[Induction of liver microsomal monoxygenases in experimental cholestasis]. The dependence of expressiveness of microsomal mono-oxygenase induction by phenobarbital upon the amount of binding sites at cytochrome P-450 active center(s) has been studied. The experimental cholestasis is accompanied by accumulation of hydroxylated derivatives of cholesterol, which possess the detergent characteristics and destruct the substrate binding sites in P-450 molecule. The possibility has been demonstrated of phenobarbital induction under conditions when the inducer-monooxygenase primary binding and metabolic steps are not involved. It is assumed that the activation of de novo microsomal protein synthesis is effected by the molecule of phenobarbital itself and not by the products of its primary hydroxylation in the microsomes.


[Participation of thyroid hormones in realization of the action of diphtheria toxin on oxidative phosphorylation in rabbit liver mitochondria]. Experiments were conducted on rats with an experimental hypo- and hyperthyroidism. In hypothyroidism there was no disturbance of the capacity to phosphorylation conjugated with respiration in the mitochondria from the liver in intravenous injection of diphtheria toxin, but in hyperthyroidism sensitivity of mitochondria of the liver to the uncoupling action of diphtheria toxin was much increased. It is supposed that of great significance for the uncoupling action of diphtheria toxin on the oxidative phosphorylation was the incretory function of the thyroid gland.


[Physicochemical changes in DNA and deoxyribonucleoprotein caused by potassium cyanate]. The influence of KNCO on the structural integrity of the DNP salt solutions was studied. By the methods of sedimentation, viscosimetry, spectrophotometry and circular dichroism it was shown that KNCO failed to induce degrading the polynucleotide DNA strands and weakened the bonds between the DNA and protein.


[Increase in the concentration of RNA in the blood erythrocytes of women in the ovulation period]. It was revealed that there was an increase (by an average of 58%) of the RNA concentration in the blood erythrocytes of women during ovulation. Measurement of the RNA content in erythrocytes can serve as an ovulation test.


[Adenylate cyclase activity in human nasal polyps under conditions of stimulation of serotonin biosynthesis (in vitro)]. Nasal polyp tissue possess adenylatecyclase activity. Under conditions of incubation of nasal polyps with the use of reserpine (an activator of serotonin synthesis in this tissue) there can be observed a statistically significant increase of adenylatecyclase activity. During the first minutes of the polyp incubation with reserpine the activity of the enzyme rose ten-fold. Participation of the adenylatecyclase system at the initial stages of morphological and biochemical differentiation, accompanying serotonin biosynthesis in human nose polyps was confirmed.


[Effect of blood serum from schizophrenic patients and from normal donors on DNA synthesis in lymphocytes]. The number of DNA-synthesizing lymphocytes in the phytohemagglutinin (PHA)-stimulated cultures of the peripheral blood of schizophrenic patients was determined. Under the mentioned conditions the number of DNA-synthesizing lymphocytes of the schizophrenic patients was 18% less than in the cultures of healthy donors. When the PHA-treated lymphocytes of normal donors were incubated with the serum of schizophrenic patients the number of lymphocytes capable of synthesizing DNA in the presence of PHA fell by 21%.


[Localization and possible development cycle of mycoplasmas and bacterial L-forms in cell cultures]. Using vital stain chlorazol-black E the authors studied the localization and behaviour of 5 mycoplasma species and the stable L-form of beta-hemolytic streptococcus of group A in various continuous cell lines. Mycoplasmas and L-forms had a definite evolution cycle in the cells. At first they are arranged extracellularly and on the surface of the cells, and then intracellularly where they multiply intensively; later they are again localized on the surface of the cells and extracellularly. This cycle proved to depend on the type of infection. The character of the localization depended on the type of the causative agent and of the culture.


[Reduction of the biological activity of Vibrio cholerae culture filtrates exposed to neuraminidase inhibitors]. Experiments were conducted on a model of edema of albino mouse paws; a study was made of the effect of neuraminidase inhibitors on the cholerogenic effect of a filtrate of cholera vibrio culture. It appeared that addition to the filtrate of inhibitors depressed its biological activity. Since no cholerogenic action was possessed by the purified neuraminidase preparations from the cholera vibrios it was suggested that there existed a chemical affinity between the region of cholerogen responsible for fixation on the cell membranes and the active neuraminidase centre.


[Analysis of water-soluble antigens of chick iris]. Three serum and twelve tissue antigens were revealed in adult chick iris by immunodiffusion and immunoelectrophoresis. Among the tissue antigens five were characteristic of the eye tissues alone: a specific iris antigen, an antigen revealed in the iris and the retina, and three antigens characteristic of the lens (the alpha-, beta- and delta-crystallines). The rest seven antigens were interorganic differing by their distribution in the tissues and organs investigated; among them one was specific of muscle tissue.


[Study of antibodies to heterologous connective tissue, isolated from sera of patients with rheumatism]. Antibodies against connective tissue elements of various bovine organs were isolated from the sera of rheumatic fever patients with the aid of immunosorbents (bovine connective tissue extract and erythrocyte stroma). The antibody preparations obtained were not identical and contained antibodies against different antigens of bovine connective tissue. The antibody preparations failed to react with human connective tissue components.


[Cytotoxic action of immune lymphocytes on "adherent" cells (macrophages) of autologous system lymph nodes during delayed hypersensitivity]. A study was made in the autologous system of the cytotoxic action of immune lymphocytes on the "adherent" cells (macrophages) of the lymph nodes of guinea pigs in delayed hypersensitivity (DH) to the streptococcus antigens and tuberculoproteins. Death of a considerable number of the "adherent" cells in cultivation of a suspension of cells of the lymph nodes of animals sensitized with the culture of streptococcus or BCG in the presence of specific antigen (thermo-stable streptococcus fraction or tuberculin, respectively) alone. Detection of death of the "adherent" cells in the autologous system can be used as one of specific and sensitive tests in studying the DH.


[Carcinoembryonic antigen in rat blood serum in nonspecific intestinal disease]. Sera of rats in which an extensive injury of the caecum was inflicted were studied by precipitation in agar. The carcino-embryonic antigen appeared in the sera of 84% of the animals 24 hours after the damage, and persisted in the majority of the animals for a period of 15-20 days; this corresponded to the period of the most pronounced regeneration of the intestinal mucosa.


[Change in the sensitivity to methotrexate of neoplastic cells cultivated in the presence of folic acid]. Cultivation of tumour L-cells in the presence of increasing folic acid concentrations led to the rise in the resistance of these cells population to metotrexate. With the subsequent cultivation, when the folic acid concentration was not increased the population of such cells became more sensitive to metotrexate even in comparison with the initial L-cells.


Cloning of canine hematopoietic cells in vitro. A modified cloning method of the agar culture of canine bone marrow cells was described. A high efficiency of colony formation was seen only after addition to the agar medium of the colony-stimulating activity (CSA) from different sources. Dog serum in a 20% concentration was used in this case. With the optimal CSA concentration there was seen a linear relationship between the number of explanted cells and the number of produced colonies. This method is suitable for determination of committed granulocyte precursor cells, as well as for the study of potential humoral regulators of granulocytopoiesis in dogs.


[Characteristics of liver regeneration and growth in 3-week-old mice of different strains]. Three-week mice of C57BL strain are characterized by low proliferative activity of hepatocytes during normal growth of the liver. Hepatocytes of mice of this strain also had low proliferative activity 44 hours after partial hepatectomy (16%). Mice of the same age, but of other strains (mongrel, CBA, CC57BR) had higher mitotic indices both during normal growth and during regeneration (42; 70 and 60%, respectively). This peculiarity in the mitotic activity of hepatocytes of mice of different strains was also present 7 days after the beginning of the experiment. The data obtained indicated the genetic determination of the level of proliferative activity of hepatocytes.


[Skin regeneration and metabolic level on administration of thyrostimulin]. A study was made of the effect of thyrostimulating hormone of the adenohypophysis on the metabolism level and the repair process of the covering tissue depending on the topography of the injuries. Under the effect of the mentioned hormone there was an increase in the level of metabolism; thus favourable conditions were created for the accelerated healing of skin wounds. Stimulation of repair process was the most distinct at the early periods of regeneration. The stimulating effect was revealed irrespective of the topography of the injuries, but was more distinct in the animals in which the wounds were inflicted on the lateral surface of the body.


[Morphological and histochemical changes in the rabbit aorta during exogenous and endogenous hyperglycemia]. Alimentary hyperglycemia and insulin deficiency were accompanied in rats by atherosclerotic affection of the aorta whose degree increased in feeding of cholesterol to such animals. The detected morphological and histochemical changes in the wall of the aorta correlated with the biochemical atherogenic shifts in the blood serum of the corresponding animals groups established earlier.


[Mitoses in hypertrophied smooth muscle tissue of the rat posterior vena cava]. Injection of colchicin to rats exposed mitotic dividing leukomyocytes in the hypertrophied muscle tissue of the posterior vena cava. Under these conditions mitotic index didn't exceed 1:1000-1:10000. Many of the cells were in the prophase, this being apparently associated with prolonged mitosis in the leiomyocytes of the vein.


[Enzymatic heterogeneity of the rat myocardium]. The histoenzymatic method was applied to the study of distribution of the activity of the redox enzymes in the myocardium of the ventricles in rats; distribution of the activity of lactic and malic dehydrogenase and of alpha-glycerophosphate proved to be the most manifest near the apex of the heart and was expressed in the presence of "spotty" areas of increased activity against the general homogeneous background of formazan deposits. The activity of mitochondrial upsilon-glycerophoric dehydrogenase was seen in all the portions of the ventricles and was characterized by an uneven distribution in the sarcoplasm with increase in the direction from the interdisc to the nucleus. Unevenness of distribution of the beta-oxybutyric dehydrogenase activity was detected in some of the animals and was pronounced in all the portions of the myocardium. The intensity of the reaction in detection of succinic dehydrogenase, NAD- and NADP-diaphorases varied but insignificantly.


[Ultrastructural changes in the gallbladder mucous membrane during temporary experimental ischemia]. Temporary ischemia of the gall bladder was induced in rabbits by ligation of the gall bladder artery with silk. Histological examination revealed vascular disorders, such as hyperemia, blood stasis and focal hemorrhages. Electron microscopic studies showed the presence of increased number dark epithelial cells, expansion of intercellular area, loosening of the basal membrane and defects in it with invagination of the epithelial cells into the submucous layer. The most striking changes were discovered after a thrice-repeated 30-minute occlusion of the gall bladder artery. The degree of destructive changes proved to depend on the number of stimulated spasms (occlusions) and not on the duration of ischemia. This gives grounds to believe that multiple circulatory disorders participated in the complicated pathogenesis of cholecystitis.


[Morphofunctional state of the cholinergic innervation of the rat pancreas during vagotomy]. Cholinergic innervation of the albino rat pancreas was investigated under normal conditions and after bilateral subdiaphragmatic vagotomy (one, three, seven, twenty one days and two months after the operation). In control animals cholinergic nerve fibers were found in all the organ structures -- both in the vascular and in the gland-duct systems. Vagotomy resulted in a short-term increase in the nerve fibers revealed at the end of the first day, followed by their decrease on the seventh day; but in two months the number of detectable nerve fibers approached the initial level.


[Toxic action of influenza virus on lymphoid-macrophagal reactions in guinea pigs]. Influenza viruses with different degrees of virulence for the human being produced various reactions of the lymphoid-macrophagal elements in the peritoneal exudate of guinea pigs inoculated intraperitoneally. The higher the virulence of the strain for the human being -- the deeper the inhibition of the lymphoid and macrophagal cells of guinea pigs. Low virulent strains of influenza virus induced a considerable functional activity of macrophages, but were devoid of the lympholytic activity. Because of close corrleation between the virulence of the virus and the cellular content of the exudate the lymphocytic-macrophagal reaction in the animals resistant to influenza virus could serve for determination of the toxic activity of the viruses under study.


[Venous stasis and state of the microcirculatory bed in the synovial membranes]. Microcirculatory bed of the synovial membranes was investigated in experiments on dogs during venous stasis. Ligation of the femoral vein and circulatory disturbances led to the alteration of the microcirculatory bed of the synovial membranes, to the overfilling of the venules. Capillary walls became thinner and there developed swellings and protrusions. The extent of the vascular wall changes depended on the calibre of the vessels. One month after the ligation of the vein congestive phenomena in the tissue of the joint capsule proved to decline. This indicated development of collateral venous circulation.


[Role of interstitial cells in prostaglandin synthesis in the kidney medulla]. An electron-microscopic study of the interstitial cells of the medulla of the kidneys was carried out after the administration of the inhibitor of prostaglandine synthesis -- indometacine. Under these conditions the amount of lipid granules in the interstitial cells increased significantly. The authors consider the results of study to be an evident proof of participation of lipid granules in the synthetic function of the interstitial cells as a "depôt" of a chemical precursor of prostaglandines synthesized by the interstitial cells.


[Multichannel recording of gastric electric activity from the surface of the human body]. Technique of synchronous multichannel stomach biopotential recording from the anterior abdominal wall surface was elaborated. Multichannel electrogastrography permitted to record selective electric oscillation of various portions of the stomach from the surface of the anterior abdominal wall. Space-time and correlation tests of the electric activity of different portions of the stomach were carried out in the course of digestion.


[Cation-exchange method of determining the state of magnesium, calcium and strontium in blood plasma]. A method of cation metabolism on cationite KY=2X8 in the balanced-salt form was applied to the study of sorption of Mg2+, Ca2+ and Sr2+ ions from physiological solutions and solutions containing blood plasma of dogs and physiological saline in different ratio. Balance constants, which permitted to determine mol fractions (or the content percentage), of "free" and "bound" ions of the corresponding metals were calculated from the experiments.


Increase in circulating stem cells following chemotherapy in man. The number of circulating granulocytic stem cells (CFU-C) was determined by the in vitro methylcellulose technique in cancer patients receiving intermittent chemotherapy. In 17 patients studied prior to therapy, the median CFU-C concentration per 2 X 10(5) mononuclear cells plated was six, compared to a posttreatment median of 23 in 21 patients (p less than 0.001). Large numbers of stem cells were obtained by leukopheresis and cryopreserved with a 99.5% median CFU-C recovery. Cyclical changes in the concentration of stem cells with maximum values of 20 times baseline were demonstrated in a patient studied at weekly intervals during multiple courses of treatment. It was estimated that, at peak CFU-C concentrations, a quantity of stem cells equivalent to that present in a bulk bone marrow harvest could be obtained from the peripheral blood by a 17-liter pheresis. These results suggest that it may be practical to obtain an adequate number of stem cells from the peripheral blood to study autologous stem cell infusion as a means of averting myelosuppression in patients receiving intensive chemotherapy.


Assessment of erythrocytic and granulocytic colony formation in an in vivo plasma clot diffusion chamber culture system. Normal rat bone marrow cells seeded into a plasma clot diffusion chamber culture developed into erythrocytic and granulocytic colonies in vivo. Chambers implanted into the peritoneal cavity of normal hosts showed erythrocytic colony numbers reaching an initial peak on day 2, declining on days 3--5, and increasing in a secondary growth phase on day 7. Day 2 colonies were evenly dispersed; day 7 colonies were grouped into discrete areas of bursts. Granulocytic colony numbers reached a peak on day 4 and gradually declined through day 7. Cells in various stages of differentiation could be detected in both colony types. Colony numbers were proportional to the number of marrow cells seeded into the chamber. Host animals treated with phenylhydrazine induced a marked increase in erythrocytic colony numbers and size and a decrease in granulocytic colony formation. Host animals treated with endotoxin suppressed erythrocytic colonies while increasing granulocytic colony size. This method may prove advantageous for the study of hematopoietic colony formation in a physiologic environment.


Decreased alpha globine mRNA in nucleated red cell precursors in alpha thalassemia. The alpha thalassemias are associated with a decrease in alpha chain synthesis. Hemoglobin H (HbH) disease is a moderately severe form of alpha thalassemia characterized by the production of 5%--20% of HbH, while alpha thalassemia trait is a milder form of alpha thalassemia. In two patients with HbH disease, the ratio of alpha chain synthesis to beta chain synthesis (alpha/beta ratio) was decreased in both bone marrow cells and reticulocytes. When isolated mRNA from bone marrow cells and reticulocytes was translated in a heterologous cell-free system, the alpha/beta ratios were lower than the intact cell ratios. These findings were confirmed by hybridization of the mRNA of both marrow cells and reticulocytes using purified alpha and beta cDNA probes. In the intact cells of two patients with alpha thalassemia trait, the alpha/beta ratios were also decreased and were similar in marrow cells and reticulocytes. Cell-free studies of translatable mRNA also demonstrated decreased alpha/beta ratios, but, unlike the HbH studies, the cell-free alpha/beta ratios were similar to the intact cell ratios. One hybridization study utilizing peripheral blood mRNA had an alpha/beta ratio consistent with the cell-free ratios. These results indicated that, in both HbH disease and alpha thalassemia trait, there was decreased alpha globin mRNA present in both nucleated red cell precursors and reticulocytes. In addition, the data suggested that there may be translational mechanisms that operate in intact HbH cells which attempt to balance globin chain production. In alpha thalassemia trait cells, no such controls appeared to be active and globin chain synthesis was directly proportional to the amount of alpha and beta globin mRNA in the cells.


Decreased life span and membrane damage of carbamylated erythrocytes in vitro. Red blood cells exposed to cyanate (CNO) in vitro have a concentration-dependent decreased cell survival time associated with an inhibition of the ability of the cell membrane to synthesize lipids. The t1/2 of rabbit erythrocytes exposed to 30 mM or 50 mM cyanate for 1 hr at 37 degrees C is reduced from the normal 24 days to 15 and 9 days, respectively. The cyanate-induced defect in membrane lipid metabolism is irreversible. Carbamylation of membrane proteins and damage to metabolism are minimized by limiting exposure in vitro to 15 mM cyanate at 4 degrees C for 30 min. Cells carbamylated under these conditions do not have a shortened life span. Levels of globin carbamylation of 0.5 moles CNO/mole hemoglobin, shown to be clinically effective in prolonging the life span of sickle erythrocytes, are obtained under these conditions and reach maximal levels after only 30 min of incubation. Carbamylation of blood in CPD anticoagulant is inferior to either ACD or heparin. The findings indicate that adequate carbamylation of sickle erythrocytes with minimal red cell membrane damage can be achieved without significant modification of the standard plasmapheresis procedure utilized by the working blood bank.


A family with red cell pyrimidine 5'-nucleotidase deficiency. Congenital hemolytic anemia associated with pyrimidine 5'-nucleotidase deficiency is reported in two siblings. Both have had moderate chronic hemolytic anemia, splenomegaly, and jaundice since early infancy. The peripheral blood smear is characterized by striking red cell basophilic stippling. As this feature has been found in all previously reported cases, it should be the clue to the diagnosis.


Protein-mediated uptake of vitamin B12 by isolated mitochondria. Protein-mediated B12 uptake by isolated rat liver mitochondria has been shown to be enhanced by plasma transcobalamin (TC-II) but not by salivary R binder in vitro. The process is enhanced by calcium and depends on active mitochondrial respiration. Following uptake, cyanocobalamin is converted to adenosyl and methylcobalamins and released from the mitochondria. TC-II appears to be required for both cellular and mitochondrial uptake of vitamin B12.


Complement-mediated granulocyte dysfunction in paroxysmal nocturnal hemoglobinuria. In paroxysmal nocturnal hemoglobinuria (PNH), infection, both viral and bacterial, disproportionate to the mild neutropenia seen in many such patients is responsible for significant morbidity. We report impaired granulocyte chemotaxis efficiency which may contribute to the problems induced by bacterial infections. PNH (but not normal) granulocytes, after exposure to very small concentrations of activated serum complement components, migrate poorly, as documented by their inhibited chemotaxis toward bacterial products or activated complement components in Boyden chambers. The granulocytes remain intact, excluding trypan blue, phagocytosing, and killing bacteria, despite this activated complement exposure. It is also suggested that this chemotactic defect may involve only a clone of cells, analogous to the clonal lysis of PNH erythrocytes; those few granulocytes capable of migration after exposure to activated complement contain normal quantities of leukocyte alkaline phosphatase (LAP), in contrast to the LAP deficiency of the overall PNH granulocyte population. Since bacterial infection may initiate or potentiate hemolysis, one of the major symptoms of the disease, these results could explain much of the morbidity of PNH.


Platelet function in the Chediak-Higashi syndrome. Platelet function studies were performed on two patients with the Chediak-Higashi syndrome, one of whom had a history of easy bruising unrelated to thrombocytopenia. Both patients had prolonged bleeding times, abnormal platelet aggregation, and a defect of platelet storage granules, manifested by reduced platelet ADP, an increased ATP/ADP ratio, increased adenine nucleotide specific radioactivity after 3H-adenine labeling, and decreased platelet uptake of radioactive 5-hydroxytryptamine. These findings confirm preliminary data in animals with the Chediak-Higashi syndrome, provide and explanation for impaired primary hemostasis in these patients, and illustrate another disorder in which platelet storage-pool deficiency occurs.


Defective platelet function following the administration of penicillin compounds. Platelet function and blood coagulation were studied in five human volunteers receiving penicillin-G in incremental doses of 1.2--48 million U/day, in six volunteers receiving ampicillin in incremental doses of 60--300 mg/kg/day (4--20 g/day), and in six volunteers receiving methicillin in incremental doses of 60--300 mg/kg/day. Coagulation tests remained normal in all 17 volunteers. However, ADP-induced platelet aggregation became abnormal in every subject except one receiving ampicillin and one receiving methicillin. Defective aggregation occurred with predictability with the following doses: penicillin-G, 24 million U/day; ampicillin, 300 mg/kg/day; methicillin, 300 mg/kg/day. All volunteers given penicillin-G and all given ampicillin experienced dose-related prolongation of bleeding time which did not occur with methicillin. Striking prolongation of bleeding time occurred only with penicillin-G in doses of 48 million U/day. Other tests of platelet function including clot retraction, platelet factor 3 availability, and collagen-induced or epinephrine-induced aggregation remained normal during the administration of these drugs. Measurement of intracellular adenine nucleotides revealed that the ADP and ATP content of platelets was unaffected. It appears that at least one mechanism by which the penicillin compounds alter platelet behavior is by interfering with activation of these cells by ADP.


Platelet inhibition by sodium nitroprusside, a smooth muscle inhibitor. The effects of sodium nitroprusside (N.P.), a pure smooth muscle inhibitor, on platelet function were studied. Platelet-rich plasmas (PRP) from normal controls and from patients receiving N.P. were studied in vitro for aggregation in response to adenosine diphosphate (ADP), epinephrine, and collagen. Platelet ADP release (release reaction) was also investigated. Normal platelets demonstrated marked inhibition of aggregation when incubated with N.P. for 3 min. Prolonging the incubation was without additional effect. ADP and ATP release from platelets in response to collagen was also inhibited. PRP from patients receiving nitroprusside at concentrations between 25 mug/min an 165 mug/min showed inhibition of aggregation when compared to findings prior to the administration of N.P. N.P. acts by inhibiting contractile proteins and thus platelet ADP release and aggregation may depend on contraction of platelet smooth muscle-like protein, thrombosthenin.


Distribution of phospholipids, fatty acids, and platelet factor 3 activity among subcellular fractions of human platelets. As compared with other methods, our recently reported method for subcellular fractionation of human platelets improves the separation of mitochondria, alpha granules, and lysosomal enzyme activities. The relative purity of these fractions has led us to undertake the present study to compare the subcellular distribution of phospholipids, fatty acids, and platelet factor 3 (clot-promoting) activity. Two findings pertaining to distribution of phospholipids were entirely new. (1) In the alpha granule zone, plasmalogen phosphatidyl ethanolamine peaked at the expense of diacyl phosphatidyl ethanolamine. (2) The fatty acid composition of the membrane lysophosphatidyl choline suggested that it may have been formed by the action of platelet phospholipase A2 activity. The fatty acids of the membranes showed a markedly asymmetrical distribution in noncholine versus choline phospholipids. The latter held 94%, 72%, and 85%, respectively, of the total content of 16:0, 18:1, and 18:2 fatty acids, whereas 55% of the 18:0, 72% of 20:4, and 67% of higher polyenoic acids other than 20:4 were esterified to the noncholine group. The most important new information related to clot-promoting activity, which, on the basis of protein content, was highest in the membrane fractions, but on the basis of phospholipid content in the nonmembranous fractions. The discussion centers on possible explanations for this novel finding.


Antibodies to factor VIII. V. Patterns of immune response to factor VIII in hemophilia A. The natural history of factor VIII antibodies was studied in 20 severe, multitransfused hemophiliacs. Two patterns of humoral immune reactivity were observed. In one group of ten, who developed antibodies after an average of 22 cumulative exposure days to factor VIII, the antibody titers increased after each antigenic stimulation or persisted for years in the absence of transfusion. These patients were designated as high-responding hemophiliacs. In the second group of ten patients, the factor VIII neutralizing activity appeared after a longer exposure period (48 days). Antibody titers remained low, and there was no significant difference in individual titers before and 8--20 days following transfusion. Antibody affinity did not increase after renewed antigenic challenge. This pattern characterized low-responding hemophiliacs. The latter group of patients benefited from repeated placement therapy required by the clinical situation.


Use of prothrombin complex concentrates in the treatment of a hemophilic patient with an inhibitor of factor VIII. The course and treatment of a life-threatening hemorrhagic episode in a patient with hemophilia A whose plasma contained a high concentration of an inhibitor of factor VIII activity is presented. The inhibitor of factor VIII was localized to the most anodal fractions of immunoglobulin G on electrophoresis, and was thus presumed to be an antibody directed against factor VIII. No therapeutic benefit occurred with infusions of massive amounts of fresh blood and factor VIII concentrates, or with a brief course of immunosuppressive therapy. Administration of standard and activated prothrombin complex concentrates resulted in reduction of the partial thromboplastin time to almost normal values and control of hemorrhage. Eight months later, another hemorrhagic episode occurred. Although a higher titer of inhibitor of factor VIII activity was still present in the patient's plasma, a beneficial therapeutic response was again achieved with standard prothrombin complex infusions.


Combined deficiency of factor V and factor VIII. A report of another case. A patient with combined factor V and factor VIII deficiency is presented. The bleeding manifestations were: easy bruising, post-traumatic bleeding, bleeding after tooth extractions. The main laboratory feature was a prolonged partial thromboplastin time which was corrected by the addition of adsorbed normal plasma but not by the addition of normal serum, hemophilia A plasma of another patient with combined factor V and factor VIII deficiency. The thromboplastin generation test was clearly abnormal and was corrected by the addition of adsorbed normal plasma but not by addition of normal serum. Prothrombin consumption was also defective. Prothrombin time was slightly prolonged too, Thrombin time, platelet and vascular tests were within normal limits and there was no hyperfibrinolysis. Factor VIII was 8% of normal, whereas factor V was 14% of normal. Factor VIII associated antigen was normal. All other clotting factors were within normal limits. The parents of the propositus were consanguineous (first cousins) but had normal factor V and factor VIII activity and normal factor VIII antigen. The same was true for other family members. The hereditary transmission of the condition appears autosomal recessive.


[Malformations, anomalies and variations in patients with severe iron deficiency]. In severe iron deficiency which frequently occurs in the population of Turkey, malformations, anomalies and variations are often observed. In 190 patients with severe iron deficiency of long duration such abnormalities could be found in 107 cases. The abnormal changes were of different character and occured in various parts of the body. In the majority multiple changes, ranging from 2 to 7 and more could be registered. 100 persons showing no iron deficiency and no anemia presented a much lower incidence of the same changes; in a second group of 54 patients suffering from a severe anemia without iron deficiency the incidence was still lower. These observations suggest that the occurrence of the abnormalities is closely connected with the iron deficiency. The character of the abnormal changes which are not susceptible to iron treatment are pointing to a prenatal origin. The diversity of the changes, the occurrence in various parts of the body and skeleton as well as the multiplicity of incidence are showing that they are due to impairment of the process of development in the embryonic organism. This view is supported by the results of the examination of the chromosomes. A distinct relation could be established between the incidence of the malformations and the occurrence of the chromosomal aberrations. As the iron deficiency in the Turkish population is mainly caused by an insufficient supply of iron with the food it is likely that by sufficient iron supply in pregnant women the incidence of malformations and anomalies caused by the iron deficiency can be prevented and by a general amelioration of the nutrition their occurrence in the population markedly reduced.


Haematological values for the Finnish reindeer. Red blood cell counts, haemoglobin, packed cell volumes and total and differential leucocyte counts as well as E-MCHC, E-MCH, E-MCV values and the osmotic fragility of erythrocytes are described for the Finnish reindeer. The samples were taken in early autumn from 52 reindeer of varying ages.


[Biologic activity of various intrinsic factor preparations in Schilling's test]. In 16 patients with pernicious anaemia investigations concerning the biological activity of 7 different Intrinsic-factor praeparations by means of the urinary excretion test were performed. Oral longterm-pretreatment with IF and biologically inactive IF-praeparations may cause false pathologic results.


[Experimental studies on population genetics of complement 3 (C3) and serum component transferin (Tf) in the population of Northern Bavaria]. Within a population sample concerning 2500 blood donors of Northern Bavaria, the population genetics of the Systems C3 and Tf have been investigated. The calculated gene frequencies are: C3S = 0,789; C3F = 0,2028; C3Var. = 0,0082; TfC = 0,9960; TfVar. = 0,0040. As a "new" variant C3F1,55 has been found.


A study of the inhalation of pentachlorophenol by rats. Part I. A method for the determination of pentachlorophenol in rat plasma, urine and tissue and in aerosol samples. Simple and flexible methods have been designed for the determination of pentachlorophenol in animal tissue, blood plasma, urine, and aerosol. The isolation of the pesticide is achieved through its extraction with benzene or hexane after acidification, derivatization, and its subsequent purification through florosil columns. A brief describption of the sampling methods is included. The described procedures are especially suited for exposure experiments where different types of samples with a large variety of PCP concentrations are encountered.


A study of the inhalation of pentachlorophenol by rats. Part II. A new inhalation exposure system for high doses in short exposure time. An exposure system has been designed which is applicable for short time, acute exposures of rats to the aerosol of pesticides. The aerosol is generated by compressed air aspiration. Larger droplets are removed by a cyclone separation. The exposure chamber has 12 inhalation sites separated from the animal containers by rubber seals which insure inhalation as the only route of exposure.


New library buildings. Part VI: Sciences Library, Brown University. Brown was one of the first universities in the nation to combine its science collections into a single library in the interest of aiding interdisciplinary teaching and research. This paper discusses the evolution of the Sciences Library and its resources, the development of the medical education program, and the physical aspects of the new library building. A fifteen-story tower, housing the collections of the physical, biological, and medical sciences, symbolizes the interdisciplinary approach to teaching and research at Brown University.


The art of planning for library personnel. A review of the planning process for personnel at the University of Cincinnati's new Health Sciences Library is discussed. The staff of two libraries were involved in the plan. The final organizational pattern encompassed present staff plus justification for additional staff who would be necessary in the expanded facility.


The PHILSOM system--one user's experience. The University of Texas Health Science Center at San Antonio joined the PHILSOM system, a comprehensive serials control network, in 1971. The experiences of the library in using the system are described. The major benefit of the system has been multiple copies of the holdings list which have made the serial records publicly accessible and significantly increased their value. Tallies of these lists' use indicate that more than half of serials-related questions are now answered directly by the users. The effects of PHILSOM on the procedures of the serials department--processing, claiming, bindery, and personnel are described. Costs to the network and the UTHSCSA Library are briefly summarized.


Secondary repair of bilateral cleft lip deformities. A two-stage approach. A two-stage procedure using previously described principles has been designed to achieve muscle-to-muscle union, narrowing of the philtrum and lengthening of the columella. In addition fistulas may be corrected simultaneously.


Reduction of very large breasts: the inferior flap technique of Robertson. The Robertson technique of reducing very large breast is decribed. In 24 patients it has proved to be a simple, reliable, reproducible procedure without complications, which provides well-shaped breasts of a normal size.


The size of the human omentum and methods of lengthening it for transplantation. The size of the omentum is variable and can only be predicted within the standard deviations. However, the lower limits of its size have now been ascertained over a large series and it is clear that it could be lengthened sufficiently to reach the vault of skull, mid-leg or mid-forearm levels in all cases. Of course, to do so will decrease its width. An alternative to pedicle transfer is to use the whole omentum as a free transplant by vascular anastomosis.


A traumatic fistula of the submandibular gland. A salivary fistula of a submandibular gland was successfully treated by excision of that gland.


Tryptophan metabolism in the isolated perfused liver of the rat: effects of tryptophan concentration, hydrocortisone and allopurinol on tryptophan pyrrolase activity and kynurenine formation. 1 The effect of tryptophan concentration on the rate of kynurenine appearance and tryptophan disappearance in the medium perfused through the isolated liver of the rat has been investigated. The effect of pretreatment of the rat with hydrocortisone or allopurinol was also examined, together with the effects of these treatments on liver tryptophan pyrrolase activity measured in vitro at the beginning and end of perfusion. 2 Hydrocortisone (5 mg/kg) injection 3 h before perfusion resulted in a four-fold increase in kynurenine production by the liver during perfusion with a medium containing either 0.1 mmol/1 or 1.0 mmol/1 tryptophan. Injection of allopurinol (20 mg/kg) together with hydrocortisone and addition of allopurinol (4 mg/100 ml) to the medium abolished the hydrocortisone-induced rise of kynurenine in the 0.1 mmol/tryptophan medium but not the 1.0 mmol/1 tryptophan medium. 3 Injection of cycloheximide (30 mg/kg) with hydrocortisone (5 mg/kg) 3 h before perfusion inhibited the hydrocortisone-induced rise of kynurenine production and the increase in pyrrolase activity measured in vitro both before and at the end of perfusion with 1.0 mmol/1 tryptophan. This last result suggests that protein synthesis is involved not only in hydrocortisone induction of pyrrolase but also in substrate induction. 4 Kynurenine production in the 1.0 mmol/1 tryptophan medium was less in both saline- and hydrocortisone-treated older rats (335-450 g) compared to younger rats (180-220 g). In agreement with a previous study, pyrrolase activity in vitro was also lower in both saline- and hydrocortisone- treated older rats at the beginning of the perfusion although activity had risen equally in both young and older rats at the end of perfusion. 5 There was little correlation between the rate of tryptophan disappearance from the medium and the activity of tryptophan pyrrolase either as measured in vitro or as indicated by the rate of kynurenine production. 6 In general, the production of kynurenine in the medium at the end of the 60 min perfusion was indicative of in vitro pyrrolase activity at the start of the perfusion. 7 It is concluded that while in vitro pyrrolase assay does not give a quantitative index of kynurenne production, it does provide a qualitative index. Furthermore, if kynurenine production in the isolated perfused liver of the rat is indicative of in vivo pyrrolase activity, then hydrocortisone must induce pyrrolase activity in vivo.


Mechanism of the indirect sympathomimetic effect of 5-hydroxytrypt-amine on the isolated heart of the rabbit. 1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethylphenylpiperazinium (DMPP). 2 The cardiac stimulant effects of 5-HT, tyramine and DMPP were inhibited by propranolol and practolol and the pA2 values obtained were similar to those obtained with noradrenaline as the agonist. 3 Responses to 5-HT, tyramine and DMPP were greatly reduced on hearts from rabbits pretreated with 6-hydroxydopamine. Such hearts had less than 7% of their normal catecholamine concentration and no fluorescence characteristic of noradrenaline in the cardiac sympathetic nerves could be demonstrated. 4 Rapid, reversible and selective tachyphylaxis to 5-HT was demonstrated during perfusion with 5-HT. In hearts desensitized to DMPP by perfusion with DMPP, responses to 5-HT were also reduced. 5 Perfusion of hearts with colchicine inhibited stimulant responses to 5-HT and DMPP but had little effect on responses to noradrenaline or tyramine. 6 Desmethylimipramine enhanced cardiac stimulant responses to noradrenaline and to a lesser extent, those to 5-HT and DMPP. Responses to tyramine were consistently inhibited by desmethylimipramine. 7 Tetrodotoxin abolished responses of the heart to electrical nerve stimulation but left responses to noradrenaline, 5-HT and DMPP unaffected. 8 5-HT, tyramine and DMPP evoked 3H-release from hearts whose neuronal noradrenaline stores had been labelled by perfusion with [3H]-(-)-noradrenaline. The pattern of release evoked by 5-HT was similar to that of DMPP but differed from that of tyramine. 9 Reducing the calcium concentration in the Tyrode solution from 3.6 to 0.2 mEq/1 did not affect 3H-overflow after tyramine but greatly inhibited that evoked by 5-HT and DMPP. 10 The results confirm that the stimulatn effects of 5-HT on the rabbit isolated heart are the result of noradrenaline release. They further suggest that the site of the release is the terminal sympathetic nerve network. The mechanism of release shows more similarities to that of DMPP (calcium-dependent depolarization and exocytosis) than to that of tyramine (neuronal uptake and stoichiometric displacement).


The different effects of D-600 (methoxyverapamil) on the release of adrenal catecholamines induced by acetylcholine, high potassium or sodium deprivation. 1 Bovine adrenal glands were perfused with Locke solution and catecholamine release was induced by acetylcholine, by a depolarizing concentration of potassium, or by omission of sodium from the perfusion fluid. 2 D-600 (methoxyverapamil) at the concentration of 30 muM produced a 23% inhibition of catecholamine release evoked by acetylcholine (0.1 mM) in the presence of physostigmine (10 muM). 3 A concentration of D-600 of 0.3 mM produced 86% and 85% inhibition in the output of catecholamines in response to acetylcholine and high potassium respectively. 4 D-600 (0.3 mM) failed to block the release of catecholamines evoked by sodium deprivation. 5 The results suggest the involvement of intracellular calcium in the exocytotic release of catecholamines induced by sodium omission.


On the actions of compounds related to dopamine at a neurosecretory synapse. 1 The effects of a number of substances related to dopamine, including all its methylated derivatives, were investigated on the membrane potential and response to nerve stimulation of cockroach salivary gland cells. 2 Only N-methyldopamine (epinine), N,N-dimethyldopamine and N,N-dimethylnoradrenaline, all with unsubstituted hydroxyl groups, directly resembled dopamine in producing a hyperpolarization which could be as large as that caused by maximal nerve stimulation. During the continued presence of these substances the hyperpolarization waned and responses to nerve stimulation declined. 3 Many of the compounds caused one or both of two other effects, namely an increase in the rate of 'spontaneous miniature hyperpolarizations' and an enhancement of the submaximal responses to single nerve stimuli. There were no obvious structural requirements for these effects.


Evidence concerning the involvement of 5-hydroxytryptamine in the locomotor activity produced by amphetamine or tranylcypromine plus L-DOPA. 1 Pretreatment of rats with p-chlorophenylalanine (PCPA; 2 X 200 mg/kg) decreased the concentration of 5-hydroxytryptamine (5-HT) in the brain. It also decreased the locomotor activity produced by tranylcypromine plus L-DOPA administration 24 h after the second dose of PCPA. 2 Pretreatment with p-chloroamphetamine, which produced a similar decrease in brain 5-HT concentrations did not decrease the locomotor response to tranylcypromine and L-DOPA. 3 PCPA pretreatment decreased the rise in the concentration of DOPA and dopamine in the brain following tranylcypromine and L-DOPA, suggesting its effect on the dopamine-induced locomotor activity was the result of this drug diminishing dopamine formation in the brain, probably by inhibiting L-DOPA uptake. 4 The locomotor activity produced by tranylcypromine and L-DOPA was not decreased by pretreatment 6 h earlier with disulfiram (400 mg/kg). This argues against the locomotor activity being due to noradrenergic stimulation. 5 PCPA pretreatment did not alter amphetamine-induced stereotypy or the circling behaviour in unilateral nigro-striatal lesioned rats.


The effect of aspirin on 5-hydroxytryptamine uptake and release by human platelets. The influence of aspirin on 5-hydroxytryptamine (5-HT) uptake and storage by human blood platelets has been investigated. Uptake of 5-HT was strongly inhibited. In 30 min aspirin released 50% of the 5-HT that had been incorporated into the platelets prior to the addition of the aspirin. These results are discussed in terms of possible interference with a 5-HT membrane receptor and the impairment of 5-HT storage in the dense granules.


Potentiation by desipramine of neuronal responses to mescaline. The effect of desipramine on responses of single cortical neurones to mescaline was studied by the microelectrophoretic technique. Both potentiation and antagonism of responses to mescaline by desipramine were observed. The antagonism may be related to the alpha-adrenolytic action of desipramine. The potentiation is unlikely to reflect the uptake blocking action of desipramine, since desipramine does not block the uptake of mescaline in the cerebral cortex. It is suggested that the potentiation may be due to a post-synaptic action of desipramine.


Calcitonin: antagonism at intestinal muscarinic receptors. The action of calcitonin was studied on the motility of isolated innervated segments of rabbit and guinea-pig intestines as well as longitudinal muscle with adherent myenteric plexus dissected from the guinea-pig ileum. Calcitonin (0.25 muM) antagonized contractile responses to acetylcholine and the cholinergic response to electrical field stimulation. This hormonal effect was relatively specific since it was not observed at nicotinic receptors or adrenoceptors, nor did calcitonin act as a local anaesthetic or directly on the contractile machinery of smooth muscle. Perivascular adrenergic and intrinsic non-adrenergic inhibitory responses also were unaffected by calcitonin. However, calcitonin did have antihistaminic properties directed against H1-receptors. The concentration of calcitonin required to achieve muscarinic antagonism in our experiments is not reached at the resting level of circulating hormone.


Effects of sympathomimetic amines on 45Ca efflux from liver slices. The efflux of 45Ca from slices of guinea-pig and rabbit liver is greatly increased by alpha-adrenoceptor agonists. Isoprenaline is much less effective. The effects of these agents on the efflux of 45Ca mirror their actions on 42K loss and suggest that the two may be related. Glucose release from both rabbit and guinea-pig liver slices is increased to a similar extent by either alpha- or beta-receptor agonists. The possible relationship between Ca and K movements and the production of glucose is discussed.


The relationship between cardiotoxicity and plasma digoxin concentration in conscious dogs. 1 The tendency of a given oral dose of digoxin to induce cardiac dysrhythmia was determined indirectly at various times after its administration to eight conscious dogs by measurement of the intravenous dose of acetylstrophanthidin necessary to induce toxic changes in the ECG. Acetyl-strophanthidin was used because its rapid elimination from the body permitted estimates to be made 45, 180 and 360 min after digoxin administration. 2 Each dog underwent four studies in which doses of 0.05, 0.1, 0.2 and 0.4 mg/kg digoxin were used in a randomized sequence allowing at least ten days between each dose. 3 Digoxin reduced the amount of acetylstrophanthidin required to cause toxic changes in the ECG; this increase in cardiac sensitivity was dose-dependent. 4 There was no correlation between plasma levels of digoxin and the tendency to dysrhythmia, since peak plasma concentrations of digoxin were reached at about 60 min after dosing whereas maximal sensitivity to acetylstrophanthidin was found 3 to 6 h after administration of digoxin. 5 These results suggest that there is little or no increased risk of cardiotoxicity during periods of transient increase in plasma levels of digoxin.


Emetine myopathy in the rat.

Emetine myopathy in the rat. 1 (-)Emetine (0.25-2.0 mg/kg i.p.) was administered to rats for up to 220 days. 2 At doses of 1.0 mg/kg or less, the animals continued to gain weight but more slowly than the untreated control animals. The physiological changes in the muscles from these animals were minimal; there was a small reduction in both the resting membrane potential and in the maximum rate of rise of the action potential. There was no atrophy or loss of muscle fibres although in the occasional muscle, hyaline fibres, necrotic fibres and split fibres were observed. There was a focal loss of myofibrillar adenosine triphosphatase (ATPase) and nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) in Type II and Type III fibres, but no such loss in Type I fibres. 3 The animals receiving 2.0 mg/kg of (-)emetine gained weight slowly for up to 20 days but then rapidly lost weight and by 30 days they were weak and emaciated. The muscles from these animals were severly atrophied and the total muscle wet weight was reduced by almost 20%. 4 The strength of the muscles from these animals was measured in vitro using direct stimulation. They were weaker than normal both in absolute terms and when expressed in terms of tension developed/unit wet weight. 5 There was no evidence of either functional or structural denervation but surgically denervated muscles from animals in this group were indistinguishable from denervated muscles from normal rats. 6 Severe structural damage was obvious in the fibres of both extensor digitorum longus and soleus. Necrotic, hyaline and splitting fibres were common and the focal loss of myofibrillar ATPase and NADH-TR activity was extensive and occurred in Type I fibres as well as in Type II and Type II fibres. 7 It is concluded that the muscular weakness induced by (-)-emetine is due to a direct effect on the muscle fibres and that this occurs at a subcellular level. There is no evidence that functional or structural denervation plays any role in the aetiology of emetine myopathy in the rat.


Effects of amino acids and convulsants on spontaneous action potentials in cerebellar cortex slices. 1 Picrotoxin selectively and reversibly suppressed the inhibitory action of gamma-aminobutyric acid (GABA), but not that of glycine, taurine or beta-alanine, on the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Strychnine reversibly suppressed the inhibitory action of glycine, taurine or beta-alanine but had no effect on that of GABA. 2 GABA, glycine, taurine and beta-alanine showed an early excitatory effect that was unaffected by picrotoxin or strychnine. 3 Studies of the dose-response relations indicated a competition between the amino acid and the convulsant at a common receptor site. 4 Kinetic analyses of the dose-response relations for the amino acids in the presence or absence of picrotoxin or strychnine indicated that the number of molecules of amino acid combining with the receptor site in order to produce a response (inhibition or excitation) was 3 for GABA, 2 for glycine, 3 for taurine and 4 for beta-alanine. There appeared to be no evidence that the response was due to the cooperativity between the amino acid receptor complexes. The number of molecules of convulsant that combined with the receptor site was 1 for either strychnine or picrotoxin. 5 Mixtures of glycine with taurine or beta-alanine, in contrast to those with GABA, appeared not to give additive inhibitory effects.


Effects of some purine derivatives on the guinea-pig trachea and their interaction with drugs that block adenosine uptake. 1 Adenosine, adenosine 5'-triphosphate (ATP), adenine, inosine and guanosine all caused concentration-dependent relaxations of guinea-pig tracheal smooth muscle in vitro. The relative potencies in descending order were: adenine greater than or equal to guanosine greater than inosine greater than or equal to adenosine greater than or equal to ATP. 2 Responses to the purine compounds were unaffected by propranolol (1 mug/ml). 3 The spasmolytic potencies of adenosine and ATP were greatly enhanced in the presence of the adenosine uptake blocking drugs dipyridamole, hexobendine or Dilazep, whereas responses to adenine were unaffected and those to inosine and guanosine were reduced. 4 The spasmolytic potencies of noradrenaline, aminophylline, prostaglandin E2 and glyceryl trinitrate were unaffected by dipyridamole, hexobendine and Dilazep. 5 It is suggested that an adenosine uptake process may exist in the trachea of the guinea-pig and that this process is inhibited by dipyridamole, hexobendine and Dilazep.


Concentration of (+/-)-propranolol in isolated, perfused lungs of rat. 1 The metabolism and the accumulation of (+/-)-propranolol have been studied in isolated lungs of the rat, perfused with an artificial medium. 2 Little or no metabolism took place during the perfusion periods (up to 10 minutes). 3 Accumulation was observed with high tissue/medium ratios for substrate concentrations of 0.2 muM to 1 mM; there was evidence for saturability, but no real plateau could be seen. The presence of two binding sites with different affinities was established. 4 Cold greatly inhibited the accumulation process at low substrate concentrations, but had no effect at 1 mM propranolol. 5 Inhibition of accumulation was measured in the presence of imipramine, desmethylimipramine, nortryptiline, chlorpromazine and of Na+-free medium. Cocaine, 5-hydroxytryptamine and noradrenaline had no effect. Lidocaine enhanced the accumulation process. Release of previously bound propranolol was accelerated in the presence of propranolol and imipramine, unaffected by a Na+-free medium and decreased by cold and by lidocaine. 6 Experiments on lung tissue slices yielded qualitatively similar results to those obtained with perfused lungs. Ouabain and KCN had no or little effect on propranolol accumulation.


Indirect effects of amino-acids on sympathetic ganglion cells mediated through the release of gamma-aminobutyric acid from glial cells. 1 All experiments were performed on rat isolated desheathed superior cervical ganglia maintained in Krebs solution containing amino-oxyacetic acid (10 muM) at 25 degrees C. 2 Influx rates of gamma-amino-n-butyric acid (GABA) were measured by incubating ganglia in 0.5 muM [3H]-GABA for 30 minutes. Influx was inhibited by 50% on adding 14.3 muM unlabelled GABA, 59.2 muM beta-alanine (BALA) or 424 muM beta-amino-n-butyric acid (BABA). 3 Efflux of [3H]-GABA into non-radioactive solution superfused over ganglia previously incubated for 60 min in 1 muM [3H]-GABA was measured. The mean resting efflux rate coefficient (k) was 0.64 +/- 0.05 X 10(-3) min-1. Addition of high concentrations of unlabelled GABA, BABA or BALA to the superfusing solution increased k by (maximally) 3.6-4.3 times; half-maximal increases occurred at the following concentrations: GABA, 16 muM; BALA, 85 muM; BABA, 606 muM. Replacement of external Na+ with Li+ or TRIS increased the resting value of k and inhibited acceleration by external amino acids. Prior incubation in 1 muM [3H]-GABA with 1 mM unlabelled GABA increased resting k 1.5 times, but did not alter the peak rate coefficient produced by external amino acids. 4 Neuronal depolarization produced by the amino acids was measured with surface electrodes. Pre-incubation in 1 mM GABA for 60 min potentiated low-amplitude responses to BALA or BABA but not those to GABA or 3-aminopropanesulphonic acid (a potent agonist with low affinity for the GABA carrier). Omission of external Na+ reduced responses to BABA but increased those to GABA. 5 Incubation in 1 mM GABA for 60 min (as required to potentiate BABA or BALA actions) increased the amount of GABA in the tissue from 0.21 to 0.73 mmol/kg wet weight. Autoradiographs in which labelled GABA was used indicated that uptake into neuroglial cells was responsible for this accumulation. 6 It is suggested that: (i) BALA and BABA are substrates for the inward GABA carrier responsible for GABA entry into ganglionic glial cells; (ii) they accelerate efflux by inhibiting carrier-mediated reaccumulation of effluent GABA by the glial cells; (iii) interstitial GABA concentrations are thereby increased to a level capable of depolarizing adjacent neurones; and (iv) this, rather than direct GABA-receptor activation, accounts for the depolarization produced by low concentrations of BALA and BABA. Potentiation of their depolarizing action after pre-incubation in 1 mM GABA is suggested to result from the increased amount of intracellular GABA available for release, and is quantitatively compatible with this increase; inhibition in Na+-free solution is due to their inability to inhibit reaccumulation of GABA under these conditions. 7 A model for the action of carrier substrates is described in an Appendix. Calculations based thereon yield increments in interstitial GABA concentration in the presence of carrier substrates compatible with those determined experimentally (up to 1 muM at rest or 3.4 muM after pre-incubation in GABA).


The inhibition by glucagon of the vasoconstrictor actions of noradrenaline, angiotensin and vasopressin on the hepatic arterial vascular bed of the dog. 1 The hepatic artery of the anaesthetized dog was cannulated and perfused from a femoral artery, the blood flow and perfusion pressure being monitored continuously. The sympathetic periarterial nerves were divided. 2 Dose-dependent increases in hepatic arterial vascular resistance (HAVR) resulted from intra-arterial injections of noradrenaline, angiotensin and vasopressin. 3 Single injections of glucagon (100 mug, i.a.) caused a transient significant fall in HAVR of 19.9 +/- 3.2%, and infusions of 25 mug/min of glucagon intra-arterially caused maintained reductions in HAVR of 16.9 +/- 4.2%. 4 After single injections of 100 mug glucagon intra-arterially the vasoconstrictor responses to noradrenaline, angiotensin, and vasopressin were reduced by about 85-95%. Recovery occurred in 8-10 minutes. 5 Intra-arterial infusions of glucagon, 2.5-50.0 mug/min, reduced the effects of test doses of noradrenaline, angiotensin and vasopressin throughout the period of the infusions. 6 Dose-response curves to the constrictor agents were constructed before, during and after intra-arterial infusions of 25 mug/min of glucagon. Glucagon caused a parallel shift of the curves for noradrenaline and angiotensin to the right, with no suppression of the maximum response. 7 Infusions of glucagon shifted the dose-response curve for vasopressin to the right, but, in contrast to noradrenaline and angiotensin, the shift was nonparallel and there was a suppression of the maximum response by about one-half. 8 A large dose of insulin, 10 iu, transiently reduced HAVR and caused a weak and very transient inhibition of the effect of test doses of noradrenaline. The characteristics of these effects were quite different from those of glucagon. 9 It is possible that the antagonism by glucagon of the vasoconstrictor responses of the hepatic arterial vasculature may be important in protecting this vascular bed from the effects of concomitantly released vasoconstrictor agents.


Heroin misuse and delinquency in a new town. The subjects of this study were eighty misusers of heroin who lived in the New Town of Crawley, West Sussex. The relationship between their criminal histories and their histories of drug misuse were examined. It was found that more of the heroin misusers than would be expected had been convicted of criminal offenses before they began to misuse drugs, while the reduction or cessation of heroin use during a four-year follow-up period was accompanied by a reduction in convictions. Some social characteristics of the male heroin misusers were compared with those of two other Crawley groups--a group of juvenile offenders who did not misuse heroin and their control group of non-delinquents. Characteristics commonly associated with maladjustment did not distinguish the heroin misusers from the juvenile offenders, nor were they found to be associated with the continued use of heroin. Analysis of the data in epidemiological terms suggested that among the necessary conditions for an outbreak of drug misuse in a particular community the availability of drugs together with socializing drug users were more important than the presence of predisposed individuals.


Psychiatric problems in systemic lupus erythematosus. Four patients with systemic lupus erythematosus (SLE) are described in whom there were major psychiatric complications. Two of these patients had cerebral lupus with psychiatric manifestations of the disease together with other features of disease activity and responding to treatment with high dose steroids. The first of these had had a ten-year history of recurrent episodes of depression before other features of the disease became evident; in the second patient recurrent psychotic episodes occurred after the onset of typical multi-system disease. The third patient had had a minor cerebro-vascular accident four years before other features of SLE became manifest, and cerebral deterioration later on in her life was probably due to hypertensive cerebro-vascular disease secondary to the renal disease of SLE. The fourth patient, a young man, had had recurrent episodes of depression and aggressive behaviour for several years and committed suicide at the age of 33.


Crohn's disease: a psychosomatic illness? We investigated the psychological status of Crohn's disease patients because 10 such patients had been referred to our psychiatric out-patient department over a period of six years, whereas if there were no association between the disease and psychiatric morbidity, the expected referral rate would be one case in 20 to 100 years. We found an association between episodes of psychiatric and physical symptoms in the case histories. We administered the Eysenck Personality Inventory and the Manifest Anxiety Scale to 28 out-patients with Crohn's disease (8 psychiatrically and 20 non-psychiatrically referred), 17 with chronic non-psychosomatic medical diseases, 43 with psychosomatic diseases and 100 with neurosis. Crohn's disease patients were significantly more anxious, neurotic and introverted than both the test norms and the non-psychosomatic medical out-patients and did not differ appreciably from the psychosomatic patients in these respect.


'Filtering' and the cognitive deficit in schizophrenia. This study attempted to clarify the nature of dysfunction in the selective attention of schizophrenics. Within the framework of Broadbent's (1971) theory of information processing it was argued that 'filtering' inefficiency should be reflected in a reduction in the discrepancy in performance on a short-term memory task between the condition of pre-instruction as to the relevant material and that of post-instruction. Three groups of subjects, 10 schizophrenics, 10 depressives, and 10 normals, matched for age and intelligence were tested on such a task. While the overall performance of normal subjects was superior to that of both psychiatric groups, depressives and schizophrenics did not differ. The normal group also showed a significantly greater improvement with pre-instruction than the psychiatric groups; again, the schizophrenics and depressives did not differ significantly, though there was a tendency for schizophrenics to benefit less than depressives from pre-instruction. It appears that 'filtering' difficulties as here defined may not be specific to schizophrenia. Alternative conceptualizations of the cognitive abnormalities shown by schizophrenics, such as slowness of information processing and difficulties in response selection, may be more useful.


A job rating scale for use in psychiatric rehabilitation. Work has been a highly valued feature of psychiatric rehabilitation programmes. The performance of patients has often been the object of scrutiny and assessment, but the jobs performed by these patients have not been so assessed. This paper describes the development and use of a job rating scale which parallels the use of patient assessment instruments.


Influence of coroners' officers and pathologists on suicide verdicts. Three-hundred-and-thirty cases of unnatural death, leading to 110 open verdicts, 110 verdicts of suicide and 110 of accident, from the Inner West London Coroner's District have been examined to see if particular coroner's officers or pathologists were associated with disproportionate numbers of suicide verdicts. No significant deviations from the expected numbers were found. Coroner's officers probably share common ideas about the features defining suicide, and so do pathologists.


Monosymptomatic hypochondriasis, abnormal illness behaviour and suicide. Two cases of chronic monosymptomatic psychogenic eye pain with abnormal illness behaviour are presented. Both failed to respond to a wide variety of treatments, and despite the accepted low suicidal risk in hypochondriasis both killed themselves. The origin, prognosis and therapy of such behaviour are discussed in this context.


A comparison between the Hamilton Rating Scale and the Beck Inventory in the measurement of depression. Correlations were made between ratings on the Hamilton Rating Scale for depression and the Inventory for measuring depression devised by Beck. Satisfactory and significant correlations were observed in only two-thirds of the patients, and often very divergent results were found in the remaining third.


Dyskinesias associated with tricyclic antidepressants. Hyperkinetic movement disorders may occur as side effects of antipsychotic drugs; and a hyperdopaminergic state induced by the neuroleptic compounds is thought to be a cause of extrapyramidal disorders such as tardive dyskinesia. We have observed two cases of the dyskinetic syndrome in patients receiving tricyclic antidepressants (TCA). Because the TCA are known to have little effect on striatal dopamine but do share with the neuroleptics potent anticholinergic activity, these cases appear to support the hypothesis that the drug-induced hyperkinetic disorders are related to a diminution of CNS acetylcholine activity as well as to an increase in dopamine activity.


Psychiatric priorities in developing countries. Many psychiatrists assert that an expansion of mental health services in the developing countries is overdue. This will only take place if: (i) the tasks of mental health care are undertaken by a wide range of non-specialist health workers, including those responsible for primary health care; and (ii) services are directed initially at a very limited range of priority conditions. The method of priority selection is discussed, and the process required for translation of priority decisions into health action is exemplified by two illustrations.


A clinical evaluation of depressives found in a rural survey in India. Those who were labelled as depressives in a rural survey were randomly divided into a Medicine group (who received antidepressive drug treatment), a Placebo group (who received placebo) and a Natural Process group (who received no treatment). The depth of their depression was assessed by Hamilton's Depressive Rating Scale before the beginning of the trial, on the 14th day and on the 28th day of trial. They were compared with a matched group of healthy controls and again with a matched group of depressives who attended an urban clinic for treatment. The results indicate that the rural depressives who never sought treatment voluntarily were not different from those who sought treatment in clinics, so far as their response to treatment is concerned.


Attempted suicide among Asian immigrants in Birmingham. This retrospective study describes the epidemiology of attempted suicide among Asian (Bangladesh, India and Pakistan) immigrants in Birmingham during the period 1969-1972. The hypothesis of no difference in the distribution of attempted suicide among native and immigrant groups was not upheld. The immigrant group was under-represented among all the admissions to Birmingham's hospitals. It is estimated that the crude adjusted rates for attempted suicide among the male and female Asian immigrants aged 15-64 years are 57 and 126 per 100,000 population per annum respectively. These are lower than the rates found among natives in Britain, but the female immigrant rate is higher than that found in India. Asian patients who attempt suicide in India and Birmingham are younger than 45 years of age, rarely abuse drugs and alcohol, and make repeated attempts infrequently. In Birmingham, however, immigrants and native patients swallow similar, mostly psychotropic, tablets and not insecticides as in India. It is noteworthy that an interpersonal dispute precedes attempted suicide more frequently among immigrant patients than among native ones in either area.


Attempted suicide among the Irish-born population in birmingham. The epidemiology of attempted suicide among Irish immigrants in Birmingham is described from data concerning 352 (138 male, 214 female) hospital admissions made during the period 1969 to 1972. Admissions from the Irish Republic and from Northern Ireland were similarly distributed, but were both grossly over-represented. The average annual rate of admission (222 male, 362 female) was probably higher than the rates in Dublin, Belfast and Edinburgh. The female patient rate (286) was greater than that of Edinburgh, but the male rate (143) was not. Fewer Irish than British admissions gave a history of previous attempted suicide or repeated this attempt. Indices of stress among immigrants were, however, greater. The importance of socio-cultural factors is discussed.


How common is anorexia nervosa? A prevalence study. During 1972-74 nine populations of schoolgirls were surveyed in respect of the occurrence of anorexia nervosa. As well as the current school year, previous years (going back variously 3-6 years) were also carefully studied within seven of the schools. Anorexia nervosa was only identified as present or having been present if the diagnosis was unequivocal: for instance, seemingly evident and severe cases which could not be traced were excluded. The condition in severe form was found to be relatively common in the independent sector of education, probably implying a social class factor. In all such schools, the prevalence was one severe case in approximately every 200 girls. In those aged 16 and over it amounted to one severe case in about every 100 girls. Overall, these schools encountered one 'new' severe case in every 250 pupils aged 16 years and over. The condition is likely to be even more common than this study allows because of the stringent limits set here on inclusion of cases and the age-bands studied. It is concluded that severe anorexia nervosa is a common condition and is probably getting more common.


Anorexia nervosa after the menopause.

Anorexia nervosa after the menopause. A patient is described who developed the classical syndrome of anorexia nervosa at the age of 52. Her illness occurred in relation to the marriages of her daughters and showed an extreme preoccupation with her body shape and a determination to slim by diet, purging and vomiting, and the hiding of food to the extent of rendering herself too weak to cope with the demands of her life. It is suggested that anorexia nervosa, though predominantly a disease of onset in adolescence, may present at any age and should be considered in the differential diagnosis of anorexia in patients over the age of 50.


Anxiety and depression after infectious mononucleosis. Thirty-six patients who had had infectious mononucleosis (IM) were followed up a year later and assessed by the Middlesex Hospital Questionnaire and by interview or (in five cases) by postal questionnaire. The results support the view that IM leads to depression in a considerable number of cases, but in this series only women were so affected.


Psychiatric aspects of narcolepsy.

Psychiatric aspects of narcolepsy. Among twenty patients with narcolepsy intelligence was normal and no characteristic personality or psychopathology was found. A family history of psychiatric disorder was present in five and a past personal history in ten. Eight had a current psychiatric disorder and twelve either a current or past psychiatric disorder. Chronic sexual disorder was present in eleven. Arousal appeared to be the mechanism by which emotions precipitated symptoms. Ten patients were found to have had difficulties at work, in marriage or in social life.


An intensive case-study of a therapeutic group. A therapeutic group with eight members was studied, using psychometric tests, improvement ratings based on pre-treatment statements of patients' hopes, and of therapists' aims rated for achievement on the basis of post-treatment interviews, and two forms of repertory grid testing. The In-Group Grid yielded a number of measures relating to outcome and to aspects of the group process. Most patients improved by some criteria, and most measures of improvement intercorrelated positively but not, in most cases, highly. Few clear relations between process and outcome measures were demonstrated.


Women senior registrars in psychiatry: background and career intentions. An inquiry was made of all women senior registrats in general psychiatry who were known to be planning to remain in psychiatry in this country. Most were hoping to work full or maximum part-time, and all except one were aiming for a consultant appointment in general psychiatry or one of the specialties. Many anticipated difficulties in realizing their ambitions because of being tied to one particular area on account of their husbands' employment. A number of solutions to this problem are suggested.


Women senior registrars in psychiatry: background and career intentions. An inquiry was made of all women senior registrars in general psychiatry who were known to be planning to remain in psychiatry in this country. Most were hoping to work full or maximum part-time, and all except one were aiming for a consultant appointment in general psychiatry or one of the specialties. Many anticipated difficulties in realizing their ambitions because of being tied to one particular area on account of their husbands' employment. A number of solutions to this problem are suggested.


The detection and significance of calcifications in the breast: a radiological and pathological study. The radiological detection of calcification is compared using xeroradiography, non-screen film and a film-screen combination. The "threshold" values of the smallest detectable size of calcification, under simulated clinical conditions, are found to be approximately 100 mum for xeroradiography and 400 mum for both the film techniques in this study. The incidence of calcification seen on the preoperative mammograms of patients with carcinoma of the breast is 48-5 per cent. Further calcification revealed by histological examination raises the overall incidence of calcification in mammary carcinomas to 63 per cent. The incidence on preoperative mammograms in benign breast disease is 20 per cent. The radiological features of calcification occurring in malignant and benign breast lesions are recorded, and no definitive distinguishing features are established. The histological appearance of calcification in malignant and benign breast disease is discussed.


Congenital aganglionosis of the entire colon in neonates. A report of six cases and their radiological diagnosis in neonates. Total colonic aganglionosis (TCA) is a variety of what is commonly known as long segment Hirschsprung's disease. This is not a rare condition, but is often unrecognized. It has a high mortality, frequently with a complicating enterocolitis. Aganglionosis of some part of the colon should be suspected in all babies who show obstructive plain film changes. In TCA the barium enema changes may easily be passed as unremarkable. However, free ileal reflux during the examination, with a transition point in the ileum, and retention of barium in the entire colon after the examination, are diagnostic.


The "central lucency" sign of lobar dysmorphism (pseudotumour of the kidney). A proved case of pseudotumour of the kidney due to lobar dysmorphism showed a "central lucency" sign, differentiating this developmental variant from an enlarged column of Bertin. This sign is described in a further case.


Factors involved in the detection of pulmonary emboli by labelling techniques. Experiments were set up to assess quantitatively the problem of detecting, by scanning and gamma-camera, labelled pulmonary emboli in the presence of background radioactivity. In vitro, a relative concentration of radioactivity of 2:1 was required to detect a 1-1 cm diameter "hot spot". The results in vivo suggest that the level of radioactivity of a pulmonary embolus situated in the centre of the lung field should be at least six times that of the circulating blood.


Intestinal cell proliferation during fractionated abdominal irradiation. In the mouse, at normal steady state of cell proliferation, the compensatory proliferative response to intestinal irradiation is such that when radiation exposures totalling 1,000 R are concentrated over the first few days of the week, summated proliferative activity for the entire week is near control levels. Symmetrically distributed exposures over a five-day treatment week (200 R daily, and especially 333 R on Monday, Wednesday and Friday) result in depressed levels of overall weekly proliferation. In these instances, the weekend break is particularly crucial. Similar results were obtained when the one-week measurement period was inserted between the third and fifth week of abdominal therapy, except in this instance, 200 R per day did not result in sub-control levels of proliferation, whereas 333 R  on M, W and F, continued to do so. The intestine seems able to maintain its barrier epithelium for extended periods of diminished cell input, provided such is not too severe and that it seems from decreased cell production rate per crypt rather than from crypt attrition. A partial explanation for this relative tolerance is given by the finding that the vast majority of proliferative cells, even those irradiated and rendered permanently incapable of further division, succeed in migrating up the villus and hence help to maintain a barrier epithelium. In that sense, nearly all cell divisions become useful, even in the face of repeated exposures.


A practical approach to transverse-section gamma-ray imaging. The object of transverse-section gamma-ray imaging is to display the concentration of radioactive material in a thin transverse slice of the body. The technique is essentially that of reconstructing a density distribution from its projections, and many methods have been developed to perform the reconstruction. This report describes the realization of three such methods, using a small digital computer PDP8 I, and their application to experimental and clinical data obtained from the Aberdeen Section Scanner: (1) simple back projection; (2) the convolution method of Bracewell and Riddle; (3) the linear integral transform method of Radon. The problems of sensitivity variation and attenuation are examined. An approximate attenuation correction procedure is described. The reconstruction method of Bracewell and Riddle was found convenient since then the data were manipulated in a manner where smoothing to reduce statistical noise and correction for absorption could both be readily incorporated.


A modified geometric factor approach to internal gamma ray dosimetry. In internal gamma-ray dosimetry, the conventional geometric factor approach, where the "effective absorption coefficient" is taken as 0 or 0-028 cm-1, irrespective of source energy, leads to significant errors especially in the low energy region. An ettempt has been made in this paper to modify the approach to increase the accuracy of calculation and to extend its usefulness to low energies while retaining its inherent simplicity. The modification consists in replacing the effective absorption coefficient by the attenuation coefficients appropriate to the source energies and taking into account the effects due to multiple scattering by using point source build-up factor. The method has been applied for the particular case of dosimetry of a sphere. Comparison of the results obtained by this method with those got from Monte Carlo computations indicates excellent agreement at higher energies and a departure of around 15 per cent only at lower energies (as against a variation of 400 per cent when conventional geometric factor approach is used).


Radiosensitization of C3H mouse mammary tumours using fractionated doses of x rays with the drug Ro-07-0582. Three fractionated X-ray schedules were used, with and without the electron-affinic radiosensitizer of hypoxic cells, Ro-07-0582, to determine the local control of first-generation transplants of spontaneous mammary tumours in C3H mice. Three or five fractions were given in either four or nine days overall time. The results were compared with acute skin reactions in other mice caused by the same treatment schedules. For a given skin reaction, the local control of tumours varied widely, from good to bad, when different X-ray only schedules were used. All three schedules using Ro-07-0582 however yielded good results. It appears that the use of the hypoxic-cell radiosensitizer took the unreliability out of these short fractionated treatments.


Late effects of x irradiation in patients treated for metropathia haemorrhagica. We have previously reported on the causes of death among 2,068 patients treated with X irradiation for metropathia haemorrhagica at three Scottish radiotherapy centres between 1940 and 1960 (Doll and Smith, 1968). This cohort of women has now been followed up for a further seven years. 500 (24 per cent) women have now died, 78 (3-8 per cent) have emigrated and 25 (1-2 per cent) could not be traced. The numbers of deaths from different causes have been compared with the numbers expected in a population of similar age and sex exposed to the Scottish national mortality rates over the same period. An excess of deaths from leukaemia (seven observed, 2-3 expected) and of cancers of the heavily irradiated sites (59 observed, 40-1 expected) continues to be observed five or more years after treatment. There is no indication of any change in the excess death rate, due to cancers of sites in the radiation field, with time since treatment up to at least 20 years after the radiation exposure. Over the same period the number of deaths from cancer of the breast was below expectation (ten observed, 22-3 expected) and no increased mortality from coronary disease was seen (102 observed, 100-9 expected). The mean dose of radiation to the bone marrow has been determined for each woman ant it is estimated that the excess rate of leukaemia in the first 20 years after treatment is about 1-1 per million women per year per rad. This figure is in accord with the estimates derived from the survivors of the atomic bomb explosions in Hiroshima and Nagasaki and among patients with ankylosing spondylitis treated with X irradiation. However, the finding of no excess risk of leukemia among women treated with irradiation for cancer of the cervix (Hutchison, 1968) suggests that the simple assumption of a linear dose-response relationship for leukaemia is incorrect, at least when high doses of radiation are delivered to a small volume of marrow.


Ultrasonic echo imaging of tissues: instrumentation. The ultrasonic pulse-echo principle is capable of providing detailed information, of considerable potential diagnostic value, on the structure of soft tissues in relation to pathology, but the present generation of ultrasonic scanners does not fully exploit this possibility. The paper discusses the principal measures necessary to achieve tissue structure visualization and quantitative characterization and describes a clinically functioning system that has been built for this purpose with particular relation to cancer diagnosis. Examples of the application of the system are given in this and an accompanying paper.


A clinical evaluation of grey-scale ultrasonography. Recent technical improvements in grey-scale ultrasound imaging have resulted in the visualization of the internal consistency of soft tissues. This permits the diagnosis of diffuse pathology and detection of small space-occupying lesions. The new technique can be used with advantage in the currently accepted obstetrical applications for ultrasound imaging as well as for new non-obstetrical applications. The method has been found to be a most informative, non-intrusive means for investigating hepatobiliary disease and for the differential diagnosis of chronic splenomegaly.


Radiation exposure to the patient in xeroradiography. The paper presents measurements of the radiation exposure required in xeroradiography of the breast and of the extremities. The nature of the radiation hazard and the most appropriate quantity by which to assess it are discussed, and it is shown that for a number of radiological procedures xeroradiographs can be taken for about the same radiation exposure to the patient as that required by conventional film techniques.


The measurement of the performance of the display system of radioisotope imaging device: the multi-element band display. An assessment has been made of the performance of the type of display system in which each display signal intensity, i.e. grey shade or colour, represents a range of count densities or counting rates. In the particular commercially available system used in this investigation eight different grey shades are used to display the image, a range of count densities beingallocated to each grey shade. It is shown experimentally that changes in the distribution of radioisotope can fail to be detected solely due to the manner in which the display is used, viz. The way in which the count density is allocated to the available grey shades. Also, it is shown experimentally that the best display performance can be achieved by using one in which the range of count densities represented by each grey shade is less than three standard deviations of the mean background [corrected] count density.


Gas myelography in the investigation of occult spinal dysraphism. In patients presenting with suspected spinal dysraphism of the occult type, particularly children, cisternal gas myelography is coming to be accepted as the radiological investigation of choice. The technique of the examination as performed on 40 such patients is described in detail. There have been no complications. Twenty-five patients showed abnormalities of the cord together with low termination and abnormal fixation of the conus. The visualization was excellent in terms both of reliability and detail. The reasons for the difficulties in demonstrating these lesions using positive contrast and for preferring gas myelography are discussed.


Xerotomography of pulmonary lesions.

Xerotomography of pulmonary lesions. Xerography in combination with tomography is a useful modality in evaluating pulmonary lesions. Comparison is made between this technique and conventional film tomography. Xerotomography is felt to be preferable although it requires considerably higher radiation exposure to the patient.


Differential diagnosis of chronic splenomegaly by grey-scale ultrasonography: Clinical observations and digital A-scan analysis. Hitherto, ultrasound examination of the spleen has been limited to the determination of size and position. Grey-scale ultrasonography involves enhanced signal-to-noise ratio so that the soft-tissue texture is displayed, and this permits the recognition of diffusely abnormal consistency. This facility was used to predict lymphomatous involvement of the spleen in patients coming to laparotomy in whom an accuracy of 77-8 per cent was achieved. Three types of splenic consistency are described in a series of 60 patients presenting with chronic splenomegaly: Very low-level echoes emanate from malignantly involved spleens. Medium-level echoes are found in various benign conditions and high-level echoes occur in various chronic inflammatory conditions. These differences were confirmed and quantitated by computerized A-scan analysis.


Report on treatment of cancer of the ovary. A malignant ovarian tumour has been diagnosed in 373 patients referred to the R.R.T.I. from January 1966 to Jun 1972. Serious ovarian carcinoma was the commonest type and occurred in 254 patients. The results in these patients are studied in detail after staging according to F.I.G.O. recommendations. Following surgery and postoperative radiotherapy, chemotherapy was started immediately in all patients with progressive disease and after randomization also in 50 per cent of the others. The three-year survival rate in Stage II patients tended to be more favourable following irridation ofthe pelvis and lumboaortic nodes (55 per cent ) than following radiotherapy restricted to the pelvic area (40 per cent). The dose should be 5-6 krad. The five-year survival was 68 per cent for Stage I, 26 per cent for Stage II and nearly zero for Stages III and IV, as well as for patients referred for treatment of a recurrence. In spite of whole-abdomen irradiation 50 per cent of the patients in the latter three groups were deceased within eight months; therefore chemotherapy should be preferred. The main problem in ovarian cancer is late diagnosis. Evaluation of results is difficult because numerous variable factors concerning pathology and treatment make it necessary to sub-divide the patients into groups too small for statistically reliable conclusions. Each treatment factor should be studied by a group of hospitals.


Calculation by computer of dose distributions for superficial gold-198 implants and the derivation of optimized distribution rules. A computer program has been written which provides two-dimensional visualization of the radiation dose distributions in the treatment surfaces aroung single-plane gold seed implants. The program was modified in order to investigate the uniformity of dose resulting from various patterns of seed arrangements, and, for a number of sizes of circular implants, practical loading schemes to produce minimum dose variations have been tabulated. Comparisons are made between dose distributions obtained from application of the derived data and those arising from application of the Paterson-Parker rules.


Treatment of thyroid cancer in 293 patients. Two hundred and ninety-three patients with thyroid cancer were treated at The Royal Marsden Hospital, London, between 1931 and 1963. Thirty-six per cent of the tumours were papillary, 21 per cent follicular, 1 per cent medullary and 42 per cent anaplastic. Surgery combined with radiotherapy formed the commonest treatment regime. Thirty-six per cent of the patients with papillary carcinoma survived for 20 years, 20 per cent with follicular tumour and 4 per cent with anaplastic carcinoma. The present series indicates that treatment influences the survival time, confirms the prognostic value of histology and age and shows that papillary node metastases do not prejudice survival.


Total three-stage oesophagectomy for cancer of the oesophagus. The technique of total three-stage oesophagectomy is described fully. Points of detail in the procedure of the abdominal, thoracic and cervical phases are emphasized. A brief note is made regarding the management of the respiratory situation at the end of the operation.


Liver abnormalities and gallstones: a prospective combined clinical, histological and surgical study. In a prospective study of 57 patients coming to elective cholecystectomy for gallstone disease, clinical, biochemical and immunological features have been correlated with the histological changes in core biopsies of the liver obtained at surgery. Only 13 liver biopsies were normal. Ten biopsies showed changes of acute duct obstruction, 16 showed minimal portal tract abnormalities and 10 showed moderate portal tract inflammation and scarring. Histological changes were more marked in male patients. Clinical and biochemical investigations were not useful in predicting histological appearance, apart from cases with jaundice at the time of operation where changes of acute duct obstruction were usually, but not invariably, seen. Atuo-antibodies were present in 50 per cent of cases tested and all persisted for at least 6 months after operation. They were commoner in patients with more marked histological changes. Operative cholangiography was of little use in predicting histological change. These findings suggest that the possibility of gallstones should be considered in the interpretation of any abnormal liver biopsy irrespective of clinical symptoms or biochemical investigations.


Brucellosis of the spine.

Brucellosis of the spine. Three cases of spinal brucellosis are presented, demonstrating involvement of the cervical, thoracic and lumbar regions respectively, and the management is discussed. Particular reference is made to the problems of establishing the diagnosis, and also the differentiation of this condition from tuberculosis of the spine.


Fluid-filled intestinal obstruction.

Fluid-filled intestinal obstruction. Three cases of intestinal obstruction are described in which the diagnosis was delayed because of the absence of gas in the bowel. The obstructed bowel was entirely fluid-filled and so abdominal distension was not marked, peristaltic sounds were not accentuated and the abdominal X-rays did not show air-fluid levels.