Abnormal ratio of membrane immunoglobulin classes in mice with an X-linked B-lymphocyte defect. CBA/N mice have an X-linked genetic defect in B-lymphocyte function manifested by inability to make antibody responses to T-independent antigens. Plasma membrane immunoglobulin (Ig) on spleen, lymph node, and Peyer's patch cells was analyzed by lactoperoxidase-catalyzed iodination, NP-40 extraction, specific immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These studies indicated that the X-linked immune defect was associated, in all three cell types, with a decrease in the ratio of cell membrane IgD analog to cell membrane IgM. This suggests either that IgD analog may be important in initiation of T-independent antibody responses or that CBA/N mice lack a subpopulation of B cells specialized to respond to T-independent antigens, and that these cells are relatively rich in plasma membrane IgD analog.


Fc-receptors, Ia-antigens, and immunoglobulin on normal and activated mouse T lymphocytes. Using antibody coated bovine erythrocytes we were unable to demonstrate Fc-receptors on either thymus cells or T cells prepared from lymph node cell suspensions by anti-Ig column filtration. However, if parental thymus or lymph node T cells were transferred to X-irradiated F1 hybrids, activated donor T cells recovered from the recipient's spleen (ATC-spleen) were shown to express Fc-receptors. Fc-receptors were also demonstrable on ATC-spleen prepared between strain combinations differing at the M-locus. In marked contrast, Fc-receptors were not detected on ATC recovered from thoracic duct lymph (T.TDL). This applied to (a) H-2-activated T.TDL derived from normal thymus cells, (b) H-2-activated T.TDL derived from thymus cells depleted of B cells, and (c) M-locus-activated T.TDL. Of these three populations, surface Ig (of B cell origin) was detected on a large proportion of the first but not on the second and third populations. Thus, the failure to detect Fc-receptors on any of these populations could not be attributed to blocking by adsorbed surface Ig. In addition, various T-cell populations were examined by a microcytotoxicity assay for the presence of cell surface Ia-antigens. 5--10% of the thymus cells, 20--30% of cortisone-resistant thymus cells, 60--70% of lymph node cells, and 60--80% of ATC-spleen and T.TDL showed Ia.


A glycoprotein associated with the membrane fraction of human B but not T lymphocytes. A method is described which employs differential centrifugation and sucrose density gradient centrifugation to isolate a membrane fraction from human lymphocytes. Membrane preparations from long-term human cultured B- and T-lymphoid lines, peripheral blood lymphocytes, tonsillar lymphocytes, and thymocytes were analyzed on 0.5% sodium dodecyl sulfate-7.5% polyacrylamide gels stained for protein and carbohydrate. The most important finding was a major glycoprotein of approximately 30,000 daltons associated with the membrane preparations from B lymphocytes. T-lymphocyte preparations did not contain readily detectable amounts of this membrane-associated component. The T-cell lymphoid line MOLT-4 was unique in that it had a narrow protein band at approximately 30,000 daltons which did not contain carbohydrate.


Functional characteristics of Peyer's patch cells. III. Carrier priming of T cells by antigen feeding. Peyer's patch T cells may serve an important role in the interaction of the host with intraluminal gut antigens. Studies presented in this paper demonstrate that T cells in murine Peyer's patches can be carrier primed for helper function in the induction of an antihapten response by feeding antigen. Carrier priming was assessed by measuring the ability of Peyer's patch cells from mice fed heterologous erythrocytes to enhance an antitrinitrophenyl (TNP) response in vitro when added to normal Peyer's patch cells cultured with TNP coupled to the erythrocyte used for feeding. Priming of T helper cells in Peyer's patches was antigen specific and occurred when erythrocytes were administered orally but not when erythrocytes were injected intravenously or intraperitoneally. Murine Peyer's patches are naturally deficient in a cooperating accessory adherent cell type(s) required for B-cell induction to humoral antibody synthesis in vitro and antigen feeding does not result in significant induction of Peyer's patch B cells to humoral antibody synthesis in vivo. Since Peyer's patch T cells can be carrier-antigen primed for helper function in the absence of B-cell induction to humoral antibody synthesis, these studies may indicate that T-cell priming is less dependent than B-cell induction on cooperating accessory adherent cells.


Synergistic and suppressive interactions among mouse T lymphocytes in the response to phytohemagglutinin. A synergistic effect in the proliferative response to phytohemagglutinin (PHA) can be observed in cultures containing a mixture of mouse CBA/Ca lymph node cells (LNC) and syngeneic CBA/T6T6 thymocytes (ThC) when compared to cultures containing only one cell type. This effect was analyzed, at various days of culture and in LNC-ThC mixtures of different ratios, by comparing the origin of the cells in mitosis (detected by caryotypic analysis), the stimulation of DNA synthesis, the number of blasts, and the percentage of blasts labeled after pulses of [3H]thymidine (detected by autoradiography). The following conclusions were reached: (a) ThC are induced to proliferate by the presence of LNC, while they are almost unresponsive to PHA when cultured alone; and (b) the strongest "synergistic" effect is exerted on LNC, whose proliferation is markedly enhanced. Evidence is presented that this last effect is not specific to the presence of ThC, but results from a dilution of LNC which retards the time when the culture reaches a critical concentration of blasts, above which proliferation progressively stops. Thus, conditions of culture allowing the response to PHA of a low concentration of LNC leads to the most prolonged T-cell proliferation. These observations may be relevant to the types of T-cell interactions, "synergistic" or "suppressive," occurring during in vitro or in vivo immune responses.


Genetic control of cutaneous basophil hypersensitivity. CBH to DNP-GL could be elicited only in responder guinea pigs which possess the genetic ability to develop classic delayed type hypersensitivity to DNP-PLL, the response to which is governed by the same gene. Since the defect in nonresponder animals seems to reside at the level of their T cells and not B cells, these results lend support to the contention that CBH, as well as DH, is dependent on and probably mediated by T cells.


Studies on the role of the host immune response in recovery from Friend virus leukemia. II. Cell-mediated immunity. Congenic mouse strains differing only at genes within the H-2 complex were found to have virus-specific cytotoxic effector cells in their spleens during or after recovery from Friend leukemia virus-induced splenomegaly. These effector cells were theta-positive T lymphocytes which functioned in vitro without help or inhibition by B lymphocytes or glass-adherent cells. The antigenic specificities recognized by the effector cells were viral-induced cellular antigens apparently different from those identified by serological techniques.


Behavioral adaptation in neonatal chicks following embryonic vestibular system rearrangement. Micro-surgery was performed on chick embryos during the second day of incubation (45-50 hours). Either one otocyst was removed or was rotated 180 degrees and reimplanted. The chicks' behavior was studied for 1-13 weeks after hatching. The unilateral loss or rearrangement of vestibular (and auditory) input led initially to abnormal behavior patterns, usually consisting of poor righting reflexes, deficits in locomotion, balance and pecking accuracy, and a pronounced head nystagmus. However, in every case, these abnormalities were corrected within a few days after hatching, so that the operated animals became almost indistinguishable from normal controls. Histological evidence confirmed the extent of the loss of the vestibular and auditory structures and nuclear amalgams. The observed capacity of the neonatal chick to adapt to this sensory loss or disorientation is a rather rare example of infraprimate behavioral adjustment or modifiability, contrasting with the frequent demonstrations of behavioral rigidity in lower forms.


Activation of phosphorylase in frog muscle as determined by contractile activity. The state of activation of phosphorylation in muscle has been reinvestigated by combining the extraction procedures of Danforth, Helmreich, and Cori with the low-temperature techniques of this laboratory. In resting frog muscle, the phosphorylase-alpha content is usually below detectability. Upon contractile activity in series of twitches, activation of phosphorylase beta to alpha took place, without activation of phosphorylase beta kinase as defined by the assay procedure. Two different experimental designs were used to examine the relation between phosphorylase activation and the myothermally determined energy turnover per twitch, and these showed, identically, that the enzyme activation is proportional to the energy per twitch.


Effect of intracranial pressure of meglumine iothalamate ventriculography. Intraventricular pressure was studied in 12 patients undergoing ventriculography with a water soluble positive contrast medium. Isovolumetric instillation of meglumine iothalamate into the lateral ventricles and the anterior part of the third ventricle caused only a small increase in ventricular fluid pressure (1.3 +/- 0.3 mmHg), but the pressure increased markedly (46.3 +/- 3.7 mmHg; P less than 0.001) when the contrast medium entered the posterior end of the third ventricle, aqueduct of Sylvius,, and fourth ventricle. This sharp increase in intracranial pressure could not be attributed solely to the postural changes or to alterations in arterial blood pressure. Possible mechanisms are discussed.


Computerized axial tomography: the normal EMI scan. Computerized axial tomography using the EMI scanner as a new method of using x-rays in diagnosis. The technique displays intracranial and orbital structures in the transverse plane. The appearances of normal EMI Scans are described and correlated with cerebral and orbital anatomy seen in transverse section.


Surgical removal at arteriovenous malformations from the brain stem and cerebellopontine angle. The author reports his surgical experience with five cases of arteriovenous malformation of the brain stem and cerebelloppontine angle causing multiple hemorrhages and severe neurological deficits. Surgical removal of the lesions had good results in four cases; there was one death.


Chronic petrous pyramid abscess presenting as a cerebellopontine angle mass. Case report. The authors present the case of a 5-year-old boy with a chronic petrous pyramid abscess and without a history of otitis media. Treatment by posterior fossa exploration and drainage with antibiotics was successful.


[Duodenal cirsoid aneurysm treated by embolization(author's transl)]. A cirsoid aneurysm of the artery to the second part of the duodenum was demonstrated by arteriography in a 31 year old man who had had two severe unexplained bouts of gastrointestinal hemorrhage. The diagnosis was confirmed by surgical intervention, and in order to avoid duodenopancreatectomy, the malformation was treated by embolization of the gastroduodenal artery during the operation.


Effect of cordycepin (3'-deoxyadenosine) on virus-specific RNA species synthesized in Newcastle disease virus-infected cells. Cordycepin (3'-deoxyadenosine) has no effect on the size or relative proportions of Newcastle disease virus-specific 18-22S mRNA species nor on the amount or size of the polyadenylic acid associated with them. Cordycepin does, however, cause an inhibition of incorporation of [3H]uridine into 50S virus-specific RNA relative to 18-22S RNA. This inhibition is probably not a direct effect of the drug on the synthesis of 50S viral RNA. Like cycloheximide, another drug which inhibits 50S RNA accumulation in paramyxovirus-infected cells, cordycepin inhibits protein synthesis as measured by amino acid incorporation. It is likely that the inhibition of 50S RNA accumulation is a secondary effect of protein synthesis inhibition. This is supported by the finding that concentrations of cordycepin and cycloheximide, which inhibit protein synthesis to the same extent, have the same effect on the ratio of 50 to 18-22S virus-specific RNA.


Replication and persistence of measles virus in defined subpopulations of human leukocytes. Replication of Edmonston strain measles virus was studied in several human lymphoblast lines, as well as in defined subpopulations of circulating human leukocytes. It was found that measles virus can productively infect T cells, B cells, and monocytes from human blood. These conclusions were derived from infectious center studies on segregated cell populations, as well as from ultrastructural analyses on cells labeled with specific markers. In contrast, mature polymorphonuclear cells failed to synthesize measles virus nucleocapsids even after infection at a relatively high multiplicity of infection. Measles virus replicated more efficiently in lymphocytes stimulated with mitogens than in unstimulated cells. However, both phytohemagglutinin and pokeweed mitogen had a negligible stimulatory effect on viral synthesis in purified populations of monocytes. In all instances the efficiency of measles virus replication by monocytes was appreciably less than that of mitogenically stimulated lymphocytes or of continuously culture lymphoblasts. Under standard conditions of infection, all of the surveyed lymphoblast lines produced equivalent amounts of measles virus regardless of the major histocompatibility (HL-A) haplotype. Hence, no evidence was found that the HL-A3,7 haplotype conferred either an advantage or disadvantage with respect to measles virus synthesis in an immunologically neutral environment. A persistent infection with measles virus could be established in both T and B lymphoblasts. The release of infectious virus from such persistently infected cells was stable over a period of several weeks and was approximately 100-fold less than peak viral titers obtained in each respective line after acute infection.


Identification of complement-receptor lymphocytes (B cells) in lymph nodes and tumor infiltrates. To monitor the distribution of lymphocyte sub-populations infiltrating tumors, a simplified modification of standard techniques was developed to identify the complement-receptor B lymphocytes in frozen tissue sections. This technique is based on binding of antibody-coated bovine erythrocytes by B lymphocytes in the presence of sub-hemolytic concentrations of mouse complement. B lymphocytes can be identified in frozen tissue sections by adherent sensitized bovine erythrocytes. The specificity of the technique for B lymphocytes was established by 1) absence of spontaneous rosette formation with bovine erythrocytes by human T lymphocytes, 2) specific binding of bovine erythrocyte-antibody-complement complexes to B cell regions of normal lymph nodes and spleen and 3) binding of erythrocyte-antibody-complement to a high proportion of chronic lymphocytic leukemia (a B cell leukemia) lymphocytes. Five transitional carcinomas studied had regions of mononuclear infiltration that were virtually devoid of complement-receptor lymphocytes. The results suggest that lymphocytes infiltrating bladder carcinomas may be predominantly T lymphocytes.


[Melatonin biosynthesis in the mammalian retina in dependence of light adaptation (author's transl)]. 1. The biosynthesis of melatonin was investigated in retinaextracts of bovine eyes in dependence of light adaptation of the animals. S-adenososyl (Methyl-14C) methionin and acetylserotonin were used as substrates. A higher melatonin-biosynthesis was found in the retina from animals which were adapted to lower illumination. 2. The effect of triamterene on the biosynthesis of melatonin in the retina was examined. An increase of melatonin was found in the presence of the diureticum, which is a pteridine compound, when retinas of animals which were kept under low illumination were investigated. The role of melatoninsynthesis in dark adaptation is discussed and it is pointed to a possible danger of blinding in patients which used triamterene. Furthermore it is suggested that triamterene also increases the melatoninsynthesis in the pineal gland and that this may possibly contribute to an understanding of the effect of the diurecticum.


Rabbit gut-associated lymphoid tissue. Major pathway for thoracic duct lymphocyte circulation. The demonstration of a preponderance of T cells in the thoracic duct lymph of rabbits prompted us to initiate cytokinetic studies using both uridine- and thymidine-labeled thoracic duct lymphocytes (TDL). Rabbits received intravenous injections of 8 to 11 X 10(8) autologous or allogeneic TDL, 95 per cent of which had incorporated 3H-uridine during a 1-hour in vitro incubation. Autoradiographs of tissues collected 24 hours after injection of TDL failed to demonstrate any trapping of label in liver or in vivo reutilization of 3H-uridine. No differences in the distribution of labeled cells were noted between recipients of autologous and allogeneic TDL. The paracortical areas of lymph nodes and periarterial areas of splenic follicles contained many heavily labeled cells; these areas therefore appear to correspond to thymus-dependent areas as in other rodents. The tonsils contained densely packed sheets of labeled cells. In the tonsillar but not in other germinal centers, evenly distributed, lightly labeled cells were seen. Small clusters of heavily labeled cells were seen in the bronchus-associated lymphoid tissue. In the appendix, sacculus rotundus, and Peyer's patches (GALT) densely packed, heavily labeled cells were seen in the interfollicular areas; fewer, heavily labeled cells were scattered throughout the dome and corona of GALT. In the dome and corona, however, there were many lightly labeled cells. The germinal centers of GALT were lacking totally in uridine-labeled cells. Some 20 per cent of TDL collected 24 hours after injection of uridine-labeled TDL were labeled, thereby reflecting considerable recirculation of TDL. Injection of 24 to 48 X 10(6) thymidine-labeled immunoblasts, obtained from TDL incubated with 3H-thymidine in vitro, into autologous or allogeneic recipients killed 24 hours later, revealed heavily labeled cells in the intestinal lamina propria, the dome, corona, and interfollicular areas of GALT, as well as throughout the spleen, lymph nodes, and tonsils. There was a 2- to 3-fold higher concentration of labeled cells in the appendiceal and mesenteric lymph nodes than in respective popliteal nodes. The potential significance of this differential distribution together with the homing-circulation patterns of these cells in GALT are discussed with regard to differentiation of IgA-producing cells. It is concluded that rabbit GALT contains a substantial number of cells belonging to the pool of recirculating lymphocytes and that B and T cells in the thoracic duct may have different rates of uridine incorporation as has been shown in other rodents.


The late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span. I. Humoral immune activity. The effect of different immunosuppressive treatments during young adulthood or humoral immune competence late in life was determined. It was found that the marked reduction in humoral immune competence in aged mice is further compromised when severe insults are administered early in life. Thus, thymectomy, splenectomy, and sublethal X-irradiation produced lasting immunodepression as measured (1) in situ and (2) by the hemolysin, direct and indirect plaque forming cell responses of adoptively transferred spleen cells. In contrast, treatment with cyclophosphamide and cortisone acetate were without effect, indicating that drug-damaged cells of the immune system were replaced by competent cells during the course of time. Decrease in immune competence of aged thymectomized animals could not be correlated with a decrease in numbers of theta-bearing T or immunoglobulin receptor-bearing B lymphocytes. The significance of the observed unequal effects of these immunosuppressants on immune competence, as they relate to disease incidence and life expectancy, are dealt with in the third paper in this series.


Influence of L-3-methoxytyrosine on monoamine synthesis in rat brain. Rats were injected i.p. with L-3-methoxytyrosine, 100 or 300 mg/kg. One h later brain, liver, heart and blood plasma were analyzed for catecholamines and their precursors. In brain Dopa as well as dopamine and noradrenaline levels were unchanged, while demethylation of L-3-methoxytyrosine might have occurred in peripheral organs since Dopa levels in liver and dopamine in heart were elevated. 3-Methoxytyramine could not be detected in brain and liver after treatment with L-3-methoxytyrosine. Monoamine synthesis in vivo was measured in whole brain by determining the accumulation of Dopa and 5-hydroxytryptophan 30 min after the i.p. injection of NSD 1015(3-hydroxybenzylhydrazine HC1, 100 mg/kg), an inhibitor of the aromatic amino acid decarboxylase. L-3-Methoxytyrosine attenuated the formation of Dopa and 5-hydroxytryptophan by about 25% in brain tissue. The effect was paralleled by a decrease in the brain concentration of tryptophan.


Change in the proportion of T and B lymphocytes in human malignant neoplasia in relation to the clinical stage. Formation of spontaneous (E--erythrocyte) and immune (EAC--erythrocyte, antibody, complement) rosettes of sheep red blood cells (SRBC) with peripheral blood T and B lymphocytes, respectively, was used for quantitative assessment of these lymphocytes populations in tumor patients and control subjects. Relative counts of T and B lymphocytes have been correlated with lymphocyte survival in short-term cultures using standard subtoxic doses of phytohemagglutinin (PHA). The mean values and SE in normal control subjects for E rosettes (T lymphocytes) were 72.8 +/- 1.2%, for EAC rosettes (B lymphocytes) 23.8 +/- 2.5% of lymphocyte population. The survival of lymphocytes in short-term cultures with PHA in control subjects was 55.3 +/- 1.1%. In tumor patients the counts of E, EAC rosettes and percentage of lymphocyte survival in short-term PHA cultures were dependent upon the clinical stage. In patients with localized tumors the values were similar to controls. In patients where dissemination of the tumorous process could be ascertained a decrease of T lymphocyte counts, an increase of B lymphocyte counts and a higher survival of peripheral blood lymphocytes in short-term cultures with PHA was found.


Migration inhibition of peritoneal cells and PHA lymphocyte toxicity in rats during methylcholanthrene carcinogenesis. Peritoneal exudate cells obtained from rats bearing primary methylcholanthrene-induced tumors were shown to be inhibited in their capillary tube migration capacity as compared to cells from nontreated control litter-mates. The survival of rat peripheral blood lymphocytes harvested from the same individuals were tested simultaneously in short-term cultures with a standard concentration of Phytohemagglutinin. Lymphocytes from tumor-bearing rats survived better than control lymphocytes in 24-hour cultures with Phytohemagglutinin. A correlation was found from a comparison of the results of these two methods. These findings are discussed with regard to the possibility of T cells depletion from peripheral lymphocyte population, together with the enrichment of this population with B cells in tumor-bearing individuals.


[Glomerulonephritis and sarcoidosis: study of a case]. A case of rapidly progressing glomerulonephritis accompanied by sarcoidosis is presented. The immunological pathogenesis of the underlying disease was shown by the positivity of the reactions for anti-IgA and anti-betal C/beta 1 A globulins and the presence of thick deposits in the mesexential matrix and some parts of the thickened basal membrane. Since generalised sarcoidosis is regarded as the expression of an immunological reaction to an unknown, diffuse antigen, this type of glomerulonephritis may be associated with the particular immunopathological condition observed in sarcoidosis.


Thymus-dependent lymphocyte function in dimethylnitrosamine-induced renal carcinogenesis is not depressed. As one measure of cell-mediated immunity, the blastogenic response of enriched spleen lymphocytes to phytohaemagglutinin (PHA) was assayed at sequential daily and weekly intervals following the administration of dimethylnitrosamine (DMN) as a single dose sufficient to induce renal tumours in 100% of surviving rats. PHA responsiveness of DMN-treated rats was not suppressed at any stage of tumour induction in contrast to rats which had been intentionally immunodepressed by neonatal thymectomy. It was concluded that DMN is unlikely to facilitate the cancer process by impairing thymus-dependent lymphocyte function.


[Immunologic types of lymphocytes in acute lymphatic leukemia during remission (author's transl)]. The rates of B and T-cell-subpopulations of lymphocytes were examined on 15 children with acute lymphatic leukemia during the first complete remission under maintenance in the Pinkel VII scheme and in 6 further cases with modification of this scheme of treatment compared to normal children in the same age groups. Further on 4 children during a relapse, on 1 during the second remission, and on 3 during  long-term remissions. The most important result was a significant reduction of B cells during intensive maintenance therapy of the Pinkel scheme. In the few cases of long-term remissions a reduction of B cells was no longer observed.


T cell leukaemia in the rat: the pathophysiology. A new transplantable lymphocytic leukaemia of the inbred Hooded Oxford strain of rat is described. Fewer than 10 cells will transfer to syngeneic recipients. Leukaemic cells bear the surface markers of thymus-derived (T) cells and recirculate from blood to lymph. In contrast to the usual thymic lymphomas of rodents the pathophysiology of the disease bears a close resemblance to human acute lymphoblastic leukaemia.


Lymphocyte surface receptors in childhood acute lymphocytic leukemia. B and T lymphocyte surface receptors were studied in the bone marrow and peripheral blood of 16 patients with childhood acute lymphocytic leukemia. T cell surface receptors were identified on the blasts of one patient. Increased percentages of T or B cell surface receptors were not found in the bone marrow of the other 15 patients. There was a negative correlation between the percentage of pathologic cells in the peripheral blood and the percentage of cells with T and B surface receptors. The results of this study indicate that childhood acute lymphocytic leukemia is a heterogeneous disease in terms of lymphocyte surface receptors and that the pathologic cells of the majority of patients with this disease cannot be identified as being of thymic or non-thymic origin.


Hemophilus influenzae b pericarditis in children. Recent experience in the diagnosis and management of Hemophilus influenzae b pericarditis is described in five children. Anterior pericardectomy appears to be the preferred method of surgical drainage because it was associated with a shorter hospitalization than pericardiocentesis or closed or open pericardotomy and removed the risk of recurrent cardiac tamponade and constrictive pericarditis. Countercurrent immunoelectrophoresis of sera and pericardial fluid was used to rapidly identify the etiology of pericarditis in four of four patients tested. The observation that three children appeared to develop pericarditis in the absence of a contiguous infectious focus suggests that bacteremic seeding of the pericardium may be important in the pathogenesis of this disease.


Neonatal intracranial hemorrhage in premature infants. Since the advent of modern methods of neonatal care, intracranial hemorrhage in premature infants, which is usually intraventricular, is probably not as uniformly fatal as generally admitted and the survivors are likely to develop post-hemorrhagic hydrocephalus. This paper is a retrospective study of 11 premature babies born between 1968 and 1972 and diagnosed as having hydrocephalus secondary to neonatal intracranial hemorrhage. Nine of these are still alive and two have died, one at 3 and one at 17 months of age. Eight underwent permanant surgical drainage of hydrocephalus. The perinatal history, laboratory data, clinical evolution, and neurological outcome were studied. Two groups of infants were identified; those with signs of acute neurological deterioration in the neonatal period who had the most severe neurological sequellae (in four cases, periventricular lesions in addition to hydrocephalus were seen on the air study and in one case confirmed at autopsy) and those showing no obvious neurological signs in the neonatal period. Of this latter group, two appear to be developing normally. The therapeutic implications of the findings are discussed.


Potassium accumulation in the perinodal space of frog myelinated axons. 1. Voltage clamp experiments were carried out on frog myelinated fibres to study the origin of the transient inward current occuring when the membrane is repolarized after long lasting depolarizing pulses (tail current denominated "Ip" by Frankenhaeuser). 2. The "tail" of inward current measured during repolarization after break of the depolarizing pulse is insensitive to external application of TTX, is abolished by external treatment with TEA or Cs and decreases when the outward K-current during the pulse is diminished. 3. The time course of the "tail" current is exponential. Its direction depends on the duration of the depolarizing pulse and on the membrane potential level at repolarization. 4. It is concluded that the tail of inward current during repolarization is carried by K-ions accumulated in the perinodal space during a depolarizing pulse. The data suggest that the tail reflects the time course of the restoration of the K-concentration to its initial level. The tail current itself contributes to this restoration depending on the Em value at repolarization. 5. It is shown that one of the two phenomenological models proposed by Frankenhaeuser and Hodgkin to account for the external potassium accumulation observed in the squid giant axon may be also applied to the Ranvier node. Assuming that the thickness of the space is 2900 A and that the K-permeability of the barrier is 0.019 cm/sec, it is possible to account for the observed changes in [K]0 during a long lasting depolarizing pulse. 6. The existence of such a barrier would introduce an electrical resistance in series with the nodal membrane of roughly 150 000 omega.


Transient current changes and Na compartimentalization in frog skin epithelium. Experimental conditions are described in which transient and positive current responses across isolated frog skin epithelia can be elicited by sudden addition of Na and Li ions (2--40 mM) in the outer bathing solutions. Subsequent return to outer Na (or Li) free conditions produce similar transient current changes but in the opposite direction. Analysis of the curve responses shows that the transient component of each curve is best described by a single, fast exponential term equation in case of Na addition to preparation unpoisonned with ouabain. In contrast, an equation including two exponential terms (a fast and a slow one) is required to fit the curve responses observed across ouabain treated epithelia or if Li is added outside. The transient responses were not significantly altered by substituying Cl for SO4(2)-anions. They were completely prevented by Amiloride (5-10(-5) M), increased by oxytocin (20 mU/ml) and markedly dependent upon the outer Na concentration. Interpreted in term of compartmental analysis, these observations suggest that a) the frog skin epithelium contains 2 separated but communicating compartments having different degrees of accessibility from outside; b) only that compartment filling at a fast rate (0.5 min) is involved in the transepithelial Na transport; c) the other one, filling at a rate of 4 to 7 min, is resplenished only under conditions where the basal pump system has a reduced activity. Tentative localization of these compartment is proposed.


Na and K movements across the membranes of frog skin epithelia associated with transient current changes. The ionic composition of the current crossing each membrane of the frog skin epithelia during a) the positive and transient current responses elicited by sudden addition of Na ions to the outer Na free medium b) the negative and transient current responses observed when Na loaded preparations are suddenly exposed to outer Na free solution was determined using isotopic techniques. It is shown that Na ions carry the current across the outer membrane while K ions are mainly involved in the transfert of charges across the inner membrane. The amount of Na accumulated by the epithelial cells during the responses is correlated to the area under the transient part of the current responses. Determinations of 24Na uptake at different time of these transient positive responses show that the unidirectional Na influx across the outer membrane decreases as a function of time. It is suggested that the intracellular Na concentration might control the Na uptake mechanism across the outer membrane. During the negative responses, the Na efflux into the outer medium is highly correlated, either in time course or magnitude, to the current response. Both Na efflux and negative current are sensitive to amiloride, suggesting that the mechanism of Na uptake by the frog skin also is able to promote Na movement out of the epithelial cells.


The comparative effects of (Ca2+) and (Mg2+) on on tension generation in the fibers of skinned frog skeletal muscle and mechanically disrupted rat ventricular cardiac muscle. The effects of intracellular Mg2+ on Ca2+-activated isometric tension generation in rat cardiac muscle fibers and frog skeletal muscle were compared. The membranous sarcolemmal barrier was removed from rat cardiac muscle fibers by mechanical disruption and from frog skeletal muscle by skinning. Tension was recorded in the fibers in bathing solutions of different Ca2+ concentrations and either 5 X 10(-5) M or 1 X 10(-3) M Mg2+ concentration (the same concentrations used in a previous study on single skinned frog skeletal muscle fibers [3]). The amount of Ca2+ required to activate the muscle increased with Mg2+ concentration for both rat ventricular muscle and frog skeletal muscle. These data indicate that intracellular Mg2+ concentration could strongly modulate Ca2+-activated tension in cardiac muscle and that very similar molecular mechanisms are responsible for Ca2+-activated tension in rat ventricular muscle and frog skeletal muscle. The possible sites of action of Mg2+ on Ca2+-activated tension are discussed.


Influence of the membrane stabilizer diphenylhydantoin on potassium and sodium movements in skeletal muscle. The membrane stabilizer diphenylhydantoin (DPH) did not alter the net content of Na, K, Ca or Mg in frog sartorius muscle freshly incubated or actively transporting Na and K following Na-loading and K-depletion. Resting influx of K from normal Ringer was significantly reduced by DPH, and this inhibition occurred in the ouabain-insensitive K-uptake. Inhibition of K-influx by DPH was overcome when [K]0 was raised to 10 mM, and Rb-influx was not sensitive to the inhibitor in 2.5 mM Rb-Ringer. Efflux of tracer K was reduced by DPH in the presence and absence of ouabain. Exchange of muscle Na was not affected under conditions in which K-exchange was significantly reduced, but DPH appeared to cause increased net loss of Na from muscles washed in Na-free medium. The inhibition of DPH of resting K-exchange was not sensitive to wide variations in [Na]0 or in [Ca]0. The results suggest that the effect of DPH on frog skeletal muscle in normal ionic environment is to reduce the resting, passive component of K-exchange across the fibre membrane. This effect is discussed in relation to the membrane stabilizing actions of diphenylhydantoin.


[Treatment of hemophilia with immunologic inhibitor of factor VIII by using "activated" coagulant fractions]. Bleeding episodes in hemophiliacs with inhibitor to factor VIII are often dramatic situations. High level inhibitors do not respond to massive amount of factor VIII and are often refractory to immunosuppressive drugs such as cyclophosphamide. In this situation it has been proposed to use "activated prothrombin complex" to control bleeding in hemophilic patients with inhibitors. A plasmatic fraction "Auto IX" has been used successfully for the treatment of an intestinal hemorrhage in a patient with an inhibitor to F. VIII. Possible mechanisms of action as well as potential thrombotic danger of such concentrate are discussed.


[Is triacetyl oleandomycin-ergotamine tartrate combination dangerous?]. The authors report a case of ischaemia of all four limbs in an adolescent following the simultaneous ingestion of triacetyl oleandomycin and ergotamine tartrate in low dosage. Two cases involving this same association of medications have appeared in the literature and attention is therefore drawn to the possible danger of use of these two drugs together.


Components of O2-uptake by excised frog nerve dependent upon externally supplied sodium ions. The steady rate of oxygen uptake of excised frog nerves equilibrated in a solution having a very low concentration of sodium ions increases to a new high steady rate when equilibrated with a solution containing a high concentration of this ion. The increase is suppressed by ouabain, indicating participation of the sodium pump. Part of this sodium-activated increase in oxygen uptake is inhibited by tetrodotoxin, indicating that passive influx of sodium ions into axons is part of the total process. Thus, two pathways for passive sodium influx into axons are suggested by these experiments. Procedures known to increase the passive permeability of axons for sodium ions also increase this sodium-activated oxygen uptake. A mechanism is proposed to explain that part of the sodium-activated oxygen uptake that is inhibited by tetrodotoxin.


New approach to antifolate treatment of certain cancers as demonstrated in tissue culture. The selective toxicity of antifolates for a variety of cancers can be improved, as illustrated by the combined administration of N5-methyltetrahydrofolate and methotrexate in tissue culture. When a variety of neoplastic cell types characterized by a deficiency of vitamin B12-dependent N5-methyltetrahydrofolate methyltransferase (5-methyltetrahydropteroyl-L-glutamate:L-homocysteine S-methyltransferase, EC 2.1.1.13) and normal adult cells are grown in media containing methotrexate and either N5-methyltetrahydrofolate or N5-formyltetrahydrofolate, not only is the selective toxicity of methotrexate demonstrated, but the advantage of using N5-methyltetrahydrofolate in place of N5-formyltetrahydrofolate is also revealed. The implications and applications of this particular combination in the treatment of human cancer are discussed.


Membrane particles on fracture faces of frozen myelin. Freeze-fracture electron microscopy reveals constant and widespread presence of membrane particles on the fracture faces of frozen myelin. In unfixed myelin frozen shortly after dissection the distribution of the particles is uniform. In glutaraldehyde-fixed and/or glycerol-impregnated myelin the particles frequently occupy a network interspersed with circumscribed particle-free areas of variable dimension. In these membranes the network of particles is propagated radially across many lamellae. Particle-rich areas are closely apposed and contrast with frequent delamination of adjacent particle-free regions. We propose that, as in other plasma membranes, the particles of myelin represent protein-containing structures intercalated across the hydrophobic matrix of a membrane with bilayer organization. Our results indicate that these structures contain sites which mutually interact at the surface of apposed membranes and may be important in maintaining the organizational integrity of myelin.


Near-fatal hemorrhage following gastrografin studies. The use of upper gastrointestinal studies followed by gastric drainage and observation is recommended for the evaluation and treatment of stomal dysfunction due to edema or gastric atony. Gastrografin though, may be precipitated out and can cause gastrointestinal bleeding if left in the gastric remenant. This agent should be used with proper precautions in the evaluation of postoperative gastric retention.


Participation of the external and internal carotid arteries in the blood supply of acoustic neurinomas. Six cases of acoustic neurinoma are presented in which the tumor is supplied by branches of the external carotid artery, with or without supply from the internal carotid artery. A new angiographic protocol for the investigation of masses in the cerebellopontine angle is suggested. According to early results of the CT scan, acoustic neurinomas always appear to be hypervascular following the injection of contrast media.


Mitogens of B and T cells from peripheral blood in rheumatoid arthritis. Patients with rheumatoid arthritis (RA), 36 cases, and normal subjects, 49 cases were studied by lymphocyte cultures stimulated by phytohemagglutinin (PHA), Concanavalin A (Con A), pokeweed mitogen (PWM) and Con A convalently bound to Sepharose 4 B (Con A-S). The comparisons between the two groups showed a significant difference between the RA lymphocytes and the control lymphocytes stimulated by PHA and Con A. However, no statistical difference was found between the two lymphocyte populations stimulated by PWM and Con A-S. In order to determine the lymphocyte population stimulated by each mitogen, separation of B and T cells from peripheral blood was performed according to the ability for the T cell population to bind the sheep red blood cells (rosette-forming cells). The T cell-rich population was only stimulated by PHA, Con A and PWM. Although the T cell-depleted population showed no response to these mitogens, a response to Con A-S was elicited.


Studies on antilymphocyte antibodies in patients with rheumatoid arthritis and systemic lupus erythematosus. Anti-lymphocyte antibodies have been demonstrated in patients with SLE and RA by immunofluorescence. They differ from those arising through iso-immunization by being cold reactive and chiefly of the IgM class. Separate anti specificities were shown for determinants on either T or B cells.


Evaluation of serum thymic hormone and of circulating T cells in rheumatoid arthritis and in systemic lupus erythematosus. The presence of a serum factor secreted by the thymus has been demonstrated in the serum of mice and man using a rosette inhibition assay. This factor is a peptide with a molecular weight close to 1,000. Its level is age dependent, being stable until the age of 6 months in mice and until 20 years in man. New Zealand Black mice show a premature cessation of thymic hormone secretion preceeding the onset of other T cell abnormalities and auto-immunity. Before any treatment the serum thymic hormone level is abnormally low in most cases of SLE even in patients under 25, an age where control subjects still show high hormone levels. Conversely, normal or high levels are found in RA, PARTICularly in patients over 40 who showed in 60% of cases a hormone level significantly higher than normal controls of the same age. In keeping with this data T cells evaluated by SRBC spontaneous rosette formation show low figures in some patients with active SLE and normal or high values in most cases of RA.


Evidence for complement activation by the alternate pathway in the arthritis of hypogammaglobulinemic patients. The chronic, rheumatoid synovitis in four patients (two children and two adults) with immunodeficiency was studied by means of immunopathological examination of synovial tissues and fluids. Their immunodeficiencies were extensively studied, with various tests for humoral and cell-mediated immunity. The two children were boys with Bruton's disease. One adult, female, had common variable immunodeficiency. One adult male had severe hypogammaglobulinemia. All patients had isolated deposits of complement component C3 in their synovial membranes, usually without traces of immunoglobulins. Depressed levels of complement component C3 were found in the joint fluid, in contrast to high levels in the corresponding serum in one patient. Components of the alternate pathway, properdin and C3A, were found in the tissues, but not components of the classic pathway, C1q and C4. The findings suggest that chronic, rheumatoid arthritis in hypogammaglobulinemic patients may be related to activation of C3 by the alternate pathway.


Study of the effects of antigammaglobulin factors on lymphocytes from patients with rheumatoid arthritis. Previous work suggests that peripheral blood lymphocytes from patients with rheumatoid arthritis have altered reactivity. The purpose of this study has been to observe the behavior of cultures of lymphocytes from patients with rheumatoid arthritis when stimulated with autologous 19S rheumatoid factor and with rabbit serum against autologous IgG fraction. The peripheral blood lymphocytes (PBL) from 15 patients with classical rheumatoid arthritis were obtained by passage of the leukocyte-rich plasma through a polyamide fiber column. The purified lymphocytes were cultured with rheumatoid factor obtained from the same donor through Sephadex G-200 chromatography. In another set of experiments rheumatoid lymphocytes were stimulated with rabbit serum containing antibodies against the IgG fraction of the same patient obtained through DEAE chromatography. After five days the lymphocytes were examined for large cells plus cells in mitosis. A positive response was defined as an increase of 5% or more in the experimental tubes when compared with the cells cultured alone. Ten healthy normal subjects were used also as lymphocyte and serum donors. These lymphocytes were cultured alone and with rabbit serum, anti-autologous IgG. 80% of rheumatoid lymphocytes responded with an average of 37% of enlarging and dividing cells when stimulated by autologous RF. The same pannel of lymphocytes responded only with an average of 14% stimulation when cultured with rabbit serum anti-autologous IgG. The response to the 7S antigammaglobulin factor from rabbit in 7 normal PBL was similar to that of rheumatoid lymphocytes. There was some relation between activity of the RA and lymphocyte response to RF and rabbit antiserum. These results could explain the lymphoid infiltration and hyperplasia of patients with RA and, on the other hand, would support the idea that entrapment of RF by leukocytes ('RA cell') would be a protective mechanism.


The failure of allogeneic cells to maintain an immune response in nude mice. Nude mice that have been injected with allogeneic thymus cells and sheep erythrocytes respond for a short time and are then unable to respond to subsequent injections of sheep erythrocytes, even if given with allogeneic thymus cells from the same or a different strain. However, they can respond to a different antigen or to the original antigen if given with congenic thymus cells. B cells from such animals are able to respond if transferred together with congenic thymocytes to irradiated hosts. It is suggested that allogeneic T cells are able to cooperate with B cells to initiate an immune response but that a further step is necessary to maintain the response, and for this congenic T cells are necessary.


Macrophages suppress direct B-cell activation by lipopolysaccharide. The influence of macrophages on polyclonal B-cell responses to lipopolysaccharide (LPS) and on a primary, specific immune response to a hapten-LPS conjugate was studied in mouse spleen and lymph node cells in serum-free and serum-supplemented cultures. Macrophages were found not to be necessary, and B cells were directly activated by LPS. In serum-free cultures of macrophage-depleted spleen cells, (a) proliferation and antibody secretion occurred at normal levels or were enhanced when compared with normal spleen cells, (b) the responsiveness of limiting cell numbers to LPS was better than in normal spleen cell cultures, (c) LPS did not increase the number or activate residual macrophages, (d) the primary specific response to a hapten-LPS conjugate developed normally, (e) peripheral lymph node cells, which are known to contain a very low concentration of macrophages, from normal or congenitally athymic (nude) mice mounted excellent proliferative responses to LPS. Furthermore, in cultures supplemented with fetal bovine serum, depletion of adherent cells resulted in enhancement of LPS-induced B-cell responses. Addition of peritoneal macrophages to adherent cell-depleted spleen cells produced suppression at all concentrations of both mitogen and adherent cells. Suppressive activity could also be demonstrated in supernatants from adherent cell cultures stimulated by LPS.


Differentiation of T cells in nude mice. Cells bearing the T-cell differentiation alloantigens TL and Thy-1 were enumerated in preparations of spleen and lymph node cells of nu/nu mice. Healthy nu/nu mice had few or no demonstrable TL+ or Thy-1+ cells whereas mice with viral hepatitis, including some born of nu/nu X nu/nu matings, had many. Healthy nu/nu mice were treated daily with the thymic hormone thymopoietin or with ubiquitin, polypeptides that induce the differentiation of TL+Thy-1" cells from TL-Thy-1- precursors in vitro. After 14 days, 20 to 40 percent of their spleen cells were of the TL+Thy-1+ phenotype typical of thymocytes and 10 to 25 percent of their lymph node cells were TL-Thy-1+, typical of later T-cell differentiation. Similar frequencies of such cells were found in untreated nu/nu mice suffering from severe viral hepatitis. These data conform to the current view that prothymocytes are preprogrammed cells whose maturation to thymocytes, normally induced in the thymus by thymopoietin, can be triggered by other agents under abnormal circumstances. Tests of T-cell function were not included in this study.


Coronary artery bypass for acute myocardial infarction. Coronary artery bypass has been done on 20 patients for acute mmyocardial infarction associated with shock, arrhythmia, and/or cardiac arrest. Twelve had had catheterization before the time of infarction. There were 3 hospital deaths, 2 late deaths, and 15 survivors. Survivors are angina-free and active 4 to 40 months postoperatively. Five patients have been recatheterized since operation, and in 4 all grafts are patent and functioning. Ventricular function was not improved in one patient, has remained the same in one, and improved in 3 patients. Although the time interval from infarction to revascularization is important, success is just as dependent on the patient's existing coronary collateral circulation. Lesions of the left main coronary artery were associated with the highest mortality. The rationale for operation in patients with acute myocardial infarction is to revascularize the marginal myocardium adjacent to the infarct and other underperfused areas when indicated. Chance for survival may thereby be increased by improvement of cardiac pumping or reversal of cardiac arrest or arrhythmia.


Infections after retinal detachment surgery. The signs and symptoms of infection after retinal detachment surgery may be subtle and frequently are overlooked during early stages. A retrospective analysis of 3,334 consecutive procedures for retinal detachment revealed 37 cases (1.1%) with postoperative infection. In 13 of these a scleral abscess and a form of endophthalmitis developed, whereas 24 had no evidence of vitreous involvement and were classified as the granuloma type. Only 43% of infected patients had positive cultures. Analysis of changes in infection rate involved comparison with changes over the years in suture material, implant material, performance of scleral undermining, drainage of subretinal fluid, number of previous surgical procedures, age of patient, use of diathermy or cryotherapy, and type of prophylactic antibiotic therapy. During the 13 years studied the rate of infection decreased from 2.2% to 0.7%. Treatment requires surgical removal of all foreign material before the inflammatory signs can be cleared. Concurrent appropriate antibiotic therapy also is recommended. With this form of treatment, all but one patient showed a satisfactory response, although 4 patients still have mild conjunctival congestion.


Splenic artery ligation in selected patients with hepatic cirrhosis and in Sprague-Dawley rats. The effects of splenic artery ligation were studied in Sprague-Dawley rats and in eight selected symptomatic patients with hepatic cirrhosis. In rats, this maneuver induced splenic infarction, reduced functional splenic mass, transiently raised platelet and reticulocyte counts and was without local complications. In seven selected patients with cirrhosis and prominent splenomegaly, the splenic artery was markedly enlarged, splenic arterial flow was greatly increased and splenic artery ligation partially lowered portal pressure. In three patients with varying cytopenias secondary to hypersplenism splenic artery ligation uniformly improved peripheral blood elements, although varying degrees of hypersplenism later recurred necessitating splenectomy in one. In five other patients, splenic artery ligation in conjunction with coronary vein ligation in four was performed for bleeding esophageal varices. Two patients later required portacaval shunting, and one other in whom operation was undertaken in desperation died of hepatic failure. Celiac-mesenteric arterioportography, operative portography, hemodynamic measurements and examination of peripheral blood elements in these eight patients suggests that splenic artery ligation in conjunction, where appropriate, with coronary vein ligation has several potentially beneficial effects. Hypersplenism may be sufficiently controlled to alleviate clinical symptoms. Arterial inflow into the portal system is reduced tending to lower portal pressure. Transheptic portal flow from the mesenteric bed is preserved. Venous anastomotic channels still functioning around the splenic pedicle and no longer draining a hyperdynamic splenic circuit may be converted into an escape route for mesenteric venous blood entering the portal system under high pressure. Nonetheless, each of these effects and their interrelationships require further study before this operation assumes a larger role in the treatment of complications of portal hypertension.


Ristocetin in the diagnosis of von willebrand's disease: a comparison of rate and percent of aggregation with levels of the plasma factor(s) necessary for ristocetin aggregation. Percent aggregation and the aggregation rate of platelet rich plasma (PRP) in response to ristocetin (1.75 mg/ml) were measured in 20 normals and 16 patients with von Willebrand's disease (v Wd), with and without the addition of acetylsalicylic acid (ASA). Percent aggregation did not clearly distinguish between normals and patients with vWd. Aggregation rate was normal in only 2 of 16 patients, and after incubation of PRP with ASA 1 of these 2 remained normal. The corrective effect of dilutions of platelet poor plasma (PPP) on the ristocetin response of washed platelets (von Willebrand's factor, vWf) was measured in 21 normals and 12 patients with vWd. All patients with vWd had abnormal levels. There was a significant correlation between aggregation rate and vWf in patients with vWd but not in normals. Both tests appear to measure closely related defects, and the aggregation rate is as specific as the vWf level for the diagnosis of clinically affected patients.


Keratomalacia.

Keratomalacia. Xerophthalmia and keratomalacia are public health problems of great magnitude which are usually associated with multiple vitamin and protein deficiencies. The authors report the case of a 27-year-old commune member who subjected herself to a bizarre protein and vitamin deficient diet for many months. This ultimately produced nyctalopia, xerophthalmia and keratomalacia with bilateral corneal perforation. Despite therapy, she remained comatose and expired shortly after admission. Ocular pathological changes included bilateral corneal melting with prolapse of intraocular contents, conjunctival epidermidalization, goblet cell atrophy and thinning of the outer nuclear layer of the retina. It is noted that ocular findings in pure avitaminosis A produced experimentalyy include epithelial atrophy followed by keratinization.


[Banding for pulmonary artery and subsequent repair in large ventricular septal defect (author's transl)]. Banding of the pulmonary artery was performed in 233 children with large, non restrictive ventricular septal defects. The group of isolated large VSDs consisted of 95 patients, of whom 8 died (8,4 per cent). 32 patients were subjected to open-heart operation for closure of the VSD and debanding. In this "two-stage group" the mortality rate was 6,3 per cent. At the second operation the pulmonary artery always should be enlarged with a pericardial patch. Our recordings up to 6 1/2 years after correction show no gradients left in cases surgically treated in this manner. The time-interval between effective banding and debanding procedure may not be limited strictly; the subsequent operation however should be done within two or three years.


[Ventricular septal defect associated with fibrous subvalvular aortic stenosis: problems in the diagnosis and in the surgical management (author's transl)]. Only 9 of more than 900 operated patients with ventricular septal defects suffered from this rare combination. The problems of the diagnosis are discussed. Only in one case this diagnosis was made praeoperatively, in 6 cases intraoperatively and in two cases only postoperatively. In the last two cases a reoperation was necessary. The surgical methods are described and the results of surgery are communicated.


[The fate of the pulmonary hypertension after ASD-closure in adults (author's transl)]. 10 female and 7 male patients, who were operated for secundum type Atrial Septal Defect with Pulmonary Hypertension, got postoperative check-ups including right heart catheterisations. The investigations were performed on the average 6.6 years postoperatively. There was a fall of the systolic pulmonary pressure and of the flow; pulmonary resistance fell in 8 cases and rose in 9. The low left ventricular cardiac index together with an elevated left atrial pressure may be the pathogenetic cause of postoperatively elevated pulmonary resistance.


Late results of aortic homograft reconstruction of the right ventricular outflow tract in infants and children. 33 infants and children between 4 months and 14 years have undergone successful reconstruction of the right ventricular outflow tract with adult sized fresh aortic homografts. The late results have been analysed and it is concluded that satisfactory results can be obtained even in infants and that the operation should be performed early to prevent secondary changes in the heart and lungs.


[Critical outflow valve obstruction under the age of one year (author's transl)]. This report represents the Brompton Hospital experience of infants and neonates with critical pulmonary valve stenosis and aortic valve stenosis. There were 25 patients with critical pulmonary valve stenosis and 8 with critical aortic valve stenosis. Critical pulmonary stenosis: Among the 25 patients up to one year of age, 11 were girls and the commonest presenting symptom was cyanosis seen in 15, the commonest physical sign being a systolic ejection murmur with a single 2nd sound. A more detailed analysis of the symptoms, signs and findings at special investigation will be presented. The evolution of a satisfactory technique of operation will be indicated in these critically ill patients, and the late follow-up will be presented. Critical aortic stenosis: There were 8 patients in this group all of whom were male. Dyspnoea was the commonest presenting symptom with a systolic ejection murmur and hepatomegaly as the commonest signs. All patients in this group underwent open aortic valvotomy and/or valvuloplasty with 3 deaths. A late follow-up of the survivors will be presented. In summary, a series of 33 patients up to the age of one year with critical obstruction of either the pulmonary or aortic valves will be presented. (his is one of the larger series to be reported in this age group.


[Surgical treatment of kinking of the internal carotid artery (author's transl)]. Report on 20 cases of non arteriosclerotic kinking of the internal carotid artery. Besides the more common resection-technique a myoplasty using the digastric muscle is performed. Regional cerebral blood flow by 133 Xenon and angiography pre- and postoperatively are compared.


[Nutritional effects following lumbar sympathectomy in arterial occlusive disease (author's transl)]. The effect of lumbar sympathectomy on regional blood-flow and on oxygen uptake of tissue has been investigated in animal experiments and in man. Lumbar sympathectomy did always result in increase of limb blood-flow, but did not significantly improve oxygen consumption of the observed extremity. This finding was manifested by marked narrowing of the arterial-venous oxyhemoglobin saturation difference suggesting that lumbar sympathectomy caused opening of arterial-venous shunts.


[Classification of mitral valve disease by clinical features and hemodynamic parameters (author's transl)]. Using the central venous oxygen saturation (SO2v) at rest and during exercise (50 Watt) a new classification of mitral valve disease is proposed, which corresponds with the recommendation of the NHA (1953). Contrary to the mostly subjective classification by clinical features, the new one results from objective hemodynamic parameters. The validity of the new proposed classification is shown using different clinical parameters.


[Operative results after mitral valve replacement with Starr-Edwards disc valves and Björk-Shiley prostheses (author's transl)]. The postoperative course of 425 patients with isolated mitral valve replacement using either the Starr-Edwards disc prosthesis or the Björk-Shiley tilting disc valve is evaluated. Both protheses showed comparable clinical results during a follow-up period between 5 months and 4 years.


[1-Year-results of anuloplastisy (Carpentier-technic) in 7 patients (author's transl)]. Of 7 patients who had Carpentier anuloplasty, two had very good, two had good and two had unsatisfactory results in postoperative cardiac catheterization one year after operation. One patient died of acute hepatitis. Reasons for the poor results are false indications and inadequate operative technic. These results show that the Carpentier-technic can well be recommended for critical use in carefully selected patients with mitral insufficiency.


[Aortic valve replacement for acute heart failure due to infective endocarditis (author's transl)]. 5 patients with primary infective endocarditis developed acute cardiac failure because of aortic valve insufficiency. 2 patients were in the active and 3 patients in the inactive stage of infective endocarditis. In 4 patients an aortic and in 1 patient an aortic and mitral valve replacement was performed. The early mortality rate (death within 30 days of operation) was 20 per cent. Once congestive heart failure starts during the course of active endocarditis surgery should be undertaken at an early date.


[Surgical treatment of coronary heart disease (author's transl)]. Until 1974 146 patients underwent coronary surgery in Hamburg. The total mortality rate for the first 100 postoperative days was 16,3 per cent. In the last years the mortality was reduced to 14 per cent. This group included all different selective and emergency surgical procedures for coronary disease. Due to the different degree of the coronary disease and/or of the impairment of the left ventricular function the mortality ranged between 0 per cent and 35 per cent. Some clinical parameters influencing the mortality rate are discussed.


[The use of laser in thoracic-, cardiac- and vascular surgery (author's transl)]. We carried out thoracic and cardiovascular operations with a 50 watt CO2-Laser. The advantage of this procedure: A minimal trauma of tissue in consequence of no use of selfcutting surgical instruments, bloodless incision at smallest area of coagulation and no possibility of displacement of infections and tumor cells. We believe that this new laser in all surgical disciplines introduced soon.


[Is transvenous cardiac pacemaker implantation with X-ray control associated with a dangerous radiation exposure? (author's transl)]. From July to December 1974 we measured the radiation exposure of the hands of the operator and assistant with 69 implantations of permanent cardiac pacemakers and recorded a dose of 0,5 mrem/min, this corresponds to 4 mrem/patient.


A prospective study of HL-A antigen phenotypes and lymphocyte abnormalities in Hodgkin's disease. In a prospective study, sixty-five histologically verified Swedish cases of Hodgkin's disease were HL-A typed. The antigen frequencies in the patient group did not deviate from a group of normal controls. The frequency of HL-A8 was slightly increased in patients over 40 years (P less than 0.05). HL-A12 was markedly increased in patients below 40 years with a favourable histopathology (P less than 0.001). No association between sex or clinical stage and distribution of HL-A phenotypes was observed. The number of T-lymphocytes in blood and the spontaneous DNA synthesis and DNA synthesis induced by concanavalin A, pokeweed mitogen, phytohemagglutinin and PPD antigen in blood lymphocytes in vitro were determined in 60 patients. A significant increase of HL-A28 was noted in patients with advanced disease (P less than 0.01) and in patients responding poorly to PPD (P less than 0.001) and PWM (P less than 0.01). No correlation between HL-A antigen distribution and T-lymphocyte counts was observed.


[Emergency direct revascularization of the myocardium in acute infarct]. A new surgical conception of urgent direct revascularization of the myocardium in acute infarction is discussed and substantiated. Clinical observations and results of 13 urgent operations for aorto-coronary shunting in 10 patients with acute myocardial infarction are analysed (double aorto-coronary shunting was performed in 3 cases). Indications to urgent revascularization of the myocardium in infarction were as follows: no effect of drug therapy during 2--3 hours since its onset, a failure to eliminate pulmonary edema and cardiogenic shock in a localized proximal occlusion of the coronary artery, revealed during a planned or urgent coronarography. Three patients were operated upon in the state of cardiogenic shock (one after reanimation), two with pulmonary edema. All these patients (excluding one with pulmonary edema) have made a good recovery. Three patients died. Good immediate and late results obtained evidence the advantage of this policy. The problems of most optimum terms for urgent revascularization of the myocardium are discussed.


[Importance of the type of blood supply to the heart in reconstructive surgery of the coronary arteries]. Anatomical data on the type of the heart blood supply are reported. Based on anatomical studies on 35 hearts, the author found the right type of blood supply in 24 cases, the left type in 4, and balanced in 7 cases. The study of coronarograms of 100 operated patients and data of the intraoperative diagnosis indicated that anatomical variants of coronary arteries extension fully agree with coronarography findings. At the same time there was no definite dependence between the type of cardiac blood supply and the degree and character of coronary arteries affection.


A case report of a hemolytic transfusion reaction caused by anti-Holley. Clinical and laboratory investigation of a black male patient, who received emergency transfusion of blood incompatible for a high incidence antigen, provided evidence for the pathogenetic importance of high titer anti-Holley antibodies with poor avidity. The red blood cells of the patient and two siblings were remarkable in being negative for two high incidence antigens, Hy and hrS, and weak for a third, Gy.


[X-ray findings in meningiomas of the tentorium cerebelli]. A roentgenological investigation of 38 patients with meningiomas of the tentorium cerebelli of the supra-subtentorial growth revealed signs of hypertension in 31 of them. The destruction of the squama occipitalis and of the superior edge of the apex of the petrous pyramid was found in 17 of these patients. Opacification of the ventricular system discerned a combination that included compression of the inferior contour of the posterior segments of the lateral ventricles or a filling defect of the trigonum of the left ventricle with deformation of the posterior segment of the III ventricle and a displacement forward of the aqueductus Sylvii. An angiographic investigation of the carotid and basilar systems determine a typical picture of simultaneous shifts, viz, upwards--of the median cerebral artery, medially--of the internal occipital artery; outwards--of the temporal-occipital artery, medially and downwards--of the superior cerebral artery. Obliteration of the sinuses rectus and transversalis comes into evidence. Opacification of the meningioma vasculature above and underneath the tentorium cerebelli makes the topical diagnosis quite convincing.


[Eye movements in animals with extirpated cerebrocortical oculomotor centers]. An investigation of dogs with removed temporal and sincipito-occipital cortical centres of the eye movements demonstrated that a number of properties of the vestibular nystagmus evoked by the rotation of the animal remain the same as they had been in this very same animal prior to the operation. These centres do not control the nature of the nystagmic movement that consists of a slow and a fast components, the combined movements of the right and left eyes, the direction of the nystagmus, the range and the nature marking the distribution of the maximal movement and of the most frequent movements during the action of the stimulus and the symmetry of the labyrinthine function. At the same time, the dissociation of the cortical centres of the eye movements brings on shortening of the vestibular post-rotational nystagmus, activation of the mechanism that monitors the rhythmic tonic deflections of the eyes, this causing diminution in the number of nystagmic eye movements and disruption in the rhythm of their movement. It also activates arbitrary movements of the eyes that occasionally turn into a spontaneous nystagmus. The abundance of arbitrary eye movements following vestibular stimulation is of frequent occurrence in children, victims of cerebral paralysis of childhood combined wit- depressed cortical function.


[Complete gastric erosions--a relatively frequent gastroscopy finding]. While by means of the semiflexible Wolf-Schnidler-gastroscope no complete erosions had been seen, they were found in 12.7% in 615 gastroscopies, carried out with glass fibre endoscopes. In nearly 80% of the patients the erosions, appearing in most cases in a larger number, were localised in the antrum ventriculi. As the most frequent concomitant disease the gastroduodenal ulcer was found. Roentgenologically in no case the diagnosis erosion was made. As to the soft tissues defects of the epithelium could rarely be ascertained, however, more frequently a foveolar pseudohyperplasia as the morphological substrate of the marginal wall. Chronic-atrophic changes of the mucous membrane in the environment of the erosions were by far more frequently to be proved than superficial gastritides or normal findings on the mucous membrane of the stomach.


[Glycoproteins in diabetes mellitus].

[Glycoproteins in diabetes mellitus]. Analyses of mucoproteins, orcin-positive protein sugar, sialic acid of the alpha2-macroglobulin, alpha1-glycoprotein, alpha1-antitrypsin, alpha2-HS-glycoprotein and beta2-glycoprotein I were carried out in 302 diabetics. In creases of concentration could be proved for alpha2-macroglobulin, alpha2-HS-glycoprotein, orcin-positive protein sugar and sialic acid. In diabetics with retinopathies the alpha2-macroglobulin concentration is significantly increased compared with diabetics without retinopathies.


[Stomach ulcer in the emergency endoscopy]. After explanation of the diagnostic gain in acute gastrointestinal haemorrhages by use of the emergency endoscopy the results and experiences are reported got in 200 emergency examinations. As cause of haemorrhage most frequency were found peptic ulcers followed by gastric erosions. In one third the erosions were associated with other sources of haemorrhage and should be accepted as cause of haemorrhage only with cautiousness. Flat acute ulcerations cannot be diagnosed endoscopically already by relatively thin-layered linings and chronic ulcerations by plications.


The aortogram and gastrointestinal bleeding. Three cases of gastrointestinal hemorrhage are reported which illustrate that the bleeding site may be missed angiographically if the study is limited to celiac and mesenteric angiograms. An abdominal angiogram must be performed as part of the radiological investigation of gastrointestinal bleeding.


Coronary graft flow and glucose tolerance: evidence against the existence of myocardial microvascular disease. Patients having coronary bypass for stable angina pectoris were grouped on the basis of the two hour plasma sugar of the glucose tolerance test: Group I, 120 mgs% (159 grafts); Group II, 120-150 (93 grafts); Group III, 150-200 (131 grafts) and Group IV, 200 (57 grafts) or patients receiving therapy for diabetes mellitus (10 patients, 21 grafts). Five of 10 diabetic patients had genetic evidence of diabetes and an average duration of therapy of 6.5 years. Blood flow was measured in 461 grafts with an electromagnetic flow probe after discontinuation of cardiopulmonary bypass in a stable state, after a 30 second graft occlusion and after injection of 15 mg of papaverine into the graft. Mean arterial pressure, graft flow and coronary resistance for each succeeding group did not vary significantly when compared with Group I. Analysis of phasic flow in 10 grafts to the left anterior descending indicates that the same proportion of flow occurs during systole and diastole in the basal state and after pappaverine. Coronary flow and resistance in patients with abnormal glucose metabolism and maturity onset diabetes do not provide evidence for the existence of myocardial microangiopathy.


Aneurysms of an aorto-coronary artery saphenous vein bypass graft--a case report. A 62 year old man with severe angina pectoris underwent aoroto-coronary saphenous vein graft implantation. After a four month asymptomatic period the patient underwent aorto-coronary graft angiography. Left anterior descending graft opacification demonstrated multiple venous aneurysmal dilations. The clinical significance of this finding is currently unknown but such saphenous vein disease warrants further investigation. Saphenous vein grafts have been utilized to replace or bypass obstructed and diseased peripheral arteries such as those of the carotid and femoral-popliteal vascular systesm. In 1967 Favaloro introduced the saphenous vein as a means for bypassing local obstructions in diseased coronary arteries of human subjects. Since the advent of the aorto-coronary saphenous vein bypass graft procedure several studies have reported pathologic alterations of these grafts at post-mortem examination or at the time of re-operation. Other investigators have also noted changes in these venous grafts when they have been implanted in peripheral vessels. We report here a patient with aneruysmal dilations of an aorto-coronary artery saphenous vein bypass graft. Furthermore, possible mechanisms which might produce such venous aneurysms and the clinical significance of such an entity are discussed.


[Characteristics of some species of microorganisms related to the genus of hemoglobinophils]. The saccharolytic capacity in respect to 14 carbohydrates, the lipolytic activity, the presence of urease, catalase, galactosidase, the formation of hydrogen sulphide and indol and also serological properties with the species agglutinating sera were studied in the representatives of the genus of hemoglobinophilic microbes: H. influenzae, H. parainfluenzae, H. aegiptius, H. haemolyticus, H. aphrophilus. There were revealed differences in the individual representatives of the genus by the enzymatic activity and serological properties. Thus, representatives of H. influenzae possessed urease activity, but all of them lacked galactosidase. H. aegiptius possessed urease and galactosidase, and H. parainfluenzae, H. haemolyticus and H. aphrophilus--galactosidase of high activity, but no urease. Representatives of each of the species were agglutinated by homologous sera only.


[Interaction of various types of cells in the production of anti-influenzal antibodies. III. Cooperation of B- and T-lymphocytes in the production of antibodies to the influenza virus]. Bone marrow and thymus cells of syngenous donors were transplanted to sublethally irradiated mice to study the interaction between the B- and T-lymphocytes in the production of antibodies to the influenza virus. Influenza virus proved to be referred to the thymus-dependent antigens; both types of the lymphocytes participated in the antibody production. The T-lymphocyte function could not be replaced by an increase in the dose of the antigen and of the amount of B-lymphocytes. The ratio of the B- and T-lymphocytes optimal for the antibody production was 1:1 or 1:2.


[Purification of an anionic trypsin from the gastric juice of the crayfish Cambarus affinis say by means of affinity chromatography]. Beside other digestion enzymes the crayfish Cambarus affinis SAY possess an anionic trypsin. This enzyme could be separated from all the other proteins of the crude gastric juice by a single affinity chromatographic step on immobilized natural inhibitor. The dissociation of the thus produced enzyme-inhibitor complex was achieved by specific elution with ben-amidine. The soluble benzamidine-trypsin-complex was dialyzed and separated by gelfiltration on Sephadex G-50. Of the ligands used Trasylol proved to be the most effective one. Trypsin isolated by this ligand was in a discelectrophoretic homogeneous state. On the other hand, trypsin purified by Soybean trypsin inhibitor and Contrykal contains impurities.


[Oeso-portal disconnection by ligature, segmental resection and anastomosis of abdominal oesophagus by means of the PKS 25 apparatus in the cirrhotic patient (author's transl)]. After a brief report of the different techniques of ligating abdominal oesophagus recommended by Vosschulte, Boerema Prioton..., the author describes his technique for resection-anastomosis with the PKS 25 apparatus. He makes a critical analysis of the method: this seems to avoid the drawbacks of the rigid, metallic ring with its narrow bore and uncertain elimination through the natural channel. By the same occasion it respects the principles, advantages and indications of the preceding methods. The author ends by the main therapeutic choices that appear to emerge for this treatment of oesophageal varices by opposition to the portal decompression operations, be it during hemorrhage or delayed emergency.


Malignant fibrous mesothelioma. Metastatic to brain and liver. A malignant fibrous mesothelioma in a 52 year old white man arising from the left parietal pleura associated with lupus erythematosus with metastases to brain and liver is reported. Asbestos bodies were found in digested pulmonary tissue but none in the primary or metastatic lesions. Light microscopic and ultrastructural studies suggest that this tumor contains mesothelial or endothelial cells, some of which revealed fibroblastic features while others disclosed epitheloid characteristics.


Studies on coagulation and fibrinolysis in pregnancy, with special reference to cold activation of factor VII. Studies on coagulation and fibrinolysis were performed on 40 healthy women who underwent an uncomplicated pregnancy. From each subject, samples were taken 6-10 times during pregnancy, and all the changes were related to the subjects' own 6-week postpartum values. Increased concentration of coagulation factors II-VII-X was revealed by Normotest. The incidence of cold activation of factor VII increased from 14% in non-pregnant women in these series to 94% in pregnant women near term. A marked increase in the proteolytic capacity was probably an effect of increased plasminogen concentration and decreased antifibrinolytic activity. The latter did not, however, parallel the immunological determination of the antiplasmins. The concentrations of antithrombin III and CI inactivator of complement both decreased during pregnancy. It is concluded that the overall effect of these changes is probably in favour of coagulation.


The ultrastructure of Trichomonas vaginalis donné before and after transfer from vaginal secretion to Diamonds medium. Cell of Trichomonas vaginalis (T. vag.) obtained from five patients with severe trichomoniasis were fixed for electron microscopy directly in the vaginal fluid. Samples of the same material from three of the patients was inoculated into Diamonds medium and propagated for 3-6 weeks. During the first 3-4 weeks in vitro the fine structure of all cells was changed. The shape of the nucleus, the size of the Golgi apparatus and adjacent vesicles, the fine structure of the chromatic granules, and the mastigont were all changed when compared to the organelles of the originally isolated cells. In addition the "ectoplasm" had disappeared, the glycogen granules had become sparse, and the number of free cytoplasmic ribosomes had increased. On the other hand, the large food vacuoles and the cell membranes generally were unchanged. Mycoplasms were observed in the original isolate and were also seen after more than 6 weeks of propagation, both as free organisms in the culture medium and within the large food vacuoles of "in vitro" cultured cells.


An extended approach through the middle cranial fossa to the internal auditory meatus and the cerebello-pontine angle. The submeningeal approach through the middle cranial fossa to the internal auditory meatus and cerebello-pontine angle after cutting the tentorium cerebelli is described. It is in some way similar to that used by Morrison & King. The approach is achieved by drilling the petrous bone to the level of the compact plate of the sigmoid sinus sulcus and to the lumen of the lateral semicircular canal. In this way it is possible to visualize safely the entire auditory-facial fasciculus, the region of the jugular foramen, the IX, X, XI, V, and VI nerves as well as the lateral surface of the brain stem. In our opinion this way should be and is preferable to the translabyrinthine approach through the mastoid process.


Immunological function of human tonsil. Surface topology of human tonsil lymphocytes using the scanning electron microscope (SEM). The surface topology of the lymphocytes in human tonsils was performed by means of the scanning electron microscope (SEM). It was revealed that human tonsils consist of both 40.7% villous and 26.6% smooth surface lymphocytes. In general, the percentage results agree with those of E and EAC binding lymphocytes of human tonsils, as previously reported. Our serial experiments using immunological techniques proved the existence of two lymphocytes (T and B cell) having immunological roles.


Seventy-year-old people in Gothenburg. A population study in an industrialized Swedish city. The objectives of this cross-sectional population study of 70-year-old people in Gothenburg, Sweden, were to make a survey of the social and medical conditions of the population, to obtain basic data for planning the care of the elderly, to contribute to the knowledge of normal ageing processes and of normal criteria within the age group, and to offer the subjects a thorough medical examination. A representative systematic sample comprised 1 148 propositi (521 males and 627 females). The study comprised a homecall part regarding basic personal data, dwelling conditions, economy, social and physical communications, previous migration, educational level, previous and any present professions, need for care, consumption of health care and drugs. Observations and measurements were done of illumination at the habitual site of reading, and a simple test of visual acuity was performed. Later on, examinations at the Out-patient Department of the Geriatric Hospital were performed, comprising in all probands general medical and ophthalmological examination, blood and urine sampling, ECG and X-ray of heart, lungs, and breasts and on subsamples, psychological, psychiatric, dental, somatometric, and audiometric examination. Furthermore, a dietary interview and a body composition examination were performed on subsamples. This first presentation deals with the design and procedure of the study, analysis of observer variation and a comparison between responders (85%) and non-responders (15%). The general design of the study, the sampling procedure, and general methods of data collection were found to be adequate. The responders were found to be representative for the population as a whole in most respects studied. The results of this study to be reported in subsequent papers will in general allow conclusions regarding the population of 70-year-olds in Gothenburg.


Preformed mRNA and the programming of early embryo development. A significant feature of the early development of fertilized echinoderm and amphibian eggs and germinating seed embryos is the utilization of genetic information that has been previously transcribed during oogenesis and seed ripening. When RNA synthesis is suppressed in the early developing embryos by actinomycin D, cordycepin, or alpha-amanitin, there is no effect on the translation of the "preformed mRNA", only a limited number have been thus far identified; microtubule and histone proteins in the fertilized sea urchin egg and carboxypeptidase and isocritric lyase in germinating cottonseed. Data obtained on the protein synthetic pattern at different times after the onset of development suggest that preformed mRNAs are made available to the translational system in a gradual process, thereby providing a molecular basis for the regulation of development. The possibility is considered that polyadenylation of mRNA, a reaction known to occur early after sea urchin fertilization, is responsible for regulating the release of preformed mRNA. It is shown that this reaction (polyadenylation) can be completely suppressed with little effect on the function of preformed mRNA. Finally, it is suggested, at least for the seed embryo system, that the formation of ATP may be a prerequisite for the activation of protein synthesis.


The "angina-producing" myocardial segment: An approach to the interpretation of results of coronary bypass surgery. The first 153 cases of saphenous vein aortocoronary bypass surgery performed at The Johns Hopkins Hospital were reviewed. Eighty-eight percent of the 140 late survivors reported significant symptomatic improvement. Seventy-one unselected patients consented to complete reevaluation at a mean interval of 6.1 months postoperatively. Vein bypass patency in this group was 66 percent. Eighty-two percent of these 71 patients had improved performance on electrocardiographic stress testing. There were no significant differences between hemodynamic status on pre- and postoperative studies regardless of the status of vein bypass patency. Repeat coronary angiography revealed a 30 percent incidence of new total occlusions of the intrinsic coronary circulation. Segmental wall motion on ventriculography was improved in 12 percent, unchanged in 50 percent and decreased in 38 percent of the segments analyzed. Localized electrocardiographic changes compatible with myocardial damage developed in the immediate postoperative period in 45 of these patients (63 percent); in 38 of the 45, these changes corresponded to new angiographic abnormalities. Physiologic mechanisms underlying symptomatic improvement were sought by identification of an "angina-producing" myocardial segment. In most instances, alleviation of angina could be related to either: (1) a patent bypass graft into an unchanged intrinsic coronary artery with presumed increased blood flow to the distal coronary segment, or (2) occlusion of the bypass graft and the corresponding coronary artery with probable infarction of previously ischemic myocardium. Current criteria for the selection of patients undergoing coronary bypass surgery are reviewed in the light of these findings. It is concluded that relief of disabling angina is the major indication for surgery. Prevention of myocardial infarction and improvement in left ventricular function are at present less reliable objectives.


Saphenous vein bypass grafts: Long-term patency and effect on the native coronary circulation. The long-term durability of saphenous vein bypass grafts and their effect on existing intrinsic coronary artery disease remain ill defined. Therefore, sequential catheterization studies were performed in patients selected for study solely on the basis of documentation of a patent graft at an earlier study performed three to nine months postoperatively; at that time 29 patent grafts were demonstrated in 20 patients. Fifteen to 36 months postoperatively (average 22 months), 27 grafts were unchanged, 1 manifested minimal luminal irregularities and 1 was occluded. In one additional patient, studied 4 months and 4 1/2 years postoperatively, the graft was widely patent and had good distal runoff at the second study. Sequential coronary arteriograms revealed that progression of disease to complete occlusion occurred in 24 percent of vessels with severe lesions proximal to a patent graft, whereas progression of disease distal to a graft anastomosis was uncommon. Of 25 vessels not receiving grafts, disease progressed in 5 (20 percent). Grafts that are patent 3 months after operation appear to remain patent for at least 2 to 3 years, and their presence does not unduly accelerate the disease process involving the native coronary arteries.


Changes in native coronary arteries after coronary bypass surgery. Role of graft patency, serum lipids and hypertension. Sixty-seven patients were studied by coronary angiography early (mean 3 weeks) and late (mean 13 months) after coronary bypass surgery to assess changes in the native coronary vessels. Among the 208 nongrafted arteries progression of disease was found in 2.9 percent. In arteries that were normal before operation, the rate was 0.7 percent; in those with luminal obstructions the rate was 7.6 percent (P less than 0.05). Progression of disease occurred in 6 of the 67 patients (8.9 percent). In five bypassed arteries (5 percent), progression of disease occurred at or near the anastomotic site; in this subset the procedure was classified a technical failure. Progression of disease distal to graft insertion occurred in 2.4 percent of cases. The greatest incidence of progression took place proximal to graft insertion, in 24.2 percent of the grafted arteries. This rate differed significantly from the rate in non-grafted arteries (P less than 0.001) and in distal segments of grafted arteries (P less than 0.001). If the grafts were patent in the late control study, the progression of disease proximally occurred at a rate of 24 percent; if they were occluded, the rate was 25 percent. The data on timing of graft occlusion suggested that graft patency was related to the proximal progression. The prevalence of hyperlipidemia or hypertension did not correlate with progression of disease in any group.


Heterografts as aortocoronary bypass conduits in human beings. Clinical and necropsy observations are described in a man in whom two sheep carotid arterial heterografts were inserted as aortocoronary bypass conduits 30 months before death, and in whom a canine saphenous vein heterograft was inserted several hours before death. All three grafts failed. The lumens of the sheep carotid arterial heterografts had closed by the time of catheterization 6 months after operation; at necropsy both grafts were totally occluded at their coronary and aortic ends and their media and adventitia were infiltrated by granulomatous inflammatory cells. Little information is available regarding the use of heterografts as coronary bypass conduits. Examination of previous reports describing heterografts for vascular reconstruction or bypass in both man and experimental animals and observations in our patient suggest that heterografts are unsatisfactory as aortocoronary bypass conduits.


Disappearance of abnormal Q waves after aortocoronary bypass surgery. Sixty-one patients were selected from 100 consecutive patients under-going aortocoronary artery bypass. The number of vessels diseased as defined by coronary arteriography and the number of bypass grafts were recorded. Review of the preoperative electrocardiograms showed an infarct pattern in 26 of the 61 patients and analysis of the postoperative electrocardiograms revealed loss of abnormal Q waves in 3 of the 26. The pre- and postoperative clinical course of these three patients is analyzed and the extent of their coronary artery disease and number of bypass grafts compared with those of the 23 patients who had persistence of the infarction pattern and the 17 patients who manifested new Q waves. Possible explanations for the disappearance of abnormal Q waves are discussed.


Massive gastric hemorrhage from submucosal arterial malformation. In a patient with massive gastric bleeding, the cause was found to be rupture of a submucosal arterial malformation. The bleeding site was identified endoscopically and the lesion was removed by local resection. This is the 28th case of this entity to be reported.


The use of soft bandage lenses in corneal disease. Forty-one patients were treated with soft bandage lenses for various types of corneal pathology. These patients have been monitored over a two-year period. Comfort was consistently achieved with cases of bullous and exposure keratopathies. It was found that the Warner-Lambert Softcon lens gave better protection in patients with VII nerve palsies than the Bausch & Lomb SOFLENS contact lens. However, little difference was noted between the two types of lenses when treating other corneal diseases. It was also found that topical medications, with the exception of steroids, caused no complications.


Influence of ammonium ions on mechanical and electrophysiological responses of skeletal muscle. Substitution of ammonium ions for sodium ion initially potentiated and then depressed twitch tension of the frog sartorius muscle. The extent of potentiation and the rate of depression of the twitch were dependent upon the concentration of ammonium ions. Ammonium ion depolarized individual muscle fibers in proportion to concentration. Maximum depolarization (33 mV) occurred in muscles equilibrated in 120 mM ammonium-Ringer for 30 min. At the higher concentration of ammonium (72--120 mM), the potentiation was quickly reversed and the tension response was eliminated completely. The gradual loss of twitch tension was accompanied by progressive decrease in the electrical excitability of individual muscle fibers. Raising the extracellular calcium concentration fivefold reduced the twitch-depressant effect of ammonium ions by maintaining excitability of the muscle fibers. Caffeine contractures (3 and 10 mM) in muscles preequilibrated in 72 mM ammonium-Ringer developed similar tensions to paired controls muscles, but the onset of tension was more rapid in the ammonium-treated muscle. It was concluded that the depression of tension could be accounted for by the loss of membrane excitability and that the evidence did not support the hypothesis that ammonium ions acted at other sites in the excitation contraction coupling.


Non-Poisson distribution in time of small- and large-mode miniature end-plate potentials. Minature end-plate potentials (MEPP's) were recorded from frog (Rana pipiens) sartorius muscle cells of 60--80 mum diam; MEPP frequency remained constant up to 3 h and was 100 times greater in 80-mum cells than in 6-mum cells. Rapid cooling or heating of preparations initiated or accentuated bursts of MEPP's. Records from cells under control conditions and from cells where the MEPP population had been reduced to the small mode showed many instances of small clusters of MEPP's occurring within 100-ms intervals, indicating quantal release interdependencies. Some small cells initially generated many large MEPP's 2 or more times the average amplitude and fewer small clusters. Analysis of the occurrence of both large- and small-mode MEPP's for both 1.0-s and 100-ms nonoverlapping bins demonstrated a highly significant deviation from a Poisson distribution with significance increasing with decreasing cell diameter and/or MEPP frequency. It is suggested that doublet MEPP's are generated from one release site and that large bursts results from the activity of several release sites, since the size of bursts decreases with cell diameter (junctional area). It is concluded that release characteristics are the same for large-mode (classical) and small-mode MEPP's and that the occurrence of MEPP's is not Poisson.