A model for the interaction of wheat monomeric and dimeric protein inhibitors with alpha-amylase. The amylase-protein amylase inhibitor system offers a unique model of specific and reversilbe protein-protein interaction. The monomeric and dimeric inhibitors, exhibiting closely related properties and interacting with the same amylase, also provide a convenient test to compare effects of monomer-monomer and monomer-dimer interactions between enzyme and inhibitor proteins.


[Epidemiology, pathogenesis and prognosis of gastric carcinoma in the light of clinical and statistical follow-up after gastrectomy (author's transl)]. Epidemiological, pathnogenetic and prognostic aspects of gastric carcinoma after a gastrectomy a long time previously are presented. Apparently an increase in the 5-year survival rate can only be achieved by an improvement in early diagnostic measures. Early, and consequently for a successful operation timely, recognition of early stages of a malignant tumor will possibly be improved by immunological methods when radiology, endoscopy, histology and cytology can no longer contribute to a considerable improvement of the diagnostic status now attained. A life worth living is possible after total or subtotal gastrectomy because initial deficiency states such as malabsorption etc. can be compensated by adaptation phenomena.


[Palmar fibromatosis (morbus Dupuytren). Comparative clinical, pathological and anatomical mass examinations (author's transl)]. Classification (119 patients) of age, sex and side distributions and the frequency of additional fibromatoses or other diseases in palmar fibromatosis (Morbus Dupuytren) showed extensive agreement with other investigations. Contractures were also found in mutiple foci with high cell density and without intensive collagen fiber formation corresponding to the proliferative or involution phase. Cells with contractile elements ("myofibroblasts") could also be demonstrated with both electron and immunofluorescence microscopes. These elements may be of importance for the formation of the contracture in palmar fibromatosis and may disappear again as the collagen becomes more mature.


[Worth and unworth of occlusion therapy in the treatment of squint (author's transl)]. The most commonly used methods for the treatment of amblyopia are based on dosed obstruction of the eye with the better function. Occlusion therapy is still the treatment of choice for severe (eccentric fixation) amblyopias. A possible impairment of the binocular neurones must be accepted in doubtful cases with the objects of a possible normalization of monocular function (visual acuity).


[Results of Implantation of Aorto-Femoral Bifurcation Prostheses (author's transl)]. From June 1974 to December 1975, 139 aorto-femoral Y-grafts were implanted at the surgical clinic of the University of Münster. The operation mortality was 4.3 percent. Among the postoperative complications were sexual disfunction and paraesthesia. For the ileo-femoral occlusions the postoperative success rate was 90 percent, combined ileo-femoro-crural changes showed good results in 60 percent of the cases. The results show that isolated reconstruction in the pelvic area is successful in most cases, even in combined ileo-femoro-crural obstruction. Only in exceptional cases a second operation (reconstruction of femoral artery) is necessary after a period of about one year.


[Alloplastic vascular substitution with a novel prosthesis. First clinical experiences (author's transl)]. 216 reconstructions with Gore-Tex-PTFE prostheses in all vascular regions are reported, particularly in the femoro-popliteal and femoro-crural regions. The best early and early longterm results are in the supra-aortal, aorto-renal and aorto-femal areas. Femoro-popliteal bypasses above the knee joint remain functional in 97 percent at an average followup observation time of 3.8 months. Below the knee, the patency rate is 84 percent at an average followup observation time of 4 months (femoro-popliteal/crural).


[Peri-operative care of diabetics (author's transl)]. The generally accepted principles of treatment of a diabetic as a case for operation or emergency are listed and substantiated with reference to the varied pathophysiological processes. In particular the preoperative attitude of the diabetic and the special anesthesiological problems are gone into.


[Assisted circulation with the heart-lung machine after cardiosurgical interventions: one year's experience with intra-aortal counter-pulsation with the heart-lung machine after cardiosurgical operations is reported (author's transl)]. In the period from September 1976 to 1977, aortic or mitral valve replacement was performed in 84 and 34 patients respectively. Cardiogenic shock occurred during or immediately after the operation in 3 and 2 patients respectively (= 8.8% and 2.4%). In spite of the use of intra-aortal counter-pulsation, none of the patients survived the acute event. During the same period, 8 (= 5%) out of 113 patients who had undergone coronary surgery needed intra-aortal counter-pulsation. 4 of them survived the acute left heart failure and at the present time are clinically healthy (N.Y. Heart Association Class II).


[Malignant polyps and early recognized carcinomas of the rectum. Morphological aspects and selective surgical treatment (author's transl)]. The lymphatic drainage of the colon and rectum originates in the submucosal layer. Therefore metastases do not arise from carcinomas confined to the mucosa, and for the same reason the WHO lately recommended to call these lesions severe atypism. The term adenocarcinoma should be reserved in the case of infiltration of the carcinoma into the submucosa. According to the features outlined above adenomas of the rectum showing severe atypism can be removed by careful excision of the mucosa. Even adenomas containing an early diagnosed adenocarcinoma up to 2.5 cm in diameter often can be cured by a local resection of the rectal wall, if no metastases have occurred. From 1971--December 1, 1977, 12 rectal adenomas with severe atypism and 14 rectal adenomas with adenocarcinoma had been removed locally without complications. After 6 years there was no recurrence of carcinoma.


[Clinical and operative aspects of liver resection (author's transl)]. On the basis of our experience in 57 liver resections (hydatid cyst in the liver 22 times, 7 hepatic cysts, 5 liver abscesses, 7 benign and 16 malignant hepatic tumors) a few tentative conclusions are drawn: A reliable diagnosis and assessment of operability is only possible on laparotomy. Echinococcus alveolaris should be operated as radically as possible. Primary hepatic tumors should be removed as well as malignant hepatomas and their metastases. Simultaneous extirpation of the primary tumor and metastases has given encouraging results so far, especially in easily resectable carcinomata of the colon and rectum. Cytostatic followup therapy is absolutely essential in all cases of malignancy.


[Rectoscopic diagnosis of the height of rectal carcinoma (author's transl)]. In 100 excisions of the rectum at the Chirurgische Universitätsklinik Erlangen the height of the tumor determined preoperatively by rectoscopic diagnosis was compared directly to the real tumor location of the fresh and unfixed specimen. In up to 58% of the cases we found a distinct discrepancy between the height determined rectoscopically and the real location of the tumor. This result shows that the decision between excision and resection must never be made on the preoperative rectoscopic information, but that the indication must always depend on the intraoperative findings. This is especially true for the disputed cases of the middle third of the rectum.


[Thrombosis prophylaxis with low doses of dextran 60 (author's transl)]. The antithrombotic effect of dextran 60 (Macrodex) was studied in a prospective, randomized trial on patients undergoing general surgery. 42 patients (group A) received 500 ml of dextran 60 intraoperatively, 49 patients (group B) received an additional dose of 100 ml dextran 60 on days 1 to 5 after operation. As tested by the 125-iodine-radiofibrinogen test 16 patients (38%) from group A, but only 2 patients (4%) from group B developed deep venous thrombosis. The difference between both groups is statistically highly significant (P less than 0,0005). The use of dextran for thromboprophylaxis was associated neither with hemorrhagic complications nor with anaphylactoid reactions. The fractionated application of a total of 1000 ml of dextran 60 resulted in a very efficient prophylaxis against deep venous thrombosis.


Dynamics of the amphibian middle ear.

Dynamics of the amphibian middle ear. Using laser speckle interferometry, we show that the directional information of acoustic signals is encoded in the motion of eardrum. Moreover, the frequency sensitivity of the auditory system is determined by the mechanical properties of the middle ear, which acts like a damped resonator.


Neurologic manifestations of Cogan syndrome. Cogan syndrome is a multisystem inflammatory vascular disease, characterized by nonsyphilitic interstitial keratitis and vestibuloauditory symptoms. Recent reports have directed attention to involvement of other organ systems. Respiratory, cardiovascular, gastrointestinal, and musculoskeletal problems are common, as are laboratory abnormalities and general symptoms such as fever, chills, and weight loss. Prominent neurologic problems in two patients prompted a review of 79 cases of Cogan syndrome. More than half had nervous system involvement, including electroencephalographic or spinal fluid abnormality, headache, psychosis, coma, convulsion, neuropathy, and stroke. Cogan syndrome should be considered when neurologic deficits are accompanied by eye, ear, and systemic symptoms.


[Physiopathological bases for a rational therapy of gout]. Rational therapy of gout must be correlated with the two basic aetiopathogenetic factors, i.e. metabolic error and the inflammatory dysreactive moment. Due to its different action mechanism, the former is responsible for the typing of adult primary hyperuricaemia: a) hyperincorporating and hyperescretory forms; b) normo-incorporating and relatively or absolutely hypoexcretory forms; c) hyperincorporating and hyposcretory forms. It would be a mistake to treat the condition chemically without knowing the physiopathology of the metabolic error. On the basis of a preliminary typing assessment, rational chemical correction of the metabolic error in gout cases can be achieved with drugs that block the enhanced endogenous synthesis of uric acid (allopurinol, etc.) or correct the metabolite renal excretion defect. Therapy of the dysreactive-inflammatory component should involve non-steroid anti-inflammatory drugs. The disadvantages of using cortisones in gout treatment are stressed.


A pilot trial of labetalol (AH 5158A): a combined alpha and beta blocker in treatment of hypertension. Labetalol (5-1 hydroxy-2 (1-methyl-3 phenyl amino salicylamide hydrochloride)) is a new antihypertensive agent having partial alpha- and beta-adrenoreceptor-blocking properties. Nine patients with mild, moderate or severe hypertension have been given this drug over periods ranging from 6-29 weeks. Labetalol was given as replacement for a beta-blocking drug providing less than satisfactory control. Adequate control of blood pressure was achieved in all nine patients. The only side-effect of note was postural hypotension which necessitated withdrawal of the drug in one patient.


Prevalence of self-injury in institutionalised retarded children. Twenty-three percent of the inpatient population of a psychopaedic hospital in New Zealand were found to have engaged in self-injury during a six month observation period. Of the 50 male and 34 female patients studied, 62 exhibited single self-injury, and 22 multiple self-injury. Self-injury consisted of head banging, face slapping, skin picking, hair pulling, self-biting, regurgitation/vomiting, and excessive painful masturbation. Twenty-five percent of these patients indulged in forms of self-injury which was potentially seriously harmful to themselves if not immediately treated. The overall percentage of such patients in this hospital was found to be much higher than that reported elsewhere.


Blood pressure levels of an urban adult New Zealand population: Napier 1973. Ninety-seven percent of a randomly selected sample of 2600 adults (age range 21 to 92 years) from the Napier City electoral area were surveyed for age and sex distribution of blood pressure. The sample included those currently receiving drug treatment for elevated pressures. There were approximately 400 in each decade and the sex ratio slightly favoured females. Casual systolic pressures rose with age whereas the diastolic rose to approximately age 50 and thereafter remained steady or slightly declined. Before age 50 years males had higher systolic pressures than females and thereafter the mean levels for females exceeded those for the males. Mean systolic pressures for this New Zealand sample population were higher by 2-4mmHg for all ages than the levels reported for the United States National Health Survey 1960-62.


The use of triacetyloleandomycin in skin and soft tissue infections: results of a New Zealand general-practitioner multi-centre trial. Fifty-one New Zealand general practitioners observed the treatment of 137 cases of skin and soft tissue infections with triacetyloleandomycin (TAO, Pfizer) over a five-month period. Nearly a third of these lesions occurred in children aged 10 years or less. "Excellent" or "good" results in 129 cases (94.2 percent) confirmed triacetyloleandomycin to be generally effective in these conditions. Twice-daily (12-hourly) oral administration proved as effective as more frequent dosage regimens and no major side-effects were encountered. Twenty cases with associated minor surgery are discussed separately.


Studies on habituation of vestibulospinal reflexes. Effects of repetitive optokinetic and vestibular stimuli upon the stepping test. The influence of repetitive applications of optokinetic and vestibular stimuli upon the vestibulospinal responses, measured by the stepping test, was investigated both in an optokinetic training and vestibular habituation test series. Repeated applications of optokinetic and vestibular stimuli modified the rotation angles of the stepping test, i.e. vestibulospinal responses, resulting in a response decline of rotation angles which was still present after 1 month.


Interest of the study of the influence of ocular fixation during caloric tests in pontocerebellar tumors. Measurement of the ocular fixation index is very useful to assess the extension of pontocerebellar tumors. Determination of the other features of central impairment of the vestibular system completes this information.


Psychological, neurophysiological and therapeutic aspects of chronic pain: preliminary results with transcutaneous electrical stimulation [proceeedings]. Psychological, neurophysiological and therapeutic aspects of chronic pain are reviewed in the light of recent progress achieved in the respective fields (alpha-feedback training; gate-control theory; transcutaneous electrostimulation; percutaneous stereoactic radio-frequency cordotomy). The efficacy of selective large fibre stimulation has been evaluated in 39 spinal cord injury patients suffering from chronic intractable pain of 6 to 35 months's duration. Stimulation was applied daily for 6 consecutive hours. Pain reflief was assessed by verbal and visual analogue scales and McGill's pain questionaire. After 1 week, total or almost total relief of pain was reported by 49 per cent, moderate relief by 41 per cent and no improvement by 10 per cent of the cases; at a 3-months follow-up the figures were 28 per cent, 49 per cent and 23 per cent respectively.


Two therapeutic experiments on stubborn pain in spinal cord lesions: coupling melitracen-flupenthixol and the transcutaneous nerve stimulation [proceedings]. A drug combination was used against sub-lesional pain with some good results. Transcutaneous stimulation was used in three cases of pain in the roots without result.


The moon illusion: a test of the vestibular hypothesis under monocular viewing conditions. The results of earlier monocular experiments on the moon illusion have been either negative or confounded. To test the role of vestibular function, 24 subjects made forced-choice distance comparisons between stimuli mounted in translucent tubes. The stimulus tube for standard distance could be positioned in three viewing angles (45 degrees up, horizontal, and 45 degrees down). A comparison tube adjustable for distance was mounted horizontally. There was a greater perception of depth in the downward looking condition. The relatively weak effects are discussed in terms of a two-hypothesis explanation of the real-life moon illusion and the poor cues for depth perception in monocular viewing.


[Current indications of coronary arteriography in coronary artery disease (with the exception of acute myocardial infarction) (author's transl)]. The indications of coronary arteriography have multiplied in recent years. Therapeutic indications have followed knowledge of the good results of revascularisation surgery. Initially limited to severe stable angina improved little or not at all by major anti-angina agents, they have been extended, in the view of many, to include various types of unstable angina where, in addition to the symptomatic improvement obtained, an attempt is made to decrease the incidence of myocardial infarction and of long term mortality. Indications relative to determination of the extent of disease may be preventive: the fear of severe coronary lesions on the basis of effort test results, the fear of a second infarction immediately following a primary lesion, or as a virtually routine examination in young individuals in order to better assess the degree of disease and to guide treatment. Diagnostic indication should be rare.


[Acquired Von Willebrand disease with chronic lymphocytic leukaemia and angiodysplasia (author's transl)]. The onset of an haemorragic syndrome in a patient with chronic lymphocytic leukaemia led to the diagnosis of acquired von Willebrand's disease secondary to an anti-von Willebrand factor antibody. Multiple angiodysplasia were shown by an arteriography done for a ruptured femoral arterial aneuvrism. The relationship between angiodysplasia and acquired von Willebrand disease are discussed.


Delayed wattle reaction as a measure of cell-mediated immunity in the chicken. The cell-mediated immune (CMI) response to diphtheria toxoid (DT) was studied in commercial broiler breeder lines. The chickens were immunized with DT in complete Freund's adjuvant 21 days before CMI assay by delayed wattle reactivity (DWR) to DT. The DWR was shown to be a valid measure of CMI and to correlate with spleen cell migration inhibition and blastogenesis assays of CMI in vitro. In addition, each criterion of CMI was met, except for the passive transfer of DWR. These criteria were delayed timing, gross morphology, histopathology of DWR, and effect of antilymyphocytic sera on DWR. The duration of DWR over a 1-year period differed in the two lines of chickens tested. A significantly greater DWR was found in one line with all birds remaining reactive for CMI whereas in the other line 16% did not have CMI by the end of the year. The differences may reflect genetic variability within and between lines in expression of CMI.


Enrichment of the murine natural killer (NK) and mitogen induced cellular cytotoxicity (MICC) cells using preparative free-flow high voltage electrophoresis. A procedure using preparative free-flow high voltage electrophoresis is described for the fractionation of murine spleen and bone marrow cells so as to obtain cell subpopulations that are either enriched in or depleted of "natural killer" (NK) cells and "mitogen-induced cellular cytotoxicity" (MICC) effector cells. A nearly three fold enrichment in the NK and MICC activities of spleen cells was achieved. The enrichment in these cells could be further increased if the phagocytic cells were removed prior to electrophoresis. When bone marrow cells were fractionated a two and a half fold increase of NK activity, and a one and a half fold enrichment of MICC activity was achieved. In both cases, other fractions were nearly devoid of NK and MICC activity. The cell recovery after electrophoresis averages 70% of the cells applied, and at least 90% of these cells were viable. MICC and NK effector cells could not be separated to a useful extent electrophoretically but were found to be separable using Sephadex C-10 gel filtration columns. The MICC but not the NK cells were retained on these columns.


Blocking of primary in vitro antibody responses to thymus-independent and thymus-dependent antigens with antiserum specific for IgM or IgD. The effect of anti-mu and anti-delta on the primary in vitro IgM response of murine splenocytes to thymus-dependent (trinitrophenylated erythrocytes) and thymus-independent (trinitrophenylated brucella) forms of trinitrophenyl was studied. The results indicate that either anti-mu or anti-delta can block the response of adult splenocytes to the thymus-dependent antigen. The thymus-dependent responses of neonatal splenocytes that bear a low concentration of IgD were also abrogated by treatment with anti-delta. In contrast, anti-mu, but not anti-delta, blocked the response of adult splenocytes to the thymus-independent antigen used. These results indicate that both IgM and IgD are receptors required for triggering cells by a thymus-dependent antigen but that only IgM receptors are required for triggering by the thymus-independent antigen used.


Alteration of the characteristics of learned taste aversion by manipulation of serotonin levels in the rat. Electrolytic lesions placed in the dorsal and median raphe nuclei of the rat brain deplete hypothalamic and telencephalic serotonin. These lesions also enhance the learned suppression of saccharin consumption which results from pairing the ingestion of a saccharin solution with the injection of a toxic drug. Pretreatment of rats with raphe lesions with the serotonin precursor DL-5-hydroxy-tryptophan (5HTP) immediately prior to the conditioning trial blocks the learning of the aversion to saccharin. In normal rats, 5HTP pretreatment also attenuates the suppressive effects of conditioning on saccharin drinking. These results differ from the findings of previous research using the flinch-jump technique. When sensitivity to shock is measured, 5HTP pretreatment in rats with forebrain serotonin depletion has been reported to restore both serotonin levels and behavior to normal. No behavioral effects are observed in normal animals. Possible explanations for the differential effects obtained in the two paradigms are discussed.


Initiation and inhibition of the release croak of Rana pipiens. A release croak is emitted by unreceptive female frogs when they are clasped by males; receptive females are silence. This report investigates the sources of stimuli which initiate and inhibit the release croak of Rana pipiens. Experiment 1 demonstrates that manual clasping of the trunk rather than the legs elicits the croak. Experiment 2 shows that denervation of the skin of the trunk prevents the release call in response to manual stimulation. Experiment 3 confirms that artificial distension of the body with fluid inhibits the release croak in response to manual stimulation. Experiment 4 shows that artifically-distended females, who are not in the normal endocrinological state that accompanies mating, are silent and receptive in response to clasping by sexually-active male frogs. The first two experiments imply that stimulation of the skin of the trunk initiates the release croak; Experiments 3 and 4 suggest that an internal afferent source inhibits the release croak and might mediate an important aspect of receptivity in female frogs.


Electrophoretic mobility of lymphocyte populations in juvenile rheumatoid arthritis. Peripheral blood lymphocytes from 16 patients with juvenile rheumatoid arthritis and 27 age-matched healthy controls have been studied, using several lymphocyte markers: electrophoretic mobility (EM), E-rosettes, immunofluorescence, and refringency. Eight patients (mean age, 6 years) were selected with a typical EM pattern--that is, a decrease in the mean EM of T cells and increase in B versus T-cell ratio. The other group of patients (mean age, 11 years) showed no significant difference when compared with their age-matched controls, with the exception of the positive refringence test. These findings suggest an impairment in the maturation of the immune system in childhood, which in turn may be responsible for the increased susceptibility to disease.


Studies on interference with tolerance induction in T cells. The mechanism of T-cell tolerance to a thymus-dependent antigen was examined, using the adjuvant polyadenylic-polyuridylic acid (poly A:U). In adoptive transfer experiments, thymus cells obtained from donor mice 2 days after treatment with a tolerogenic dose of bovine gamma-globulin (sBGG) did not cooperate with bone marrow (BM) cells in irradiated recipients challenged with aggregated BGG (aBGG). In contrast, thymus cells from donors given sBGG plus poly A:U retained their helper activity, as assayed by hemagglutination and rosette formation of spleen cells. The effect of poly A:U in preventing tolerance induction was also demonstrable in the cortisone-resistant population, in that thymus cells from cortisone-treated donors that had received sBGG and poly A:U retained their helper function. The presence of suppressor cells and the effect of poly A:U on their stimulation were also examined. sBGG-treated thymus cells suppressed the response of BGG-primed spleen cells in lethally irradiated mice, whereas thymus cells from donors treated with sBGG and poly A:U were not suppressive. These observations show that poly A:U prevents tolerance induction and the development of suppressor activity in T cells.


B and T lymphocytes in blood and cerebrospinal fluid in acute aseptic meningitis. B and T cells in blood and cerebrospinal fluid (CSF) were calculated by using the surface membrane immunoglobulin marker for B cells and the capacity to bind sheep erythrocytes to form 'rosettes' as a marker to T cells. Patients with acute aseptic meningitis due to mumps virus or other etiologic agents and with various chronic neurological diseases were investigated. Significantly higher T-cell and lower B-cell values were observed in CSF than in blood in all three groups. No significant differences were found between the three patient groups. An elevation of B cells and a depression of T cells were observed in blood in patients with aseptic meningitis during the course of the disease.


Surface immunoglobulin characteristics of B-lymphocyte developmental states and B-lymphocyte colony-forming cells. B-lymphocyte colony-forming cells and various B-lymphocyte developmental states were examined for expression of surface immunoglobulin. B-lymphocyte colony-forming-cells appeared to possess a significantly greater amount of surface immunoglobulin than did newborn 'virgin' B lymphocytes. In terms of surface immunoglobulin content and physical property characteristics (established previously) B-lymphocyte colony-forming cells resembled a more mature B-lymphocyte subset. This subset, as characterized in previous studies, consists of mature virgin B cells that develop from the newborn virgin B cells via a process of nonspecific antigen-induced differentiation. An alternative possibility that B-lymphocyte colony-forming cells are memory B lymphocytes has not been eliminated by this study.


Inhibition of B-cell function by concanavalin-A-induced suppressor cells. The in vitro immune response of normal spleen cells to the thymus-independent antigen dinitrophenylated levan (DNP-LE) was found to be inhibited by suppressor cells induced previously by concanavalin A (Con A) in vitro. At various suppressor to target cell ratios, the level of suppression observed was comparable to that seen in anti-sheep erythrocyte (SRBC) responses. Consequently, it is suggested that B cells constitute a direct target for Con-A-induced suppressor cell activity.


A T-cell marker in mouse fibroblast x T-lymphocyte somatic cell hybrids. Continuous hybrid cell lines have been generated by the fusion of allogeneically primed murine T lymphocytes with mouse L-cell-derived fibroblasts of the line 613. The resulting hybrid clones express one or more T-cell-specific surface components identifiable by radioiodination of intact cells followed by NP-40 solubilization of membrane proteins and sodium dodecyl sulfate polyacrylamide gel electrophoresis. These markers are stably expressed by the hybrid lines after several months of passage.


Thymic microenvironment: selective activities of soluble and insoluble components. Two components of the thymic microenvironment have been separated, and their biological properties have been studied. The first component, soluble thymic factor (STF), after injection into syngeneic recipients, provoked a temporary decrease in thymic weight on day 7, concomitant with an increase in the level of T cells in lymph nodes (but not in the spleen), followed by a general hypertrophy of lymph nodes peaking on day 21. In contrast, after the injection of the second component, insoluble thymic fraction (ITF), there was an increase in the number of prothymocytes in the thymic subcapsulary cortex, followed by general thymic hypertrophy on days 14 and 21. STF is believed to trigger a selective migration of lymph-node-seeking T cells from the thymus, whereas ITF seems to play a role in the differentiation step preceding that imparted by STF.


Long-term therapy with tolfenamic acid pINN. A clinical and toxicological study with special reference to clinical and chemical laboratory parameters. 48 patients with rheumatic diseases underwent long-term treatment with a new antirheumatic compound, tolfenamic acid pINN. The dosage was 2 capsules of 100 mg 3 times daily. At the time of summing-up 9 patients had been treated for one year, 41 for 6 months and 7 had been eliminated after 1 month of treatment, because of side-effects in the form of diarrhoea, dyspepsia, vomiting and 1 ulcer patient got an attack of duodenal ulcer. Of the 41 patients who completed the 6 month trial 33 reported good therapeutic effect. A significant fall in the erythrocyte sedimentation reaction (p less than 0.01) was observed. 19 patients reported side-effects in the trial period, but at the end of the trial only 5 complained of side-effects. In the male patients occasional slight dysuria was the most common side-effect. Of the 9 patients who were treated for one year all reported a good effect from the preparation and none of them complained of side-effects after 1 year of treatment. Apart from eosinophilia in 2 patients, who were eliminated from the trial because of diarrhoea, none of the laboratory values showed any signs of the preparation having any toxic effects.


[Angio-immunoblastic lymphadenopathy].

[Angio-immunoblastic lymphadenopathy]. A report is presented on four cases of angioimmunoblastic lymphadenopathy. In this recently individualized entity, adenomegaly with fever and cutaneous eruption is associated with polyclonal hypergammaglobulinemia and autoimmunization, especially of anti-erythrocytic type. The lymph nodes are homogenized by a lymphoplasmo-immunoblastic granuloma with angiogenesis. The disease could be attributed to hyperplasia of B lymphocytes with a deficit of T cells, which would explain the autoimmunization. It appears in some cases to be triggered by accidents of drug intolerance. Prognosis is poor and the course of the disease is nearly always fatal in the long or short term. It is difficult to ascertain whether prolonged remissions, either spontaneous or therapeutic, can be considered actual cures.


Switch in immunoglobulin class production observed in single clones of committed lymphocytes. Mouse spleen cells, after stimulation with lipopolysaccharide, were cloned in culture. After 4 to 5 days, the daughter cells were stained and examined for immunoglobulin class with double immunofluorescent reagents. A switch of the stained color of these cells was observed, implying a switch from imunoglobulin M to immunoglobulin G production in the progeny of a single B cell.


Irreversible inhibition of sodium entry sites in frog skin by a photosensitive amiloride analog. A photosensitive binding reaction is described in which an analog of amiloride is bound to sites that control sodium entry into frog skin. This reaction results in irreversible inhibition of net sodium transport.


Hormonal basis for breeding behavior in female frogs: vasotocin inhibits the release call of Rana pipiens. Inhibition of the release call in gravid female frogs facilitates maintenance of the male's clasp so that oviposition and spawning can occur. Arginine-8 vasotocin inhibits the release call by causing an accumulation of water and internal pressure.


Immunologic studies of colonic cancer: evaluation of immunocompetence. Detailed immunologic studies were done on 29 patients with colorectal cancer. The plasma level of circulating carcinoembryonic antigen, the in vitro reactivity of the peripheral blood leukocytes (PBL) to colorectal-tumor-associated antigens (CTAA), and the competence of the T cell population were determined. The in vitro reactivity of the PBL to CTAA was determined by a lymphoblastic response and leukocyte migration inhibition. The competent T cell population was determined by enumerating the T and B cells, the rosette-inhibiting titer of antithymocyte globulin, and the reactivity to skin test antigens. An arbitrary score ranging from 0 (low immunocompetence) to 100 (high) was assigned to the results of each test. The mean score on the immunocompetence quotient (ICQ) which ranged from 22 to 100 was judged to reflect the immunocompetence. The sequential ICQ of individual patients strongly suggested that this information reflected the immunocompetence of patients with cancer of the colon.


Pulmonary complications in the immunocompromised patient. A diagnostic approach to pulmonary complications in the immunocompromised patient is outlined. The importance of early lung biopsy in selected patients is emphasized and the various techniques available are discussed. Successful early diagnosis and management of opportunistic infections ia a challenge for the clinician, bacteriologist and pathologist, and requires these close collaboration.


A multicentre study of the susceptibility of a variety of bacteria to cephalothin, cefamandole, tobramycin and gentamicin. A multicentre study of antibiotic susceptibility was performed in South Africa. Sensitivity to cephalothin, cefamandole, tobramycin and gentamicin was tested on a variety of aerobic and anaerobic bacteria. Two disc susceptibility techniques were used, i.e. the Kirby-Bauer technique (aerobes) and the broth-disc method (anaerobes); minimum inhibitory concentrations (MICs) were determined according to the International Collaborative Study techniques, and regression lines for individual centres were constructed. Satisfactory lines were obtained for cephalosporins, but, in some centres, problems were experienced with the aminoglycosides. Variations in MICs for Haemophilus influenzae were probably due to an inoculum effect. Accumulative percentage tables of the number of strains inhibited were compiled, and the comparative performance of the antibiotics was assessed.


Human lymphocyte-mouse myeloma somatic cell hybrids: selective hybrid formation. Fusion of unfractionated human lymphocytes with mouse myeloma cells resulted in proliferating hybrid colonies, almost all producting human Ig. We examined whether this high frequency of Ig production was the result of selective formation of human B lymphocyte-mouse myeloma hybrids, rather than induction of Ig genes in T lymphocytes. Unfractionated peripheral lymphocytes and B lymphocytes from patients with the common variable form of agammaglobulinemia formed proliferating somatic cell hybrid colonies. In contrast, peripheral lymphocytes from a patient with agammaglobulinema who lacked B lymphocytes, as well as albumin gradient fractions of peripheral blood which do not contain B lymphocytes, failed to produce somatic cell hybrids with three different myeloma parent cell lines. B, T, and precursor lymphocytes all had Sendai virus receptors, as witnessed by viral agglutination. We conclude that fusion of human lymphocytes with mouse myeloma cells results in selective hybrid formation, rather than activation of Ig genes in disparate cell types. Only B lymphocyte-mouse myeloma heterokaryons form hybrid cells.


Fusion of T and B cells.

Fusion of T and B cells. Hybrid cells were prepared by fusin an immunoglobulin-secreting mouse myeloma lin e (B cell) with an allogenic T-cell lymphoma which expresses the surface antigen Thy 1. The resulting hybrids expressed H2 antigens of both parental cells and secreted the immunoblobulin of the myeloma parent but did not express the Thy 1 antigen of the lymphoma parent. Twenty-one hybrids were formed from fusion of the same myeloma line with TNP-SRBC-primed spleen cells. Most of the hybrid lines exhibited characteristics expected for the fusion of the myeloma to B lymphocytes. No hybrids between the myeloma line and spleen T cells were identified as none of the hybrids expressed the T-cell-specific antigen Thy 1. We discuss possible reasons for failure to produce hybrids with T-cell characteristics in these types of fusion.


Coronal and sagittal reconstruction in computerised tomography. As useful and dramatic as axial computed tomograms are, severe limitations have been encountered. Most of these involve the accurate location of masses and, as in angiography, projections in several planes are essential. Recent advances in both hard and softward allow three millimeter slice thicknesses at low radiation dosage. Coronal and sagittal reconstructions are practical and obtained with ease. The computerized tomogram is invaluable in complementing standard neuroradiological procedures and, in some cases, allows definitive diagnosis. This degree of accuracy is not possible without multiplane reconstructions.


Immunological studies on myasthenia gravis: operative indication and cell-mediated immunity. An important aspect of the management of patients with myasthenia gravis is the decision to recommend thymectomy. Hitherto, many investigators have reported the relationship between the operative effects and such factors as age, sex, duration of symptoms, or degree of germinal center proliferation in the myasthenic thymus. However, these reports are not practical aids in deciding the indication for thymectomy in an individual myasthenic patient. The currently accepted indications of thymectomy for myasthenic patients are (1) the thymomatous patient, especially those with malignancy, and (2) the nonthymomatous patients who are resistant to medical treatment. From our present data we would add the following as an indication of the operation: (3) patients who have high T-cell subpopulation levels with highly blastogenic activities and strong skin test reactivities. In order to assure good operative results in myasthenic patients, surgeons should examine their patients' preoperative immunological states.


Epidermal growth factor potentiates cortisone-induced cleft palate in the mouse. Epidermal growth factor (EGF) injected into pregnant mice increased the frequency of cleft palate (CP) in cortisone-treated mouse fetuses. EGF alone produced proliferation and thickening of the epithelium of the palatal processes, but CP was not significantly increased over saline injected controls. Cortisone alone produced thinning of the palatal epithelium and caused CP in 61 percent of formed fetuses. The combination of EGF and cortisone treatment induced CP in 100 percent of formed fetuses; epithelial thickening still occurred with the combination treatment. Thus, EGF may be teratogenic under special circumstances. These observations suggest that the relative thickness of the palatal shelf epithelium may not be a critical factor in the fusion of the palatal shelves.


Inhibition of B cell cytotoxicity by aggregated IgG and immune complexes. The presence of immune complexes or aggregated IgG in the microlymphocytotoxicity assay may cause inhibition of cytoxity. When HLA-A and-B antigens are the subject of the test the effect is minimal; however, when B cell alloantigens are being examined the effect is marked. The pattern of inhibition in the later case and the fact that B lymphocytes preincubated with immune complexes are resistant to cytotoxic lysis by anti-B cell sera suggests that immune complexes and aggregated IgG inhibit cytotoxicity by prevention of antibody binding rather than by complement consumption.


Ampicillin-resistant Hemophilus influenzae. Ampicillin-resistant Hemophilus influenzae had not been identified in Fresno, California, before June 1976. In the 12 months that followed, eight resistant type B strains and three resistant nontypable isolates were cultured from patients treated at two hospitals that provide nearly all of the acute pediatric inpatient care for the area. Two of the resistant strains were obtained from patients with invasive infections and represented 4.2 percent of Hemophilus influenzae isolated from blood, cerebrospinal fluid or joint aspirates during the 12 months. The remaining six resistant type B strains were obtained from 117 patients, and were the predominant organism in cultures of other sites, primarily respiratory secretions. In two of three patients infected with nontypable organisms, resistance appeared to emerge during therapy with ampicillin. Measurement of beta lactamase was a practical and accurate method for differentiating between ampicillin-sensitive and resistant strains. All ten of the beta lactamase-positive isolates tested had minimal inhibitory concentrations (MIC) for ampicillin of 15 mug per ml, or less. In contrast 30 beta lactamase-negative strains had MIC's of 1.5 mug per ml, or less, of ampicillin. Our results indicate that ampicillin resistance has become a significant problem in the Central Valley of California and probably the entire state.


[Esophageal sound for electrocardioversion and simultaneous electric stimulation of the heart]. In extrathoracic as well as oesophageal electrode technique sometimes in most cases short insignificant asystolias following the electric cardioversion are observed. In individual cases, however, an immediate electrostimulation of the heart may be necessary. An oesophageal sound was developed which may be used for cardioversion as well as for stimulation if necessary. With the help of this sound the effectiveness of the electric atrial and ventricular stimulation and the electrocardioversion was proved.


[Recurrent gastrointestinal hemorrhage in a gastric neuroma]. Ulceration of the gastric mucous membrane and acute gastric haemorrhage are feared complications of a gastric neuroma. It is reported on a patient of 42 years who had recurrent gastrointestinal haemorrhage in spite of the resection of his stomach. By gastroscope an ulcus was proved paracardially in the upper corpus. The ulcus rendered post operationem as exulcerized neuroma by histologic test.


[T-lymphocytes in the peripheral blood. Study on 113 patients with malignant melanoma]. In the present study, we determined the absolute and the percental numbers of T-lymphocytes in 113 patients with malignant melanomas, of whom 50 had metastases and 63 did not. The findings were compared to those in a control group of 22 persons. The patients with melanomas were divided up into clinical stages: stage I (primary tumour), II (metastases in the local lymph nodes), and stage III (systemic metastases). There was a statistically significant reduction of T-lymphocytes in all patients with melanomas, but there were no significant differences between the three stages. Therapy with DTIC did not lead to any major reduction in T-lymphocytes, possibly because of subsequent treatment with BCG. We found no clear correlation between the reduction of T-lymphocytes and an unfavourable prognosis.


[Circumscribed intraventricular hemorrhage]. Circumscribed intraventricular haemorrhages are very rare. The clinical picture showed the symptom of the subarachnoid haemorrhage and additional local symptoms (e.g. hemiparesis, psychic disorders). Neuroradiologically, signs of a space-occupying process in the ventricle are found. A differential diagnosis is not possible. The operation sucks off the haematoma and removes the thin membrane of the haematoma. Sources of the haemorrhage may be damage of the vascular wall, microangiomas and microeneurysms which are destroyed by the haemorrhage.


Serious delayed rectal haemorrhage following uncomplicated appendicetomy. Report of a case. A 17-year-old girl developed considerable haemorrhage per rectum 7 days after an apparently uncomplicated appendicetomy with ligature and invagination of the appendix stump. The appendix was normal. Persistent haemorrhage and a fall in HB led to a second laparotomy on the 11th post-operative day. The catgut ligature on the appendix stump was found to have slipped off, and it was assumed that there had been bleeding from the appendix stump into the caecum. The appendix stump was re-sutured and re-invaginated. After this there was no more rectal bleeding. Histological examination of the basal section of the appendix showed a small longitudinal extramural branch artery. There was probably a normal variant of the blood supply to the appendix where the basal part receives its blood supply from the caecum.


[Sick behavior of patients with rheumatic diseases]. The illness behavior of 119 patients with rheumatic disorders (predominantly nonarticular rheumatism) has been studied. The behavior differed in relation to the rheumatological diagnosis, the personality and the previous stress situations.


Immunosuppression after cholecystectomy. The effect on immune functions of cholecystectomy under combined anaesthesia was studied in nine patients. The parameters examined were the leucocyte and differential count, the T-and B-lymphocyte count, and the lymphocyte transformation induced by phytohaemagglutinin, concanavalin A, pokeweed mitogen and purified protein derivative of tuberculoprotein. The anaesthesia and operation decreased the total lymphocyte count in the peripheral blood. No significant change occurred in the proportion or absolute number of E-binding (T) lymphocytes. The proportion of EAC-binding (B) lymphocytes increased, although no change was observed in the lymphocytes with surface immunoglobulin representing another B-cell marker. A statistically significant decrease was found in the lymphocyte response to all the mitogens used both in cultures with isolated lymphocytes and in whole blood. The changes returned to the pre-induction level on the third postoperative day. These finding suggest a transitory decrease of cell-mediated immunity after cholecystectomy.


Electrical stimulation in delayed union of long bones. The role of electricity in the promotion of fracture union of long bones in human beings requires further investigation. An electric stimulator was devised through which 15 microamperemeter current was applied to the fractured long bones of 20 patients with delayed union. The best results were obtained in cases where the negative electrode was introduced at the fracture site and the positive electrode was placed proximal to the fracture area. In 90 per cent of cases treated by different methods in this series, union occurred within an average period of 9 1/4 weeks. The rate of infection following introduction of electrodes for electrical stimulation was 20 per cent.


[Hairy cell leukemia in the light of an observed case]. A case of hairy-cell leukaemia was observed in a man aged 40 years. The diagnosis was based on the whole of clinical investigations and laboratory investigations, especially cytoenzymatic examination of leukaemic cells and examination of their structure in electron microscope. In treatment radiotherapy was appleid initially followed by splenectomy.


Subjective detection of vertical acceleration: a velocity-dependent response? Human subjective thresholds and directional sensitivity were investigated as a function of vertical linear acceleration with head erect. A hyperbolic (r=0.94) relation emerged between threshold latency and acceleration magnitude (range 0.005 to 0.06 g). This implies that detection was determined by attainment of a given velocity (21.6+/-2.65 cm/sec) rather than the acceleration magnitude per se. Re-analysis of previous data from horizontal accelerations conducted with head erect and supine revealed similar hyperbolic relations (r=0.98 in both cases) with velocity constants of 22.6+/-1.28 and 32.4+1.96 cm/sec respectively. From these findings it is inferred that with head erect (i.e. normal attitude re gravity) the thresholds to predominantly utricular (horizontal accel.) and saccular (vert. accel.) stimulation were similar (P greater than 0.7). However, with head "supine" the saccular threshold was increased to approx. 1.5Xnormal (P less than 0.001). The results also confirmed a previously reported difficulty in the subjective detection of the direction of vertical movement.


The plasma levels of 25-hydroxyvitamin D in patients with various liver diseases and the response of 25-hydroxyvitamin D to vitamin D treatment. The mean plasma levels of 25-hydroxyvitamin D (25-OH-D) were measured before and after the administration of 2000 units of daily oral vitamin D2 for a period of 2 weeks in 9 normal infants and children, 7 infants with neonatal hepatitis and persistent neonatal hepatitis, and 4 infants with congenital biliary atresia. The mean plasma level of 25-OH-D increased significantly from 19.5 +/- 3.7 (S.E.) ng/ml to 34.0 +/- 6.8 (S.E.) ng/ml after administration of vitamin D2 in controls (p less than 0.05). The mean plasma level of 25-OH-D also increased from 8.0 +/- 2.1 (S.E.) ng/ml to 22.1 +/- 2.6 (S.E.) ng/ml after vitamin D treatment in hepatitis group (p less than 0.05). In patients with congenital biliary atresia, vitamin D treatment did not affect eh plasma levels of 25-OH-D.


Antinuclear antibodies in juvenile chronic arthritis. One hundred patients with juvenile chronic arthritis (JCA) were studied with respect to granulocyte-specific and organ-nonspecific antinuclear antibodies (GS- and ON-ANA) in relation to clinical features of disease. Seventy-two were girls and 28 boys. Sixty-seven patients had IgG ANA, 31 IgM, 10 IgA, 6 IgD, 19 IgE and 35 had ANA, which fixed complement C3. Sixteen of 17 sera containing IgG GS-ANA were from girls. The prevalence of IgG GS-ANA increased with the number of joints affected. No patient with the acute febrile type of the disease had IgG GS-ANA or CS fixing ANA. The prevalence of IgG ON-ANA did not differ significantly in the mono-, pauci-, polyarticular and acute febrile types of JCA. Patients showing clinical activity more frequently had IgG and IgM ANA and C3 fixing ANA. The high titers of ANA were most often seen in girls. Chronic uveitis occurred in 10 of the patients and IgG ANA were present in sera from all of these.


Inhibitory and promoting effects of subliminal pendular rotation on optokinetic nystagmus in man. The influence of vestibular stimulation by subliminal pendular rotation on the optokinetic nystagmus in normal human subjects is discussed. Cortical OKN with pendular rotation was promoted in three indexes--eye speed, frequency, and total amplitude. The subcortical OKN increased markedly when the slow phase of OHN and the compensatory eye movement resulting from the pendular rotation were in the same direction. However, it was inhibited when the two directions were mutually opposed. From the results obtained in the present experiment and in the previous study by the author, it can be concluded that the vestibular organs' effect on visual function is not only promotive but also inhibitive.


Successful transfer of adaptation acquired in a slow rotation room to motion environments in Navy flight training. Two flight students, grounded for the reason they were highly susceptible to motion sickness, completed their training after gradually adapting to 10 rpm, achieved by executing head movements during small stepwise increases in angular velocity. Subject 1 executed a total of about 77 000 head movements with a period of 5 months and Subject 2 executed about 108 000 head movements within a period of 42 days. The transfer of adaptation acquired in the laboratory to most motion environments aloft was good; the notable exception involved weightless maneuvers in the case of Subject 1. Both were on flight status when contacted recently. The opportunity was taken to assess the current motion sickness susceptibility in Subject 1 in the fall of 1975. He reached our (mild) motion sickness endpoint, in the rotating room, at 17 rpm: the average endpoint is 7--8 rpm. Some practical and theoretical implications are discussed.


Enhancement of phytohemagglutinin-induced DNA synthesis of mouse thymocytes and T-lymphocytes by a neutral protease of polymorphonuclear leukocytes. Mouse thymocytes were poorly triggered in vitro with phytohemagglutinin (PHA) to induce DNA synthesis and the response was markedly enhanced by culture supernatant (SUP) of polymorphonuclear leukocytes (PMN). The PMN factor was nondialysable, heat-labile and precipitated with 65% ammonium sulphate. Its molecular weight was approximately 19,000 on sephadex G-75. The sephadex fraction had a proteolytic activity on 3H-acetyl hemoglobin at neutral pH. The protease seemed to be a chymotrypsin-like enzyme on the basis of inhibition profile using various protease inhibitors. The thymocyte-helping activity in the protease fraction was absorbed by affinity columns of protease inhibitors. The PMN-protease also enhanced the DNA synthesis by antigen-stimulated lymph node cells and by PHA-stimulated T-lymphocytes, but not by LPS-stimulated B-lymphocytes. Only the lymphocytes already been stimulated with antigen or mitogen received preferentially the helping action by PMN-protease. The helping activity was effectively absorbed by PHA-stimulated thymocytes but not by nonstimulated thymocytes. These evidences seems to suggest that acceptor sites for the protease, newly developed on lymphocyte surface after stimulation, may play an important role in the enhanced DNA synthetic response.


B- and T-cells and intracellular Ig-synthesis of peripheral lymphocytes in children with asthma and/or previous adeno-tonsillectomy. Studies of IgG, IgA and IgM in serum, the number of circulating T- and B-cells, and the number of Ig-containing blast cells after pokeweed mitogen stimulation of peripheral lymphocytes in vitro were performed in children who had been found previously to have low IgA levels in serum and saliva. The first group comprises 24 children with tonsillectomy performed approximately 3 1/2 years earlier, among whom several cases of atopic diseases had been found. In these children, low IgA levels were found continuously, while the numbers of B- and T-cells and the number of IgG, IgA, IgM and IgE-containing blast cells were within normal levels. The second group comprises 28 children with recurrent and chronic respiratory infections, which often preceded attacks of asthma. Very low IgA levels were found in these children associated with a decreased number of T-cells, increased numbers of lymphocytes with membrane bound IgA and IgE and an increased number of IgE-containing blast cells. The third group comprises 20 children with severe extrinsic asthma. In these children, slightly decreased levels of IgA and low levels of IgM were found. Furthermore, the number of circulating T-cells was reduced and, in addition, an increased number of lymphocytes with surface IgE was observed.


Passive transfer of streptozotocin induced diabetes mellitus with spleen cells. Studies of synogeneic and allogeneic transfer to normal and athymic nude mice. This study shows passive transfer of streptozotocin induced diabetes mellitus in mice. Transplants of spleen cells from BALB/c mice, streptozotocin treated for 5 days, induced diabetes in normal BALB/c recipients. Treatment of transplants with anti-theta and complement resulted in a significant decrease in the degree of diabetes. Athymic nude mouse recipients of BALB/c background also developed diabetes after transpant of spleen cells from both syngenic and allogenic (C-7/Bl/6) donors. It is concluded that passive transfer of chemically induced diabetes in mice is practicable, in both syngeneic and allogeneic combinations, and that thymus derived lymphocytes are significant in this process.


Concanavalin A-induced activation of lymphocytic choriomeningitis virus memory lymphocytes into specifically cytotoxic T cells. When spleen cells, which have been primed to Lymphocytic Choriomeningitis (LCM) virus during a primary infection several months previously, are stimulated in vitro with Con A. highly specific secondary cytotoxic effector cells are generated. The degree of cytotoxicity revealed by such Con A-stimulated cells is higher than that of non-incubated spleen cells harvested nine days following the primary infection, and the effect is totally inhibited by anti-theta serum plus complement treatment of the effector cells immediately before the cytotoxic test.


Extrahepatic obstruction of the portal vein with bleeding from the gallbladder. Report of a case. A case of extrahepatic obstruction of the common bile duct and the portal vein by a retroperitoneal neurolemmoma is described. In the initial stages portal hypertension with hepatofugal collaterals and bleeding from oesophageal varices existed. Then gradually, hepatopetal anastomoses developed, partly via veins in the wall of the gallbladder. Such venous collaterals tend to reduce the portal hypertension, but may cause bleeding from the gallbladder.


Autoantibodies in untreated and treated essential hypertension. I. Using the indirect immunofluorescence method, autoantibodies (AB) of IgG and IgM classes were investigated in sera from 161 consecutive patients with essential hypertension and compared with those from 78 healthy normotensive subjects of the same composition by age and sex, and without any family history of hypertension. The frequency of one or more AB was as high in 78 untreated (15.3%) as in 83 treated patients (13.0%) and was in the controls 9.0% (n.s.). In the treated patients, the AB were associated with heart involvement (p less than 0.02). In the untreated patients, antinuclear antibodies of IgG class were associated with BP (p less than 0.01) and fundus grading (p less than 0.005). A family history of hypertension was found in 23.5% of the hypertensive males with AB and in 9.0% of the normotensive males (p less than 0.10). These results are discussed in relation to reports of an association of AB with cardiovascular diseases. It is concluded that the presence of AB in essential hypertension is not necessarily due to drug induction.


Gastrointestinal and other side-effects from the use of aspirin and related drugs; biochemical studies on the mechanisms of gastrotoxicity. A multifactorial basis has been shown to exist in the development of gastric damage induced by aspirin and related N.S.A.I. drugs. Aspirin-induced gastric damage is characterized by a variety of physical and biochemical changes induced in the gastric mucosa which occur at different stages after administration of the drug. Aspirin only causes gastric ulceration and massive haemorrhage in the stomach when the stomach has been sensitized by the prior exposure to moderate stress conditions (which may resemble anxiety or psychologic stress). A model of ulcer development in which aspirin or other N.S.A.I. drugs are given to rats or pigs exposed to brief periods of stress has been described. Using this more sensitive assay procedures can be explored for reducing the gastric damaging effects of N.S.A.I. drugs. One such procedure involves chemical modification of the carboxylic acid moiety of aspirin.


An outbreak of pneumocystis pneumonia in children with acute lymphocytic leukemia. Between Jan 1 and Oct 31, 1975, a cluster of ten cases of pneumocystis pneumonia occurred in children with acute lymphocytic leukemia (ALL) at the James Whitcomb Riley Hospital for Children in Indianapolis. The risk of infection appeared to be related to the intensity of chemotherapy. Furthermore, illness developed in nine of the ten patients between 30 and 100 days after initiation of therapy, suggesting a period of heightened susceptibility to infection. An indirect immunofluorescent test was used to detect antipneumocystis antibodies in serum samples collected from patients with pneumocystis pneumonia and their contacts. Members of the Riley Hospital staff who had close contact with infected children had a higher prevalence of elevated antibody titers (7/12) than other staff members (2/22; P = .004) or parents of infected patients (0/8; P = .01). This suggests that transmission of pneumocystis may occur within the hospital environment.


Continuous low dose peripheral vein pitressin infusion in the control of variceal bleeding. Continuous low dose peripheral vein pitressin has been shown to be effective in controlling variceal bleeding in seven episodes of bleeding in six patients. No significant side-effects were seen. The expense, delay and hazard associated with superior mesenteric artery catheterization for selective arterial pitressin infusion were avoided. If these results can be reproduced, low dose peripheral vein pitressin infusion may prove to be a valuable addition to the treatment of bleeding esophageal varices.


Aspirin hepatotoxicity.

Aspirin hepatotoxicity. A case of aspirin hepatotoxicity in a 46-year-old male with rheumatoid arthritis is discussed, and this adverse reaction is reviewed. The patient was started on 900 mg aspirin four times daily; five days later the dose was increased to 1200 mg four times daily. After six days' therapy of 4.8 g aspirin daily, the serum salicylate level rose to 25 mg/100 ml and liver enzymes became elevated. Aspirin was discontinued and ibuprofen, 600 mg four times daily, begun. Eight days after cessation of aspirin therapy, the patient's liver enzyme values returned to normal. Previous case reports and studies of aspirin-induced hepatotoxicity are reviewed. It is concluded that aspirin-induced hepatotoxicity occurs much more frequently in patients with rheumatoid arthritis and other connective tissue disorders than previously recognized.


Spherophakia: a case report.

Spherophakia: a case report. A case of spherophakia with unilateral traumatic phacometecesis is presented and the treatment of the postextraction sequelae by contact-lens therapy is described.


A fibreendoscopic study of acute upper gastrointestinal hemorrhage in Nairobi, Kenya. A prospective survey of acute upper gastrointestinal hemorrhage in the major government hospital of Kenya was done using fibre-optic esophagogastroduodenoscopy. Of 66 African patients presenting with hematemesis and melena, a precise visual diagnosis was made in 89%. Duodenal ulcer was most common, accounting for 53%, but esophageal varices occurred in 20%. Gastric ulcers and esophagitis were surprisingly infrequent. There was a correlation between hemorrhage from esophageal varices and schistosomiasis distribution. Variceal bleeding occurred in a young age group (mean age 28 yr) and correlated closely with the presence of splenomegaly. These findings have implications for the diagnostic approach and management of patients from areas of endemic schistosomiasis.


Renosplenic shunt for control of esophageal variceal hemorrhage. The left renal vein was used to perform a renosplenic (38 patients) or an adrenosplenic (5 patients) shunt in forty-three patients with esophageal variceal hemorrhage. All patients were successfully decompressed without recurrence of variceal bleeding in the postoperative period. One shunt thrombosed six months postoperatively and one kidney was removed because of venous hypertension and spontaneous rupture two days postoperatively. Overall mortality was 16 per cent, including a 22 per cent mortality in the emergency group.


[Anomalous fusional movements: the sensorimotor aspect of anomalous binocular vision (author's transl)]. It has been demonstrated that, besides sensory adaptation phenomena, sensorimotor phenoma may also develop in concomitant esotropia. The existence of the latter entity can be shown particularly by means of prisms and is interpreted as fusional in origin. It is therefore defined as 'anomalous fusional movements'. The features of these anomalous fusional movements were studied in a group of 30 patients, mainly in order to investigate their finality. Correlations were evaluated between anomalous fusional movements and entities previously described by different names according to the interpretation given them by various authors.


[Carcinoembryonic antigen in retinoblastomas (author's transl)]. In 47 patients (46 children and 1 adult) with unilateral and bilateral retinoblastoma, the titer of the carcinoembryonic antigen (CEA) was determined. The CEA titer of children with active retinoblastomas was 1.44 +/- 0.26 ng/ml (x +/- SEM). Those patients whose retinoblastoma was inactivated by therapy did not show a significantly lower CEA titer. In the group of children with one eye removed because of a unilateral retinoblastoma, the CEA titer was significantly (P less than 0.1) lower. The globes of 25 children were examined histologically. In those cases with invasion of the optic nerve or choroid, the CEA titer was significantly higher (P less than 0.1) as compared with those where the tumor was limited to the retina alone.


[Fluctuations in the accomodation of the human eye to mono- and binocular fixation (author's transl)]. Using an objective infrared technique, the deviation of the mean of accomodation during mono- and binocular fixation and the degree of fluctuation were measured for four male probands. 1. For two men, the additional impulse of convergence in binocular vision reduced deviation and fluctuation. 2. In every case, fluctuation and deviation increased with increasing theoretical value of accomodation. 3. Increased values of accomodation were linked to greater fluctuations so that loss of image quality could be somewhat compensated for.


Studies on the influence of ochratoxin A on rat lenses. The influence of ochratoxin A on enzyme activities and on the content of free adenine nucleotides and intermediates of glycolysis in rat lenses was investigated. For a period of eight weeks, five times weekly, albino Wistat rats received ochratoxin A in 0.1% NaHCO3, dosed 1/100 LD50, via stomach tube. All measurements were made at the end of the experiment. Decreased contents of ATP, G-6-P, sum of fructose, and F-6-P were observed, but pyruvic acid, AMP, and DAP increased. Relatively decreased activities of enzymes MDH, ALD, HK, GK, and PK were established. The influence of ochratoxin A on the carbohydrate metabolism of rat lenses with respect to tranparency is discussed. There were no significant differences in absolute lens weight in animals treated by ochratoxin A and controls.


Experimental cataracts in rats due to tryptophan-free diet. A tryptophan-free diet induces posterior subcapsular cataracts and reversible corneal opacities in young Wistar rats. Compared to the controls there is a significant decrease of body weight, lens fresh weight, and water-soluble lens protein. Protein separation by isoelectric focusing shows diminished alpha-, beta-, and gamma-crystallin fractions. If tryptophan is restored to the diet after 24 days, new clear lens fibers are laid down again, indicating that the mechanism of protein synthesis has not been permanently damaged by tryptophan-deficiency.


[Electron microscopic observations on the effect of laser beams on the retina of the rabbit (author's transl)]. After laser irradations, retinas of 13 rabbits were examined by electron microscope. The laser focus was set between 30 min and 140 h or 6 weeks in advance. The anatomical separation between the retina and the connective tissue of the choriocapillary in all the lesions is preserved by an intact Bruch's membrane. Destruction of the pigment epithelium, rod layer, and outer granular layer occurs in the early stages after coagulation. Later the nuclei of the rods show various stages of degeneration with simultaneous increases in the volume of the Müller's cells. The cytoplasma of the Müller's cells penetrates the nuclei of the sensory cells undergoing degeneration. Proliferation of the pigment epithelium begins after about 20 h. The first appearance of macrophages in the retina is visible after 30 h. Between 92 and 140 h in the area of the pigment epithelium, variously differentiated cells, which partly contain pigment granules and lamellary inclusion bodies, form. Some cells or cell groups which are visible might represent histiocytes within the Bruch's membrane 35, 45, 68, and 92 h as well as 6 weeks after coagulation. They partly cross the outer layer of the Bruch's membrane and neighboring connective tissue of the choroid. According to our studies, pigment epithelial cells, choroidal histiocytes, and Müller's cells participate in the phagocytosis.


Frequency of lymphocytes bearing Fc receptors and surface membrane immunoglobulins in normal, persistent lymphocytotic and leukemia cows. Fluoresceinated, heat-aggregated bovine immunoglobulins (B-IgG) and human immunoglobulins (H-IgG) were used to detect a receptor for the crystallizable fragment (Fc) of the immunoglobulin molecule on peripheral blood lymphocytes (PBL) of cattle. The aggregated and B-IgG and H-IgG bound to the bovine PBL, but aggregated H-IgG was found to be more sensitive for the detection of Fc receptors. The specificity of aggregated H-IgG binding to the Fc receptors was established by demonstrating that antigen-antibody complexes inhibited this binding, and unaggregated H-IgG did not bind significantly to PBL. Double-labeling experiments suggested that all Fc+ cells have surface immunoglobulins (SIg), a marker for B lymphocytes. The percentage of Fc+ and SIg+ cells in normal animals was 9.5% (range 4-15%) and 16.2% (range 4.5-30.2%), respectively. Persistent lymphocytotic cows had 2.71 times more Fc+ and 3.85 times more SIg+ lymphocytes than did normal cows. Cows with lymphosarcoma had a lower percentage of Fc+ and SIg+ cells than did cows with persistent lymphocytosis. Cases with thymic lymphosarcoma and those with the skin form of leukemia had normal percentages of Fc+ and SIg+ cells.


alpha1-Antitrypsin deficiency in nonsmokers. The clinical symptoms, measurements of pulmonary function, and interpretations of thoracic roentgenograms in 18 patients with alpha1-antitrypsin deficiency associated with the PiZ phenotype are reported. The patients had never smoked and had little or no exposure to occupational and urban air pollution. The findings were compared with those in a group of patients who also had the PiZ phenotype, but who were smokers. The results showed that the clinical course, rate of pulmonary-function deterioration, and appearance of the thoracic roentgenograms in persons who had never smoked are variable and suggested that other factors, in addition to phenotype and environmental pollutants, are determinants of the chronic obstructive pulmonary disease that develops in these patients. Many of these patients lived into their sixth and seventh decades, suggesting that those patients who avoid respiratory irritants do not necessarily have an ominous prognosis. These are important considerations in the diagnosis and treatment of patients who have this deficiency.


[Problem oriented pediatric record (author's transl)]. The object of this paper is the presentation of the problem griented medical record now in use at the Department of Pediatrics of the Faculty of Medicine of the University of Valencia. The main documents of this medical record (problem list, discharge summary, anamnesis and physical examination summary, and medical record summary) are given describing the characteristics of format and the rules for its completion. The relationships between the main documents are shown.


Disorders of suppressor immunoregulatory cells in the pathogenesis of immunodeficiency and autoimmunity. A series of suppressor cell systems regulate virtually all immunologic processes. Disorders of these systems have been identified in association with a number of diseases. An abnormal number of activated suppressor T-cells have been seen in some patients with common variable hypogammaglobulinemia and in some with selective IgA deficiency. Suppressor T-cells that inhibit immunoglobulin synthesis also develop in an animal model of immunodeficiency, the agammaglobulinemia of the bursectomized bird. Non-T-cell suppressor cells are a pathogenic factor in the humoral immunodeficiency associated with multiple myeloma. At the other end of the spectrum of immunologic response, a reduction in functional activity of suppressor T-cells has been implicated in the pathogenesis of autoimmune diseases. The disorders of suppressor cells that have been shown in immunodeficiency and autoimmunity are important when developing rational strategies for prevention and therapy of these immunologic disorders.


Plasma cofactors of platelet function: correlation with diabetic retinopathy and hemoglobins Ala-c. We studied 29 diabetic patients (eight without and 21 with retinopathy) and 29 matched control subjects for hemoglobins Ala-c and plasma levels of fibrinogen, von Willebrand factor, and factor VIII/von Willebrand factor antigen. Hemoglobins Ala-c were elevated in all diabetic patients, regardless of retinopathy (P less than 0.001); fibrinogen was elevated only in those with retinopathy (P less than 0.001); and plasma von Willebrand factor was clearly elevated in those with proliferative retinopathy and minimally, if at all, elevated in those with background or no retinopathy. Plasma from five diabetic patients with proliferative retinopathy and five control subjects was tested for its ability to enhance the ADP-induced platelet aggregation of normal or von Willebrand platelet-rich plasma; no differences were found. We conclude that elevated levels of fibrinogen and von Willebrand factor, both recognized plasma cofactors of platelet function, are associated with proliferative diabetic retinopathy. A plasma factor that enhances ADP-induced platelet aggregation could not be found in diabetic plasma, and we doubt that increased von Willebrand factor is responsible for its finding by others.


T-lymphocyte variant of hairy-cell leukemia. Immunohematologic studies on cells from a patient with the clinicopathologic syndrome of hairy-cell leukemia showed that the neoplastic cells had receptors for sheep erythrocytes and therefore had human T-lymphocyte characteristics. The leukemic cells did not have the membrane receptors or immunoglobulin markers of B lymphocytes or monocytes nor did they synthesize immunoglobulin. A lymphoid cell line established in vitro from the cells had the same T-lymphocyte characteristics. The lymphoid cell line is positive for tartrateresistant acid phosphatase, forms rosettes with untreated sheep erythrocytes, and reacts with an anti-T-lymphocyte antiserum. Thus the syndrome of hairy-cell leukemia may occasionally result from the neoplastic proliferation of T-lymphocytes as well as from the more usual B-lymphocyte form. This situation is analogous to that described previously in chronic lymphocytic leukemia and other lymphoproliferative disorders.


Educational objectives in rheumatology for medical students. Very little information is currently available with respect to what medical students should learn about clinical rheumatology, and an investigation was undertaken to determine what they should know in this area.


Decreased T cell levels in patients with warts. Thymus-derived lymphocyte (T cell) levels were determined in 72 healthy patients who had viral warts, in 21 healthy patients who had been cured of warts from one to 15 years previously, and in 35 age-matched normal controls who had no history of warts. The mean percentage of lymphocytes that formed rosettes with sheep erythrocytes was less in patients with warts and patients previously cured of warts than in normal controls (P less than .001 and P less than .001, respectively). The number of total T cells/cu mm was decreased in untreated patients with warts (P less than .01) but was normal in patients cured of warts for more than one year. In addition, the morphology of the rosettes in the two patient groups differed from the controls; 32% had small numbers of sheep erythrocytes bound loosely to T cells compared with a rosette of numerous erythrocytes closely adherent to the T cell in 91% of the controls. The results suggest a defect of cellular immunity in many healthy patients with warts.


Mycosis fungoides with pulmonary involvement. A complete remission. Biopsy specimens from a 21-year-old man showed mycosis fungoides involving the skin and lungs. Usually such a case represents a fulminant and fatal course of the disease. This patient had a complete remission of his pulmonary disease following sequential therapy with cyclophosphamide, vincristine sulfate, methotrexate, leucovorin calcium, and cytarabine (COMLA).


Rheumatic disorders in primary biliary cirrhosis. Eighty-three patients with primary biliary cirrhosis were investigated to determine the prevalence of rheumatic disorders. 14 had scleroderma, which tended to be mild but in several patients produced severe systemic manifestations. The CRST syndrome (calcinosis, Raynaud's phenomenon, sclerodactyly, telangiectasia) was only identified twice. There was an increased incidence of HLA A1+B8 in those patients with scleroderma. As well as those with scleroderma, 4 patients had a destructive arthropathy resembling avascular necrosis. 4 patients had an inflammatory arthritis, without specific features, but the frequency was no greater than might be expected in the general population.


Prophylactic use of intra-aortic ballon pump in aortocoronary bypass for patients with left main coronary artery disease. Aortocoronary bypass surgery in patients with left main coronary artery disease is reported to have an operative mortality of between 1.4 and 39%. It is generally accepted that the operative mortality in this group of patients is considerably greater than in routine bypass candidates, presumably due to the large amount of myocardium threatened by a single lesion. In an effort to preserve threatened left ventricular myocardium, intra-aortic balloon pumping was instituted prophylactically prior to sternotomy in 20 consecutive patients with left main coronary artery disease (luminal narrowing greater than 50%). Sixty per cent of these patients had New York Heart Association Class IV angina, 25% had Class III, and 15% Class II. Fifty per cent of the patients in this group presented with unstable angina. Operative patients requiring left ventricular aneurysmectomy and/or valve replacement, were excluded. No operative deaths have been encountered in 20 consecutive patients managed in this manner. One patient displayed signs of myocardial infarction in the postoperative period. Correctable peripheral vascular ischemic complications of pump insertion were encountered in three patients. Preliminary results from this ongoing study support the hypothesis that prophylactic intra-aortic balloon pumping is a low risk procedure that should be utilized routinely in aortocoronary bypass surgery for left main coronary artery disease.


Paraplegia following intraaortic balloon assistance. In a patient receiving intraaortic balloon counterpulsation following myocardial revascularization, paraplegia developed two days post-operatively. Postmortem examination demonstrated a dissecting hematoma of the thoracic aorta and spinal cord infarction. The neurological deficit is thought to be due to embarrassment of spinal cord blood supply, and mechanisms of injury are discussed.


Familial syringomyelia: a report of four cases. The clinical and neurological features of four siblings (2 male, 2 female) affected by syringomyelia are described. A fifth sister was affected by an acoustic neurinoma. Since neither parent showed signs of syringomyelia, this is considered to be a datum substantiating the dysembryogenetic theory of the syringomyelia syndrome.


Methylene blue injection. An intraoperative guide in small bowel resection for arteriovenous malformation. Injection of methylene blue dye into the superior mesenteric artery of a patient with arteriovenous malformation of the small bowel was helpful in identifying the field of resection. Preoperative selective angiography is essential in identifying this rare cause of gastrointestinal bleeding.


[Structural and functional organization of the vestibular apparatus in rats maintained under weightless conditions for 19.5 days aboard the satellite "Cosmos-782"]. Vestibular apparatus was investigated in rats subjected to weightlessness for 19.5 days in the satelite "Cosmos-782" and experienced acceleration on launching and landing. Some structural and functional changes were noted. They were seen in otolith clinging to the utricular receptor surface and in the peripheral arrangement of the nucleolus in the nuclei of the receptor cells. It is also possible that increased edema of the vestibular tissue resulted in destruction of some receptor cells, and within the otolith--changes in the form and structure of otoconia. In the horizontal crista the cupula was separated.


[Characteristics of the lymphoid cells of rabbits]. By means of scanning electron microscopy it has been stated that the thymus gland, spleen, paratracheal lymph node, Peyer's patches and appendix in an intact rabbit of "Shinshilla" strain have T- and B-lymphocytes in different proportion. T-lymphocytes are seen as spherical cells with rough surface, with a few microprocesses, have 3.0 +/- 0.1 mcm--4.7 +/- 0.2 mcm in diameter depending on their location. B-lymphocytes are seen as spherical cells with a considerable amount of microvilli on their surface, have 2.9 +/- 0.1 mcm--4.4 +/- 0.1 mcm in diameter depending also on their location. In the thymus gland, cells with rough surface, a few microprocesses and crater-like hollows prevail. In the spleen and lymph node, most of the cells are of similar diameter and have microvilli on the surface. Lymphoid population in the Peyer's patch and appendix is represented by large cells with microprocesses.


Combined nuclear and supranuclear defects in ocular motility. A clinicopathologic study. A 65-year-old man suffered a midbrain infarct after coronary artery bypass surgery. He was left with a severe neuro-ophthalmologic deficit consisting of paralysis of upward and downward vertical gaze, weakness of adduction of the left eye, a dilated fixed left pupil, and partial right Horner's syndrome. He died 31 months after the episode. Postmortem examination disclosed an infarct involving parts of both oculomotor nuclei as well as supranuclear structures thought to be involved in the mediation of vertical eye movements.


Colorimetry by a new principle.

Colorimetry by a new principle. A simple and informative method is described for determining the type and extent of color defects. The subjects' responses are registered automatically on a chromaticity diagram that is based on the newtonian model. Color defects are readily identifiable by a skewing of the normal central gray area toward the defectively perceived color. The examination permits independent variation of hue and saturation for each color and requires less than five minutes for the entire procedure. Unlike conventional color tests, the present method indicates exactly what colors are or are not seen at any level of saturation.


Nasopharyngeal and adjacent neoplasms: a clinico-pathologic and immunologic study. Thirteen cases of nasopharyngeal carcinoma (NPC) and 16 cases of non-NPC tumors in the nasopharynx or in adjacent locations were investigated clinically, immunologically, and pathologically. All tumors were classified according to the TNM classification, and the stage and course of the disease was correlated with the histological tumor type, the T- and B-cell distribution in tumor tissue and in the peripheral blood, as well as with antibody titers against Epstein-Barr virus (EBV). The results showed a positive correlation of decreased T- and B-cells in tumor tissue and of decreased T-cells in the peripheral blood with the extend of the tumor in both NPC and non-NPC cases, with  some exceptions of lymphocyte rich neoplasms (lymphoepithelial carcinoma and malignant lymphoma). Antibodies against EBV (early antigen and capsid antigen) became progressively elevated with increasing tumor stage in NPC-cases but not in non-NPC cases. The latter, however, was observed only in two histological types of NPC's: anaplastic carcinoma and lymphoepithelial carcinoma; titers in the remaining tumor types stayed insignificant.


[Immunity in leukemia: reason for onset of leukemia, agent for successful therapy of leukemia]. Authors present the facts which indicate that in human medicine there is immunity against malignant tumors and leukaemia through T lymphocytes immunological control. The appearance of leukaemia in a certain number of persons is due to reduced immunity in the patient or weak antigen immunogenicity of leukaemic cells. Authors also present evidence for the existance of tumor antigens same as in leukaemic leukocytes in human pathology. These antigens belong either to still undiscovered viruses of human leukaemia, as is the case of reverse transcriptase of RNK virus, found in leukocytes of 95 percent of patients with acute leukaemia, or they are new antigens formed by combination of cell genoma and virus genoma, or by depression of the gene which were active only during the foetal life under the influence of oncogenic chemical substances or viruses. The evidence is given too, concerning the existence of immune response in human medicine, in the form of cytotoxic antibodies or sensitized T lymphocytes to tumor antigens which can be demonstrated in vitro by the test of colonial growth inhibition of tumor cells. As the immunity does not operate against tumor or leukaemic cells, the reason for it must be sought in the disorder of the afferent part (weak immunogenicity of tumor antigens, tolerance of tumor antigens, etc.), or of the efferent part of the immune response (the presence of blocking factors in the patient's plasma). At the end, the authors also discuss about the attempts of immunological treatment of acute leukaemia, and the results to this date are encouraging.


Detection and separation of lymphocytes with specific surface receptors, by using microparticles. Horse anti-(human lymphocyte) globulin was immobilized together with fluorescein labelled dextran in spherical microparticles of polyacrylamide (AHLG-particles). The particles had a diameter of 1-5 micrometer and a density of 1.12g/cm3, with globulin exposed on the surface. Human lymphocytes bearing the antigen (thymus-derived lymphocytes) bound the particles, which were easily detected by fluorescence microscopy. In this way, about 58% of circulating human lymphocytes were able to bind AHLG-particles at 23 degrees C. Non-specific binding was low, only 3% when human serum albumin was present in the buffer, and only 4% when non-specific horse globulins were incorporated in the microparticles. The cell-particle complexes could be separated from cells that had not reacted by density-gradient centrifugation in Ficoll/metrizoate. The viability was not changed after the separation procedure. The number of cells binding AHLG-particles corresponded well the the relative amount of T-cells. When the cells binding AHLG-particles were separated from the lymphocytes, the number of T-cells decreased remarkably, indicating that the antibodies bind preferably to the T-cell population. Concanavalin A immobilized in microparticles was sufficiently exposed to initiate the agglutination of the lymphocytes. The agglutination was completely inhibited by preincubating the microparticles with alpha-methyl mannoside.


[General pharmacological studies on tramadol, a potent analgetic agent (author's transl)]. The general pharmacological properties of 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal) are described and compared with those of other strong narcotic analgetics. In behavioral studies tramadol in high doses had a primarily stimulating effect in mice and rats and a sedative effect in rabbits and dogs. The Straub tail phenomenon, a reaction typical for mice administered morphine, was observed only after subtoxic doses of tramadol. In i.v. doses tramadol generally caused a weak central inhibition of non-stimulated and electrically stimulated brain activity in unanesthetized rabbits. Muscle tone and motor coordination in rats and mice were only slightly affected by the drug, in contrast to the effect of morphine. Unlike other strong analgesics tramadol in doses of 5--20 mg/kg i.v. did not cause respiratory depression and even clearly increased respiratory volume and rate in conscious rabbits and anesthetized dogs. In cats and dogs i.v. doses of tramadol up to 10 mg/kg were well tolerated in the cardiovascular system. Tramadol has a slight, papaverine-like spasmolytic effect and no effect on gastrointestinal motility or urinary and electrolyte excretion. The drug showed no antipyretic properties in rabbits. It inhibited edema in rats and guinea pigs but had no antiproliferative effect in the cotton pellet test in rats. Tramadol did not inhibit monoamine oxidase activity or cause enzyme induction in the rat liver.


Pathologic findings in the aortocoronary vein grafts. A scanning electron microscope study. Examination of totally or partially obstructed human aortocoronary vein grafts, obtained at different time intervals after the bypass operation, has shown that the initial occlusive process is due to thrombosis and may appear a few hours or days after surgery. The cellular phase of intimal proliferation affecting most of the grafts becomes apparent about 4 weeks after the operation. After 1 year the intimal hyperplasia acquires a cell-poor, fibrotic character; the graft usually remains patent. About one-half of the vein grafts obtained 3 or more years after the operation show complicated atherosclerotic lesions. These findings indicate that most of the vein grafts undergo extensive structural changes and some may show similar degenerative lesions as they develop in the coronary arteries.


Immunodiagnostic of multiple sclerosis by estimation of lymphokines in vitro and in vivo. The basis of our investigations is a hypothesis about immunomechanisms responsible for aetiopathogenesis of multiple sclerosis including immungenetic connection (predisposition) and autoimmunity (pathogenesis). Some new results about cellular immunity using cell electrophoresis mobility technique, especially sensitization against normal brain tissue antigen (NTA) and investigations of lymphokines in cerebrospinal fluid are represented. The intention of this paper is to demonstrate a combined diagnostic regime for early detection of multiple sclerosis as well as for follow-up studies in course of treatment.


[B-lymphocytes in multiple sclerosis: studies concerning their levels in the blood and cerebrospinal fluid]. In this paper the B lymphocyte population was investigated by fluoresceinated immunoglobulin assay in peripheral blood and cerebrospinal fluid (CSF) in M.S. patients and other neurological diseases taken as control. In peripheral blood there was no significant difference in two groups considered. In CSF there was a higher percentage of B-cells only in M.S. patients. This datum was more evident when the percentage of B cells was simultaneously determined in CSF and blood. It can be hypothesized the existence of subpopulations of B cells synthesizing Ig in the CST.


Heterogeneity of human T lymphocytes to bind sheep red blood cells in multiple sclerosis patients and controls. The present studies were performed as a result of the report that the human T-cells may be composed of heterogeneous subpopulation in the sense of their ability to bind SRBC. In this paper, the diversity of human peripheral lymphocytes in M.S. patients, other neurological diseases and controls were investigated by means of an interesting approach based on the heterogeneity of humnan T-lymphocytes examined by the rosette formation of SRBC (E rosette) in two different reaction media.


[Rosette-forming lymphocytes in the peripheral blood of normal children]. The study included 180 healthy children distributted into age groups from newborns to 16 years of age. The subpopulations of early E and EAC (T and B) rosette forming lymphocytes were determined. It was found that the main difference is placed in percentual mean values of the newborn where the value of T lymphocytes is less than for the rest of the ages studied, remaining stable beginning at the age of one year. In newborns, the values of B lymphocytes are greater; later, they drop but remain stable also since the age of one.


Recovery of immune competence after tumour resection in mice: correlation with loss of suppressor elements. Changes in the immune competence and levels of suppressore elements were assessed by mitogen stimulation and in vitro antibody production, after resection of a transplantable sarcoma. Spleen cells from tumour-resected animals were found to have depressed responses to conA as well as to the antigens SRBC and DNP-LPS. This inability to respond was gradually overcome and, by Day 21 after resection, spleen cell competence had returned to normal levels. Suppressor cells isolated from the spleens of tumour-resected animals were capable of suppressing the conA response and PFC response of normal syngeneic spleen cells in vitro. The ability to suppress the conA response of normal cells disappeared by Day 1 after resection, while the ability to suppress the anti-SRBC and anti-DNP PFC response of normal cells disappeared by Day 8 and Day 14 respectively. Serum from tumour-resected mice was also found to be suppressive to the conA response of normal spleen cells. The inhibitory material responsible for suppression eluted with the Ig-containing fraction on Sephadex G-150. This inhibitory material gradually disappeared from the serum of tumour-resected mice and was no longer apparent by Day 14. Therefore, it appeared that the return of normal lymphocyte function after tumour-resection was concomitant with the disappearance of splenic suppressor cells and suppressive serum factor.


The T and B lymphocyte content of lymph nodes and spleen in Hodgkin's disease. Lymphocytes from tumour-bearing lymph nodes in 15 patients with Hodgkin's disease, and lymphocytes from 6 spleens infiltrated by Hodgkin's tissue and 6 tumour-free spleens were studied using T and B lymphocyte markers. For comparison, lymphocytes from 16 tumour-free lymph nodes were similarly assessed. It was found that the tumour-bearing nodes showed a predominance of T lymphocytes compared with the control nodes, whereas in involved splenic tissue the proportion of T lymphocytes was slightly reduced compared with uninvolved spleens.


Weber--Christian syndrome in infancy.

Weber--Christian syndrome in infancy. A review of Weber-Christian syndrome in infancy is presented along with the report of two cases. Both infants had low serum properdin levels, and one patient showed remissions of his disease when he was T-lymphocytopenic. This suggests that the T-lymphocyte may have an important role in the pathogenesis of Weber--Christian syndrome.


Cell-mediated immunity in pregnant patients with and without a previous history of spontaneous abortions. The percentage of T-cells was studied in pregnant patients with a previous history of spontaneous abortions, in patients without such a history and in nonpregnant controls. The percentage of T-cells remained unaltered during the three trimesters of normal pregnancy. In patients with a previous history of spontaneous abortions, the T-cell percentages were lower in the second and third trimesters than in non-pregnant controls, but the values did not differ statistically from corresponding values in those patients with no previous history of spontaneous abortion (normal pregnancy). The phytohaemagglutinin (PHA)-induced transformation of lymphocytes was depressed in the second and third trimesters of both patients with a normal pregnancy and those with a previous history of spontaneous abortions. Thus, while the percentage of T-cells remained unaltered during pregnancy, their response to PHA falls in the second and third trimesters.


Posterior polymorphous keratopathy.

Posterior polymorphous keratopathy. Seven cases with posterior polymorphous changes of the cornea are reported. After clinical and pathological examination of the above cases, as well as a short review of the literature, the following points are made: (1) Some cases are congenital, being either familial or sporadic, but others are acquired. (2) The term "posterior polymorphous keratopathy" covers all the variants of the condition and is preferred to the traditional "posterior polymorphous dystrophy". (3) The congenital type is a mild variant of the mesodermal dysplasia, whereas the acquired type follows local disease. (4) The condition can be static, but over 50% of cases are slowly progressive, calling for penetrating keratoplasty.