Natural anti-tumor serum reactivity in BALB/c mice. II. Control by regulator T-cells. By a complement-dependent cytotoxicity test, 37 sera from 1- to 18-month-old BALB/c mice were tested for natural anti-tumor and anti-thymus immune reactivity. The level of anti-tumor and anti-thymus antibodies increased with age, and a high individual variability, particularly evident in the older animals, was found. The appearance of the spontaneous antibodies was correlated to the T-cell status of mice. Animals with the higher spleen T-cell content were those with the higher anti-thymus and the lower anti-tumor natural antibody level, and vice versa. In T-deprived mice the anti-tumor response increased, whereas the anti-thymus response was not influenced. An inoculum of T cells from young to older syngeneic mice yielded a decrease of the anti-tumor response and an increase of the anti-thymus response. Homeostatic immunologic mechanisms, in which the cellular and the humoral system alternate in the tumor cell control, are suggested.


The primary structure of human urogastrone. Urogastrone is a potent inhibitor of gastric acid secretion which is present in human urine. Its existence has been known for over 30 years but it has only recently been isolated in a sufficiently pure form for detailed structural studies to be undertaken. Two separate polypeptides beta- and gamma-urogastrone were isolated. The structures were established by carrying out enzymic degradations of S-carboxymethyl and S-carboxamidomethyl derivatives with trypsin, chymotrypsin, thermolysin and a protease derived from the fungus Armillaria mellea. Sequences of the smaller peptides thus obtained were determined by the dansyl Edman method. Partial acid hydrolysis of urogastrone itself gave fragments containing single intact disulphide bonds, and oxidation then allowed the direction of individual bonds to be established. Beta-Urogastrone was shown to be a 53-amino acid residue polypeptide containing three disulphide bonds, and gamma-urogastrone had an identical sequence but lacked the C-terminal arginine residue. Urogastrone was subsequently found to be structurally related to mouse epidermal growth factor in that 37 of the 53 residues were commonly located in each polypeptide. Furthermore, as both peptides has similar effects upon gastric acid secretion and upon epidermal growth, urogastrone was also a human epidermal growth factor. The 16 variable residues were spread across the molecule, all apart from two were compatible with single base changes in the triplet condons, and the overall effect was to make uorgastrone more acidic than EGF. The smallest biologically active unit has not been defined but at least six residues can be removed from the C-terminus without causing a reduction in potency.


Angiography in gastointestinal bleeding. Over a four-year period, eight patients with documented gastrointestinal bleeding had angiography as a part of their investigation and treatment at the Department of Radiology, Victoria General Hospital, Halifax, Nova Scotia. A review of these eighty cases has been carried out and angiography has been found to be both safe and reliable in the diagnosis of gastrointestinal bleeding. Cautiously administered intra-arterial pitressin infusion therapy will arrest bleeding in about one-third of cases and in most others will reduce blood loss so that a critically ill patient may be made more fit for subsequent surgery. Patients who have recently received intravenous pitressin should not be given intra-arterial pitressin.


Effects of selective forebrain noradrenaline loss on behavioral inhibition in the rat. Virtually total depletion of cortical and hippocampal noradrenaline by stereotaxic injection of 6-hydroxydopamine into the fibers of the dorsal noradrenergic bundle produced no impairment in acquisition learning of a runway response for food reward. Extinction of this response, once learned, was markedly slower in the treated group than in controls, the treated animals perseverating in rapid running to the goal box even with no food present there. Similarly, no impairment was found on acquisition of a continuously reinforced lever-pressing response for food. Extinction of this response, however, was again slower in the treated group. Subsequent acquisition of a successive light-dark discrimination task was also slower in the treated group, with these animals perseverating in responding to the negative stimulus. Although selective forebrain noradrenaline loss does not impair the acquisition of appetitive responses, the suppression of responses in the absence of reward is impeded. A parallel is drawn with those effects found classically after surgical lesion to the hippocampus.


Inhibition of theophylline clearance by troleandomycin. The effect of troleandomycin, a macrolide antibiotic, on theophylline elimination was examined in eight patients with chronic asthma. Clearance from serum was reduced by 50 +/- 6% (mean +/- SD) during administration of 250 mg troleandomycin four times daily. Reduction of clearance persisted to a lesser degree in one of these patients examined while receiving 250 mg troleandomycin daily. An increase in serum theophylline concentration can thus result from initiating troleandomycin in asthmatic patients receiving continuous treatment with theophylline. This may be at least a partial explanation for the apparent benefit of troleandomycin in chronic asthma and also suggests that possibility of inducing theophylline toxicity, including seizures, as was observed in one of the patients in this study.


Histamine receptor--bearing peripheral T lymphocytes in patients with allergies. The effect of histamine on the capacity of T lymphocytes to form E rosettes was tested in 10 healthy subjects and in 13 patients with allergies. Histamine had no effect on the capacity of T lymphocytes to form E rosettes in healthy subjects, but significantly inhibited the E rosette formation of T lymphocytes in patients with allergies.


5'-Nucleotidase in different populations of mouse lymphocytes. The activity of 5'-nucleotidase in different populations of intact lymphocytes was studied using biochemical, cytochemical and radioautographic methods. In some strains of mice the results showed a consistent difference in 5'-nucleotidase (AMPase) content between intact thymic and splenic lymphocytes. In the R III, C 57, BALB/c, CBA and Cd-1 strains AMPase activity in the isolated splenic cells was foru to 10 times the activity of intact thymocytes. In highly enriched populations of splenic T and B cells the average AMPase activity was about the same. From separate assays it was seen that the AMPase activity in highly enriched populations of lymphoctes was variable so that within one experiment the T cells seemed to have the higher AMPase activity while in other experiments B cells shown to be more active than T cells. Ultrastructural radioautography was done to count AMPase positive cells within T and B cell populations, the latter identified b  binding of I125-labelled anti-immunoglobulin. It was seen that about 50% of B cells, but only about 10% of T cells, were positive for AMPase. It is suggested that there is a subpopulation within B and T cell populations with a high membrane AMPase activity and another subpopulation with less or no enzyme activity. It is also suggested that the activity and/or the proportion of  these positive cells is changing within the splenic cell population. By using cortisone to deplete the immature cells from the thymus it was seen that the remaining mature cells have about the same AMPase activity as did the immaturecells, and thus mature T cells must gain their high acitivity after leaving the thymus. By incubating splenic lymphocytes with Concanavalin A it was also seen that the immature transformed cells had the same amount of enzyme as did untransformed cells.


Histochemical demonstration of unsaturated hydrophilic lipids with palladium chloride. Compounds in which olefinic linkages are accessible to aqueous reagents reduce the chloropalladite ion [PdCl4]2-, to metallic palladium. This reaction is used in a histochemical method whereby hydrophilic unsaturated lipids are stained dark brown or black. The specificity of the new method has been confirmed by means of solvent-extraction and chemical blocking procedures and by comparison with other histochemical techniques. Yellow staining of collagen, keratin and cytoplasm is probably due to attachment of the chloropalladite anion to proteins. The yellow background can be largely decolorized by treating the sections with aqueous pyridine, which forms colorless complexes with divalent palladium. A standard technique for staining with palladium is presented and the method is discussed in relation to other histochemical procedures that demonstrate unsaturated lipids.


Histocompatibility requirements for cellular cooperation in the chicken: generation of germinal centers. Cyclophosphamide-treated newly hatched chicks were transplanted with histocompatible, semiallogeneic and allogeneic combinations of B (bursa) and T (thymus) cells from newly hatched donors. At the age of 5 weeks the birds were studied for an anti-SRBC response and for the generation of germinal centers in the spleen. The results of these experiments are summarized as follows. i) Allogeneic bursal stem cells have the capacity to restore the bursal structures of CY-treated recipients, but not the germinal center or anti-SRBC formation. ii) When allogeneic B cells are combined with T cells histocompatible or semiallogeneic with them, a restoration of the germinal center formation is achieved, but not to the same level as observed in normal birds or in CY-treated birds transplanted with histocompatible or semiallogeneic B cells. iii) Allogeneic B cells, even when complemented with T cells histocompatible with them, fail to restore the antibody production against SRBC; this is achieved only after transplantation of B cells histocompatible or semiallogeneic with the recipient. These findings indicate that germinal center formation is dependent on cooperation of histocompatible or semiallogeneic B and T cells, and furthermore, that an additional factor provided by the host is involved. Studies with transplantation of histocompatible and histoincompatible 'empty' splenic stromata revealed that the additional factor is not related to the splenic stroma.


Suppression of IgE antibody production in SJL mice. II. Expression of Ly-1 antigen on helper and nonspecific suppressor T cells. Under appropriate conditions of immunization combined with irradiation, SJL/J mice show a high and persistent anti-DNP IgE antibody response. Spleen cells transferred from normal untreated SJL mice suppress this response. Elimination of Ly-1+ cells, but not of Ly-2+ cells, abolished the capacity of spleen cells to suppress the IgE response. Thus of the three T cell Ly subclasses presently identified, Ly-1, Ly-2,3, and Ly-1,2,3, the normal SJL spleen cell which suppresses the IgE response of irradiated-immunized SJL mice belongs to the Ly-1 set. It is not known whether this Ly-1 cell suppresses the IgE response directly or by helping another cell in the recipient. The carrier-specific helper cell activity for IgE and probably IgG1 antibody response belongs to Ly-1 subclass in the SJL strain also.


Enhancement by irradiated T cells of human plasma cell production: dissection of helper and suppressor functions in vitro. The addition of irradiated T-enriched lymphocytes to B cell-enriched fractions of human peripheral blood or to unseparated mononuclear cells stimulated the differentiation of plasmacytoid cells in culture with pokeweek mitogen beyond the synergy obtained by the addition of unirradiated T cells. This stimulation was observed in both the proportion and absolute number of plasmacytoid cells recovered from the cultures, and in the amount of IgM detected in culture supernatants by a hemagglutination inhibition assay. Irradiation-induced enhancement was observed with normal and hypogammaglobulinmic T cells, but not with monoclonal T cells from two patients. Inactivation of T cells by heating or by repeated freezing and thawing did not produce the same effects as did irradiation. These data suggest that cell-mediated suppressor function in man is selectively radiosensitive, while helper activity is not. Irradiation may be a useful method for the functional isolation of helper cells and for the manipulation of the balance between suppressor and helper cell activities.


Characterization of DNA used to assay sera for anti-DNA antibodies; determination of the specificities of anti-DNA antibodies in SLE and non-SLE rheumatic disease states. Commercial 14C-labeled KB cell DNA, widely used to assay sera for anti-DNA antibodies, was chromatographed on benzoylated-naphthoylated-DEAE-cellulose (BNDC) and on hydroxyapatite (HAP). On BNDC, only 25% of the 14C label eluted with 1 M NaC1 (KB fraction I) characteristic of ds-DNA. Fifty-five percent of the label eluted with 50% formamide-1 M NaC1 (KB fraction II) characteristic of ss or denatured DNA. On HAP, however, none of the 14C label eluted with 0.2 M phosphate buffer as anticipated for ss-DNA, but, rather, all of the 14C label eluted with 0.4 M phosphate, characteristic of ds-DNA. after pretreatment with S1 endonuclease of Aspergillus oryzae, which selectively digests ss regions, however, 42% of the 14C label was lost from the 0.4 M phosphate peak. These results indicated that more than half of this 14C-KB-cell DNA preparation was ds-DNA with ss regions which was undetectable by HAP chromatography. 3H-ds-DNA and circular 3H-ss-DNA prepared from T7 and phiX174 bacteriophage, respectively, were found to be chromatographically pure on both BNDC and HAP. None of 10 non-SLE sera (rheumatoid arthritis 3, mixed connective tissue disease 4, scleroderma 1, ulcerative colitis 1, and pulmonary fibrosis with chronic active hepatitis 1), previously believed to contain anti-ds-DNA antibodies on the basis of KB cell DNA testing and detectable antibodies against KB fraction 1 or T7 DNA: all of 10 KB cell DNA positive SLE sera had antibodies against both. Additionally, none of the 10 non-SLE sera had antibodies against KB cell DNA when retested with DNA that had been pretreated with S1 endonuclease. Seven of these 10, however, as well as all 10 SLE sera, had antibodies against phiX174 DNA, KB fraction II DNA and alkali-denatured T7 DNA. The data support the conclusions that 1) false positive tests for anti-ds-DNA antibodies can result from contamination of ds-DNA with ds-DNA having ss regions, and 2) non-SLE sera do not contain antibodies specific for ds-DNA at levels comparable to those found in SLE sera but rather contain high levels of antibodies reacting with ss regions or mixed DNA.


A rapid quantitative assay for lymphotoxin. A rapid quantitative assay for lymphotoxin was developed with the use of a mouse cultured lymphoid cell line, L1210 as the target cell. The assay produces results which are substantially in agreement with assays employing fibroblasts as targets. After incubation with lymphotoxin containing samples, target cells were labelled with [3H]thymidine and harvested with a Multiple Automated Sample Harvester (MASH). The MASH allows multiple replicates to be obtained from which the calculation of an I50 (50% inhibition) point and lymphotoxin specific activities can be performed with high statistical reliability by means of probit transformation and analysis.


Cefamandole and ampicillin therapy in experimental Haemophilus influenzae meningitis. Cefamandole and ampicillin were compared in the therapy of experimental Haemophilus influenzae meningitis in rabbits. Three dosages of each drug were administered as a continuous intravenous infusion for 8 hr to 24 infected animals. Samples of serum and cerebrospinal fluid (CSF) were obtained at 0, 4, and 8 hr for determination of antibiotic concentrations and bacterial titers in CSF. Serum levels of cefamandole were higher, but CSF concentrations of both antibiotics were similar. With the 60-mg/kg per hr dose, the mean serum level was 106 +/- 61 mug/ml for cefamandole and 58 +/- 32 mug/ml for ampicillin (P less than 0.05). With this dosage the mean level in CSF was 7.3 +/- 8.4 mug/ml for cefamandole and 9.5 +/- 5.4 mug/ml for ampicillin (P = 0.26). The percentage penetration ([concentration in CSF/concentration in serum] X 100%) was higher for ampicillin (mean, 18.8% +/- 8.9%) than for cefamandole (mean, 5.6% +/-  3.8%) with all dosages tested (P less than 0.001). The rate of bacterial killing in vivo during therapy was similar with both drugs. The efficacy of cefamandole and ampicillin given intramuscularly for five days (250 mg every 8 hr) was examined in 42 rabbits. Twelve of 14 untreated control rabbits died within 24-72 hr of inoculation. In contrast, 11 of 14 rabbits treated with cafamandole and 10 of 14 rabbits treated with ampicillin were cured of their infections. Cefamandole compared favorably with ampicillin in the therapy of experimental H. influenzae meningitis.


Haemophilus influenzae meningitis in infant rats: role of bacteremia in pathogenesis of age-dependent inflammatory responses in cerebrospinal fluid. Abnormalities in cerebrospinal fluid associated with meningitis due to Haemophilus influenzae type b were characterized in infant rats. After intranasal inoculation of bacteria, the development of intense bacteremia (greater than 10(4) colony-forming units/ml) correlated with cultures of cerebrospinal fluid positive for H. influenzae, with pleocytosis, and with hisotologic evidence of meningitis. The degree of pleocytosis was related to the age of the animal, the amount of time since inoculation, and the severity of the meningitis.


Medical and educational malpractice issues in patient education. This paper discusses the concept of educational malpractice as a cause of prolonged patient morbidity equal in magnitude to medical malpractice. Statements by national groups sanctioning and urging increased patient education efforts are reviewed. An example of specially designed problem-oriented patient education materials development, the concept of an "Educational Prescription," the place for the "Educational Prescription" in problem-oriented medical records, and the value of hospital-based patient education as a cost-containment activity.


Environmental influence on ovulation and embryonic development in Rana pipiens. Environmental effects on ovulation and embryogenesis in Rana pipiens were assessed using both freshly-captured fall animals and laboratory-conditioned females which had undergone vitellogenesis in the laboratory. Frogs in both categories were divided into two groups. Ovulation was hormonally induced in one group of females prior to cold exposure and in the second group of animals following an 8-week-period at 4 degrees C with an 8L 16D photoperiod. The incidence of both ovulation and normal embryonic development was increased following exposure of the animals to low temperatures and short daylength. Those animals which only partially ovulated prior to cold treatment did not respond to hormone injections following the period of cold exposure. Examination of the ovaries of these females revealed a much greater degree of oocyte resorption than was found in frogs whose initial ovulation was induced only after exposure to cold temperatures. The administration of ovulation-inducing hormones prior to artificial hibernation may thus have initiated a phase of oocyte resorption which progressed even at 4 degrees C. The incidence of ovulation was similar in wild-caught and laboratory-conditioned females, but eggs from the latter showed a much lower percentage of development to Shumway stage 20. This effect may have been related to differences in the environmental factors to whcih the two groups were exposed during oogenesis.


Tension reduction and alerting in man following chronic cerebellar stimulation for the relief of spasticity or intractable seizures. Neurologically impaired patients on therapeutic regimens of chronic cerebellar stimulation for periods ranging from 4 to 29 months (mean = 12.8 months) commonly reported amelioration of tension and/or anxiety. Cerebral palsy patients emphasized tension reduction while seizure patients primarily reported increased alertness. Increased alertness and improvement in speech and mood were also noted by many patients. These changes correlated significantly with symptom reduction and functional improvement. Although the mechanisms of these changes are not yet clear, psychological and neurological explanatory hypotheses were presented.


Large-field trichromacy in protanopes and deuteranopes. Protanopes and deuteranopes do not accept the classical dichromatic matches when field size extends to 8 degrees visual angle. Their unique matches of spectral yellow to a mixture of red and green are then mediated by the photoreceptors of small-field dichromacy interacting with a photoreceptor with the spectral sensitivity of rhodopsin. Our data suggest that large-field trichromacy is a general feature of protanopia and deuteranopia.


A study of specificities of antinuclear antibodies in juvenile rheumatoid arthritis. The sera from 77 children with juvenile rheumatoid arthritis were studied for the presence of antinuclear antibodies, rheumatoid factor, and for antibodies to seven well-characterized nuclear antigens which occur in specific rheumatic diseases of adults. These included: Sm, RNP, DNA, RNA, RAP, SS-A, and SS-B. Forty-nine percent of the sera from patients with JRA contained ANA. The most common pattern was speckled. The frequency of all other positive tests was too low (13%) to make correlations with disease states. However, a small group of girls with polyarticular and late-onset disease had a high incidence of RF or RAP. These two antibodies were not associated with each other as they are in adult RA.


Prevalence of of alpha 1-antitrypsin Pi types among newborn infants of different ethnic backgrounds. alpha 1-antitrypsin phenotypes were determined in cord sera of 1,010 healthy term infants of black, white and Hispanic background, by the crossed immunoelectrophoresis technique of Fagerhol and Laurell. Among the black group, M prevalence (97%) was higher than among the Hispanic group (88%). MS prevalance in the Hispanic group (6.7%) was higher than among black (1.5%) or white (3.9%) infants. Among those with an M pattern a "step" variant representing a shift of the relative amounts of protein in the major peaks of the M pattern, was found in 96% of neonates, but only among 9.8% of infants one months to two years of age and 18% among children two to ten years of age, regardless of race. Quantitative values of alpha 1-antitrypsin were not decreased among MS and MZ infants.


Pontocerebellar atrophy combined with vestibular-reticular degeneration. A 41-year-old woman was hospitalized in 1939 with neurologic signs from which there was complete recovery over a two-year period. In 1965 she was readmitted because of increasing forgetfulness and inability to care for herself; there were no neurologic deficits. In June 1970 torticollis developed and persisted until her death 15 months later. No cerebellar signs were elicited, but increased muscle tone was prominent. The brain showed remarkable flattening of the inferior surface of the cerebellum; the pons was small. The medullary substance of the cerebellum and each branchium pontis appeared completely demyelinated. Transverse fibres were apparently absent in the central basis pontis. Microscopically in addition to the pontocerebellar atrophy there was degeneration of the vestibular system, reticular formation of the medulla oblongata and medial longitudinal fasciculi. The inferior olives showed only moderate neuronal degeneration in the caudal areas. Basal ganglia and thalamus showed some involvement in the pathological process. It is postulated that the vestibular-reticular system atrophy was the anatomic substrate for the torticollis, and apparently overshadowed cerebellar signs, which are ordinarily associated with pontocerebellar atrophy.


Stimulus-bound repetitive synaptic firing caused by ethanol in sympathetic ganglion. The effects of ethanol, 0.1 to 1.0 M, on synaptic transmission, preganglionic axonal fibers and the ganglion cell were examined by extracellular and intracellular recording in isolated bullfrog sympathetic ganglia. Within the concentration range 0.2 to 0.8 M ethanol caused stimulus-bound repetitive postganglionic responses (SBR) to single preganglionic stimuli. The presynaptic origin of ethanol-induced SBR was confirmed by recordings of repetitive synaptic potential responses to single stimuli, and by absence of repetitive responses in myelinated preganglionic axons and in ganglion cells stimulated antidromically. Ethanol acted synergistically with Cs+ to produce SBR more intense than that caused by either agent alone. The postganglionic SBR caused by ethanol was suppressed by concentrations of d-tubocurarine, lidocaine, or tetraethylammonium that had little or no effect on synaptic transmission. Ethanol also blocked synaptic transmission, but this occurred secondary to the initial excitatory effects, and in the concentration range 0.4 to 1.0 M. The present data, together with previous studies of ethanol at neuromuscular junction, indicate that synaptic excitatory effects of ethanol are unrelated to hyperosmolarity or cholinesterase inhibition and represent a primary action of ethanol on prejunctional nerve endings.


A large birefringence signal preceding contraction in single twitch fibres of the frog. 1. When a single muscle fibre was externally stimulated to give a propagated action potential, a large decrease in light intensity was measured with the fibre positioned between crossed-polarizers oriented at +/- 45 degrees with respect to the fibre axis. This large optical signal begins just after stimulation and its man phase precedes the development of positive tension. 2. The peak (or plateau) amplitude of the signal, expressed as the peak (plateau) change in light intensity, delta I, divided by the resting light intensity, I, was typically (minus) 1 to 3x10-3 and the time-to-peak (plateau) was 4 to 6 ms (20 degrees C). 3. When mechanical activity was minimized by stretch or Ringer replacement with D2O or hypertonic solution, the peak tension response was reduced in far greater proportion than the peak optical response, suggesting that the early optical signal is not due to changes in tension or gross fibre movement. 4. The magnitude of the optical response was increased by nitrate and double-shock stimulatin, procedures which potentiate the twitch response. 5. The optical signal was shown to propagate along the fibre length with a conduction velocity appropriate to the surface action potential. 6. The above results suggest that the large, early birefringence signal reflects a step or steps in the sequence of events leading to contractile activation.


The optical properties of birefringence signals from single muscle fibres. 1. The optical retardation of single muscle fibres at rest and the optical properties of the large, early birefringence signal detectable during a twitch (Baylor & Oetliker, 1975, 1977a) were investigated. 2. The resting birefringence, B, which is the factor relating resting retardation, R, to the light path length through the fibre, L, was found to be 2.25 x 10-3 (i.e. R = 2.25 X 10-3 X L) and to be independent of wavelength ( lambda = 480-660 nm). 3. When the angle of incidence, psi, of the crossed polarizers with respect to the fibre axis was varied, the resting light intensity and large, early change in light intensity were related by the function sin2 psi-cos2psi. When the net phase shift, phi lambda, of a narrow longitudinal strip of fibre plus compensator was varied, the resting light intensity was described by the function (1-cos phi lambda), whereas the early change in light intensity followed sin phi lambda. These results make it likely that the optical mechanism underlying the early birefringence signal is a change in retardation. 4. When a narrow longitudinal strip of fibre was illuminated by monochromatic light in the range 480-690 nm, the magnitude of the signal varied approximately as expected if the retardation change is independent of wave-length. 5. The spatial characteristics of the signal were examined by moving a small slit of light across the fibre width as well as by measuring the signal collected from the entire fibre width as a function of wave-length. The results from both experiments support the idea that the large, early change in retardation is due to a volume-related rather than surface-related structure. 6. Under the assumption that the retardation change is distributed as fibre volume, its average magnitude was calculated. For fibres in normal Ringer the peak of the early retardation change compared with resting is about 1.7 x 10-3, and for fibres in D2O Ringer about 0.7 x 10-3.


Birefringence signals from surface and t-system membranes of frog single muscle fibres. 1. When the tonicity of Ringer is increased above 2-5 times normal and a single fibre stimulated externally, the large, early birefringence signal preceding twitch tension (Baylor & Oetliker, 1975, 1977 a,b) is sufficiently reduced and delayed so as to reveal a small but distinct signal ('1st component") preceding it. For an average-sized fibre, the deltaI/I of the 1st component was (minus) 1 to 2 x 10-5. 2. The time course of the 1st component superimposed with the surface action potential simultaneously recorded by an internal micro-electrode. The polarity of the 1st component reversed with compensation. 3. From these characteristics, the 1st component is thought to arise from a small change in optical retardation of the surface membrane due to the action potential. 4. When a fibre was impaled with two micro-electrodes, retardation changes accompanying small hyperpolarizing and depolarizing current steps were detected. In some cases the polarity of the observed signal was opposite in sign to that expected for a retardation change only from the surface membrane. 5. Because the anatomical orientation of the T-system appears to be primarily transverse rather than longitudinal, these signals of opposite polarity are probably, on balance, due to retardation changes from the membranes of the T-system. 6. The possible origin of the large birefringence signal preceding contraction is discussed.


Functional electrical stimulation of the extremities: part 1. Functional electrical stimulation of the extremities (FES) is a new method for the rehabilitation of paralysed paretic patients. Small, electronic stimulators are worn by the patient, who can voluntarily control the electrical currents applied to his paralysed muscle. These currents activate the disabled extremities and make them at least partially functional once more. This paper presents a short history of FES and discusses recent advances and problems in the field. A detailed account of present work with single- and multi-channel stimulation of paralysed legs is given, as well as some research data on upper extremity stimulation.


A comparison of chloramphenicol and ampicillin as bactericidal agents for Haemophilus influenzae type B. In tests of bactericidal action against H. influenzae type b strains isolated from patients with meningitis, chloramphenicol was found to be far more reliable than ampicillin in dealing with large inocula, and more rapidly effective against both large and relatively small inocula. These findings provide a laboratory explanation for the somewhat better record of chloramphenicol as an agent for treatment of haemophilus meningitis.


Tumor immunity to murine plasma cell tumors. III. Detection of common and unique tumor-associated antigens on BALB/c, C3H, and NZB plasmacytomas by in vivo and in vitro induction of tumor-immune responses. Tumor-associated antigens (TAA) were demonstrated on plasmacytomas derived from BALB/c, NZB, and C3H mouse strains, by in vivo and in vitro techniques. By immunizing the appropriate F1 hybrid mice with these tumors, it was possible to show that all the plasmacytomas expressed cross-reactive tumor-associated transplantation antigens. When cytotoxic lymphocytes (CL) were induced in vitro by the coculturing of syngeneic or F1 hybrid spleen cells with irradiated plasmacytoma cells, "shared" and "unique" plasmacytoma TAA were demonstrable. This was accomplished by inducing CL in vitro against one syngeneic plasmacytoma and assaying for lytic activity on a range of 51Cr-labeled BALB/c, NZB and C3H plasmacytoma cells in vitro. In a second in vitro assay, unlabeled plasmacytoma cells were tested for their ability to inhibit the lysis of a particular 51Cr-labeled plasmacytoma, with the use of CL induced in vitro against it. The possibility that these TAA were "self" antigens was excluded by demonstrating in the inhibition assay that they were not present on T lymphomas and spleen cells of the same strain, and that CL "autosensitized" in vitro could not significantly lyse 51Cr-labeled plasmacytoma cells in vitro. From both in vivo and in vitro studies of immunity to these tumors, it was concluded that any one plasmacytoma line possesses multiple TAA of both shared and unique types.


In vitro antitumor effect of lymphoid cells from Corynebacterium parvum-treated mice: effect of route of C. parvum administration. Corynebacterium parvum administration in CBA mice resulted in the stimulation in the peritoneal exudate and other lymphoid organs  of cells which nonspecifically inhibited the tumor growth in vitro. The distribution of the antitumor activity in different organs was dependent on the route of C. parvum injection. Both ip and iv treatments stimulated antitumor activity in the peritoneal exudate, whereas the sc route was ineffective. Only iv treatment stimulated the antitumor activity in the blood, and only the sc route produced the antitumor activity in the lymph node. The antitumor activity following the sc treatment was confined mainly to nodes draining the site of C. parvum injection. All routes of treatment provoked some antitumor activity in the spleen, although the degree of the activity varied with the route in the order of ip, iv, and sc. The antitumor activity in all organs peaked between 4 and 14 days after C. parvum injection. This activity in all organs, except the spleen, disappeared by day 42 post treatment. The results are discussed in the light of the in vivo observations on the antitumor effects of C. parvum.


Antitumor immunity, V.BCG-induced growth inhibition of murine tumors. Effect of hydrocortisone, antiserum against theta antigen, and gamma-irradiated BCG. Dimethylbenzdithionsaphthene (DBDN)-induced fibrosarcoma transplantable in syngeneic Swiss mice was a weakly immunogenic tumor and did not regress spontaneously. BCG from India, when incubated with the lethal dose of DBDN-induced fibrosarcoma and subsequently inoculated sc into the susceptible animal markedly inhibited growth of the tumor. Animals that did not show any tumors developed tumor-specific immunity. BCG, if administered separately and not inoculated with the tumor cells, did not show similar response. The close contact between the BCG organism and the tumor cell seemed to be an essential requirement for BCG-induced tumor-growth inhibition. Hydrocortisone-treated animals showed tumor growth even when a BCG-tumor admixture was incorporated, indicating the immunologic nature of the phenomenon. Animals preinoculated with anti-O-serum also showed tumor growth when the BCG-tumor admixture was given. This, however, pointed out a major role of O-bearing lymmphocytes in BCG-induced-tumor-growth inhibition.


Effect of electrical stimulation of the thoracic spinal cord on the function of the bladder in multiple sclerosis. We treated 40 patients who had multiple sclerosis and bladder symptoms with thoracic spinal cord electrical stimulation. Bladder and sphincter dysfunction was evaluated by cystometry and electromyography. Subjective improvement was noted in 77.5 per cent of the patients and documented improvement was found on cystometry and electromyography in 42.5 per cent. By electrical stimulation of the spinal cord we have demonstrated varying degrees of restoration of voluntary and reflex control of the bladder and sphincter.


A survey of blood and other tissue parasites of leopard frogs Rana pipiens in the United States. In a survey of blood and other tissue parasites from 137 leopard frogs, Rana pipiens complex, purchased from 13 commercial vendors in 8 states in the United States, Trypanosoma pipientis was found in 2 R. p. berlandieri, Toxoplasma ranae in 1 R. pipiens, Isospora lieberkuehni in 1 leopard frog, Haemogregarina magna in 44, Lankesterella minima in 3, Leptotheca ohlmacheri in 3 and microfilariae of Foleyella sp. in 6. The report of I. lieberkuehni is presumably a new host record. Haemogregarina temporariae (Nöller,, 1920) nov. comb. is established as a new combination for Nematopsis temporariae.


Improvement of rheumatoid arthritis following splenectomy for Felty syndrome. A patient with Felty syndrome underwent splenectomy because of persistent high fever, leg ulcer, and granulocytopenia. Subsequently, his rheumatoid synovitis went into prolonged remission. In addition, the leg ulcer healed; his WBC count, hemoglobin level, temperature, ESR, and weight returned to normal; the rheumatoid factor titer dropped substantially; and the antinuclear antibodies disappeared. These changes have persisted to the present time, more than 5 1/2 years after surgery.


New antirheumatic agents: Fenoprofen calcium (Nalfon), naproxen (Naprosyn), and tolmetin sodium (Tolectin). The new antirheumatic agents, fenoprofen calcium, naproxen, and tolmetin sodium, are effective in the management of rheumatoid arthritis.  Their efficacy is comparable, but not superior, to that of aspirin in usual oral doses. These agents also may be useful in degenerative joint disease and ankylosing spondylitis and as analgesics and antipyretics; however, there are insufficient data available to establish their efficacy and dosages for these uses. The incidence of adverse reactions, including gastrointestinal bleeding, is lower with these agents than with aspirin; thus, these drugs may be useful substitutes in patients who cannot tolerate the gastrointestinal effects of aspirin.


Sodium pertechnetate Tc 99m scanning of the abdomen. Diagnosis of an lleal duplication cyst. A sodium pertechnetate Tc 99m scan of the abdomen gave positive results in a 5-year-old girl with recurrent abdominal pain and lower gastrointestinal bleeding. An ileal duplication cyst lined by gastric mucosa was found at operation. Abnormal localization of sodium pertechnetate Tc 99m can be observed in any condition with ectopic gastric mucosa.


[Ophthalmic use of clindamycin-2-phosphate (author's transl)]. Bacterial and clinical experiments for ophthalmic use of clindamycin-2-phosphate (CLDM-2-P) were performed and the results were summarized as follows. 1. The distribution of sensitivity for 100 strains of Staphylococcus aureus isolated in 1975 was in the range of less than or equal to 0.19 approximately greater than or equal to 100 mug/ml, and majority of them (96.0%) were in less than or equal to 0.39 mug/ml. 2. The serum concentration by intramuscular injection of 300 mg and 600 mg CLDM-2-P in a single dose respecitvely reached the peak level after 2 hours and decreased gradually until 12 hours in both of them. 3. Ocular penetrations were examined in rabbit eyes. (1) After instillation of 1% CLDM-2-P solution, the aqueous level reached the highest after 1 hour and measurable after 6 hours. (2) After subconjunctival injection of 5 mg/0.5 ml CLDM-2-P, the aqueous level reached the highest after 2 hours and decreased until 6 hours. (3) After intramuscular injection of 100 mg/kg, the aqueous concentration was recognized from 1 to 8 hours, and peak was reached after 1 hour. 1 to 8 hours, and peak was reached after 1 hour. Aqueous-serum ratio in 1 hour was 37.13%. The ocular tissue concentrations at 2 hours showed relatively high levels in both of outer and inner parts of the eye. 4. The intramuscular injection of CLDM-2-P, 300 approximately 1800 mg daily, against suppurative ocular infections revealed excellent effects on cases of external hordeolum, acute chalazion, lid abscess, orbital phlegmone, corneal infiltration, corneal ulcer, and iridocyclitis purulenta. 5. Side effects: Two cases out of 22 cases complained of diarrhoea and bitter taste after injection, and able to be treated continuously by the drug. No abnormal findings in hepatic and renal tests were observed and no servere side effects like allergic reactions were recognized.


[Malignant mediastinal lymphoblastic lymphoma with t-cell ALL (author's transl)]. 29 cases of T-cell derived lymphoblastic lymphoma and T-ALL have been analyzed. There is a striking prevalence of the male sex. In the peripheral blood we often find initially an excessive number of white blood cells combined with normal values for the other constituents in about half of the patients; This may be an expression for the rapid occurrence of leukaemia in T-cell lymphosarcoma. In addition to systemic ALL-therapy we performed X-ray irradiation of the mediastinum in 8 of our patients. This yielded to significantly longer first complete remissions. All patients with T-cell LSA/ALL with or without mediastinal mass should be treated in this manner. Cytochemically a strong focal acid phosphatase reaction was found to be acharacteristic of these cells. It has proved to be a screening method for this disease. The cells are T-cell derived and their pattern of surface markers is similar to that found in fetal thymocytes.


Diagnosis and treatment of hemorrhage in patients with hiatal hernia. A retrospective study examined the clinical course of 32 patients with hiatal hernia in whom hemorrhage of the upper gastrointestinal tract was a prominent symptom. Hemorrhagic esophagitis was the most common source of bleeding. Duodenal ulcer, gastritis, and gastric ulcer of the herniated stomach were other less frequent causes of hemorrhage in these patients. Hemorrhage from esophagitis is usually mild and chronically recurrent. Surgical correction of the hiatal hernia and reflux is adequate treatment for the patient with hemorrhage from esophagitis or gastritis of the herniated stomach. Hemorrhage from duodenal ulcer as well as gastric ulcer requires a procedure directed at these lesions. Because of the association of upper gastrointestinal bleeding in hiatal hernia with lesions other than esophagitis, a vigorous diagnostic approach with endoscopy is essential.


Control of myocardial performance early after open-heart operations by vasodilator treatment. The hemodynamic effects of vasodilator treatment (afterload reduction) with nitroprusside at a constant heart rate were studied in 24 patients early after aorta-coronary bypass grafting. In 12 patients, dose-response relationships were determined. Graded incremental infusions of nitroprusside produced progressive decreases in mean arterial pressure (MAP), right and left atrial pressures, and stroke work index. Stroke volume index and cardiac index rose significantly until MAP was reduced below the range of 80 to 90 mm. Hg, and then they fell to base-line levels owing to insufficient preload. In an additional 12 patients, MAP was reduced with nitroprusside to the range of 80 to 90 mm. Hg, and left atrial pressure was then restored to base-line levels during continued vasodilator administration. This sequence resulted in further augmentation of stroke volume index to a level higher than that produced by nitroprusside alone. We conclude from this investigation that nitroprusside is a clinically useful agent for primary or adjunctive therapy of mild-to-moderate low cardiac output states immediate postoperatively and that simultaneous regulation of left ventricular preload and after load during its administration is necessary in order to achieve maximal hemodynamic benefit.


Late lesions in aorta-coronary artery vein grafts. Aorta-coronary artery vein grafts, obtained from 2 patients 37 and 59 months after an aorta-coronary bypass operation, showed extensive mural changes characterized by degenerative tissue lesions, loss of normal morphological features of the intima, and extracellular accumulation of lipids. Both patients had increased plasma triglyceride levels.


[Effect of electric stimulation of the hypothalamus and limbic formations on vestibular-somatic reflexes]. Chronic experiments on rabbits which had electrodes implanted into the hypothalamus, amygdalar area and hyppocampus have shown that electrostimulation of these brain structures which brought about different emotional and behavioral reactions during preliminary test produces a distinct modulating effect on the vestibular (rotatory and post-rotatory) nystagmus and labyrinthine posture-tonic reflexes.


Abnormal chemotaxis in patients with cutaneous anergy. Chemotaxis of polymorphonuclear leukocytes and mononuclear leukocytes was studied in six patients who had persistent cutaneous anergy. Four had previous infections (three fungal and one caused by Mycobacterium kansasii), one had sarcoidosis, and one had late-onset immunoglobulin deficiency. Our data indicate that some patients with persistent cutaneous anergy have a combined defect of leukocyte function. Lymphocytes incubated in vitro with mitogen failed to elaborate active lymphocyte-derived chemotactic factor when compared with controls. Polymorphonuclear leukocytes and mononuclear leukocytes responded poorly to normal chematactic factors compared with controls. The abnormal mononuclear leukocyte chemotaxis may play a role in the persistent cutaneous anergy of these patients.


Otologic and otoneurologic injuries in divers: clinical studies on nine commercial and two sport divers. In the past two decades, we have seen a great increase in the number of injuries from commercial and sport diving. During this time, our knowledge of the physiology and pathophysiology of diving has also increased. As a result, we now can accurately diagnose and successfully treat many of these injuries. Of the commercial and sport divers examined as pateints in the Department of Otolaryngology at the University of Texas Medical Branch in Galveston, Tex., between September, 1974, and May, 1975, 11 showed positive otologic and otoneurologic findings which are reported herein. One patient was surgically explored for an oval window fistula. In localizing and classifying these injuries, we have utilized extensive and broad-based test batteries, which include complete history, otologic and otoneurologic physical examination, audiometry, a central auditory test battery, and a vestibular test battery. These tests are described. The findings in each of the divers are illustrated and analyzed. This article further describes the use of these test batteries, which were employed to localize otoneurologic pathology in this sample of injured divers. Based on these cases, we have expanded and modified Edmonds' classification of the etiology of vertigo related to diving. We feel that the test batteries which we describe, or similar tests, should be part of the otologic and otoneurologic workup of injuries divers.


ENG analysis of 150 cases of posterior fossa disease. Analysis of the ENG records of 150 patients with well substantiated neurologic disease involving the structure of the posterior fossa revealed a high incidence of diminished optic fixation inhibition (DOFI) of caloric induced nystagmus. DOFI is defined as less than 50 percent decrease of speed of the slow phase when eyes are open and fixated. The whole group was subdivided into seven subgroups according to type and location of disease and the incidence of DOFI was found to vary significantly in the different subgroups. The highest incidence was found in the group of cerebellar mass lesions and in the group of degenerative diseases, most of which had cerebellar involvement. A review of the literature reveals work done by others showing that suppression of vestibular reflexes induced by high speed turning and also habituation of caloric induced nystagmus is dependent on optic fixation inhibition (opto-vestibular reflex.). It has been shown that the flocculonodular lobe of the cerebellum has an inhibitory effect on the effects of vestibular activity by both destructive and stimulating techniques. Afferent and efferent pathways between the cerebellum and primary vestibular reflex arcs have been extensively described. It has been shown that cerebellar nodulectomy severely interferes with acquisition of habituation and retention of previously acquired habituation. Since habituation and suprression of vestibular nystamus depend on optic fixation inhibition and equally on the cerebellum, it is reasonable to infer that the opto-vesitubular inhibitory reflex is mediated by the crebellum. The clinical data of the 150 cases were analyzed for correlation of DOFI and other cerebellar signs. This analysis gives a high incidence of correlation: 66 percent of the cases having DOFI also had other cerebellar signs, whereas only 19 percent of cases that did not have DOFI had other cerebellar signs. These data lend further support to the inference that the cerebellum is involved in mediation of the opto-vestibular inhibitory reflex. Under most circumstances visual perception of the environment during movement depends on an inter-reaction between the vestibulo-oculomotor and the opto-vestibular reflexes. Eye movements during head movements are entirely different with eyes closed than with eyes open and fixating. In fact, it can be shown that ocular fixation is far more efficient during head movements than it is during movement of an object with head stationary. It is probable that fixation in the former case is the result of vestibulo-oculomotor slow phase activity modified by the opto-vestibular inhibitory reflex and elimination of the fast phase. A defect in the latter should result in a sense of spatial insecurity during movement by virtue of altered visual perception. The opto-vestibular inhibitory reflex is a central descending reflex probably mediated through the cerebellum. It is easy to test during and ENG. It is essential to normal visual perception during head movement...


The mesocaval "H" graft: experience with 22 cases. During the past 32 months, 22 consecutive unselected patients who had bled from oesophageal varices have undergone mesocaval "H" graft operations. There have been nine deaths, three in the early and six in the late postoperative periods. Two deaths were the result of bleeding complicating severe primary fibrinolysis and three were due to disseminated sepsis, one originating from an infected shunt. Continued alcohol intake may have contributed to five of the late deaths. Ten of the 19 patients who left hospital developed some degree of hepatic encephalopathy easily controlled by diet and medical therapy. However, in one case the development of grade IV coma necessitated ligation of the shunt to reverse the coma. Patency of the shunt was demonstrated in all but one patient. Recurrence of bleeding occurred only in this patient and the one in whom the shunt was ligated. Although the operation had a comparatively low operative mortality, the long-term mobidity and mortality were no better than those of the more conventional portacaval anastomosis.


[Responses of neurons in the nucleus isthmi region of the frog to optic nerve stimulation]. Neuronal responses were studied in the nucleus isthmi area of Rana temporaria. The animals were immobilized by diplacine, a curare-like drug. Single neurons in this area had no background activity. After single-pulse electric stimulation of the contralateral optic nerve these neurons discharged as a rule with one action potential only, its minimal latency being 20-110 msc. The latencies decrease significantly when the stimulus intensities were increased from threshold to maximal, indicating development of summation process in the corresponding afferent pathway. Only 14 per cent (7 of 57) of neurons responded to stimuli exciting myelinated optic fibres and not exciting the ummyelinated ones. All the nucleus isthmi neurons discharged with unstable latency; this means that these neurons were excitated not antidromically. The functional role of nucleus isthmi in Anurans is discussed.


Influence of the duration of second stage labor on perinatal outcome and puerperal morbidity. Obstetric data from 4403 nulliparas were analyzed in order to determine whether the duration of the second stage of labor influences perinatal outcome or maternal puerperal morbidity. No significant increase in the frequency of perinatal mortality, neonatal mortality, or low 5-minute Apgar scores was noted with long second stages. An increase in the incidence of low 1-minute Apgar scores was observed only in those infants who were not monitored. An increase in puerperal hemorrhage after more than 3 hours of second stage labor was attributable to those patients delivered by midforceps operations. It appears that it is unwarranted to terminate labor simply because an arbitrary period of time has elapsed in the second stage.


T and B cells in pregnancy.

T and B cells in pregnancy. The present study reports on the relative percents and absolute numbers of peripheral blood total T, active T, and B lymphocytes in pregnant women throughout gestation. These data agree with other studies reporting normal T and B cell populations during pregnancy.


Lymphocyte subpopulations in human malnutrition: cytotoxic and suppressor cells. Lymphocytes in the peripheral blood of young children with protein-calorie undernutrition were evaluated for surface markers and function. Thymus-dependent lymphocytes were reduced and the immunoglobulin-bearing B lymphocytes were unchanged. The relative proportion of the remaining "null" lymphoid cells was increased. Null cells and, to a lesser extent, B lymphocytes showed cytotoxic activity against xenogeneic target cells and suppressed phytohemagglutinin-induced DNA synthesis by normal T lymphocytes. It is suggested that these alterations in lymphoid subpopulations contribute to depressed cell-mediated immunity in malnutrition.


Relationship between visual orientation and susceptibility to motion sickness. 24 male subjects were divided into 3 groups, on the basis of their susceptibility to motion sickness. All subjects were then required to set a luminous line in an apparently vertical position while viewing the line from a body position which was deviated 70 degrees laterally from the upright. No visible frame of reference was available. A significant relationship between motion sickness susceptibility and errors in judging the vertical was discovered, the "intermediate" susceptibility group making the greatest errors. The role of the vestibular system in visual orientation and motion sickness is discussed. The result also indicates the potential value of using perceptual performance as a tool in the study of motion sickness and its correlates.


[Hydroelectrolytic disturbances secondary to high flow lavage used for the prevention of posthemorrhagic encephalopathy in cirrhosis]. The authors carried out high flow intestinal lavage during gastrointestinal bleeding in cirrhotics in order to obtain rapid elimination of blood from the intestine and thereby reduce the risk of encephalopathy. The fluid used had been developed for preparation of the colon for surgery and was responsible for water and electrolyte disturbances with water and salt retention. Without criticising the principle of lavage in the prevention of encephalopathy, the authors express certain reserves with regard to the use of this solution and suggest the use of a sodium-free substance remaining within the intestinal lumen (hypertonic mannitol) which does not cause any water/electrolyte imbalance, is more effective and would appear to have a slight though definite action on the resorption of ascites.


Prenatal diagnosis of achondrogenesis.

Prenatal diagnosis of achondrogenesis. An achondrogenic fetus, in whom the diagnosis was made prior to delivery by plain abdominal X-rays, is presented. The intrauterine characteristic roentgenographic manifestations are the short dense tubular bones of the extremities. An early diagnosis in fetuses with this disease can be made on a plain abdominal X-ray in the 22nd-24th week of gestation.


Radiological diagnosis of pontine angle tumours. The following methods of radiological examination are suitable aids in the diagnosis of pontine angle tumours: plain radiographs and tomograms of the petrosal bone, cisternography of the pontocerebellar cistern with positive- und negative-contrast media, vertebral arteriography and computer tomography. In some 80% of cases of pontine angle tumour, plain X-rays and tomograms can disclose changes. In the case of vestibulocochlear neurinoma confined to an intracanalicular localization, only cisternography with a positive-contrast medium supplies diagnostic information. Cisternography with a negative-contrast medium is a suitable method of radiological examination in the case of larger vestibulocochlear neurinomas, which protrude into the pontocerebellar cistern, and also for the remainder of pontine angle tumours. The technique we use in this cisternography is described and evaluated with reference to 28 patients.


Transcatheter embolization for treatment of diverticular hemorrhage. Two patients underwent transcatheter embolization for control of massive diverticular hemorrhage after vasopressin infusion had failed to control the bleeding. The role of angiography in the management of diverticular bleeding is discussed. If surgery is being considered, angiography should be utilized to localize the bleeding site and to permit limited colonic resection. Transcatheter embolization is proposed as an alternative to operative intervention.


Benefits and prognoses following 10 years of a fluoride mouthrinsing program. This paper is based upon the mean annual amounts of fillings (filled surfaces) and the DMFS among 6/7- to 15/16-year-old children. Each age group comprised about 450 children. Cross-sectional recordings were available prior to the start of a caries-preventive program based on 2-weekly fluoride rinses. Cross-sectional and longitudinal DMFS recordings were different during the 10 years of observation. This indicates benefits exceeding the present 70% reduction in need for fillings and 50% improved caries prevalence. The ratio fillings needed for giving the DMFS score among 13- to 14-year-old children was found to improve from 1.60 to 1.16. Based on the cumulative amounts of fillings and the ratio of fillings/DMFS, a DMFS of 15 may be expected in 4 years among children 15-16 years old. This caries prevalence is not markedly different from DMFS recordings among Scandinavian children living in fluoride areas.


The role of granulocytes in colony stimulation by human white blood cells in agar cultures. Enhancement and inhibition of CSA. The effect of polymorphonuclear granulocytes (PMN) on colony stimulating activity (CSA) was studied in double layer cultures of human Ficoll Isopaque separated white blood cells (mononuclear cells = MNC). Previously published data have been confirmed that granulocytes are able to enhance or inhibit MNC derived CSA. Further analysis of the mode of action of PMN in vitro indicates that the enhancing activity ascribed to granulocytes coincides with low CSA in MNC basal layers. In contrast, in cultures with high levels of CSA as provided by lysed red blood cell enhancement rather than concentrations of PMN are sufficient to induce inhibition of colony growth. A very similar effect to that achieved with basal layer derived CSA could be obtained with conditioned media of PMN and MNC short term liquid cultures. The data indicate, that enhancement and inhibition of colony growth reflect a specific reactivity of granulocytes (PMN) to a given CSA level in the cultures. These findings are discussed in terms of a speculative role of PMN in a negative feed back control mechanism regulating granulopoiesis in vivo.


The effect of adrenaline, insulin and hydrocortisone on human peripheral blood lymphocytes studied by cell surface markers. Changes in numbers of peripheral blood lymphocytes from healthy individuals were calculated from samples collected before and after parenteral administration of adrenaline, insulin and hydrocortisone, respectively. A marked increase in circulating lymphocytes was noted in response to adrenaline and insulin. However, subpopulation analysis showed a decrease in the proportion of T-lymphocytes, estimated as cells forming rosettes with sheep red blood cells after incubation in the cold and a corresponding increase in proportion of lymphocytes having receptors for C3 (non-T lymphocytes). In contrast, lymphocyte numbers were unaffected by hydrocortisone. The results indicate that a decreased proportion of circulating T-lymphocytes and an increase of non-T-lymphocytes may be the result of adaptive changes in response to various forms of stress and hence is to be expected in several clinical conditions.


Prevention of autoimmunity in experimental lupus erythematosus by soluble immune response suppressor. Young NZB/W mice, treated with injections of soluble immune response suppressor (SIRS)(supernatant from mouse spleen cells exposed to concanavalin A), showed decreased immunoglobulin levels, less antibody to cell nuclei, less proteinuria, and less renal pathology as compared with NZB/W mice receiving a control preparation.  Thus, SIRS administration beginning at an early age appears to be an effective therapy of the autoimmune disease in NZB/W mice.


Surgical experience with postinfarction ventricular aneurysm. Fifty-eight patients had surgical treatment of postinfarction ventricular aneurysm. Resection was performed in 47 patients and plication in 11. There were 44 combined procedures,  mostly myocardial revascularizations. Indications for operation included congestive heart failure, angina, arrhythmias, and thromboembolic phenomena. All aneurysms were documented by cineventriculography, and 54 patients had coronary cineangiograms. Left ventricular end diastolic (LVED) pressures ranged from 25 to 50 in 25 of the patients but did not affect mortality. Hospital mortality (14% overall) was directly proportional to degree of coronary artery disease--single vessel, 0; double vessel, 10%; triple, 24%. Nine patients are alive more than six months postoperatively and 37 are alive from six months to eight years postoperatively. We conclude that aneurysmectomy is the procedure of choice for ventricular aneurysms that are hemodynamically significant or have produced ventricular clots, arrhythmias, or embolic phenomena. An LVED of greater than 25 mm Hg does not contraindicate operation, but triple vessel coronary disease increases the risk.


Psychologic response to coronary artery bypass. This study reports the psychologic findings in 30 patients undergoing this operation. Approximately one third developed postcardiotomy delirium, an occurrence consistent with that after other forms of open-heart surgery. Acceptance of the operation as opposed to preoperative anxiety, depression or denial, adequate comprehension of the proposed procedure, and a stable postoperative environment seem associated with less postcardiotomy delirium. Preventive preoperative therapeutic suggestions based on these findings are given.


Reevaluation of neonatal Hemophilus influenzae infections. Hemophilus influenzae infections are increasing in frequency in the general population. As a result this organism must be considered an etiologic agent of disease in the neonate. Proper culture technics must be routinely employed to isolate this fastidious organism, and appropriate antimicrobial therapy must be instituted in infants suspected of having sepsis or meningitis. Three cases of H influenzae infection occurring in neonates are presented.


Peripheral lymphocyte count and suppopulations of T and B lymphocytes in benign and malignant diseases. It is well known that there are many independent and inter-related clinical and pathologic factors which influence the prognosis of patients with benign and malignant conditions. Lymphocyte level is an index of cell-mediated immunity which is important in host defense against cancer. But it is surprising that a simple test such as peripheral lymphocyte count could be correlated with clinical stages and survival results in patients with Hodgkin's disease, non-Hodgkin's lymphoma and non-lymphomatous solid tumors. Regarding the latter, lymphocyte count had prognostic values in patients with cancer of the bone, Ewing's sarcoma; breast; colon; kidney, neuroblastoma; uterine cervix, and other sites. In general, higher lymphocyte counts before therapy correlated with longer survival. Using newer immunologic techniques, T and B lymphocytes can be identified and the different subtypes of leukemia, immunodeficiency and lymphoproliferative diseases have been studied intensively. Chronic lymphocytic leukemia represents a proliferation of B cells, while the Sezary syndrome represents that of T lymphocytes. There is a qualitative and quantitative disturbance of Blymphocytes in patients with multiple myeloma. In Hodgkin's disease, there is hyperactivity of the B cells and functional defect of the T cells. Finally, the nodular non-Hodgkin's lymphoma resulted from neoplastic transformation of the B lymphocytes. In several nonmalignant autoimmune conditions, abnormality of T-cell or B-cell counts has been reported. For example, T cells were reported to be decreased in patients with ulcerative or granulomatous colitis and in patients with rheumatoid arthritis, However, it needs to be pointed out that, in 1973, Farid and associates (44) reported a significant increase in T and a proportionate reduction of B rosette in 17 patients with untreated Grave's disease and 16 with Hashimoto's thyroiditis as compared with 24 normal and eight goiter controls. In 1975, six publications later, they (143) had to announce a retraction because further studies by them and by other investigators could not repeat the earlier results. Despite variations and lack of standardization of the test systems, some consistent deviations of T-lymphocyte and B-lymphocyte counts have been reported. T lymphocytes were quantitatively decreased in patients with carcinoma of the brain, breast, head and neck, liver, lung and urologic organs and with malignant melanoma. In general, there is a marked decrease of T cells with increasing stage of disease and a return of T cells to normal level after successful therapy. Cellular immunity is depressed, often lasting for years after localized radiation therapy, whether or not the thymus is included in the treatment field...


A new in vivo assay of human lymphocyte-mediated immunity to melanoma. Lymphocytes from melanoma patients more frequently inhibited the growth of human melanoma cells in the hamster cheek pouch than did lymphocytes from normal donors. Growth inhibition was accomplished with a much lower ratio of target cells to lymphocytes than in in vitro assays. The hamster cheek pouch assay can be used to study the relationship of blocking factors and humoral antibodies to cell-mediated immunity against human cancers.


Total T lymphocytes in primary bronchial carcinoma. Percentage and absolute levels of circulating T lymphocytes were measured in 48 patients with bronchial carcinoma. These were compared with control values from nine healthy adults and 19 age-matched patients with benign disorders. A further 20 patients who had been given postoperative immunotherapy after complete resection of bronchial carcinoma were also studied. There was no significant difference in the mean percentage T cells between the groups. Lymphopenia, however, was a feature of the bronchial cancer patients with metastatic disease. This resulted in a significant diminution of absolute T cells in this group. There is no evidence, with the technique employed in this study, of a total T-cell deficiency in early bronchial carcinoma.


Platelet interaction with collagen fibrils in flowing blood. II. Impaired adhesion-aggregation in bleeding disorders. A comparison with subendothelium. Anticoagulated whole blood from patients and control subjects was circulated through an annular perfusion chamber in which the fibrillar collagen of alpha chymotrypsin-digested subendothelium and intact subendothelium were exposed. The blood flow conditions corresponded to those in arteries (830 sec-1 wall shear rate). Platelet surface interaction was measured morphometrically. Decreased adhesion to fibrillar collagen associated with normal spreading and normal adhesion-induced formation of platelet thrombi was found with blood of patients with von Willebrand's disease and the Bernard Soulier Syndrome, indicating a defect in the initial attachment reaction of platelets with collagen. Platelets of patients with thrombasthenia did normally adhere to the collagen fibrils and also lost their subcellular organelles during this reaction, but they totally failed to adhere to each other. In storage pool disease platelet thrombus formation was consistently inhibited whereas adhesion and spreading was inhibited in some patients and normal in others. In contrast adhesion was always normal after ingestion of aspirin which consistently caused a marked inhibition of platelet thrombi. These findings correspond -- in essence -- to those previously described on intact subendothelium. However, the observed defects are more pronounced on the fibrillar collagen than on intact subendothelium.


[Congenital bronchoesophageal fistula--a case study (author's transl)]. This report deals with a patient with a congenital bronchoesophageal fistula, type "H", which was diagnosed only at age 43. This is an extremely rare defect and, if not recognized shortly after birth, it usually will stay unrecognized despite the fact that it causes recurrent pneumonias or localized bronchiectasis. The diagnosis of such a case is difficult and usually only possible with the help of a variety of diagnostic tests. The deciding factor is the recognition of the congenital defect. The subsequent surgical treatment including resection of the canal and closure of the fistula is a relatively simple operative procedure.


[Etiology and diagnosis of thoracic kidney (author's transl)]. Intrathoracic mass lesions revealed on routine chest-x-rays may represent high renal ectopia. This is particularly true in cases of dorso-basal location and in the absence of symptoms. On a case herein reported the value of excretory urography as important diagnostic procedure is demonstrated. The significance of angiographic features for etiological classification will be discussed. A comprehensive review of the relevant literature is given.


[Implantation of the intraaortic balloon catheter through the aorta ascendens (author's transl)]. In intraoperative cardiac low out-put syndrome balloon implantation through the ascending aorta can be accomplished for secure and rapid installation of IABP, if sternotomy has occurred and successful insertion through the common femoral artery has proven to be impossible. The disadvantage of rethoracotomy for explantation of the balloon catheter can be accepted without additional risk.


[Leiomyosarcomas of the inferior vena cava. Report of a case and review of the literature (author's transl)]. A 55-year-old female with leiomyosarcoma of the middle segment of the inferior vena cava was successfully operated, 2 years ago. The literature is reviewed and pathology, symptoms, diagnosis and differential diagnosis, therapy and prognosis are thoroughly discussed.


[The importance of inputimpedance of QRS-regulated pacemakers (author's transl)]. As smaller the inputimpedance of a QRS-inhibited or synchronous pacemaker as higher the necessary energy for regulation. A method for measurement of inputimpedance of pacemakers is described. These impedances from several types are determined. It is a necessity to lead an intracardial ECG with a loading resistor like the used pacemaker.


[Validity of thermodilution cardiac output determination in the presence of pulmonary insufficiency (author's transl)]. The thermodilution (TD) technique can be considered as the most useful method for cardiac output (CO) determinations in clinical routine. However, surgical procedures for pulmonary stenosis or atresia frequently induce pulmonary insufficiency (PI) of various degree; due to abnormal flow conditions, this may interfere with the validity of transvenous CO-determinations. This experimental study shows that the TD technique is accurate even in the presence of PI. This observation may be explained by the fact that PI results, on the one hand, in a higher distribution volume and, on the other hand, in an increased transit time of the indicator; both of these factors have opposite effects on CO calculations, thus possibly leading to a balance of either error.


[Intramyocardial calcification of unknown origin (author's transl)]. A case of intramyocardial calcification is presented. The etiology can neither be explained by history, nor by clinical or histological examination. The diagnosis was made by cardiac catheterization and angiocardiography. This showed that the calcification had occurred mostly in the myocardium of the left ventricle and interventricular septum. Because of chronic heart failure surgery was indicated and large amounts of the calcified mass were removed by means of an open heart operation. One and a half years later the patient is much improved though clinical signs of heart failure persist. Possible causes of myocardial calcification are discussed and the problems of surgical intervention outlined.


A method for radioactive antiglobulin testing with 125I labeled anti-IgG. The present report describes a method for 125I anti-IgG antiglobulin testing. The method involves the use of a labeled DEAE cellulose IgG fraction of goat anti-human IgG globulin. Leukocyte-free red blood cells were used in the test procedure. Both the labeled antiserum and the red blood cell suspensions were diluted in normal rabbit serum to prevent non-specific uptake of labeled antiserum by normal, uncoated red blood cells. The results of the study show that the method is highly reproducible and relatively easy to perform once the labeled anti-IgG is prepared. Furthermore, the use of labeled antiserum permits analysis of antiserum specificity by radioimmunoelectrophoresis. The problem of determining anti-IgG/IgG binding ratios remains the major disadvantage to using the method to determine precise amounts of human IgG coating red blood cells.


A simple method for the cryopreservation of human lymphocytes at -80C. A simple and inexpensive method for the freezing of human blood lymphocytes at -80 C is described. Lymphocytes were frozen in either polystyrene tubes or polyolefin bags. Optimal recovery of cells was obtained when 5% DMSO and 62% plasma were used as cryoprotectants. Viable cell recovery, as assessed by response to phyto hemagglutinin (PHA) and pokeweed mitogen (PWM), was greater than 80% after 60 days of storage. In addition, percentages of T and B lymphocytes were essentially unchanged. The excellent viable cell recovery in polyolefin bags suggests that it is possible to cryopreserve large numbers of lymphocytes in a single container.


Human peripheral blood "null-lymphocytes", a highly enriched pool for granulocytic stem cells (CFU-C). A "Null"-lymphocyte preparation containing a high concentration of granulocytic stem cells (CFU-C) was isolated from human peripheral blood. 3 lymphocyte purification procedures were shown to produce an enrichment of CFU-C: 1. Removal of mononuclear phagocytes by iron phagocytosis and plastic adherence procedures. 2. Passage through Ig anti-Ig columns. 3. Removal of E-rosette-forming T cells. A combination of all 3 purification steps resulted in a 30- to 40-fold enrichment of CFU-C in the final "Null"-lymphocyte population as compared to the initial lymphocyte fraction isolated by Ficoll-Urografin density gradient centrifugation.


[Role of immune RNA in the interaction of T- AND B-lymphocytes]. "Immune" RNA preparations were obtained from the total population and also from the T- and B-lymphocytes of the spleens of the QBA line. Intact bone marrow cells or splenic cells activated with antigen served as target cells for the "immune" RNA. Investigations were carried out in the system of syngenic transfer. To study the target cells in the activated population of the spleen elimination of T-or B-lymphocytes was realized immediately after the incubation of the suspension of the splenic cells with the RNA preparations with the aid of anti-theta-or anti-B-antilymphocytic sera. T-lymphocytes served as the source of the biologically active RNA in the total preparation. B-lymphocytes of the spleen and the bone marrow served as target cells for the RNA of the cells of thymus origin. However, to detect the inducing action of the RNA simultaneous presence in the population of T- and B-lymphocytes is necessary.


[Comparison of the immunodepressant effect of antimacrophage, antilymphocyte and antithymocyte sera following immunization with influenza virus A2]. An immunodepressive action of the anticellular sera was cause by the competition of the serum and viral antigens, as well as by the specific influence of the sera on the corresponding cells. The antimacrophagal serum decreased the monocyte content in the peripheral blood, peritoneal exudate, and retarded the antibody formation in the lymphoid organs. The antilymphocytic serum depressed the development of the plasma cell reaction in the lymph nodes and the spleen, this being expressed in a depression of the increase of the serum antihemagglutinin titre. The antithymocytic serum shortened the period of the active antibody formation.


[Therapeutic effectiveness of anticoagulants in the acute phase of cerebral infarction]. 500 patients who were admitted to hospitals in acute phases of brain infarctions were treated by intravenous administrations of spasmolytical drugs. 518 patients with similar conditions, besides spasmolytical drugs received anticoagulants (heparin and phenilin). In patients with expressed neurological disorders treated by anticoagulants there was a highly significant improvement, including an increase of the percent of moderate improvement and a drop in the lethality, In those patients with mildly expressed neurological disorders who received anticoagulants an improvement was also marked, but not so distinctly. In cases with slight neurological disorders the different outcomes were not significant. The highest effectivesness of anticoagulants was marked in infarctions, due to thrombosis. The effectiveness indices in patients due  to stenosis with angiospasms were not significant.


Control of streptomycin and isoniazid in malnourished children treated for tuberculosis. In 12 malnourished children, who were treated for tuberculosis, plasma levels of streptomycin and isoniazid were followed. Streptomycin was administered i.m. in a dose of 25-50 mg/kg/24 hours. High initial plasma levels were reached (mean: 44.3 mug/ml at 30 min). Streptomycin levels were followed for 5 hours and the mean plasma level at that time was 17.0 mug/ml. From the present data a plasma half life of streptomycin of 3.5 hours has been estimated. It is advised that streptomycin should not be given in doses above 25 mg/kg/24 hours to avoid potential toxic plasma levels especially if plasma levels cannot be measured. It is also concluded from our study that renal function is not affected in malnourished children to an extent where streptomycin clearance is greatly affected. Isoniazid was given orally, 10 mg/kg/24 hours. From 30 min to 6 hours after administration, mean plasma levels of isoniazid above 0.5 mug/ml were observed. In all children measurable plasma levels were obtained. It is concluded that also children with malnutrition can absorb isoniazid after oral administration. From our data it is suggested that the majority of the children in our study were rapid inactivators of isoniazid.


Immune complexes in cystic fibrosis.

Immune complexes in cystic fibrosis. Eleven patients with cystic fibrosis (CF) chronically infected with mucoid P. aeruginosa and ten patients without P. aeruginosa infection were examined for occurrence of circulating immune complexes, for immune complex deposits in the dermo-epidermal junction of the skin and for precipitins against P. aeruginosa, S. aureus, H. influenzae and D. pneumoniae antigens. The serum concentrations of haptoglobin, orosomucoid, immunoglobulins, C1q, C3, C4 and total haemolytic complement, antinuclear and rheumatoid factor activities as well as white blood cell counts and erythrocyte sedimentation rates were determined also. The results indicated that 6 patients from the chronically P. aeruginosa infected group, exhibiting a spectrum of serum precipitins against P. aeruginosa antigens, also had immune complexes in the serum, while only one patient (suffering from selective IgA deficiency) in the group without P. aeruginosa infection was positive for soluble immune complexes. Granular deposits of IgM was found in the skin of 10 of the chronically P. aeruginosa infected patients and in 7 of the patients without P. aeruginosa infection. A few pactients in both groups had dermo-epidermal deposits of C1q, C3 or fibrinogen as well. Eight of the patients in the chronically infected group and five in the group without P. aeruginosa infection had organ non-specific antinuclear factors. The haptoglobin levels appeared to be elevated in the chronically infected patients (p less than 0.05). None of the other parameters showed any significant difference between the two groups.


Anesthesia for diagnostic procedures.

Anesthesia for diagnostic procedures. Invasive procedures such as angiography, pneumoencephalography and bronchography are often facilitated by the skillful administration of carefully selected anesthesia. The advantages of general anesthesia versus an awake patient during cerebral angiography are not yet resolved. Although computerized tomography and myelography can usually be accomplished with no anesthesia and local anesthesia, respectively, in children and in confused, uncooperative patients, sedation or general anesthesia may be necessary.


Vestibular syndrome and vascular anomaly in the cerebello-pontine angle. During the investigation of patients presenting symptoms related to the Vth and VIIth nerves, frequently associated symptoms relevant to the VIIth nerve were found, such as tinnitus, disequilibrium or vertigo. On the other hand, there also came to our attention patients whose major complaints were of VIIIth origin, especially of the vestibular component, and who occasionally presented associated symptoms of Vth or VIIth nerve involvement. Following the successful treatment of trigeminal neuralgia and hemi-facial spasm by liberation of the Vth and the VIIth nerve from the mechanical irritative lesion, frequently a vascular loop anomaly, it was postulated that the same cause could be responsible of tinnitus and vertigo, secondary to irritation of the VIIIth nerve, in some cases. The clinical picture of VIIIth nerve involvement in the posterior fossa, either isolated or associated with facial pain or hemi-facial spasm, is presented together with the results of surgical treatment in 5 cases.


Clinical and hemodynamic results of intraortic balloon counterpulsation and surgery for cardiogenic shock. Forty-two patients with cardiogenic shock (CS) secondary to myocardial infarction were treated with intra-aortic balloon pumping (I.A.B.P.). In 14 patients C.S. was associated with ventricular septal defect (V.S.D.) and in four with mitral regurgitation (M.R.) secondary to rupture of the posterior papillary muscle. All patients were resistant to conventional medical therapy. Shock was reversed in 20 of the 24 patients in C.S. without mechanical complications. After 24 to 48 hours of I.A.B.P., cardiax index (C.I.) increased from 1.38 to 2.00 L./min./M2, systolic arterial pressure (S.A.P.) from 83 to 96 mm. Hg, urinary output (U.O.) from 10 to 56 ml. per hour, and pulmonary wedge pressure (P.W.P.) decreased from 22 to 16 mm. Hg. Three patients treated with I.A.B.P. alone survived more than 1 year; of the 13 patients who were balloon dependent, four have undergone emergency surgical procedures and two were long-term survivors. In all patients with mechanical complications, I.A.B.P. resulted in significant clinical and hemodynamic improvement. P.W.P. decreased from 19 to 15 mm. Hg, and U.O. increased from 13 to 38 ml. per hour while S.A.P. remained unchanged. In patients with V.S.D. the pulmonary/systemic flow ratio (P/S) declined from 3.5 to 2.8; in patients with M.R., "V" wave amplitude decreased by 8 mm. Hg. Emergency surgery was performed in 10 patients with V.S.D. and in three patients with M.R. and there were eight long-term survivors (13 to 27 months). It is concluded that I.A.B.P. is an effective means of supporting the circulation in C.S. Of the 42 patients with C.S. treated by combining I.A.B.P. and emergency surgery, 13(31%) were long-term survivors (20 +/- 6 months).


Eisenmenger's syndrome in pregnancy: does heparin prophylaxis improve the maternal mortality rate? Seven consecutive patients with Eisenmenber's syndrome, cared for by the obstetric team in conjunction with the cardiology service, were reviewed to assess the possible role of prophylactic heparin therapy and intensive care on the outcome of these patients. In each patient, the diagnosis of Eisenmenger's syndrome was established by the demonstration of equal pulmonary arterial and aortic pressures with a predominantly right-to-left shunt at cardiac catheterization. Five of the seven patients died as follows: Three patients died between the fifth and eighth post-partum days, one patient died during the twenty-sixth week of pregnancy, and one patient died on the fifth postoperative day following tubal ligation. All of these five patients received prophylactic heparin therapy. In three patients, heparin therapy was complicated by excessive bleeding during the postoperative or postpartum period. Autopsy examination in two patients revealed no evidence of thrombosis in the main pulmonary arteries and no pulmonary infarction, contrary to the antemortem clinical suspicion. The two survivors did not receive prophylactic heparin. They comprised one patient who had normal delivery and one patient who underwent tubal ligation and induction of abortion. We conclude that the prohibitive mortality rate of Eisenmenger's syndrome during pregnancy, puerpurium, or surgical procedures probably cannot be modified with prophylactic heparin therapy. Anticoagulant treatment does not prevent deterioration of patients and probably compounds the problem by causing significant bleeding.


Long-term angiographic assessment of the influence of coronary risk factors on native coronary circulation and saphenous vein aortocoronary grafts. The influence of smoking, hyperlipidemia, and glucose intolerance on graft patency and rate of progression of obstructive disease in the native circulation was assessed in 99 patients 1 1/2 years after aortocoronary bypass grafting. There were 24 patients in whom none of these risk factors was identified. There were 42 patients with one, 29 with two, and four with three risk factors. Overall graft patency rate was 74%. Graft patency was not significantly influenced by any of these factors either singly or in combination. Progression of obstructive disease in both proximal and distal segments of grafted vessels and in nongrafted vessels was not significantly increased by the presence of one, two, or three risk factors. Over all, there was progression in 56% of segments proximal to grafts, in 8% distal to grafts, and in 14% of nongrafted vessels. Longer term studies will be required to establish any adverse influence of these risk factors on saphenous vein bypass grafts and native circulation.


Aortic stenosis, angina pectoris, and coronary artery disease. The relationships between aortic stenosis, coronary artery disease, angina pectoris, and myocardial infarction were examined in 173 patients with isolated calcific aortic stenosis who had coronary arteriography as well as cardiac catheterization. All were over age 40 and had definite cardiac symptoms; 156 later had aortic valve replacement. Coronary lesions narrowing the lumen by 50% or more were present in 37% of patients aged 40 to 59 and 68% of those aged 60 to 82. Coronary disease was present in 64% of patients with angina pectoris and 33% of those without angina. Angina which occurred only in association with dyspnea on exertion was associated with coronary disease in 45% of instances, whereas angina which also occurred on exertion without any dyspnea or which occurred with emotional stress, after meals, during sleep, or at rest unprovoked was associated with coronary disease in 80% of instances. Patients with coronary disease without any chest pain or with atypical pain considered nonanginal were men, usually over age 60, with congestive heart failure as the predominant symptom. Electrocardiograms showing transmural inferior or anterolateral infarction nearly always indicated coronary disease, while QS patterns in Leads V1-2 occurred frequently with normal coronary arteries. Serum cholesterol was elevated in 23% of those with coronary disease and 8% of those without. A group of patients with moderate aortic stenosis could be identified, with aortic valve areas of 0.55 to 0.80 cm. per square meter, in whom coronary disease was the sole or chief cause of symptoms. The operative mortality rate with aortic valve replacement was 9.6% in those with coronary disease and 1.4% in those without significant coronary disease. Coronary disease is frequently present in patients with calcific aortic stenosis, particularly in those over 60, those with angina, and those with symptoms despite only moderate aortic stenosis. The type of anginal syndrome, the ECG evidence of transmural infarction, and the coronary risk factors provide additional clues for clinical diagnosis.


Correlative study of regional left ventricular histology and contractile function. In 110 patients with documented coronary artery disease, transmural biopsy of the anteroapical region of the left ventricle was performed during aortocoronary bypass grafting. Biopsy specimens were semiquantitatively graded microscopically for myocardial fibrosis as an indicator of chronic ischemic damage. Preoperatively, systolic wall motion of the region from which the biopsy specimen was taken was semiquantitatively graded as showing normal motion, hypokinesia, akinesia or dyskinesia on ventriculography. Wall motion-histologic correlations, taking into account both electrocardiographic evidence of anterior infarction and ST-T abnormalities, were then established. Overall, there was fair agreement (72 percent) between functional and histologic assessment of the left ventricular region evaluated, both qualitatively (normal versus abnormal, 72 percent agreement) and quantitatively (degree of abnormality, correlation coefficient 0.66, P = 0.005). The 22 patients with electrocardiographic evidence of anterior infarction had various degrees of abnormal regional motion and myocardial fibrosis. Discordance between wall motion and histologic findings was most common (50 percent of instances) in the 34 patients with anterior ST-T changes without infarction and generally was manifest as abnormal motion with normal histologic features. By contrast, normal motion and abnormal histologic features represented the most common type of discordance (22 percent of instances) in the 54 patients without either anterior infarction or ST-T deviation. These data provide a basis for inference of myocardial morphologic features (fibrosis) from assessment of ventriculographic wall motion and the electrocardiogram. They may thus be useful in predicting the potential functional benefits of bypass grafting of coronary arteries supplying abnormally contractile segments of the left ventricle.


Angiographic evaluation of saphenous vein bypass grafts: artifactual "occlusion" caused by dual sources of flow. Angiography after coronary bypass surgery has engendered conflicting reports regarding the effect of grafting on proximal lesions. Analysis of a series of postoperative arteriographic injections demonstrates that routine studies may produce artifactual "occlusion" caused by altered or competitive flow relations. High pressure contrast injection can reveal persistent stenotic lumens at sites of apparent complete occlusion. Thus, angiographic technical factors and not surgical sequelae may be responsible for the disparate reports on this subject.


Standardized disk-diffusion susceptibility test for Haemophilus influenzae. The emergence of ampicillin-resistant strains of Haemophilus influenzae has emphasized the need for an improved practical method for routine susceptibility testing of clinical isolates. We have previously described a simplified medium for quantitative dilution susceptibility testing that is composed of Mueller-Hinton medium plus Supplement C (Difco). In the present study, paired broth-dilution and disk-diffusion susceptibility tests with ampicillin and chloramphenicol were performed on 100 strains of Haemophilus (95 H. influenzae and five H. parainfluenzae), including 30 strains with previously documented ampicillin resistance. Disk-diffusion tests were performed in exactly the same manner as the standardized Kirby-Bauer procedure used for less fastidious organisms, except that supplemented Mueller-Hinton agar plates were incubated in an increased-CO2 atmosphere. Using this method, ampicillin-susceptible strains of Haemophilus produced zone diameters of 22 mm or more, while ampicillin-resistant strains produced zones of 18 mm or less. All strains were chloramphenicol-susceptible and produced zone diameters of 30 mm or more. This method would allow routine disk-diffusion testing of isolates of H. influenzae by hospital diagnostic laboratories, using a clear medium that closely resembles unsupplemented Mueller-Hinton agar.


Aortic aneurysm eroding the esophagus. Case report and review. A 71-year-old woman developed dysphagia and hematemesis with an endoscopic diagnosis of esophageal submucosal hematoma. Post mortem examination demonstrated an aorto-esophageal fistula as the etiology of her hematemesis. The differential diagnosis of upper gastrointestinal bleeding in the elderly patient without cirrhosis is discussed. A review of the literature on aorto-esophageal fistula is included.


Platelet function and immunologic parameters in von Willebrand's disease following cryoprecipitate and factor VIII concentrate infusion. Results of functional and immunologic tests of factor VIII and of platelet function were followed in two patients with severe von Willebrand's disease who were given cryoprecipitate during preparation for surgery. Initial correction of factor VIII coagulant activity was found to persist from 48 to 72 hours. Correction of immunologically measured factor VIII persisted for 48 hours and correlated with the patients' platelet response to ristocetin aggregation. Bleeding times were corrected for only 6 to 8 hours and showed fairly good correlation with the ristocetin aggregation factor, as suggested by Weiss. The administration of commercial factor VIII concentrate corrected all parameters except the bleeding time and the ristocetin aggregation factor measurement.


von Willebrand's disease and hemorrhagic telangiectasia: association of two complex disorders of hemostasis resulting in life-threatening hemorrhage. The clinical and laboratory findings in a patient with uncontrolled gastrointestinal bleeding secondary to combined hemostatic defects (von Willebrand's disease and hemorrhagic telangiectasia) are described. Evidence for von Willebrand's disease was found in five family members, but no other affected relative was found to have hemorrhagic telangiectasia. Complete assestivity, factor VIII antigen and von Willebrand factor levels. The patient described also was evaluated for her response to transfusion utilizing these same measurements. Previous reports of the coexistence of hemostatic defects with hereditary hemorrhagic telangiectasia are reviewed. The importance of complete hemostatic evaluation of patients with mucocutaneous bleeding is stressed in light or current knowledge of the diagnostic specificity of available laboratory tests.


Spectrum of immune response abnormalities in different clinical forms of tuberculosis. In an attempt to explain the reasons for the development of different clinical forms of tuberculosis in different persons, their immunologic status was compared to their clinical patterns. The spectrum of immunologic abnormalities correlated with the clinical forms. Also, an inverse relationship between cell-mediated and humoral immune responses was observed. Immunologic abnormalities reverted to normal concomitant with clinical improvement on chemotherapy, suggesting that the abnormalities were the result of the illness rather than its cause. Malnutrition could have been the underlying factor for the immunologic deficiencies seen in some patients.


Error in anti-DNA antibody radioimmunoassay after gallium scanning. Significant interference with the accurate measurement of anti-DNA antibodies occurs after gallium-67 scanning. The observed effect is dependent on the radioimmunoassay used. False-negative results are observed with a modified Farr assay whereas false-positive results are noted in the millipore filter assay. These spurious values are the result of persistent radioactivity in the patients' sera after administration of 67Ga citrate.


Optochiasmatic arachnoiditis: remarks on a case of the cystic form of the disease. In a series of 80 patients with surgically proven optochiasmatic arachnoiditis, only one case with an exclusively cystic form of the disease was found and is reported here. Certain changes, within a relatively short (6 months) period of time, of the neuro-ophthalmologic and neuroradiologic features are described in detail and discussed.


Tonsilloadenoidectomy. Personal observations in 15,000 cases. The indications for removal of tonsils and/or adenoids are discussed, along with preoperative assessment, operative technique, treatment of postoperative haemorrhage, aftercare, and results.