[State of the contractile apparatus during the development of a pathological process in the muscles. III. The nature and sequence of the structural changes in the contractile apparatus in Zenker's necrosis]. Using polarized ultraviolet (UV) fluorescence microscopy, it was shown that the local damage of muscle fibres causes in their morphologically unchanged parts the alternation of regions, being in different functional states referred to as "pseudocontraction" and "superrelaxation". The pattern of UV fluorescence anisotropy suggests that conformation of contractile proteins by "pseudocontraction" is similar to that at contraction, though changes in sarcomere length do not occur. The "superrelaxation" is characterized by a desorganization of myofilaments. During the spreading of Zenker's necrosis, the "pseudocontraction" is seen transferred first into "superrelaxation", and then into irreversible contracture and rigor. "The boundary of Zenker's necrosis" overlaps with the boundary of the self-propagating irreversible contracture. There is no proper boundary of Zenker's necrosis, because the destructive changes are observed over all the muscle fibre. Contraction nodules arise in the regions of "superrelaxation" and follow the changes of the contractile system, peculiar of contracture. The study of the influence of medium ionic composition on the development of Zenker's necrosis suggests that the arising and spreading of destruction are inseparably associated with the irreverrsible changes of intracellular membrane structures, and with the possibility of propogation of the damage signal by these structures along muscle fibres.


[Effect of vacuolization on the sodium concentration in an isolated muscle fiber]. Using the Perkin Elmer flame photometer sodium and potassium concentrations have been measured in muscle fibers from the m. ileofibularis of Rana temporaria. After 30 minutes preincubation in the Ringer solution, made hypertonic by the addition of 0.22M glycerol, the muscle fibers were incubated in the normal Ringer solution for 30 min. These fibers showed a vacuolation and an increase in total fiber sodium up to 37.2 mmol/l +/- 5.9 S. E., or 45.8 mmol/kg H2O +/- 7.3 S. E. No significant changes in potassium concentration were observed. Then, the fibers were exposed again to the Ringer solution containing 0.22 M glycerol. This procedure caused the disappearance of vacuoles and decrease in fiber sodium concentration down to 17.7 mmol/l +/- 1.6 S. E., or 21.8 mmol/kg H2O +/- 2.0 S. E. The effect of vacuolation was not blocked by ouabain (1.10(-4) M). It is suggested that the vacuoles have a high NaCl concentration. A model for NaCl and water accumulation in T-tubules is presented.


[DNA synthesis and cell reproduction during hemopoiesis in the common frog in the course of spring under a varying temperature regimen]. The proliferation of grass frog hemocytoblasts and differentiation of various lines of hemopoiesis have been studied by means of repeated injections of 3H-thymidine during two spring months. The ability of population of hemocytoblasts to change the size of its proliferative pool is supposed to be regulated by the interaction of thermal and photoperiodical factors. The differentiation of separate lines of hemopoiesis begins in various seasons and depends, in various degrees, on the temperature. The neutrophil and thrombocyte lines are most labile, the erythroid line is most independent. Seasonal characters of erythropoiesis are discussed under comparative aspect.


[Transformation of mouse lymphocytes stimulated by phytohemagglutin depending on their cultivation conditions]. Conditions were elaborated to cultivate splenocytes of mice in medium-199 (Soviet production) changed a little by the addition of 200 mM of glutamine, 6 mM glucose, 60 unit/l of insulin, 5.10(-5) M 2-mercaptoethanol (final concentration), and of 5% serum of new-born calf. In such conditions of cultivation the value of the lymphocyte transformation coefficient lies within 3 and 10.


Clinical and immunological evaluation of 5 cases of mycosis fungoides in advanced stages. Five patients with mycosis fungoides, hospitalized in the Division of Radiotherapy and Medical Oncology of the Ospedale Civile, Pordenone, from January 1975 to December 1978, were studied and treated as non-Hodgkin lymphomas. All patients had evidence of disseminated disease: 3 with bone marrow infiltration, 1 with splenic involvement and 1 with lymph node involvement. Three patients were treated with CVP, resulting in 2 complete remissions that lasted 18 months and 1 PR greater than 50% maintained for 7 months. One patient was treated with ABVD with a PR greater than 50% maintained for 10 months. The last patient was treated with prednisone and then with CV, but expired from pulmonary embolism after 1 cycle. Lymphocyte function, using E and EAC rosette and PHA, was evaluated before therapy in all patients: in the 2 patients who obtained a CR, an improvement in T-lymphocyte function was noted after therapy. The chromosome pattern of peripheral blood lymphocytes was altered before therapy in only one patient. Even if the follow-up period is still relatively brief, the duration of the 2 complete remissions must be stressed. In addition, a strict correlation between T-lymphocyte function and response to therapy was revealed in our study.


An electronic method for counting human T and B cell rosettes. This study reports the adaptation of an electronic particle-counting method for the enumeration of T cell and B cell rosettes of human lymphocytes. This method and the conventional hemocytometer method were compared in parallel on seventeen T cell and seven B cell rosette enumerations in a blind study design. All data were analyzed for statistical significance; correlation coefficents were calculated. There was significant agreement between both methods for T cells at p less than 0.001 (mean particle counter 80.6% +/-11.3 mean hemocytometer 76.7+/-8.2%) and for the B cells at p less than 0.002 (mean particle counter 22.5+/-9.7, mean hemocytometer 23.4+/-5.12). These results demonstrate that the electronic particle counter is useful as a rapid, convenient, semi-automated method for the enumeration of T cell and B cell rosettes.


[Zollinger-Ellison syndrome].

[Zollinger-Ellison syndrome]. Three patients with Zollinger-Ellison syndrome are reported. In the first one, on the base of fibroduodenoscopy, an ulceriform cancer was found in the region of Vater's papilla in duodenum, with a penetration to pancreas and the elimination of gastrinoma (duodenectomy with right-side pancreas resection) led to the clinical healing, normalization of stomach secretion and the rest of the laboratory tests. Six years after the operation, the patient had no complaints and is with well preserved capacity for work. A gastrinoma, hazel-nut size, localized in the distal end of Wirsung's canal was concerned in the other two patients, that led to multiple recidivation and complications (hemorrhages and fistulas) of the duodenal peptic ulcer. One of the patients, due to the complications, underwent 7 resections and the other -- 3 but in neither of the two a radical operative intervention was performed (gastrinoma elimination or total gastrectomy) due to which one of them died four years and the other -- 8 years after the first operation and the onset of the clinical manifestations. Only the present radical operation treatment could lead to permanent results.


[Serotonin metabolism in the tissue of glial brain tumors]. Content of serotonin was distinctly decreased in human brain glial tumors and in transplanted rat gliomas. Activities of 5-hydroxytryptophane decarboxylase and mitochondrial monoamine oxidase were also lowered as compared with the normal state. Content of tryptophane (the main precursor of serotonin) was increased in human and animal tumor tissues; 5-hydroytryptophane was not found in gliomas. A decrease in the tryptophane hydroxylase activity occurred apparently in glioma tissues. The decrease in activity of 5-hydroxytryptorphane decarboxylase, found in tissues of brain glial tumors, might be considered as an adaptive mechanism, since content of serotonin was increased in the tumor tissues after administration of exogenous 5-hydroxytryptophane.


[Mycoses of genital organs of girls - therapeutic problems (author's transl)]. The therapeutic effectiveness of poliene antibiotics, such as nystatin, polyfungin, and pimafucin, was comparatively analysed in the context of mycoses of the genital organs of girls in various periods of development. Early detection of fungi in genital organs, the oral cavity, rectum, and urethra is of great importance to mycosis treatment  of children. Whenever antimycotic treatment is followed by recurrent outbreaks, all persons in the child's closer environment have to be examined at any rate.


[Experimental pneumonia caused by an association of H. influenzae and the influenza virus]. Experiments in 400 non-inbred white mice indicated that the association of influenza virus A2 Hong Kong with H. influenzae enhanced the pathogenic action of the causative agents and led to the unfavorable clinical outcome only in those cases when these agents penetrated the body simultaneously, or when viral infection preceded bacterial infection. In those cases when influenza infection appeared in the presence of bacterial infection, the pathological process developed as a monoviral disease. The morphological changes in the lungs of the mice infected with H. influenzae corresponded to lesions caused by influenza virus and were manifested by pronounced hemodynamic disturbances.


[Effect of copolymers of N-vinylpyrrolidone and acrylic acid on individual stages of immunogenesis]. The analysis of NA-5 and NA-6, copolymers of acrylic acid and N-vinylpyrrolidone obtained by the method of radical copolymerization, indicated that these copolymers, while having no toxicity characteristic of polyacrylic acid known to be a powerful agent for stimulating immunogenesis, increased the migration of stem cells, and the processes of T and B lymphocyte spreading, as well as sharply enhanced the effect of interaction between T and B lymphocytes and partially replaced the helper function of T cells; all these actions finally enhanced immune response in the body. A decrease in the toxicity of copolymers was found to be in linear relationship with the percentage of the links of acrylic acid, whereas the adjuvant activity of the copolymers remained unchanged.


[Dynamics of T- and B-lymphocytes in the infectious process according to quantitative cytochemical findings]. Cytophotometric analysis with the use of autologous erythrocytes showed that T lymphocytes had the lowest RNA content and poorly differentiated lymphocytes had the highest RNA content, while in B cells an intermediate RNA level was observed, thus, the relative content of RNA could indicate to which particular system different peripheral blood cells belonged. In active infectious process, irrespective of the etiology of the disease, a decrease in both relative and absolute amounts of T lymphocytes and an increase in the amounts of poorly differentiated and B lymphocytes were observed.


[Effect of the color of visual stimuli on evoked human cortical potentials]. In subjects with normal colour vision and in those with its acquired defects, evoked potentials (EPs) were recorded in the primary and secondary areas of the visual cortex in response to monochromatic stimuli of equal energy and equal brightness. It is shown statistically that in case of stimuli of equal energy the EPs'characteristics were determined by the intensity and the colour of signals, whereas in case of equally bright stimuli the form, peak latencies and EP amplitude were actually dependent on the colour tone. These specificly colour changes in EPs were absent in colouranomals. The causes of a considerable individual variability of the connection between EP form and the colour are discussed. It is suggested that specific colour effects in the occipital EPs are caused by sensory opponent mechanisms of the visual system. It is shown that EPs may be used as an objective method for the estimation of colour discrimination in human subjects.


[Production of lymphotoxin by human lymphocytes. II. Stimulation by purified tuberculin]. A total of 43 lymphocyte culture (LC) from 12 adults (aged 32--48 years) and 21 children 6--7 years of age were studied. In PPD-stimulated adults LC stimulation ratio ranged from 8 to 39%; their cytotoxic activity, i.e. lymphotoxin (LT) production, was determined by staining target L cells with crystal violet and measuring protein synthesis in surviving target cells by radioactive amino acid incorporation. In children blastogenic response occurred in 11 out of 21 PPD-stimulated LC studied, but only 8 supernatant culture fluids were toxic to L cells and 3 were not. These findings were confirmed by repeated tests 3 weeks later. Probable correlation of BTL and LT production with the functional state of specific immunity to tuberculosis is discussed.


[Different effect of testosterone on polypotential stem hematopoietic stem cells and immunocompetent B-lymphocytes]. A research was made to study the dynamics of the proliferative, colony-forming and migration capacity of stem hemopoietic cells in (CBA X C57Bl) F1 hybrid mice under the influence of testosterone propionate, 10 mg/100 g, as well as the migration of immunocompetent B lymphocytes from the bone marrow to the spleen and the accumlation of their progeny, antibody-producing cells, in the spleen. The immunodepressive effect of testosterone was manifested by a decrease in the migration of B cells and the number of antibody-producing cells in the spleen. On the contrary, testosterone had a stimulating effect on the functional activity of stem hemopoietic cells, increasing their proliferation and migration. Under conditions of the suppressed erythropoietic differentiation of multipotent stem hemopoietic cells the injection of testosterone resulted in an increase in the number of antibody-producing cells in the spleen. This suggests that the stimulation of erythropoiesis and immunosuppression, induced by testosterone, are interconnected and determined by the direct action of the hormone on the cellular cycle of the stem cells, as well as by their prevailing differentiation towards the erythroid series, resulting in the decrease of their differentiation into B cells.


The mechanism of lysine-vasopressin hemostasis in bleeding esophageal varices. The effect of vasopressin on the blood flow through experimentally induced esophageal varices and on the musculature of the lower end of the esophagus has been studied. The blood flow was measured by 85Kr injection into the portal vein and selective recording of the radioactivity of the blood flow through the varices. Simultaneous portography and recording of the portal and arterial blood pressure were performed. Following i.v. administration of vasopressin, there was seen a decrease in portal pressure and transient increase in arterial blood pressure. Simultaneously there was observed a decrease in blood flow through the varices, which were no longer visible at portography, while intra-esophageal pressure was increased. It is concluded that there is a dual mechanism of the effect of vasopressin on bleeding from esophageal varices. It reduces the portal pressure and it contracts the esophageal musculature with resultant compression of the afferent radicles to the submucosal esophageal varices.


Vestibular recruitment and decruitment.

Vestibular recruitment and decruitment. Serial Thermal Vestibulometry with the application of increasing caloric stimuli (corresponding to decreasing temperature of water at successive irrigration of the ears) was performed on normal subjects and patients with lesions in the central nervous system involving the statoacoustic subsystem. The normal values and 'slope' values (i.e.increase in degrees of velocity of slow component of nystagmus in response to each 4 degrees C change in water temperature) were computed to yield values of the normal vestibulogram. The values obtained in patients were compared with those of the Normograms and the following diagnostic patterns observed: (a) Hypograms, (b) Hypergrams, (c) Central Vestibular Decruitment. Central Vestibular Recruitment has been explained on the basis of the locus of the lesion leading to involvement of the nystagmogenic area in the lower part of the reticular formation, suprasegmental neurones in the vicinity of the vestibular nuclear complex, and partial destruction of the complex itself, each being responsible alone or in combination. Hypergrams presumably result from suprasegmental lesions, e.g. in cerebrum and stem components. Central decrittment follows neural lesions in the vestibular subsystem. Hypograms are found in vestibular nuclear pathology. Furthermore, it helps in charting a plan for therapy, viz. head and balance exercise, in particular, in the sense that his exercise is not helpful in cases with central decruitment but is in peripheral one. An explanation for this has been put forward.


The maturation of vestibular nystagmus in infancy and childhood. The displacements, durations, and velocities of the slow and fast components of both the primary and secondary nystagmus induced by constant angular acceleration were measured in 46 normal children 1 month to 11 years old. There were significant changes in nystagmus parameters in respect to maturation. The young infant had larger amplitude, higher velocity beats than the older child during both the primary and the secondary nystagmus. Parameters describing both the primary and the secondary nystagmus reached their peak values and terminated earlier in the infant than in the older child. Although the slow component velocity during secondary nystagmus was much slower than during the primary nystagmus at all ages, the secondary nystagmus/primary nystagmus ratio was significantly greater in early infancy. Thus, in infancy, as compared with later childhood, the vigor of the secondary nystagmus was disproportionately greater than the primary nystagmus. These results were discussed in relation to the maturation both of vestibular responsiveness and of vestibular adaptation.


Plasticity of the vestibulo-ocular reflex. The plasticity of the vestibulo-ocular reflex (VOR) was investigated by examining three different processes, namely vestibular habituation to repeated head angular velocity steps, vestibular compensation after hemilabyrinthectomy, and vestibular compensation in patients suffering from unilateral Ménière's disease. The first two processes were examined in the cat, while the third process was studied in man. A quantification of these processes was obtained by computing some parameters characterizing the diagrams of the slow cumulative eye position (SCEP) and the slow phase eye velocity (SPEV) or by using the nystagmic responses to identify the main parameters of VOR. Finally, an attempt was made to interpretate the plasticity of VOR in terms of a multilevel hierarchical organization of the system controlling vestibularly induced eye movements.


Adult T cell leukemia. Histological classification and characteristics. Adult T cell leukemia was classified into two distinct types, monomorphic and pleomorphic, according to their histological and cytological features. The former type is composed of uniform neoplastic cells with round or slightly indented nuclei without any marked deformation. The latter type, on the other hand, occupies a unique position in lymphocytic leukemias with the following characteristics: a) onset in adulthood, b) an acute and subacute course, c) well-differentiated T cell origin of the neoplastic cells, d) pleomorphism of the neoplastic cells with markedly deformed nuclei, e) diffuse proliferation of the neoplastic cells without nodular pattern, f) histologically heterogeneous features of lymph nodes frequently admixing a cluster of normal lymphocytes, proliferation of macrophages and dendritic cells, and well-developed high endothelium venules, g) high incidence of skin lesions due to the infiltration of neoplastic cells, and h) exclusively limited localization of patients' birth places.


Mitogenic stimulation of human lymphocyte subpopulations by Lathyrus odoratus lectin. Investigation was made of the mitogenic activation by Lathyrus odoratus (LATH) lectin and phytohaemagglutinin (PHA) of human T-enriched and non-T lympohcytes isolated by nylon wool filtration and sheep erythrocyte rosette depletion, respectively. LATH stimulated only weakly the T-enriched and non-T fractions as compared to PHA which strongly stimulated the T-enriched population and weakly stimulated the non-T cells. Removal of phagocytic cells from the unfractionated lymphocytes caused only a slight reduction in the response to LATH. The responses of mixtures of T-enriched and non-T lymphocytes were similar to that of unfractionated lymphocytes. The LATH lectin seems, therefore, to be neither a pure T nor a pure non-T cell mitogen, since both populations must be present for optimal response. When alpha-methyl-D-mannoside was added to unfractionated lymphocytes together with LATH, there was a strong inhibition of thymidine incorporation. D-glucose and N-acetyl-D-glucosamine diminished the stimulation effect to a lesser degree.


Do bursa-derived T cells exist?

Do bursa-derived T cells exist? In order to study the bursal origin of T cells, 18-d chromosomally-marked bursa cells were transplanted into 18-d chick embryos treated with cyclophosphamide (CY). Transfer of bursa cells restored not only the humoral immune functions but also the mitogenic responses of peripheral blood lymphocytes against phytohaemagglutinin and concanavalin A (Con A). Transplanted bursa cells proliferated primarily in the recipients' bursa. Only 8 out of 209 Con A responsive spleen cells were of donor origin, but no donor-derived cells were observed in the thymus. These findings suggest that cells in the 18-d embryonic bursa are already committed to the B cell lineage, and are not capable of migrating into thymus and of developing into mature T cells.


The 24Na-transport increasing effect of veratrine in frog sartorius muscle influenced by the tonicity, composition and temperature of the external environment. The influence of tonicity, ionic composition and temperature of the incubating medium on the increasing effect of veratrine on 24Na transport in the frog sartorius muscle has been studied. (1) The effect of veratrine applied during 24Na loading on the rate coefficient for sodium loss depended on the tonicity of the medium. The rate of loss of 24Na from muscles loaded in the presence of veratrine was not affected if the muscles had been equilibrated in hypertonic medium. However, when treating the muscles with veratrine in isotonic medium during 24Na loading, we obtained a twofold increase in the rate coefficient for sodium loss. (2) The effect of veratrine applied during the desaturation period on 24Na efflux was also found to depend on the tonicity of the medium. Veratrine applied during the desaturation period increased the 24Na efflux in muscles equilibrated in isotonic Ringer's solution. However, when the muscles were equilibrated in hypertonic medium, veratrine did not influence 24Na efflux, not even after the rate of 24Na loss had been decreased by ouabain. (3) Hypertonic medium inhibited the Li uptake-enhancing effect of veratrine, while in isotonic medium veratrine had a marked enhancing effect. (4) In hypertonic medium lithium inhibited the otherwise characteristic increasing effect of veratrine on 24 Na uptake. (5) The increase of intracellular sodium concentration as a result of incubation in cold, potassium-free Ringer's solution did not influence the 24Na exchange-increasing effect of veratrine in isotonic medium. (6) The increasing effects of 0.1 and 0.5 mM veratrine on 24Na influx had the same degree at room temperature. However, at 5 degrees C 0.5 mM veratrine increased 24Na influx to a greater extent than 0.1 mM. (7) On the basis of our earlier experiments it has been suggested that the site of action of the 24Na uptake-increasing effect of veratrine could be the neural structures in the muscle equilibrated in hypertonic media. The present experiments confirm this suggestion and at the same time demonstrate that there are substantial differences in the mechanism of the sodium transport of veratrine-treated neural and muscle membranes, which become more apparent in hypertonic medium.


Acquired hydrocephalus. IV. Determination of the absorption rate of albumin from the cerebrospinal fluid. By quantitative isotope ventriculography (QIV), the absorption rate (lambda 2) of albumin in the cerebrospinal fluid (CSF) was determined. Regard was paid to the rate constants for the exchange of the albumin molecule between the serum and extravascular phase. The rate constant lambda 2 and mean biological transit time Tmb-2 were determined in 22 patients suspected of acquired hydrocephalus. QIV revealed that 8 patients were hydrocephalic, while 13 were non-hydrocephalic, and the findings were uncertain in one. In the patients with acquired hydrocephalus, it was demonstrated that lambda 2 and Tmb-2 were significantly reduced as compared with the non-hydrocephalic patients. By means of QIV, a curve was calculated and plotted for the biological decay from the head--the retention curve. From the initial slope of this curve (0--24 hours), the rate constant lambda 2 was calculated. A comparison of lambda 4 and lambd 2 revealed a highly significant correlation, which means that the retention curve gives an acceptable measure of the absorption rate of CSF-albumin.


Effect of coronary arterial bypass surgery on exercise-induced ventricular arrhythmias. Long-term follow-up of a prospective randomized study. The effect of coronary arterial bypass surgery on exercise-induced ventricular arrhythmias and their relation to sudden death was examined in 102 patients with stable angina pectoris randomly assigned to medical and surgical therapy (54 and 48 patients, respectively). Symptom-limited treadmill tests were performed at entry and at 1 and 5 years. The surgical group demonstrated significant improvement in exercise performance at 1 year compared with the medical group, and at 5 years exercise-induced ischemia as evidenced by S-T depression and exertional angina remained substantially decreased in the surgical group with little change in the medical group. However, the frequency and severity of exercise-induced ventricular arrhythmias in each group remained unchanged at 1 and 5 years from those at entry. Similar results were obtained from an evaluation of ventricular arrhythmias in the electrocardiogram at rest. With the exception of exercise-induced ventricular tachycardia and fibrillation, no relation was found between ventricular arrhythmias and sudden death. Coronary bypass grafting does not decrease the frequency or severity of exercise-induced or resting ventricular arrhythmias. In patients with stable angina pectoris, with the exception of ventricular tachycardia and fibrillation, exercise-induced ventricular arrhythmias are poor predictors of sudden death. The data suggest that exercise-induced ventricular arrhythmias may not be related to ischemia but to other effects of exercise such as cardiac stimulation by catecholamines or other factors.


Surgery for life-threatening ventricular tachyarrhythmias. Among 203 left ventricular aneurysmectomies performed since 1970, the operative mortality rate was 18.7 percent. In 49 patients (24 percent), left ventricular aneurysmectomy was performed for refractory life-threatening ventricular arrhythmias. Eight additional patients had coronary bypass grafting without ventricular aneurysmectomy. One of these patients had bypass grafting followed later by ventricular aneurysmectomy. All 56 patients had underlying coronary artery disease. The operative mortality rate was 19.6 percent. In patients with a recent myocardial infarction, the rate was 60 percent, whereas it was 11 percent in patients with a remote myocardial infarction. Other high risk variables in these patients included coronary bypass grafting without myocardial resection, and an elevated left ventricular end-diastolic pressure. The late mortality rate was 17.9 percent, but only one of these deaths was sudden and unexpected. The 35 long-term survivors have been followed up for a mean of 40.7 months (range 7 to 92 months). Of these, 20 remain on antiarrhythmic medications for palpitation or documented ventricular premature complexes, whereas 15 are free of detectable rhythm disturbances and do not require antiarrhythmic agents. Only 4 of 35 (11 percent) have had recurrent documented ventricular tachycardia. Left ventricular aneurysmectomy may be performed for refractory ventricular tachyarrhythmias with an acceptable operative mortality, particularly if the patient has survived longer than 6 weeks after myocardial infarction. Although epicardial mapping techniques may be useful in localizing the reentrant pathway of the ventricular tachycardia, ventricular aneurysmectomy without mapping techniques produces a satisfactory clinical result in the vast majority of long-term survivors.


Acquired von Willebrand disease associated with an inhibitor to factor VIII antigen and gastrointestinal telangiectasia. A patient with acquired von Willebrand disease and gastrointestinal telangiectasia is described. He presented with the recent onset of spontaneous hemorrhage and demonstrated a prolonged bleeding time, reduced factor VIII coagulant (FVIII:C), and undetectable factor VIII-related antigen (FVIIIR:AG) and ristocetin cofactor (FVIIIR:WF). Following transfusion of cryoprecipitate, there was a smaller than expected immediate increase in FVIII:C, FVIIIR:WF and FVIIIR:AG, with a rapid return to baseline levels and no secondary increase in FVIII:C. An inhibitor could be demonstrated in the patient's plasma which markedly decreased the level of FVIIIR:AG in normal plasma whereas it only weakly decreased the activity of FVIIIR:WF and FVIII:C. The inhibitor was contained in the immunoglobulin G(IgG) fraction of plasma and lacked precipitating properties. This inhibitor demonstrates a specificity not previously seen in spontaneous antifactor VIII antibodies. Our report also demonstrates that ristocetin-induced agglutination of platelets is not always the most sensitive method for detecting an inhibitor in acquired von Willebrand disease.


alpha-Naphthyl acetate esterase activity--a cytochemical marker for T lymphocytees. Correlation with immunologic studies of normal tissues, lymphocytic leukemias, non-Hodgkin's lymphomas, Hodgkin's disease, and other lymphoproliferative disorders. Cytochemical identification of T lymphocytes on the basis of alpha-naphthyl acetate esterase (NAE) activity was compared with immunologic markers for cell suspensions and/or cryostat sections of 113 specimens. Nonneoplastic tissues (peripheral blood, lymph nodes, spleens, tonsils, thymus, and pleural fluid) and specimens from various lymphoproliferative disorders, including acute and chronic lymphocytic leukemia, lymphosarcoma cell leukemia, hairy cell leukemia, non-Hodgkin's lymphomas of B-and T-cell types, and Hodgkin's disease, were evaluated. T (E-rosetting) cells demonstrated several patterns of NAE reactivity: 1) a strong globular reaction product, the most specific pattern for T-cell identification, 2) granular cytoplasmic staining, or 3) no reactivity. B lymphocytes revealed a granular pattern of NAE staining, were devoid of enzyme, or, in rare instances, exhibited strong NAE activity. Percentages of lymphoid cells with strong (globular) NAE activity closely paralleled T-cell (E-rosette) values in the majority of cases, with the best correlations observed for peripheral blood studies. However, discordant results were noted for some neoplastic and nonneoplastic tissues, including cases of T-cell lymphoma or leukemia. Markedly discrepant results were noted for thymic lymphocytes, most of which revealed E-rosette formation and weak or absent NAE activity. Lymph nodes involved by Hodgkin's disease demonstrated a heterogeneous pattern of staining in E-rosetting cells and in Reed-Sternberg variants. Cryostat section studies of reactive lymph nodes and nodular lymphomas demonstrated strong NAE staining in lymphoid cells of T-cell (interfollicular, internodular) areas, with little or no positivity in follicles or nodules (B-cell areas). NAE staining patterns further suggested that T cells comprise part of the follicular cuff and possibly represent a minor population of some neoplastic nodules. Although NAE determinations do not represent a consistently reliable alternative to immunologic methods for T-cell identification, this easily applicable cytochemical marker is complementary to other techniques in assessing neoplastic or nonneoplastic tissues, particularly cryostat sections. (Am J Pathol 97:17--42, 1979).


The epidemiology of forcible rape.

The epidemiology of forcible rape. Problems of measurement of the incidence of rape are considered, and empirical findings are summarized regarding prevalence, demographic and psychiatric characteristics of offenders, spatial and temporal distribution of offenses, victim-offender relationships, and evidence about recidivism and progression of crimes. Findings are discussed in the framework of blame models and their implications for treatment and prevention.


Nature of load dependence of relaxation in cardiac muscle. Relaxation of spontaneously contracting single rat cardiac cells with an effective sarcoplasmic reticulum was shown to be sensitive to load, as previously described for intact mammalian ventricular cardiac muscle. Caffeine and tetanic stimulation could modify load-dependent relaxation in intact papillary muscle from cat or rat into a load-insensitive relaxation. Although such load dependence was demonstrated to be normally absent in frog ventricular cardiac muscle, in the present study it could also be made moderately manifest under specific conditions, e.g., high calcium, low sodium, or ouabain. The appearance of load dependence during relaxation in cardiac muscle thus emphasizes the presence of an effective sarcoplasmic reticulum.


Glyconeogenesis from lactate in frog striated muscle. The rates of 14carbon incorporation into CO2 and glycogen from [U-14C]-lactate and [1-14C]acetate in frog sartorius muscles were compared. The rates of incorporation into CO2 were similar, while the rate of incorporation of lactate into glycogen was more than 200-fold larger than that of acetate incorporation. It is concluded that the pathway of lactate incorporation into glycogen does not involve Krebs cycle intermediates and is extramitochondrial. To test the possibility that the pathway of lactate incorporation involves net reversal of a pyruvate kinase, the changes in phosphoenolpyruvate and pyruvate concentrations during stimulation of lactate incorporation into glycogen were measured. There wer none. The mass action ratio of pyruvate kinase was calculated. This value was two orders of magnitude from the equilibrium constant and it was concluded that reversal of pyruvate kinase was a very unlikely pathway. To test the possibility that a pathway involving the oxaloacetate-to-phosphoenolpyruvate step was involved the muscles were treated with 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase. The treatment resulted in decreased incorporation of lactate into glycogen.


Lower gastrointestinal bleeding with negative or inconclusive radiographic studies: the role of colonoscopy. The records of more than 1,000 patients who underwent colonoscopy were reviewed. The study group consisted of 55 of these 1,000 patients who had persistent unexplained bleeding per rectum and negative radiographic examinations. Colonoscopy was helpful in defining the site of bleeding in approximately 50 per cent of the patients studied.


Variability of glaucomatous visual field defects in computerized perimetry. Normal subjects are able to maintain a stable level of performance throughout a test session of 30 min, using 0.5 s exposure time. Test points placed in normal areas of glaucoma cases behave similarly, whereas test points in relative scotomatous parts of the field show not only a lower sensitivity level but also a tendency to a decline of the performance level and/or a higher threshold variation. Change of exposure time showed remarkable effects on the performance level at defect points, an increase to 1 s causing a stabilization on an improved level and a decrease to 0.25 s giving a deterioration. The results are discussed in terms of noise admixture to the signal. According to this model an increased noise amplitude by impaired retinal function reduces the performance level and augments the variation. On the other hand, an increased exposure time of the test object, which causes a stabilization of the process on an improved performance level, may be interpreted as a reduction of the noise amplitude.


[Influence of glycosaminoglycan synthesis of cultured cornea stroma cells by variation of culture condition]. Cultured cells derived from bovine corneal stroma synthesize all types of sulfated glycosaminoglycans and distribute these macromolecules into topographically different compartments in a reproducible manner. Each compartment is characterized by a typical glycosaminoglycan distribution pattern. Corneal fibroblasts synthesize in vitro only small amounts of keratan sulfate in contrast to the in vivo conditions. We have, therefore, investigated the synthesis and topographical distribution of sulfated glycosaminoglycans as influenced by different culture conditions. The following results were obtained: 1) Cocultivation of epithelial and stromal fibroblasts from bovine cornea led to an increased incorporation of radiosulfate into sulfated glycosaminoglycans by about 50% as compared to the theoretical value. Glycosaminoglycan distribution of mixed cultures into different compartments showed no similarity compared with pure epithelial or stromal fibroblasts. 2) Addition of native or heat inactivated anterior chamber fluid to the culture medium was followed by a twofold increase of [35S]-sulfate incorporation and by an augmented intracellular and pericellular accumulation of labeled macromolecules. 3) Reduction of the incubation temperature led to a reduced synthesis of glycosaminoglycans without influencing their topographical distribution. Growth of stromal cells on type I collagen was accompanied by a reduced glycosaminoglycan synthesis of about 25%. Extracellular macromolecules reached only half of the normal value, while intracellularly their concentration was slightly increased. 4) None of the variations of the culture condition led to a significant change of the distribution pattern of sulfated glycosaminoglycans. Especially, no significant increase of keratan sulfate biosynthesis could be detected.


[Reparative processes of the iris after irradiation with the argon-ion laser (author's transl)]. The reparative processes of the pigmented iris of the rabbit were analysed with ultrastructural methods. 1. Clearing of the damaged area by macrophages is the first step in the reparative processes. Clump cells are macrophages which are observed from the first day of the injury until the ninth week. 2. Repair of the anterior surface of the iris is largely finished after 32 days. 3. The repair of collagenous fibres reaches its maximum activity 32 days after irradiation. 4. The pigment epithelium has only an insignificant regeneration potential. 5. Irradiation of the iris by the argon-ion laser results in an atrophic, hyperpigmented scar. The rapid regeneration of a lesion induced by the argon-ion laser in the rabbit iris casts doubt as to whether this method could be applied to the human eye with equal success.


[Information conveyed by electroretinography (author's transl)]. Clinical evaluation of the function of the human retina by subjective, psychophysical tests can be complemented by objective, electrophysiological methods such as electroretinography. The electroretinogram (ERG) is a transient action potential generated by the vertebrate retina in response to light. Using standardized stimulation, after assessing the normal range of the ERG the investigator can establish early diagnosis, improve prognostic statements and document the course of retinal diseases. A method to selectively stimulate the rod- and cone-system, developed by Gouras and co-workers, has proved to allow further differentiation of heredodegenerative diseases of the retina. The ERG monitors objectively the function of the retina in infants uncapable of cooperating in psychophysical tests and in patients suffering from opacities of the optic media. ERG results should be evaluated synoptically with psychophysical data, ophthalmoscopy, fluoresceinangiography and possibly with EOG and VER recordings. Under experimental conditions the ERG serves to monitor the sensitivity of the retina in vivo as well as in vitro in physiological, pharmacological and toxicological studies.


Changes in the electroretinogram and visual evoked potentials during general anaesthesia. Ten patients (one male and nine females), aged 33.2+/-12.0 years, were given electrophysiological studies before and during general anaesthesia. A mixture of thiopentone sodium, halothane, and nitrous oxide was used for anaesthesia. Electroretinogram (ERG) and visual evoked potentials (VEP) were recorded with scalp electrodes, and an averaging technique was used to improve signal-noise ratio. The recordings were made under standard conditions 15 to 20 min after induction of the anaesthesia. The amplitudes of the a- and b-waves of the ERG were significantly diminished whereas their latencies remained unchanged. The peak-to-peak amplitudes of the early components N1 and P2 of the VEP were significantly lowered, and the latencies of N0, P1, and N1 were prolonged by anaesthesia. These modifications are suggested to reflect metabolic changes in the sensitive layers of the retina and in the optic tract.


[A check method for controlling the radiophosphorus-counting system (author's transl)]. Handle probe and counting system for radiophosphorus test can be checked by the use of a 64 nCi Strontium-90 radiator established inside a plexiglas cylinder. Counting system adjustment to 40 dB amplifier and 0.70 discriminator resulted in 1710cpm+/-2% standard deviation. This check method is suitable for controlling the counting system before tumor measurement. Advantages of this test method are low expenses, stability of the radionuclide, and riskless use of beta-radiator.


[Morphology of the primary damage caused by the argon-ion laser to the iris of the pigmented rabbit (author's transl)]. The effects of the argon-ion laser upon the iris of the pigmented rabbit were analysed by ultrastructural methods. 1. Apart from the physical parameters of the energy source, the damage strongly depends on the concentration, location, and distribution of the iris pigment. 2. The irradiation of the iris results in the formation of a crater. Depending on the distance of the epicentre of the impact, various degrees of ultrastructural damage are observed. a. The region immediately adjacent to the crater lumen at a revealing distance of 25 microns consists of homogenous collagenous masses, revealing a vacuolar structure. As the only residuals of destroyed cells, melanin granules are observed within the homogenous masses. b. Destruction of the collagen fibrils and their disintegration into subfibrils with elimination of all cell compartments is found in an area ranging from 25 microns to 300 microns from the wall of the crater. c. Damage to the chromatin structure is visible up to a distance of 300 microns to 375 microns from the wall of the crater. 3. Characterised by an invasion of macrophages into the damaged area, the cleaning phase starts 24 h after irradiation. 4. The results of this experiment indicate that because of the great energy dose required for man with the inherent widespread tissue damage and low probability of a lasting iridectomy, the cw argon-ion laser appears to be an unsuitable energy source for clinical iridectomy.


Pigmentation of the cornea: review and case history. The patient described in this paper exhibits a previously undocumented condition, "annular pigmentation of the cornea." The irregularly circular distribution of pigment is associated with anterior membrane dystrophic changes of the microcystic type and endothelial guttata. Systemic investigation revealed a severe iron deficiency anemia which was treated with total dose infusion of iron. In the absence of a histologic specimen, a speculative etiology is suggested based on systematic exclusion of various causes of corneal pigmentation. A simplified classification of pigmentary changes of the cornea is offered and on this basis a focal dystrophic process is suggested as the cause of this case of annular pigmentation of the cornea.


An appraisal of maximal faradic stimulation of pelvic muscles in the management of female urinary incontinence. Measurement of the urethral pressure profile enables a group of women to be defined whose urinary incontinence is due to sphincter weakness. In such cases a significant degree of improvement, both symptomatic and in the profile amplitude, follows treatment by maximal faradic stimulation of the pelvic muscle and perineal muscle exercises.


[Chronology of the replication of sex chromosome bands in lymphocytes of normal subjects and patients]. The replication sequence of the bands carried by chromosomes X and Y has been studied in normal individuals and in patients with structural abnormalities of the X. By comparing the segment with that of the autosomal bands (which had been previously studied), it was shown that the normal early X replicates in early X-phase for its R-bands and in late S-phase for its Q bands. The late X replicates entirely in late S-phase, and the sequence of band replication is not as stringent as for the early X and the autosomes. The study of fourteen cases of anomalies of chromosome X in females showed the following: in balanced reciprocal X-autosome translocations the rearranged X most often replicates early and the normal X late. Both show a normal replication sequence of their bands. In non-balanced X-autosome translocations, inactivation of the autosome fragment attached to the AUTOSOME FRAGMENT ATTACHED TO THE X may take place. In Xq- or in ter rea (X;X) (pter;pter), band p22 has a delayed replication. In iso-Xor Xp-, the long-arm-band sequence of replication shows a variation comparable to that of the late X in fibroblasts. These replication modifications are likely to induce partial inactivations or changes in activity which correspond to the so-called position effect in Drosophila.


Inheritance of extra triradii of palmar interdigital areas II and IV. Data obtained from 423 individuals were analyzed for mode of inheritance of extra triradii on palmar interdigital area II and IV separately, and in combination. It indicates that a single dominant allele A for extra triradius in the area II, and an allele D in the area IV, may be responsible for the presence of the patterns in the respective area, with 75 to 80 per cent penetrance. There are numbers of individuals in which extra triradii are present in both interdigital areas II and IV. The mode of inheritance has been estimated from the data obtained and was found to have co-dominant alleles A and D for the presence in their respective areas. Further analysis revealed the existence of three alleles. A and D for presence, and 0 for absence. The alleles A and D are co-dominant, if combined in the genotype AD, but either allele is dominant in heterozygous combination with 0.


46,XX/46,XX,r (2)(p25q37) mosaicism: clinical and cytogenetic studies. A severely mentally retarded and physically handicapped girl is described who has 46,XX/46,XX,r(2)(p25q37) mosaicism. This is the first ring 2 chromosome to be described in Man. Studies of the behaviour of the ring showed that it was stable in diploid cells which had increased in frequency over a period of seven years, but unstable in tetraploid cells which were at a much higher frequency than in normal individuals. It is concluded that in some cases the phenotypic consequences of ring chromosome formation may be due more to their disturbing the regulation of cell division than to the loss of genetic material. Current models of ring chromosome behaviour do not account for the induction of tetraploidy.


Trisomy 3 (p23-pter) resulting from maternal translocation, t (3 ; 4)(p23 ; q35). We describe a patient with partial trisomy 3p resulting from maternal translocation, t(3:4)(p23;q35). The male newborn who died at the age of 22 hours presented with distinct facial features including a square-shaped face with prominent forehead and depressed temporal regions, prominent cheeks, short broad nose, left cleft lip and cleft palate, malformed ears, and a receding mandible. Further findings were flexion deformities of the fingers with finger-like thumbs and mild cutaneous syndactyly 2/3 and 4/5, hypoplastic penis and scrotum with no palpable testes. He probably had a congenital heart defect and situs inversus abdominalis. Many of these features have been reported in other patients with distal trisomy 3p.


Double aneuploidy: partial trisomy 21 and XO/XXX in a family with 12/21 translocation. A female patient with mild mental retardation with spatial perceptual difficulties, microcephaly, depressed nasal root, receding chin, webbed neck, low hairline, shield chest, cubitus valgus, scoliosis and dermatoglyphic findings not characteristic of Down's syndrome is reported. In addition to X/XXX, she had a partial trisomy 21 of the short arm-centromere-proximal long arm segment due to maternal t(12;21) translocation. Two phenotypically normal siblings carried the balanced translocation.


[Partial trisomy for the distal part of the short arm of chromosome 11 due to paternal translocations 11/5]. A girl with partial trisomy for the short arm of chromosome 11 resulting from an unbalanced translocation 46,XX,der 5, t(5,11) (p 15,p14) pat is described. The clinical findings are compared with those of other patients with partial trisomy 11p. The translocation in the balanced form was present in the fater, the brother, and the grandmother of the proposita.


[Del (13) (q33). Exclusion of esterase D (ESD) from 13q33 and q34]. A de novo del (13) (q33) was found in a 14-month-old boy with hypospadias. Phenotype anomalies included growth retardation, psychomotor retardation (QD = 64), microcephaly with brachycephaly, a round, flat and asymmetrical facies, a normal nose bridge, a small, pointed chin. The patient is heterozygous ESD 2-1. The gene localization may thus be excluded from bands 13q33 and q34 and assigned to bands q31 or q32, if its previous assignment to the q3 region is confirmed.


The 5q- and additional chromosome anomalies in two patients with acute myeloid leukemia. Two elderly women had acute myelogenous leukemia with rapidly fatal course. On initial marrow and unsttimulated blood examination, the 5q- chromosome and additional number and structural chromosome analomalies were observed. The specificity of these findings is discussed.


[Is the sodium ionic channel a cyclic hexapeptide? (author's transl)]. A cyclic hexapeptide affords a model of an ionic channel, permeable to Na+ but not to K+. The selective fixation of tetrodotoxin and saxitoxin could occur through six hydrogen bonds, one with each of carbonyles of the crown exposed at the outside of the membrane.


[Partial monosomy due to long-arm deletion of chromosome 11 : del (11) (q23) (author's transl)]. A girl, who died at 25 days of age, was found to have a partial monosomy due to a 11q23 leads to 11qter deletion. The main clinical findings were trigonocephay, facial dysmorphia, and congenital heart disease. A review of developmental and dysmorphic features of the seventeen recognized cases is presented.


[Comparison of the transmission of three trisomies by males and females in the newt Pleurodeles waltlii (author's transl)]. In the newt Pleurodelles waltlii, males and females trisomic for chromosomes 8, 10 and 11 are fertile. Crosses between such trisomics and diploids were carried out. Progeny analysis showed that an extra chromosome is transmitted to half of the gametes of both males and females trisomics. The extra chromosome apparently causes interference in the regular mechanics of meiotic division, so that trisomics throw nonparental aneuploids and polyploids in their progenies. Moreover, some descendants develop chromosome anomalies during embryonic life ; thus, the progeny of trisomics include diploids, parentaltype trisomics, and embryos with new chromosome anomalies. Morphology and chromosome anomalies of the embryos are compared. A possible explanation for the secondarily acquired anomalies are discussed.


[Therapeutic possibilities in occular complications of chromosomal aberrations (author's tansl)]. The principal occular complications of chromosomal aberrations are : strabismus, cataract, ptosis, nystagmus. Each of these can benefit from surgical treatment but one has to take into account the unfavorable prognosis due to mental deficiency.


Cellular immune response to measles, mumps, and vaccinia viruses in multiple sclerosis. The cell-mediated immune response to measles, mumps, and vaccinia viruses was studied in MS patients, normal controls, and neurological disease controls using a lymphocyte proliferation assay. A small but significant difference was found in the response to measles between the MS and normal control groups but not between the MS and neurological disease control groups. In each of the groups, the response of both peripheral blood leukocytes and purified T-cells to measles was significantly less than the response to mumps or vaccinia. The lower response to measles was not due to the presence of blocking factors or to lack of antigenicity of the measles virus preparation used in the assay. These findings suggest that differences exist in the normal immune response between these viruses. Precise quantitation of the immunological response to viruses in MS and other disease states will depend on identification of the various functionally reactive cell populations.


Presence of lymphocyte membrane surface markers on "small cells" in a pineal germinoma. A 16-year-old boy was operated on via an occipital transtentorial craniotomy for a pineal tumor. Routine histological examination of the tissue revealed it to be a germinoma, as characterized by the presence of two cell populations: large cells and small, lymphoid-appearing cells. The cells were evaluated in a single-cell suspension for the presence of lymphocyte membrane surface markers; small cells exclusively were found to have such markers. A T-lymphocyte membrane marker was present in 51% of the small cells, whereas 15 to 18% of the small cells had a B-lymphocyte membrane marker.


Rheumatic disease in Jamaica.

Rheumatic disease in Jamaica. The relative prevalence and clinical pattern of the major rheumatic diseases in the patient population of a teaching hospital in Jamaica were studied over the 3-year period 1974--7. The prevalence of systemic lupus erythematosus approached that of rheumatoid arthritis (RA). All grades of severity of RA were seen, and there was an unusually high proportion of females with RA. Rheumatic fever and exacerbations were relatively common, and in the absence of carditis differentiation from infective polyarthritis, especially gonococcal, was occasionally difficult.


Palindromic rheumatism. II. Failure to detect circulating immune complexes during acute episodes. Thirty-eight samples of blood and 2 of synovial fluid were obtained from 19 patients suffering from palindromic rheumatism. In 12 cases samples were obtained from the same patient both during and between acute attacks. The presence of immune complexes was sought by a C1q-binding test. Most patients gave negative results: moderately elevated levels were obtained in a few. Broadly the pattern of results showed that individual patients were either positive or negative irrespective of whether they were in an attack or in remission. C3 and C4 measurements showed no significant abnormalities, confirming previous studies. Patients with elevated C1q-binding tests tended to be seropositive. We speculate that these are patients more likely to develop rheumatoid arthritis.


Immunoglobulin classes in skin basement membrane in systemic lupus erythematosus: clinical significance and comparison with classes of serum anti-DNA antibodies. Biopsies of apparently normal skin were obtained from 30 unselected patients with systemic lupus erythematosus. The immunoglobulin class distribution of the immune deposits at the dermal-epidermal junction was determined in order to assess associated disease patterns and to investigate the possibility that the immunoglobulin classes in the skin were an indication of the classes of serum anti-native DNA antibodies. Biopsy specimens containing IgG deposits were obtained from 10 patients with more active disease and a greater incidence of glomerulonephritis than those patients with only IgM deposits or negative biopsies. However, in this unselected group of patients the immunoglobulin class of the immune deposits did not necessarily indicate the class of serum anti-native DNA antibodies. Therefore biopsy of clinically uninvolved skin will not always identify SLE patients with an immunological restriction to IgM antibody production.


Epidemiology of dermal leishmaniasis in the Rio Doce Valley, State of Minas Gerais, Brazil. Dermal leishmaniasis is prevalent in the predominantly settled agricultural areas in the Rio Doce Valley in the eastern part of the State of Minas Gerais, Brazil. The disease has been recorded almost equally in both sexes. Cases have been confirmed in all age groups but youths aged ten to 14 years form the population segment at greatest risk to infection. Cases of single cutaneous lesions, multiple cutaneous lesions and muco-cutaneous lesions have been recorded in the area. Isolates of parasites include representatives of the Leishmania mexicana and L. braziliensis complexes and at least one parasite that does not fit into either category. Infections have not been detected in small mammals (mainly rodents) but about 3% of dogs are infected. The phlebotomine fauna includes no species (or close relatives of species) previously incriminated as vectors of mexicana and braziliensis infections in Brazil. In the complex and confusing epidemiological situation in the Rio Doce Valley it seems unwise to apply traditional specific names to Leishmania of the area.


Abnormal haemoglobins in the Sudan savanna of Nigeria. I. Prevalence of haemoglobins and relationships between sickle cell trait, malaria and survival. The prevalence of different haemoglobins and their interaction with malaria have been studied in Garki, Kano State, Nigeria. Sickle cell trait was present in 24% of newborn and 29% of those aged over five years. Hb.AC was present in 0.7%. Frequency of both haemoglobin variants was greater in Hausa than Fulani. Sickle cell anaemia was almost invariably fatal in early childhood. The distribution curve of percentage of Hb.S in sickle cell trait subjects was normal, and did not demonstrate any high frequency of a gene for alpha-thalassaemia. The presence of beta-thalassaemia minor could not be tested, but Hb.S/beta-thalassaemia was not detected. Hb.S gene frequency appears to have been maintained by a fitness in heterozygotes of 21% over normal homozygotes; increased fertility and high mutation rate did not make any apparent contribution. Hb.AS subjects had on average lower frequency and considerably lower densities of Plasmodium falciparum trophozoites than Hb.AA from the age of 30 to 59 weeks; density was less in sickle cell trait up to age three years in the dry season only. It is suggested that the survival advantage and hence the prevalence of sickle cell trait may be greatest in some hyperendemic areas and less where malaria transmission is extremely high or when it is high and unvaried.


Abnormal haemoglobins in the Sudan savanna of Nigeria. III. Malaria, immunoglobulins and antimalarial antibodies in sickle cell disease. Subjects with sickle cell disease were identified in (i) a whole population sample (2742) Garki District, Kano State, Nigeria, and in (ii) the 534 infants born into the population during five years. Eleven (2.1%) newborn had Hb.SS, as was expected from gene frequency (0.146). Prevalence was maintained in the first year of life, but fell to 0.4% at one to four years and to 0.05% (one person) over the age of nine years. Antimalarial intervention for two transmission seasons was followed by an apparent but not significant decrease in Hb.SS mortality. There was one male aged about 40 years who had Hb.SC (the expected number was three). Hb.SS children were compared to normal subjects at the same age, the same village and the same survey; they had significantly less than the expected Plasmodium malariae infection (P less than 0.01) and lower than median P. falciparum densities while below five years (P less than 0.05). Over one year of age, they tended to have below average indirect fluorescent antibody (IFA) (P less than 0.01), indirect haemagglutinating antibody (IHA) (P less than 0.01) titres and number of precipitin rings (not significant) against P. falciparum antigen, and IFA against P malariae (P less than 0.01). They had above average IgM (P less than 0.05), but their IgG concentrations did not differ from normal. We conclude that (i) sickling is sufficient to protect against P. malariae in Hb.SS but not Hb.AS; (ii) sickling prevents intense P. falciparum infection in Hb.SS, as in Hb.AS; (iii) in Hb.SS, there is less antigenic stimulus and hence less antibody against P. falciparum (like Hb.AS) and P. malariae (unlike Hb.AS); (iv) although less intense, malaria is frequently fatal in Hb.SS, especially in age-group one to four years (unlike Hb.AS); (v) IgM levels are high in Hb.SS in response to frequent infections other than malaria (unlike Hb.AS).


Schistosoma mansoni: ultrasonically detectable motor activity responses to 5-hydroxytryptamine in vitro. The ultrasonic method compared favourably with other methods for monitoring schistosome motor activity in vitro, being able to detect and differentiate between the activity responses of Schistosoma mansoni to 5-hydroxytryptamine at concentrations down to 1 X (10(-6) M. This was taken to indicate suitable sensitivity for the application of the ultrasonic method to other drug studies.


A comparative synchronous coronary surgery survival study. Utilizing patient criteria published by the Veterans Administration Cooperative (VAC) Study, a cohort of 229 surgically treated patients was retrieved from the Milwaukee Cardiovascular Data Registry. These patients were all operated on by one surgeon during 1972 to 1974. Four-year survival of this group was compared with that of the medically treated cohort of 310 patients from the VAC Study. Operative mortality was included in all surgical groups. The cumulative 4-year survival of both groups revealed a 95 to 85% advantage for surgical therapy. In patients with three-vessel disease, the cumulative survival favored surgical therapy--94% compared with 80% in the medically terated cohort--and in patients with triple-vessel disease and a normal left ventricle, surgical therapy again showed better results: 100% compared with 88%. Patients with two-vessel disease and a normal left ventricle who underwent surgical intervention had slightly better 4-year survival than those who had medical treatment--100% versus 95%--and those with two-vessel disease and an abnormal left ventricle had a 93% survival after surgical treatment compared with 84% for those with medical treatment. For patients with single-vessel disease, there was no difference in survival between the surgical and medical cohorts.


Late coronary bypass graft flow: quantitative assessment by roentgendensitometry. Quantitative assessment of the flow in 45 saphenous vein aortocoronary bypass grafts in 30 patients was performed by a roentgendensitometric technique. Detalis of the technique are given. Mean graft flow for all grafts measured in the early postoperative period (two weeks) and again in the late postoperative period (six months to 3 years; average, 1.5 years) significantly decreased (72.6 +/- 34.7 to 57.4 +/- 28.6 ml/min; p less than 0.01). Mean graft diameter also significantly decreased over the same period (3.5 +/- 0.6 to 3.0 +/-  0.6 mm; p less than 0.01). Differences could not be related to graft site or to the time interval between early and late recatheterization. Changes in diameter did not correlate with changes in flow. During a 3-year follow-up, saphenous vein grafts significantly decreased in diameter and flow but still functioned adequately; and vein grafts generally remained larger than the recipient arteries. The determinant of adequacy of flow is the native coronary bed.


Bradykininase and protease inhibitors in seminal plasma of fertile and infertile men. The level of protease acrosin in the seminal plasma of oligozoospermic men was significantly higher than that of normozoospermic men. The amount of bradykininase in the seminal plasma was very high in both normozoospermic and oligozoospermic patients. When the acrosin and kininase content was referred to one million spermatozoa, seminal plasma kininase was significantly enhanced in oligozoospermic men, while the acrosin activity was similar in normozoospermic fertile men and infertile men. Human seminal plasma inhibitor I (HUSI I) increased along with sperm count. Human seminal plasma inhibitor II (HUSI II) showed no change. The motility of spermatozoa was depressed in oligozoospermic patients.


Late results of extra-anatomic bypass.

Late results of extra-anatomic bypass. Clinical progress and results were reviewed in 100 consecutive patients who underwent extra-anatomic bypass procedures for brachiocephalic and aortoiliac occlusive disease during the past 15 years. Of 113 procedures in this group, extra-anatomic bypass of the brachiocephalic vessels, axillo-femoral bypass, and femorofemoral bypass were performed. Although these procedures were performed in high-risk patients to avoid intrathoracic and intra-abdominal reconstruction or to circumvent undesirable anatomic areas, a low operative mortality was achieved. Symptomatic improvement, augmented Doppler ankle pressure index, and high limb-salvage rate were noted. Life-table analysis has confirmed prolonged five-year graft patency. The suspected high-risk characteristic in this group was corroborated by high progressive mortality observed particularly after axillo-femoral bypass and was due primarily to the severity of associated diseases. Analysis of the late results of extraanatomic bypass confirms the safety and effectiveness of this procedure in poor-risk patients.


Reoperation for recurrent coronary artery disease: causes, indications, and results in 168 patients. Of the 13,049 patients who underwent coronary artery bypass surgery, 168 underwent a second or third operation because of the failure of the first. The early mortality was eight of 168. Good to excellent results were obtained in 141 patients. The cumulative survival rate was 82% at six years. Graft failure and the progression of atherosclerosis to a critical lesion were the most common reasons for reoperation, and perioperative myocardial infarction and incomplete initial operation were the least common. Long-term follow-up showed a peak of graft failure and progression of disease in nongrafted arteries at three years and decreased thereafter. Progression of distal disease in grafted arteries was not temporally related and was uncommon. Thrombosis of the vein graft could be related most frequently to the distal circulation rather than the vein graft itself.


Use of saphenous vein to extend and relocate coronary arteries: clinical experience during extensive reconstructive operations of the aortic root. Eight patients with advanced disease of the aortic root involving the origins of the coronary arteries have been operated on with resection of the entire aortic root including the ostia of the coronary arteries. Reconstruction was performed by insertion of a composite prosthesis; extension and relocation of the proximal portion of the coronary arteries was accomplished with saphenous vein segments. Two patients had infected aortic valve prostheses, three patients had acute aortic dissection and three had annuloaortic ectasia. Seven of eight patients survived the operation, the only operative death occurring in a patient submitted to an operation in a shock state following rupture of the aorta. There was, however, a high incidence of subsequent late deaths resulting from continued infection and from central circulatory failure. An analysis of this series of patients suggests the possibility that a reconstruction that relocates and extends the proximal portion of the coronary circulation may provide a total blood flow that is inadequate or inappropriate, and further suggests that the methods used in the reconstruction of the proximal circulation may be critical to the prevention of myocardial hypoperfusion.


Traumatic neuroma: a complication of transcanal labyrinthectomy. Transcanal labyrinthectomy is frequently unsuccessful in controlling vertigo due to intractable Meniere's disease. It may in fact make the condition worse due to the formation of a traumatic neuroma. The translabyrinthine vestibular nerve section is more reliable, but the morbidity is greater. Therefore, the transcanal procedure is usually recommended as the initial procedure, but the patient is warned that a second more extensive procedure may be necessary to control dizziness.


Differences between the carbohydrate units of cell-surface glycoproteins of moust B- and T-lymphocytes. Carbohydrate units of cell-surface glycoproteins of mouse B- and T-lymphocytes, labelled in their sialic acid residues by the periodate/NaB3H4 method and in their galactose residues by the galactose oxidase/NaB3H4 method after neuraminidase treatment, have been studied. Glycopeptides were prepared from the labelled cells by Pronase digestion and fractionated by concanavalin A affinity chromatography into two fractions (A and B). Alkali-labile oligosaccharides were isolated after mild NaOH/NaBH4 treatment by gel filtration. The alkali-labile oligosaccharides were further analysed by t.l.c. To study the relative proportion of neutral mannose-rich carbohydrate units (fraction C) in lymphocyte glycoproteins, glycopeptides were also prepared from unlabelled cells and subjected to concanavalin A affinity chromatography after N-[3H]acetylation of their peptide moiety. The major alkali-labile oligosaccharide component of both cell types was identified as galactosyl-(beta 1 leads to 3)-N-acetylgalactosaminitol. T-Lymphocytes were characterized by a high proportion of this oligosaccharide and a lower proportion of alkali-stable fraction A glycopeptides, whereas the opposite was observed for B-lymphocytes. The relative proportions of the concanavalin A-binding fractions B and C were similar in both cell types. The differences observed may correlate with the different surface properties of B- and T-lymphocytes.


Inhibition of degradation of insulin by ophthalamic acid and by a bovine pancreatic proteinase inhibitor. We have previously observed that, on subcutaneous administration, a significant proportion of insulin is degraded at the site of injection. The present paper reports that the degradative activity of slices of rat adipose tissue can be inhibited in vitro by ophthalmic acid, a natural analogue of glutathione, and by bovine pancreatic proteinase inhibitor, whereas it is increased by the addition of reduced glutathione.


The analgesic activity of imidazopyridine derivatives. Analgesic and antipyretic activities of 2-(4-(2-imidazo-[1,2-a]pyridylphenyl)propionic acid (Y-9213) were studied with various experimental models. The analgesic activity of Y-9213 was found to be more potent than that of indometacin and morphine in the silver nitrate, Randall-Selitto, and phenylquinone writhing tests. Y-9213 also showed an analgesia in the tail pinch and electric stimulation test. On the warm water induced foot withdrawal reflex, Y-9213 was more effective in spinal-sectioned mice than in intact mice similarly to mephenesin and diazepam. Y-9213 was also proved to possess antipyretic activity as potent as indometacin and to be devoid of morphine-like property. Y-9213 exhibited little effect on the respiration and cardiovascular system in dogs. Y-9213 was found to be rapidly absorbed and eliminated from the blood with a half-life of about 2.5 h in rats. These findings indicate that Y-9213 may be an effective and well tolerated antipyretic and analgesic agent.


1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido [1,2-a] pyrimidine-3-carboxamide (Chinoin-127), a potent non-narcotic analgesic and antiinflammatory agent. 1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido[1,2-a]pyrimidine-3-carbamide (Chinoin 127), a non-narcotic analgesic with potent antiinflammatory activity is described. Chinoin-127 is more potent as an analgesic in the hot plate, Randall-Selitto and writhing tests than is acetylsalicylic acid (ASA) and an effective antiphlogistic agent in a battery of tests (carrageenin, kaolin and dextran induced rat paw edema, Northover test, carrageenin induced abscess, implanted cotton pellet method, adjuvant arthritis) used for measuring antiinflammatory activity. The PG-synthesis inhibitors (indometacin, suprofen) were found to be devoid of analgesic activity, and great test-dependent variations in their antiinflammatory effect were observed. They proved to be inactive in the Northover test. Unusual grade of inhibition in the carrageenin-induced rat paw edema test was obtainable by the simultaneous administration of Chinoin 127 and indometacin.


Synthesis and pharmacological properties of 3-O-derivatives of 1,2,5,6-di-O-isopropylidene-alpha-D-glucofuranose. A series of 3-O-derivatives of 1,2,5,6-di-O-isopropylidene-alpha-D-glucofuranose were prepared and tested for their pharmacological activity in comparison with tribenoside, a well known drug structurally related, and with other anti-inflammatory agents. Almost all the compounds had a very low toxicity and few of them showed a notable antiinflammatory and antipyretic activity and were able to clearly decrease the venous wall permeability.


General pharmacological properties of 4-(p-chlorophenylthio)butanol (W-2719). 4-(p-Chlorophenylthio)butanol (W-2719), a compound that inhibits histamine release from sensitized leukocytes also decreased tracheal smooth muscle tonus, inhibited synthesis and release of immunologically induced SRS-A (slow-reacting substance of anaphylaxis) in the rat and antagonized the in vitro activity of SRS-A. Furthermore, it significantly inhibited the platelet release reaction induced by collagen in vitro but not ex vivo. On the other hand, W-2719 did not possess marked CNS activity nor did it adversely affect the blood pressure, heart rate or respiratory rate. There was no evidence for sympathetic or parasympathetic activity. It had weak antipyretic activity, but exhibited no anti-inflammatory or analgesic activity.


Pharmacological study of a new non-steroidal anti-inflammatory drug: protacine (CR 604). The pharmacological activities of 3'-(4-[2-(1-p-chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropylglutaramate(+/-)dimaleate (protacine, CR 604), a new indolyl derivative with strong anti-inflammatory, analgesic and antipyretic activities, are described. The dose-dependent activity of protacine on inflammation has been shown both in short-term experiments, like the hind paw edema induced by carrageenin and several other irritants, and long-term tests, like the aminoacetonitrile-induced osteolathyrism, the adjuvant-induced arthritis and the cotton pellet-induced granuloma. The analgesic activity of the drug has been evidenced in the phenylquinone-induced writhing and the Randall-Selitto tests, and the antipyretic effects in the yeast-induced hyperthermia in rats. Other general pharmacological effects have been studied, too. Contrarily to several other anti-inflammatory drugs, including indometacin, showing advers effects at doses which are in the same range of those active on experimental inflammation, protacine shows these effects to a minor degree and at doses which are much larger than those pharmacologically active. The therapeutic index of protacine therefore is superior to that of other anti-inflammatory drugs.


[Usefulness and adverse effects of intrathecal metrizamide instillation (author's transl)]. Radiographic quality as well as adverse effects of intrathecal metrizamide instillation was prospectively investigated in thirty-three clinical cases admitted to the department of neurosurgery, University of Tokyo Hospital, and Kantoh Teishin Hospital. Metrizamide CT cisternography was performed in fifteen cases using in most cases 10 ml of 170 mg I/ml solution through lumbar route. Eleven cases exhibited "normal" pattern CSF circulation and the remaining four, "delayed" pattern. Eight cases (53%) experienced headache, nausea, and/or vomiting several hours after the instillation. All of these belong to the "normal" pattern group. Four cases of "normal" pattern received electroencephalographic examinations before and after metrizamide instillation. Three revealed appearance of negative spike and slow wave burst or sharp waves one to twenty-four hours after the instillation, along with penetration of metrizamide into brain parenchyma. Diagnostic quality was interpreted as "good" in eleven cases. Small acoustic neurinoma, pituitary adenoma, arachnoid cyst, and subdural hygroma were diagnosed among others. Metrizamide ventriculography was done in four cases. No untoward effect of significance was attributed to metrizamide per se. Cervical myelograpy and/or CT myelography was done in fourteen cases using, in most cases, 10 ml of metrizamide 170 mgI/ml. Polytome tomography with metrizamide instillation through lateral cervical puncture was highly diagnostic, whereas, ordinary X-ray with lumbar instillation yielded less satisfactory results. CT myelography in cases of subarachnoid block required good consideration on instillation site and positioning of the patient. Six cases (50%) among twelve cases where metrizamide had run into the cranial cavity experienced headache, nausea, and/or vomiting to a lesser degree than those of cisterno graphy. Metrizamide is the first contrast agent ever made which can be safely introduced into human subarachnoid space, if administered judiciously, nervous. However, metrizamide is weakly toxic to central system and provokes minor untoward effects as well as electroencephalographic abnormalities and, sometimes, clinical convulsive seizure. It would be wiser to restrict the dosage of metrizamide in cisternographic study, expecially in cases of "normal" pattern CSF circulation, to 1.2 gI or 7 ml of 170 mg I/ml solution. Routine use of X-ray cisternography should thus be discouraged because it needs higher concentration of metrizamide in the intracranial cisterns.


Slow actions of hyperpolarization on sodium channels in the membrane of myelinated nerve. The mean sodium current, I, and the variance of sodium current fluctuations, var, were measured in myelinated nerve during a depolarization to V = 40 mV applied from the resting potential (VH = 0) or from a hyperpolarizing holding potential VH = -28 mV. From I and var the relative variations in the number N and the conductance gamma of sodium channels following changes of the holding potential were calculated. Hyperpolarizing the membrane from VH = 0 to -28 mV increased N by a factor of 3.7, whereas gamma decreased by a factor of 0.53. These actions of holding potential on sodium channels develop slowly since 500 ms prepulses to 0 or -28 mV do not alter the values of N and gamma.


Log-linear models in the analysis of disease prevalence data from survival/sacrifice experiments. This paper considers the problem of analyzing disease prevalence data from survival experiments in which there may also be some serial sacrifice. The assumptions needed for "standard" analyses are reviewed in the context of a general model recently proposed by the authors. This model is then reparametrized in log-linear form, and a generalized EM algorithm is utilized to obtain maximum likelihood estimates of the parameters for a broad class of unsaturated models. Tests based on the relative likelihood are proposed to investigate the effects of treatment, time, and the presence of other diseases on the prevalences and lethalities of specific diseases of interest. An example is given, using data from a large experiment to investigate the effects of low-level radiation on laboratory mice. Finally, some possible directions for future research are indicated.


[Effect of thymectomy on induction of immunologic tolerance in the effectors of delayed hypersensitivity]. The influence of thymectomy (Tx) on induction of tolerance of delayed type hypersensitivity effectors (DHE) was examined. Tx did not interfere with induction of tolerance to sheep red blood cells (SRBC) achieved with combined injections of the massive dose of the antigen and cyclophosphamide (Cy). Tx resulted in prolongation of unresponsiveness. The injection of mice with the massive dose of SRBC alone also resulted in tolerance formation. However, this type of tolghtly depressed formation of DHE in intact but not in Cy treated mice. The results obtained are in agreement with the idea of the existence of diverse mechanisms of tolerance induction (clonic-deficient and suppressor). These data also suggest the existence of two subpopulations differing in susceptibility to Cy and Tx in DHE effectors and their precursors.


[Lymph node cell composition and DNA content in their different lymphocyte populations in mice with tumor induced by murine Moloney sarcoma virus]. The ratio of T and B lymphocytes and DNA content in population enriched by these cells were analysed in the lymph nodes of BALB/c mice with progressively growing sarcomas induced by the MSV Moloney and in untreated mice. T lymphocyte enriched fractions have a higher DNA content in comparison to fractions enriched with B lymphocytes. Sarcoma development promotes a decrease in the relative number of macronucleolar lymphocytes and simultaneous decrease of micronucleolar ones in the lymph nodes, particularly in the regional ones.


[Ultrastructure and antigens in differentiation of thymus lymphocytes in human embryogenesis]. Thymus lymphocytes of 7--8-week human embryos have nuclei of irregular form with 1--3 distinct nucleoli characterized by absence of compact chromatin or heterchromatin. The electron-dense cytoplasm of these cells contains polysomes and an insignificant number of mitochondria. No receptors to sheep red blood cells and T antigen are revealed on their surface. In 11--12-week human embryos one can observe a decrease in the size of thymus lymphocytes, appearance of heterochromatin in their nuclei and receptors to sheep red blood cells (79%), and T antigen (60%) on the cell surface. Subsequently the quantity of compact chromatin in thymus lymphoid cells increases, and the cells acquire definitive properties and structure.


Philadelphia-chromosome-positive pre-B-cell leukemia presenting as blast crisis of chronic myelogenous leukemia. Cytogenetic studies of chronic myelogenous leukemia (CML) have shown that the majority of hemopoietic cells originate from pluripotential stem cells affected in this disease. Evidence that lymphocytes are also progeny of these stem cells, however, has been indirect. Philadelphia-chromosome-positive leukemic blasts from a 4 10/12-yr-old boy with CML in blast crisis had features characteristic of pre-B leukemic cells, including expression of cytoplasmic IgM and absence of surface immunoglobulin. Additional immunologic, enzymatic, and pharmacologic characterization of these cells supported their pre-B-cell phenotype. Together, these features provide direct evidence for CML stem cell ancestry to lymphocytes of the B-cell lineage.


The binding of ouabain to normal and chronic lymphocytic leukemic lymphocytes. The binding of the cardiac glycoside, ouabain, to cells had been used to quantify the number of active cation pumps. In this study, lymphocytes were incubated with 3H-ouabain and the equilibrium binding analyzed for the maximal number of specific binding sites. Lymphocytes from normal peripheral blood bound 44,200 +/- 9920 molecules/cell, compared with 29,200 +/- 8370 molecules/cell for the lymphocytes of chronic lymphocytic leukemia (CLL) subjects. This difference was significant (p less than 0.01) and did not reflect a lower number of sites on B cells than T cells, since B-cell-enriched lymphocytes from normal peripheral blood showed the same ouabain binding characteristics as the standard T-cell-rich preparation. Although monocytes bind threefold more ouabain than lymphocytes, the small monocyte contamination (3.0%) in normal lymphocyte preparations could not account for the difference between normal and CLL. The fewer ouabain binding sites on CLL lymphocytes may reflect both their smaller size (by 10%) and lower mitotic activity compared with lymphocytes from normal peripheral blood.


Activation of human lymphocyte subpopulations by protein A from Staphylococcus aureus bacteria. Cowan I strain Staphylococcus aureus bacteria were found to be mitogenic for human peripheral and cord blood lymphocytes. Experiments with lymphocyte supopulations otained by nylon wool filtration and/or E-rosette separation revealed that T-lymphocytes are the main target cells, whereas isolated B cells did not respond significantly. Further experiments suggested that B cells could be activated in the presence of mitomycin-treated T cells. Null cell-enriched lymphocyte suspensions could be stimulated by Con A but not by the bacteria or by PHA.


Noxythiolin (Noxyflex), aprotinin (Trasylol) and peritoneal adhesion formation: an experimental study in the rat. Clinical and experimental studies have suggested that noxythiolin and aprotinin may prevent intraperitoneal adhesion formation. A comparison was therefore made of their efficacy in preventing the reformation of adhesions following surgical lysis in a controlled trial using rats. Neither noxythiolon nor aprotinin had any significant benefit over surgical lysis alone. The mortality rate was high in the noxythiolin-treated group.


Fetal breathing movements and other tests of fetal wellbeing: a comparative evaluation. Sixty pregnant women whose fetuses were considered to be at high risk were intensively studied with fetal and placental function tests. Fetal breathing movements were studied with real-time ultrasound and the amount of time spent breathing and the variability of the breath-to-breath interval were measured. A reduction in the amount of time the fetus spent making breathing movements and decreased variability were indicative of fetal compromise. When these results were compared with those of other tests of fetal wellbeing measurement of fetal breathing movements and ultrasound assessment of growth were more sensitive tests of fetal wellbeing than the biochemical measures (urinary oestrogen, human placental lactogen, pregnancy-specific beta-1-glycoprotein, and unconjugated oestriol concentrations) or fetal heart rate. The predictive value was  highest with serum unconjugated oestriol but the results of other tests were similar. Study of fetal breathing movements or an ultrasonic assessment of growth may provide a better screening test for fetal compromise than biochemical estimations.


Quantitative analysis of stance in late cortical cerebellar atrophy of the anterior lobe and other forms of cerebellar ataxia. (1) Methods have been developed to measure, analyse and document postural sway. The main parameters studied were: average sway amplitude; length of the sway path per unit time; sway direction and sway position histograms; and the frequency spectra of the antero-posterior and lateral sway components. (2) Postural ataxia was quantitatively studied in three groups of patients with cerebellar lesions: (a) late atrophy of the anterior lobe, (b) tumours of the cerebellar hemisphere and (c) tumours within the vestibulo-cerebellum. Characteristic differences were found. (3) Patients with anterior lobe lesion show a specific 3 Hz postural tremor in the antero-posterior direction. The tremor can be evoked by sudden destabilization in incipient cases. Less characteristic and smaller in amplitude is a mainly lateral sway component with an average frequency of 0.5 Hz. This is also seen in cases with spinal ataxia. Visual stabilization of posture is frequently preserved. Its amount does not correlate with general instability of posture. Tremor and characteristically exaggerated intersegmental responses between head, trunk, hips and legs are interpreted as the consequence of hyper-excitability of postural reflexes in these patients. (4) Patients with lesions of the hemispheres show only slight postural instability without directional preference. Their sway parameters with eyes open are within the 2 sigma range of normals and there is no significant difference from normals in these parameters even when the eyes are closed. Therefore these patients cannot be distinguished from normals by means of their platform recordings. (5) Two patients with posterior vermal and flocculo-nodular lesions were very unstable without preferred axis or frequency of instability. In contrast to the anterior lobe group the instability was characterized by the absence of intersegmental movements.


Failure of 5-hydroxytryptophan to increase lumbar MSR amplitude in rats paralyzed with experimental allergic encephalomyelitis. Doses of the 5-hydroxytryptamine precursor, 5-hydroxytryptophan, which markedly increased lumbar monosynaptic response (MSR) amplitude in control rats failed to do so in rats paralyzed with experimental allergic encephalomyelitis (EAE). However, lumbar MSR amplitude could be increased in EAE rats just as in control rats by tetanically stimulating the dorsal root. Post-tetanic potentiation of MSR amplitude occurred in the EAE paralyzed rats both prior to and following 5-hydroxytryptophan injection. It was concluded that, as has been reported for the peripheral system in EAE guinea pigs, central nervous system 5-hydroxytryptamine neurotransmission is impaired, at least in the lumbar spinal cord, in EAE rats with hindlimb paralysis.


Coccidial infection with Eimeria tenella and caecal defaecation in chicks. 1. The periodicity of caecal defaecation was investigated in chicks infected with Eimeria tenella. The birds were illuminated for 12 h/d (07.00-19.00) and faeces were collected at 3-h intervals for up to 21 d. 2. In uninfected birds caecal faeces were never collected during the dark period. During the periods 07.00-10.00 h, 10.00-13.00 h, 13.00-16.00 h and 16.00-19.00 h, caecal defaecation occurred on approximately 44, 19, 55 and 91% of the total number of days respectively. 3. In infected birds production of haemorrhagic caecal faeces began from between 90 and 156 h after infection and continued during both light and dark periods for between 12 and 48 h. After this period, no caecal faeces were observed for between 39 and 120 h. Normal caecal defaecation resumed from between 198 and 264 h.


Predictive value for survival of lymphocytes and polymorphonuclear leukocytes in patients with sepsis. To study their value in predicting prognosis, tests were performed on peripheral blood lymphomononuclear cells and polymorphonuclear leukocytes in 34 critically ill patients with sepsis. Intially, the number of lymphomononuclear cells was reduced by 32% compared with healthy control subjects and was 42% lower in those who died than in survivors. The values remained low in those who died. The numbers of T and B cells, determined by rosette formation using sheep and mouse erythrocytes, did not change during the period of observation. Intially, K cell activity was decreased by 48% compared with normal activity. In those younger than 65 years, K cell activity was 68% lower in patients who later died than in survivors. It returned to normal at 20 to 30 days and decreased in those who died. Polymorphonuclear leukocyte adherence was decreased by 50% compared with healthy control subjects and tended to be lower in those who died. Chemotactic migration of polymorphonuclear leukocytes and intracellular killing of Staphylococcus aureus and Pseudomonas aeruginosa were not impaired. It was concluded that the lymphomononuclear cell count, K cell activity and adherence of polymorphonuclear leukocytes were decreased in patients with sepsis and that the values were useful in predicting prognosis.


Elective management of the patient who has bled from esophageal varices. Variceal hemorrhage can be controlled by nonsurgical means in over 50% of patients. As a result, their general hepatic status can often be improved by preoperative preparation for the elective procedure. The major problem following elective end-to-side portacaval shunting is encephalopathy; it occurs in up to one half of patients who undergo this shunting procedure. Mesocaval shunting has been proposed as a better operation because of lower frequency of encephalopathy; however, the authors' experience has not confirmed this. Distal splenorenal shunting, as shown by the results of a prospective controlled trial, does have a lower frequency of encephalopathy, but the initial morbidity and mortality are higher and an improvement in the duration of survival is not yet evident.


Morphologic and ultrastructural characteristics of T-cell acute lymphoblastic leukemia. The morphology, ultrastructure, and acid phosphatase activity of the leukemic cells of 11 cases of T-cell acute lymphoblastic leukemia (T-ALL) were studied. Distinctive small cells with markedly hyperchromatic convoluted nuclei comprised from 2 to 25% of the leukemic cells in the blood and bone marrow smears of 10 of the 11 patients. Similar cells were found in only four of 47 cases on non-T, non-B-ALL. Many of these small leukemic cells exhibited ultrastructurally nuclear membrane reduplication and nuclear blebs and splits. The presence of these small leukemic cells with markedly hyperchromatic convoluted nuclei in ALL is strongly suggestive of T-ALL. This cytomorphologic finding, when combined with the presence of strong focal acid phosphatase activity, lends even greater predictability of a T-cell process.


Atypical T-cell leukemia terminating Hodgkin's disease. A case of Hodgkin's disease is described which developed into a terminal illness characterized by a malignant proliferation of T-cells. The leukemic cells, after optical and ultrastructural analysis, were distinct from those of myelomonocytic, acute lymphoblastic, chronic lymphocytic as well as prolymphocytic leukemia. Their relationship with the T-cell lineage seemed to be confirmed by a highly positive E-rosette test and by cytochemistry which showed focal positivity of acid phosphatase. The importance of this T-cell malignant proliferation is discussed, especially with regard to cellular interactions in Hodgkin's disease.


Disseminated histiocytosis X: analysis of prognostic factors based on a retrospective study of 50 cases. This work is a retrospective study of 50 cases of DHX, collected over a period of 27 years. 24 children died, 26 are still alive. The prognosis for DHX was neither dependent on age (usually occurring in children under 2 years) nor on histological findings but on the extent of the lesions. It was possible to establish a clinical staging system distinguishing 2 groups. One, where the disease was severe and almost always fatal, often included the combined symptoms of thrombocytopenia, spontaneous anemia, jaundice, hepatosplenomegaly, respiratory insufficiency and absence of osteolytic lesions. The other, with a favorable prognosis, was characterized by skin lesions, diabetes insipidus, exclusively radiological pulmonary involvement and multiple bone lesions. In cases where death did not occur, DHX was often chronic, frequently persisting for 2 years or more and leading to serious sequelae such as diabetes insipidus, growth stunting, intellectual retardation, blindness or deafness.


The T-lymphocyte as a diploid reference standard for flow cytometry. T-lymphocytes prepared from the peripheral blood of normal individuals exhibit uniform postmitotic DNA contents that are constant from individual to individual when fixed in ethanol and stained with mithramycin, or when fixed in formalin and stained with acriflavine-Feulgen and analyzed by flow microfluorometry. T-lymphocytes fixed by either method are stable on storage for several months. These cells are suitable for use as an external diploid reference standard for flow cytometric detection of cells with abnormalities in postmitotic content exceeding 5% of diploid reference. Cells with abnormalities in postmitotic DNA content of less than 5% can be detected in mixtures containing both normal and malignant cells by multiparameter analysis.