280 mm Hg/s and Vpm from 27.8 to 55.7/s. Functional improvement in individual wall segments amounted to 500% in the mean. Ejection fraction increased from 54 to 76%. Enddiastolic volume remained unchanged while endsystolic volume decreased from 67 to 33 ml/1.37 m2 (p less than 0.002). In three patients the bypass occluded or myocardial infarction occurred intraoperatively. Postoperative findings at rest and during exercise were unchanged as compared to preoperative values. Following successful bypass surgery ventricular function at rest did not change. During exercise, however, a marked improvement in overall and in regional ventricular function was found.


Anterior pituitary function in women with postpartum hemorrhage. Thirteen asymptomatic women with postpartum blood loss of at least 500 cc were evaluated for anterior pituitary endocrine function. Insulin tolerance tests and TRH stimulation tests were done and determinations made for serum growth hormone, cortisol, thyrotropin, and prolactin. There was no laboratory evidence of pituitary dysfunction in this group of 13 patients. Subclinical hypopituitarism in women with previous postpartum hemorrhage would appear to be uncommon.


[Effect of cordycepin on the activation of RNA and protein synthesis at the early inhibition stages of Agrostemma githago embryos]. In embryos of Agrostemma githago pre-rRNA, ribosomal, heterogeneous, and transfer RNA is transcribed at 0 to 3 hrs of inhibition. An essential amount of hnRNA/mRNA is polyadenylated and can be prepared by affinity chromatography on poly(U)-sepharose columns. At very low concentrations of cordycepin synthesis of poly(A)+-RNA is especially inhibited. At increasing concentration of cordycepin the synthesis of ribosomal RNA is inhibited too. According to these results cordycepin is a suitable inhibitor to study the function of post-transcriptional polyadenylation of mRNA at the regulation of early protein synthesis of imbibing Agrostemma embryos. Incorporation of [3H]-leucine into protein occurring from 0 to 3 hrs of inhibition is not remarkably inhibited by cordycepin. These results may indicate that neither synthesis of mRNA nor its polyadenylation nor the polyadenylation of stable mRNA is involved in the regulation of early protein synthesis.


The effects of methylprednisolone on the complications of coronary artery surgery. Complications of coronary artery surgery were analyzed in a prospective controlled study of 150 patients, one group receiving methylprednisolone before temporary cardiopulmonary bypass. The patient population was comparable in both the groups. The number of deaths were the same in both the groups, myocardial infarction and cardiac arrhythmias were definitely lower in the Solu-Medrol group. Cerebral vascular accidents were higher in the control group and there were none in the drug treated group. Incidences of pulmonary embolism was reduced by the drug. Oxygen consumption by the tissues was higher in the Solu-Medrol treated group. There were no known complications of the drug, such as stress ulcer and infection. One patient did receive prophylactic antibiotics. Solu-Medrol was deliberately given in patients who were known to have uncomplicated duodenal ulcer. Post-operative bleeding in patients with duodenal ulcer was not noted. This could be explained due to the short acting nature of Solu-Medrol. We feel that Solu-Medrol does minimize serious sequelae of heart-lung machine in coronary artery surgery.


[X-ray microanalysis of elements in epon-embedded animals tissues]. X-ray microanalysis was performed on ultrathin sections of tissues from six rats, four of which having been exposed to experimental metabolic disorder by overdoses of NaCl and Ca-Vit. D2, respectively. It was demonstrated that the elements Cl, Si, P, S, Ca and traces of Fe are identifiable quantitatively in arteriolar walls of colon, heart and kidney even after conventional electron microscopic preparation (fixation, dehydration and Epon embedding). Depending on the pretreatment considerable differences in elemental quantities between animal groups were observed. The reliability of these findings must be confirmed by further tests on a greater number of individuals.


Central thickness in corneal disorders.

Central thickness in corneal disorders. In the single individual the central corneal thickness (CCT) shows only small variations. Therefore CCT has been studied in a number of corneal diseases in order to investigate if this dimension might contribute to the diagnosis or to the understanding of the pathogenesis. Normal CCT was found in hereditary dystrophies with the exception of the macular dystrophy of Groenouw (type II), which showed a significantly reduced thickness. Reduced CCT was found in chronic degenerations of leutic, tuberculous or indefinite nature. Marginal degenerations of Fuchs-Terrien type also showed reduced CCT. The possible role of abiotrophic processes in this corneal thinning is dicussed. Endothelial dysfunction is indicated by increased CCT. This occurs in bullous keratopathy and in many acute disorders. Vascularisation of the cornea does not preclude the occurrence of normal or even reduced thickness.


Differentiation of mouse T-lymphocytes. 19 Characterization of thymocyte precursors in bone marrow by one G velocity sedimentation. Bone marrow cells were transferred into 700 R X-irradiated syngeneic mice, and regeneration of the thymus was demonstrated by determining the total amount of DNA in the thymus. The amount of DNA in the regenerated thymus 9 days after X-irradiation paralleled the number of cells injected, the range being 0 to 10(6) cells. These results indicate that regeneration during this period reflects the proliferation of thymocyte precursors existing in bone marrow cells, therefore such can be used as an indicator to determine the number of thymocyte precursors. Thymocyte precursors were separated from spleen colony forming cells and soft agar colony forming cells by one G velocity sedimentation. Thymocyte precursors (more than 4.3 mm/hour sedimentation rate) sedimented faster than did spleen colony forming cells (peak at about 3.0 mm/hour) and Thy-1 antigen was already evidenced on the cell surface as demonstrated by complement dependent cytotoxicity. Soft agar colony forming cells also sedimented faster, suggesting that cells destined to become one type of cell are larger than multi-potential stem cells.