Pathways of D-fructose catabolism in species of Pseudomonas.

Cell-free extracts of D-fructose grown cells of Pseudomonas putida, P. fluorescens, P. aeruginosa, P. stutzeri, P. mendocina, P. acidovorans and P. maltophila catalyzed a P-enolpyruvate-dependent phosphorylation of D-fructose and contained 1-P-fructokinase activity suggesting that in these species fructose-1-P and fructose-1,6-P2 were intermediates of D-fructose catabolism. Neither the 1-P-fructokinase nor the activity catalyzing a P-enolpyruvate-dependent phosphorylation of D-fructose was present in significant amounts in succinate-grown cells indicating that both activities were inducible. Cell-free extracts also contained activities of fructose-1,6-P2 aldolase, fructose-1,6-P2 phosphatase, and P-hexose isomerase which could convert fructose-1,6-P2 to intermediates of either the Embden-Meyerhof pathway or Entner-Doudoroff pathway. Radiolabeling experiments with 1-14C-D-fructose suggested that in P. putida, P. aeruginosa, P. stutzeri, and P. acidovorans most of the alanine was made via the Entner-Doudoroff pathway with a minor portion being made via the Embden-Meyerhof pathway. An edd- mutant of O. putida which lacked a functional Entner-Doudoroff pathway but was able to grow on D-fructose appeared to make alanine solely via the Embden-Meyerhof pathway.


Comprehensive rehabilitation of patients having chronic low back pain.

Seventy-two patients having chronic back pain, representative of high-risk demographic and personality populations, received a broad range of therapeutic modalities designed around the theme of self-regulation. The self-regulation principle was used in: (1) biofeedback training for teaching self-regulated muscle relaxation; (2) psychological counseling emphasizing self-control techniques for the management of stress and anxiety, including assertion training; (3) patient-regulated medication program; (4) patient involved case conferences; (5) physical therapy program emphasizing reconditoning; (6) comprehensive vocational rehabilitation services; (7) a series of educational lectures; (8) a therapeutic milieu designed for relaxation, recreation and socialization. Utilizing a success criteria of functional physical activity at discharge (average length of stay, 45 days) and levels of vocational restoration (employable, in training, or employed at 30 days postdischarge), 57 of the patients demonstrated unimpaired physical functioning levels and 59 of the patients were at success levels of vocational restoration.


Electromyographic study of duration of muscle activity in sit-up variations.

The external oblique, rectus abdominis, and rectus femoris muscles of 17 college women were studied electromyographically in 8 sit-up variations to determine the best variation for maximizing abdominal muscle activity and minimizing hip flexor activity. Integrated action potentials and movement phases of each variation were recorded simultaneously. The duration of muscle activity within the movement phases was analyzed. The variables of hook-lying/long-lying, feet supported/feet unsupported, and slow/fast speed of performance were examined. The hook-lying unsupported slow and fast variations were best for maximizing abdominal muscle duration of activity and for minimizing rectus femoris muscle duration of activity. Greatest duration of activity for all muscles occurred in the long-lying supported fast variation. Supporting the feet in both hook and long-lying fast variations was more effective for increasing activity duration of all muscles than the slow supported variations. Speed of performance seemed to be as important as support of the feet or leg position in increasing duration of muscle activity.


The role of the silastic prosthesis in the management of gastroschisis.

We reviewed data on 43 patients with gastroschisis treated at The Hospital for Sick Children, London, between 1959 and 1975. In the past five years, the overall mortality has been reduced from 76% to 33%. The introduction of the Silastic silo has been the most important single factor in this improvement. Mortality may be further reduced by achieving all-layer closure following thorough bowel decompression and stretching of the abdominal wall.


Dacron grafting from the aorta to the distal profunda femoria arteries via the obturator foramina.

We discuss the possibility of the use of the obturator foramina as routes and the distal profunda femoris arteries as sites for anastomosis in the presence of infected grafts in the groins as a successful solution to an otherwise tragic complication of arterial grafting.


[Lysosomes, cellular digestion and immune processes].

The article presents a survey of the available literature concerned with the problems of relationships between the functions of the lysosomal apparatus of cells of the reticuloendothelial system and immune processes. A connection between the primary lysosoma and endocytic vacuole, desintegration of absorbed antigens by micro- and macrophages, the significance of antigenic information transmitted by macrophage to an immune lymphocyte, and realization of the immune response are traced carefully and in succession. Participation of lysosomas in antigen-antibody reactions (anaphylaxis, Arthus' phenomenon, supersensitivity of a delayed type) and their role in induction of immune tolerance and in some autoimmune processes are also considered.


Studies on thyroid and hypophysary thyrotrophic hormone (TSH) in Down syndrome.

Serum TSH was studied in 22 patients with Down syndrome, from 4 to 15 years old. In 6 of these patients radioidine uptake by thyroid gland after 2 and 24 hours of administration and clearance rates before and after TSH stimulus (10 mul-IM) were measured. Results show that serum TSH was normal in 17 patients and above normal limits in 5 patients. Thyroid uptake after 2 hours as well clearance rates, both below normal, had a response to TSH stimulus with normal or below values. These data along with previous reports, suggest, that in children with Down syndrome, there is a thyroid dysfunction in which a slow response no TSH stimulus seems to be the basic defect.


Fleck corneal dystrophy.

Fourteen members of four families with fleck systrophy of the corneal stroma were examined and studied. Corneal and lens changes were noted in all patients. Corneal sensation was normal. Corneal biopsies were performed on two patients and a corneal button of a patient with fleck dystrophy and keratoconus was studied. Light and electron microscopy and histochemical studies showed this dystrophy to consist of abnormal keratocytes with variable numbers of membrane-limited intracytoplasmic vacuoles containing a granular to fibrogranular material that stains positively for mucopolysaccharide. This appears to be the first reported incidence of a dominantly inherited disorder of mucopolysaccharides affecting the eyes.


On the action of triamterene on isolated cell membranes.

Recently there have been recurring reports on extrarenal and expecially on antiarrhythmic effects of triamterene, the latter ones being observed particularly in cases of digitalis intoxication. Considering the digitalis-antagonistic effects, which are also observed in the course of experimental investigations, it was assumed that triamterene, a potassium-saving diuretic, displaces cardiac glycosides from their binding sites in cardiac membranes. The binding of [3H]-g-strophanthin ([3H]-ouabain) and the activity of the (Na+ + K+)-ATPase in the presence of different concentrations of triamterene have been studied with isolated cardiac cell membranes (human; bovine) and human erythrocyte membranes. Inhibition of the binding of the cardiac glycoside and the enzyme activity was only observed for very high concentrations of the active component. These observations are indicative of non-specific effects. Triamterene applied in the presence of different concentrations of strophanthin (10(-9)--5 X 10(-7) M) did not display protective effects on the (Na+ + K+)-ATPase activity. In experiments aimed at chromatographic separations, it could be shown that [3H]-triamterene binds to membrane proteins different from those binding [3H]-g-strophanthin, the latter having been shown to be present in the (Na+ + K+)-ATPase containing fraction. From the results of these experiments it may be concluded that there is no interaction between triamterene and strophanthin on the membrane bound receptor for the cardiac glycoside. [3H]-Triamterene shows concentration dependent binding to cell membranes. This binding is affected to different degrees by Mg++, K+, Na+ and Ca++. The binding sites show low affinity but high binding capacity for triamterene. The significance of this fact remains to be established.


[Stimulating effect of B-lymphocytes in mixed cultures on autologous T-lymphocytes in chronic lymphatic leukemia].

Two different cellular populations among the circulating lymphocytes were separated by using a technique based on the T lymphocytes capacity to form nonimmune rosettes with sheep red blood cells. The first population (P) is essentially composed of T lymphocytes, the second (population S) is made up mainly of type B lymphocytes. This technique was applied in the study of circulating lymphocytes in 11 patients with chronic lymphocytic leukaemia and was satisfactory both for good reproducibility and for its ability to obtain vital separate lymphocytes. Normal reactivity to PHA and PWM of population P and normal capacity to form E rosettes with SRBC were found. In mixed culture of T lymphocytes stimulated by B cells of the same patient significant blastic response was observed.


Actin and myosin-linked calcium regulation in the nematode Caenorhabditis elegans. Biochemical and structural properties of native filaments and purified proteins.

Calcium regulation of actomyosin activity in the nematode, Caenorhabditis elegans, has been studied with purified proteins and crude thin filaments. Actin and tropomyosin have been purified from C. elegans and shown to be similar in most respects to actin and tropomyosin from rabbit skeletal muscle. The actin comigrates with rabbit actin on polyacrylamide-sodium dodecyl sulfate gel electrophoresis, forms similar filaments and paracrystals, and activates the Mg2+-ATPase of rabbit myosin heads as efficiently as rabbit actin. Nematode tropomyosin has a greater apparent molecular weight (estimated by mobility on polyacrylamide-sodium dodecyl sulfate gels) than the rabbit protein, yet it forms Mg2+-paracrystals with a slightly shorter periodicity. Native thin filaments extracted from nematodes activate rabbit myosin subfragment 1 Mg2+-ATPase in a calcium sensitive manner; the extent of activation is threefold greater in 0.2 mM CaCl2 than in the absence of calcium. This observation suggests that the thin filaments contain components which are functionally equivalent to vertebrate troponins. Calcium is also required for maximal activation of the Mg2+-ATPase of purified nematode myosin by pure rabbit F-actin. C. elegans therefore has both myosin and thin filament-linked calcium regulatory systems. The origin of the actin, tropomyosin, and myosin from different tissues and the use of genetic analysis to answer questions about assembly and function in vivo are discussed.


Fluorescence energy transfer between Ca2+ transport ATPase molecules in artificial membranes.

The purified ATPase of sarcoplasmic reticulum was covalently labeled with N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (1,5-IAEDANS) or with iodoacetamidofluorescein (IAF). In reconstituted vesicles containing both types of ATPase molecules fluorescence energy transfer was observed from the IAEDANS (donor) to the IAF (acceptor) fluorophore as determined by the ratio of donor and acceptor fluorescence intensities, and by nanosecond decay measurements of donor fluorescence in the presence or absence of the acceptor. The observed energy transfer may arise by random collisions between ATPase molecules due to Brownian motion or by formation of complexes containing several ATPase molecules. Experimental distinction between these two models of energy transfer is possible based on predictions derived from mathematical models. Up to tenfold dilution of the lipid phase of reconstituted vesicles with egg lecithin had no measurable effect upon the energy transfer, suggesting that random collision between ATPase molecules in the lipid phase is not the principal cause of the observed effect. Addition of unlabeled ATPase in five- to tenfold molar excess over the labeled molecules abolished energy transfer. These observations together with electron microscopic and chemical cross-linking studies support the existence of ATPase oligomers in the membrane with sufficiently long lifetimes for energy transfer to occur. A hypothetical equilibrium between monomeric and tetrameric forms of the ATPase governed by the membrane potential is proposed as the structural basis of the regulation of Ca uptake and release by sarcoplasmic reticulum membranes during muscle contraction and relaxation.


Tightly bound nucleotides of the energy-transducing ATPase, and their role in oxidative phosphorylation. I. The Paracoccus denitrificans system.

1. The coupling ATPase of Paracoccus denitrificans can be removed from the membrane by washing coupled membrane fragments at low salt concentrations. 2. This ATPase resembles coupling ATPases of mitochondria, chloroplasts and other bacteria. It is a negatively charged protein of molecular weight about 300,000. An inhibitor protein in bound tightly to the ATPase in vivo, and can be destroyed by trypsin treatment. 3. ATP and ADP are found tightly bound to the coupling ATPase of P. denitrificans, both in its membrane-bound and isolated state. The ATP/ADP ratio on the enzyme is greater than one. 4. Under de-energised condtions, the bound nucleotides are not available to the suspending medium. When the membrane is energised however, the bound nucleotides can exchange with added nucleotides and incorporate 32Pi. 32Ppi is incorporated into the beta and gamma positions of the bound nucleotides, but beta-labelling probably does not occur on the coupling ATPase. 5. Uncouplers inhibit the exchange of the free nucleotides or 32Pi into the bound nucleotides, while venturicidin (an energy transfer inhibitor) and aurovertin stimulate the exchange. 6. The response of the bound nucleotides to energisation is consistent with their being involved directly in the mechanism of oxidative phosphorylation.


Tightly bound nucleotides of the energy-transducing ATPase, and their role in oxidative phosphorylation. II. The beef heart mitochondrial system.

1. Beef heart mitochondrial ATPase, in both the membrane-bound and isolated form, contains tightly bound ATP and ADP. Each mol of ATPase contains about 2.2 mol ATP and 1.3 mol ADP. 2. In the absence of ATPase activity, these nucleotides exchange only slowly with nucleotides in solution. The exchange rate is increased during coupled ATPase activity, but not when the ATPase is uncoupled. 3. Oligomycin and dicyclohexylcarbodiimide inhibit exchange of the bound nucleotides, as does the ATPase inhibitor protein, although in each case some residual exchange occurs. Aurovertin, although inhibiting phosphorylation, does not inhibit the exchange. This is discussed in terms of the reversibility of these inhibitors. 4. The stimulation of exchange seen during coupled ATPase activity requires energisation of the ATPase molecule. Using the exchange reaction as a probe of energisation, it is deduced that energy can be transferred between different ATPase molecules. 5. It is proposed that coupled ATPase activity and phosphorylation in submitochondrial particles involve the tight nucleotide binding sites and the (weak) ATPase site, while uncoupled ATPase activity involves only the weak site.


Isolation and characterization of an inhibitory subunit of the Mg2+--Ca2+-ATPase of Escherichia coli.

1. Stimulation of the Escherichia coli ATPase activity by urea and trypsin shows that the ATPase activity both in the membrane-bound and the solubilized form is partly masked. 2. A protein, inhibiting the ATPase activity of Escherichia coli, can be isolated by sodium dodecyl sulphate polyacrylamide gel electrophoresis of purified ATPase. The inhibitor was identified with the smallest of the subunits of E. coli ATPase. 3. The molecular weight of the ATPase inhibitor is about 10,000, as determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis and deduced from the amino acid composition. 4. The inhibitory action is independent of pH, ionic strength or the presence of Mg2+ or ATP. 5. The ATPase inhibitor is heat-stable, insensitive to urea but very sensitive to trypsin degradation. 6. The Escherichia coli ATPase inhibitor does not inhibit the mitochondrial or the chloroplast ATPase.


Studies concerning the specificity of the effect of leucine on the turnover of proteins in muscles of control and diabetic rats.

The protein anabolic effect of branched chain amino acids was studied in isolated quarter diaphragms of rats. Protein synthesis was estimated by measuring tyrosine incorporation into muscle proteins in vitro. Tyrosine release during incubation with cycloheximide served as an index of protein degradation. In muscles from normal rats the addition of 0.5 mM leucine stimulated protein synthesis 36--38% (P less than 0.01), while equimolar isoleucine or valine, singly or in combination were ineffective. The three branched chain amino acids together stimulated no more than leucine alone. The product of leucine transamination, alpha-keto-isocaproate, did not stmino norborane-2-carboxylic acid (a leucine analogue) were ineffective. Leucine and isoleucine stimulated protein synthesis in muscles from diabetic rats.Leucine, isoleucine, valine and the norbornane amino acid but not alpha-ketoisocaproate or beta-hydroxybutyrate decreased the concentration of free tyrosine in tissues during incubation with cycloheximide; tyrosine release into the medium did not decrease significantly. Leucine caused a small decrease in total tyrosine release, (measured as the sum of free tyrosine in tissues and media), suggesting inhibition of protein degradation. The data suggest that leucine may be rate limiting for protein synthesis in muscles. The branched chain amino acids may exert a restraining effect on muscle protein catabolism during prolonged fasting and diabetes.


The relationship between DNA strand-scission and DNA synthesis inhibition in HeLa cells treated with neocarzinostatin.

Neocarzinostatin inhibits DNA synthesis in HeLa S3 cells and induces the rapid limited breakage of cellular DNA. The fragmentation of cellular DNA appears to precede the inhibition of DNA synthesis. Cells treated with drug at 37 degrees C for 10 min and then washed free of drug show similar levels of inhibition of DNA synthesis or cell growth, or of strand-scission of DNA as when cells were not washed. If cells are preincubated with neocarzinostatin at 0 degrees C before washing, the subsequent incubation of 37 degrees C results in no inhibition of DNA synthesis or cell growth, or cutting of DNA. Isolated nuclei or cell lysates derived from neocarzinostatin-treated HeLa S3 cells are inhibited in DNA synthesis but this can be overcome in cell lysates by adding activated DNA. A cytoplasmic fraction from drug-treated cells can stimulate DNA synthesis by nuclei isolated from untreated cells, whereas nuclei from drug-treated cells are not stimulated by the cytoplasmic fraction from untreated cells. By contrast, neocarzinostatin does not inhibit DNA synthesis when incubated with isolated nuclei, but it can be shown that under these conditions the DNA is already degraded and is not further fragmented by the drug. These data suggest that the drug's ability to induce breakage of cellular DNA in HeLa S3 cells is an essential aspect of its inhibition of DNA replication and may be responsible for the cytotoxic and growth-inhibiting actions of neocarzinostatin.


Single-strand nicking of DNA in vitro by neocarzinostatin and its possible relationship to the mechanism of drug action.

Neocarzinostatin, a protein antibiotic with anti-tumor activity was found to place single-strand scissions in DNA in an in vitro reaction. The drug's cutting activity was strongly dependent on the presence of 2-mercaptoethanol or dithiothreitol but some cutting did take place in the absence of reducing agent at very high drug levels and prolonged incubation. The requirement for reducing agents could not be replaced with NAD+, FAD, NADH or H2O2 and the strand-scission reaction was not affected by Mg2+, EDTA or intercalating agents. Similar profiles of heat-inactivation of neocarzinostatin were found whether activity was measured by the scission of DNA strand either in vitro or in HeLa cells treated with the drug. Furthermore, both of these parameters corresponded closely with the ability of the modified drug to inhibit DNA synthesis and growth of HeLa cells. By column isoelectric focusing it was shown that all four activities are associated with the same protein band (pH 3.28). From these data we conclude that the cytotoxic activity of neocarzinostatin and the nicking of DNA strands in vitro appear to reside in the same protein.


[Some properties of transport ATPases in functionally different muscles].

The properties of Ca-transporting system in sarcoplasmic reticulum membranes in fast and slow frog muscles as well as some properties of sarcolemma Na, K-ATPase of the same object were investigated. The rate of Ca2+ uptake, Ca-ATPase activity and Ca/ATP ratio for the reticulum of fast muscle demonstrated higher values than those for the reticulum of slow muscle. The rate of Ca2+ accumulation by the fragments of the rectus reticulum and Ca/ATP ratio were found to decrease under the influence of acetylcholine (0.05-5 mM). The transport system of the sartorius reticulum was found to be less sensitive to acetylcholine. The peak activity of Na, K-ATPase in femoral muscles of the frog occurred at 80 mM NaCl and 60 mM KCl, whereas in the rectus abdominal muscle it equalled 100 mM NaCl and 40 mM KCl. Thus, Na, K-ATPase activity in the slow muscle was predominantly higher than that in the mixed (femoral) muscles. If the sarcolemma preparations of the muscles of both types the inhibitory effect of acetylcholine on Na; K-ATPase was registered. The enzyme of slow muscles exhibited higher sensibility to acetylcholine.


[The functional coupling between MM isozyme of creatine phosphokinase (EC 2.7.3.2.) and MgATPase of myofibrils and (Na, K)ATPase of plasma membrane in heart cells].

The functional role of particulate MM isozyme of creatine phosphokinase (CPK) bound to heart myofibrils has been studied. It has been shown that in the presence of heart myofibrils and MgATP creatine phosphate can be used to rephosphorylate ADP formed in the MgATPase reaction. The rate of creatine phosphate splitting is determined by the kinetic properties of myofibrillar MgATPase and by the kinetic parameters of myofibrillar CPK. It has been found that a purified heart plasma membrane preparation contains high CPK activity. CPK isozyme bound to plasma membrane of heart cells is identical to MM isozyme of CPK and is able to rephosphorylate effectively ADP, formed in the (Na K)ATPase reaction. The rate of creatine phosphate splitting in these coupled reactions is sensitive to ouabain and is determined by the kinetic parameters both of the (Na, K)ATPase and plasma membrane CPK. The results obtained indicate the important role of myofibrillar and plasma membrane CPK in the intracellular energy transport processes.


[Kinetic analysis of hydrolysis of free ATP and MgATP by natural actomyosin].

Computer analysis of experimental data published in 1-3 allowed to establish the presence of two non-interacting inequivalent hydrolytic sites in actomyosin molecule, one of them being specific for binding and hydrolysis of free ATP, the other--for MgATP. Thus both species of ATP are the substrates of actomyosin ATPase. Actomyosin molecule seems to bind on more (in additon to two active sites) substrate molecule (MgATP) at some non-catalytic regulatory site. The formation of the enzyme-substrate complex having three ATP molecules (one molecule of free ATP and two--of MgATP) is accompanied by the loss of the activity. An approach to the research of kinetic equations for complex systems considerably decreasing a number of variations to consider is given in this work.


[Mechanism of action of some quinoline alkaloids on respiratory chain of mitochondria].

The mechanism of action of some quinoline alkaloids and their derivatives on respiratory chain of rat liver and Candida lipolytica yeast mitochondria was studied. The alkaloids were shown to inhibit electron transfer in the respiratory chain. The site of their action is localized between b and c cytochromes. Besides their ability to inhibit electron transfer in the respiratory chain, alkaloids are shown to be specific inhibitors of "exogenous" NADH-dehydrogenase of C. lipolytica yeast mitochondria. In addition to their inhibiting properties alkaloids can stimulate ATPase activity of mitochondria. O-alkylation of pseudane-IX permits to differentiate the inhibiting and uncoupling properties of this alkaloid.


[Studies on specific elution of rabbit muscle phosphofructokinase with allosteric ligands].

The specific elution of rabbit skeletal muscle phosphofructokinase (PFK) from DEAE-cellulose is studied in the linear gradient of different allosteric ligands. Citrate and fructose-6-phosphate elute PFK at concentrations of 1.0 and 2.5 mM respectively, i.e. without increasing the ionic strength of the starting buffer (similar to 0.12). The specificity of elution is confirmed by comparison of the ionic strength of these solutions with that of buffer eluting PFK in buffer gradient (mu=0.17) as well as by comparison with the eluting ability of other ligands. Fructose-1,6-diphosphate elutes PFK only at the concentration of 5.5 mM which corresponds to the ionic strength 0.17. MgATP and AMP are inefficient as specific eluents whereas ATP and ADP elute only a small part of PFK with concomitant substantial increase of the ionic strength (up to 0.17--0.18). These results are discussed in terms of a charge compensation mechanism as a result of the displacement of PFK conformers equilibrium under the influence of the allosteric ligands.


Studies on the regulation of glycolysis in isolated fetal rat hepatocytes.

The contribution to the glycolytic flux by glycogen breakdown versus glucose phosphorylation has been determined in isolated fetal rat hepatocytes, prepared in different media and subsequently incubated with different glucose concentrations. A high glucose concentration in cells prepared in a medium containing a high concentration of inorganic phosphate decreases the contribution to the glycolytic flux by glycogenolysis to less than 15%. It is suggested that one of the factors which initiate glycogenolysis in the living animal after birth is a lowered blood glucose concentration, independent of hormonal changes. Under conditions where glycogenolysis does not contribute the larger part to the glycolytic flux, the control of glycolysis is shifted from glycogen breakdown to the glucose phosphorylation step and phosphofructokinase.


Suppressor cells in tumor bearing mice and rats.

Suppressor macrophages in spleens of tumor bearing mice and rats were found to inhibit "in vitro" reactivity of lymphocytes to T and B cell mitogens and to allogeneic cells in the mixed lymphocyte tumor cell interaction and the "in vitro" generation of secondary cytotoxic effector cells. We propose that similar suppressor cells may play an important role in the general immunosuppression of tumor bearing hosts and in the inability of tumor bearing hosts to effectively reject the tumor.


[Effect of phospholipase A on erythrocyte and thrombocyte aggregation].

A study was made of the effect of plasmin and trypsin on the phospholipase activation, and also of the action of phospholipase A (cobra venom) on the release reaction and the erythrocyte and thrombocyte aggregation. Trypsin and fibrinolysin proved to activate phospholipase, this being accompanied by the accumulation of nonesterified fatty acids in the blood serum. Phospholipase A caused a release of the thromboplastic factor from erythrocytes and thrombocytes and their aggregation. The later is inhibited by albumin and EDTA. It is suggested that the action of the proteolytic enzymes on the blood formed elements was realized through the phospholipase activation.


[Role of the kidneys in the pathogenesis of lithium poisoning].

Lithium intoxication was induced in rats by intraperitoneal administration of lithium chloride in a daily dose of 200 mg/kg (0.22 LD50) for 6 days. Polyuria connected with pathological changes in the epithelium of the convoluted tubules and depression of the antidiuretic hormone--acid mucopolysaccharides system in the area of the straight kidney tubules was observed on the 6th day of the experiments. Oligouria and death of some of the animals on the 7th experimental day was caused by severe lesions the kidney structure. Further observation (30 days) demonstrated that, along with the regeneration processes, there developed a marked sclerosing ofthe kidney tissue. A conclusion was drawn that severe lithium intoxication was associated with the development of acute renal insufficiency. Functional reserves of the kidneys after the cessation of lithium chloride administration remained lowered for a long period.


[Effect of vasopressin on the ATP-ase activity of microsomal fractions of rabbit heart and liver].

It was shown that intravenous injection of vasopressin in a dose of 5 pressor units per 1 kg of body weight led to changes in the ATP-ase activity of the heart and liver microsomes in one hour. These changes coursed in a different direction, i.e. ATP-ase activity of the heart microsomes increased, and ATP-ase activity of the liver microsomes decreased.


[Effect of parathyroid hormone and thyrocalcitonin on the cell membrane Na, K-ATP-ase of rat brain and kidney].

The influence of parathyroid hormone (PH) and thyrocalcitonine (TCT) on the enzymatic activity of ATP-ase systems of the membrane specimens of the cerebral cortex and renal cortex was investigated in experiments on rats. It was found that parathyroid hormone increased the activity of Na, K-ATP-ase and Ca-activated ATP-ase transport of the membranes in the brain and the kidneys both in vivo and in vitro. TCT caused analogous, but less expressed changes of the ATP-ase activity. Both hormones showed no influence on the Mg-ATP-ase activity of the both organs. It is supposed that the PH hormone influenced the membrane structures with the ATP-ase activity directly, while the action of TCT on them was mediated.


[Tissue-specific inhibition of cellular proliferation in Ehrlich ascites tumor].

The extract of cells of ascitic Ehrlich's tumour (chaloun) and its cell-free fluid produced a marked inhibitory action on the cell proliferation of this tumour four hours after the administration. The effect is tissue-specific, more pronounced in the extract and depends on the dose of the antigen. Eight hours after the extract or the cell-free fluid administration the mitotic activity in the tumour proved to increase in comparison with control; this indicated the presence of a short-lived chaloun action on the G2-phase of the mitotic cycle and synchronization of cell division.


[Liver chalones].

Administration of a liver extract and the blood serum of adult intact mice and also of the blood serum of practically healthy persons to CBA X C57B1 hybrid mice produced a sharp depression of the mitotic activity of hepatocytes in the regenerating liver after its partial removal. The extract of the regenerating liver and the blood serum of the animals with the regenerating liver failed to depress mitoses in hepatocytes. The blood serum of man with the postnecrotic active cirrhosis of the liver not only failed to depress mitoses in the hepatocytes, but even caused an increase in their count. It is supposed that there was a reduction of the chalone concentration in the cirrhotic liver.


[Electron-cytochemical study of ATP-ase activity in the brain after death].

The lead method was applied to determine the localization of the ATP-asic activity in the rat and human brains at different periods after death. This activity was revealed in the cytoplasm of the cells, chromatin and the nucleolus, and also in the synaptic terminals. In the vascular capillaries the product of reaction was localized in the basal layer and on the cytomembrane of the endothelial cells. The results obtained pointed to a good preservation of the ATP-asic activity in the postmortem brain.


[Histo-enzymatic activities of the peritoneal serosa covering the splenic capsule in various rodents].

The peritoneal cells of the splenic capsule have no phosphatasic acid acitivity in the three species studied. However they have an ATPasic acitivity in the Rat and the Rabbit's spleen, and a 5'nucleotidasic activity in the Guinea-Pig. These cells are not phagocytic and probably have different origins according to the species.


Guinea worm inguinal adenopathy.

Genital involvement of Dracunculus medinensis is uncommon, and when it does occur, it usually involves the scrotum. A case has been described in which the inguinal gland was involved producing a bubo simulating that caused by other commoner conditions. It is suggested that the microscopical examination of a wet preparation of bubo aspirates should routinely be practised, especially in tropical countries.


Tonic inhibitory influence of a supraspinal monoaminergic system on presynaptic inhibition of an extensor monosynaptic reflex.

Presynaptic inhibition of the extensor (quadriceps, QUAD) monosynaptic reflex (MSR) in unanaesthetized decerebrate cats was antagonized by imipramine hydrochloride (2-5 mg/kg), 5-hydroxytryptophan (75 mg/kg) and a specific 5-hydroxytryptamine (5-HT) neuronal uptake blocker, fluoxetine hydrochloride (Lilly 110140, 0.25-6 mg/kg). These effects of imipramine and fluoxetine were partially reversed by the 5-HT antagonist, cyproheptadine hydrochloride (5 mg/kg), and completely reversed by the application of a thoracic cold block which prevents supraspinal inputs to the caudal spinal cord. Imipramine, however, failed to antagonize this inhibition in animals pretreated with either DL-p-chlorophenylalanine (p-CPA, 300 mg/kg i.p. for 2 consecutive days) or DL-a-methyl-p-tyrosine methyl ester hydrochloride (a-MPt, 125 mg/kg i.p. 16 and 4 h prior to the experiment). Cyproheptadine (2.5--5 mg/kg); phenoxybenzamine hydrochloride (2.5-5 mg/kg) and a cold block enhanced the inhibition of this extensor MSR but a cold block failed to alter the inhibition in animals pretreated with p-CPA or a-MPT. Presynaptic inhibition of the flexor (posterior biceps-semitendinosus, PBST) MSR was however not blocked by imipramine, fluoxetine or a cold block nor enhanced by cyproheptadine or phenoxybenzamine. The effects of the drugs tested and a cold block on the excitability of the QUAD group Ia afferents were reciprocal to those on the MSR during presynaptic inhibition. The results of this study indicate that descending tonically active systems (1) involving 5-HT and noradrenaline, antagonize presynaptic inhibition of the QUAD but not the PBST-MSR, (2) decrease the excitability of the QUAD Ia afferents and (3) increase the excitability of QUAD motoneurones.


A quantitative rotational model for studying serotonergic function in the rat.

Unilateral injection of 5,7-dihydroxytryptamine (4 mug/4 mul) into the medial forebrain bundle of rats produced serotonin depletions of 65% and 70% in the ipsilateral corpus striatum and ipsilateral forebrain, respectively. These animals showed a dose-dependent increase in contralateral turning (rotational behavior) when pretreated with a peripheral decarboxylase inhibitor and then injected with L-5-hydroxytryptophan in doses ranging from 5 to 100 mg/kg i.p. Injections of p-chloroamphetamine, which releases endogenous stores of serotonin, produced ipsilateral turning which could be blocked by prior serotonin depletion. Systemic administration of the catecholamine drugs L-DOPA, apomorphine and D-amphetamine never elicited consistent turning in either direction in these animals. These data indicate that the turning response of rats with unilateral destruction of brain serotonin nerve terminals provides a sensitive tool for quantifiably studying changes in serotonergic function.


Characteristics of nondepolarizing neuromuscular block: (I) post-junctional block by alpha-bungarotoxin.

The characteristics of neuromuscular block produced by alpha-bungarotoxin, a post-junctionally active polypeptide toxin purified from snake venoms, have been studied in vivo in 12 anaesthetized cats, using the sciatic nerve-tibialis anterior muscle preparation. The onset of the neuromuscular block was slow and without fasciculation. The block was persitently progressive. The time course of the block depended on the dosage. In general, 0.1 mg/kg of alpha-BuTX appeared to approximate the threshold dosage while 0.2 mg/kg completely eliminated the twitch response in 2-5 hours. No recovery was observed in 8-30 hours. Larger doses accelerated the progression of the block. During the block, tetanic contractions and train-of-four twitches did not fade. The post-tetanic twitches were markedly facilitated. The block was antagonized by edrophonium, neostigmine, pyridostigmine, and succinylcholine, but the antagonism was less effective and shorter-lasting than that observed on curare-block, and the block always resumed the projected progression. Attempts were made to explain the observed difference between alpha-BuTX- and dTc-induced neuromuscular blocks by the practically permanent nature of block and the purely post-junctional site of action of alpha-BuTX. It was concluded that a pure post-junctional block is not characterized by fade, which rather might be a pre-junctional effect of some nondepolarizing neuromuscular blocking agents like d-tubocurarine.


Enhancement (by ATP, insulin, and lack of divalent cations) of ouabain inhibition of cation transport and ouabain binding in frog skeletal muscle; effect of insulin and ouabain on sarcolemmal (Na + K)MgATPase.

Using small, intact frog muscles, the basic properties of Na+ and K+ transport were shown to resemble those of the (Na+ + K+)Mg2+ATPase (EC 3.6.1.3) isolated from skeletal muscle. (a) External K+ is essential for Na+ exit and K+ entry after the muscles are Na+-loaded and K+-depleted; (b) the ouabain concentration causing maximum inhibition of recovery is the same for transport as for the inhibition of the isolated enzyme. Ouabain causes a decrease in the sorbitol space and causes muscle fibre swelling. Absence of Ca2+ and Mg2+ inhibits recovery of normal Na+ and K+ concentrations and increases the sorbitol space. Insulin stimulates K+ uptake and Na+ loss in intact muscles but has no effect on the isolated sarcolemmal (Na+ + K+)Mg2+ATPase. Absence of divalent cations, addition of external ATP and of insulin enhance the ouabain inhibition of recovery. Bound ouabain was measured using [3H]ouabain and [14C]sorbitol (to measure the extracellular space). The process of binding was slowly reversible and was saturable within a range of ouabain concentrations from 1.48 X 10(-7) to 5.96 X 10(-7) M. From the nonexchangeable ouabain bound, the density of glycoside receptors was estimated to be 650 molecules per square micrometre of membrane surface. The absence of divalent cations, addition of external ATP and of insulin significantly enhanced the amount of ouabain bound. Substitution of Na+ and K+ by choline greatly reduced the bound ouabain.


Cell proliferation kinetics and drug sensitivity of exponential and stationary populations of cultured L1210 cells.

Drug sensitivity and cell cycle parameters of L1210 cells in culture in exponential (10(5) to 4 x 10(5) cells/ml) and plateau phase (greater than 8 x 10(5) cells/ml) of growth were compared. The percentage of cells in G1, S, and G2 + M for exponential and plateau-phase cultures was 24.1, 70.0, and 5.9, and 42.5, 45.6, and 11.9, respectively. These values correspond to those reported previously for early and late L1210 mouse leukemia cells. Cell survival (measured by cloning) after drug exposure showed that actinomycin D, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, chlorozotocin, and streptozocin were all equally lethal to cells in both phases, and 1-beta-D-arabinofuranosylcytosine, high-specific-activity (20Ci/mmole) [3H]thymidine, vincristine, daunomycin, adriamycin, and 5-fluorouracil were more lethal to exponential cells than to plateau-phase cells. The percentage kill by S-phase-specific agents such as 1-beta-D-arabinofuranosylcytosine and[3H]thymidine corresponded well with the percentage of cells in S. Finally, 1,3-bis(2-chloroethyl)-1-nitrosourea was more toxic to plateau cells than to exponential cells.


Preservation of in vitro biological functions in regional lymph node lymphocytes in squamous head and neck cancer.

Regional lymph node lymphocytes from patients with squamous cancer of the head and neck were tested in vitro for their ability to proliferate in response to phytohemagglutinin, concanavalin A, and allogeneic stimuli in one-way mixed lymphocyte culture. Their ability to act as cytotoxic effectors in phytohemagglutinin-dependent cellular cytotoxicity was also evaluated, and all results were compared to normal lymph node or blood lymphocytes. The regional lymph node lymphocytes retained proliferative capabilities equal to those in control lymph nodes or blood, whereas they were unable to mediate phytohemagglutinin-dependent cellular cytotoxicity. However, this was not a tumor-related effect because normal lymph node lymphocytes were also ineffective in this assay. The failure of the regional immune response to control early tumor growth could not be accounted for by generalized nonspecific immunosuppression in regional lymph node lymphocytes, inasmuch as these cells demonstrated normal in vitro activity.


Immunosuppressive activity of ascitic fluid from patients with cancer metastatic to the peritoneum.

We have examined the immunosuppressive effects of ascitic fluids from patients with advanced cancer metastatic to the peritoneum and compared them with noncancerous abdominal or pleural effusions, serum from cancer patients, or the proteins human serum albumin and bovine gamma-globulin. The ascitic fluids from cancer patients produce a nontoxic, dose-dependent suppression of DNA and protein synthesis of phytohemagglutinin-stimulated human peripheral blood lymphocytes. This suppression reached 100% with an ascitic protein concentration of 4 to 6 mg/ml, whereas control effusions, serum from cancer patients, or added extraneous proteins were not suppressive. Ascitic proteins also suppress the mixed lymphocyte reaction and the response of human peripheral blood lymphocytes to the antigen keyhold limpet hemocyanin, in vivo, the primary plaque-forming response to sheep red blood cells in mice could be suppressed, and this suppression was not due to antigenic competition.


Phase 2 study with Baker's Antifol in solid tumors.

One hundred thirty-eight adults with advanced cancers were treated with Baker's Antifol. The complete response + partial response rate was only 10%. Best responses were obtained in 31 patients with lung adenocarcinoma (complete response + partial response, 13%), in 25 patients with colorectal carcinoma (partial response, 16%), and in 6 patients with renal cell carcinoma (partial response, 50%). Two partial responses occurred in 15 patients with squamous cancer. No significant responses were seen in 27 patients with other adenocarcinomas, 13 with sarcomas, 14 with melanomas, and 8 with miscellaneous tumors. The most frequent toxicities were dermatitis, stomatitis, gastrointestinal symptoms, and mild myelosuppression. The incidence of dermatitis was significantly decreased by shortening the schedule of Baker's Antifol administration from 5 to 3 days. Baker's Antifol has some degree of antitumor activity, and studies of combination of this agent with other effective chemotherapeutic agents are indicated.


Does exercise conditioning delay progression of myocardial ischemia in coronary atherosclerotic heart disease?

The data regarding the effect of physical of physical conditioning on the progression of myocardial is chemia, although suggestive of a favorable influence, are in no way definitive. Efforts to alter the physical activity habits of our population should not supersede efforts directed to alter the major risk factors. The emphasis in the prevention of coronary atherosclerotic heart disease for the general public should be on the well established cardinal risk factors, that is, hypercholesterolemia, hypertension, and cigarette smoking. The National Postinfarction Rehabilitation Study, when completed, may demonstrate how physical conditioning influences the progression of myocardial ischemia. However, "moderate activity is a part of a balanced satisfying living and is the safe and sane hygienic prescription of the thoughtful physician for his patients, the high risk and the healthy alike.


[Characterization of the (Na+-K+)-ATPase from endometrial plasma membranes of immature mammals].

The (Na+-K+)-ATPase in plasma membrane from Mammiferous endometrium is characterized by the Mg/ATP ratio equal to one, and by a distinct affinity for Na+ (1.3 mM) and K+ (2 mM). The activity is maximum for pH 7.4-7.5 in presence of Mg++ 2mM and ATP 2 mM, Na+ 140 mM and K+ 10 mM.


The amino acid composition of actin and myosin and Ca2+-activated myosin adenosine triphosphatase in chronic canine congestive heart failure.

The Ca2+-activated myosin ATPase and the amino acid compositions of actin and myosin were determined for preparations from chronically failing dog hearts. Hypertrophy and congestive heart failure were produced by combined tricuspid valve insufficiency and pulmonary artery stenosis. Control, shamoperated, and noncardiac circulatory failure (inferior vena cava constriction) dogs also were studied. All hearts were divided into right ventricle, septum and left ventricle and each sample was individually analyzed. Calcium-activated ATPase decreased in the failing hearts and showed a distinct gradient of depression from right to left ventricles. There were no changes in ATPase activity among the other groups. The amino acid composition of actin was the same regardless of origin. The amino acid composition of myosin was unaltered except that cystine/2 residues were markedly decreased in failing heart myosin. The same gradient of depression was present as was found for Ca2+-activated myosin ATPase. This study suggests that protein metabolism is abnormal and that altered proteins are produced in hypertrophy and congestive heart failure. It appears that these changes do not affect all proteins, since actin was normal by the parameters studied. It is clear that the stressed ventricle is the most severely involved, but the entire heart is altered to some degree. Thus, we conclude that altered protein metabolism may be an important primary factor in the genesis of heart failure.


Development of left ventricular hypertrophy in young spontaneously hypertensive rats after peripheral sympathectomy.

The effects of peripheral sympathectomy with nerve growth factor antiserum (NGFAS) on blood pressure, systemic hemodynamics, myocardial function, myocardial hypertrophy, and renin were studied in male spontaneously hypertensive (SH) rats of the Okamoto strain and normotensive control Kyoto-Wistar (WKY) rats. NGFAS prevented the developing of hypertension in the SH rats but did not alter blood pressure in the WKY rats. The NGFAS-treated SH rats developed the same hemodynamic abnormalities as the sham-treated rats, including increased peripheral vascular resistance and depressed cardiac output; Indices of left ventricular performance, including peak flow velocity, stroke power, stroke work, dP/dtmax, and flow acceleration (dF/dt), were diminished in the SH rats compared to the WKY rats. NGFAS treatment further depressed ventricular function in the SH rats, but had little effect on the WKY rats; Plasma renin activity in both the SH and WKY rats was unaffected by NGFAS treatment. Although NGFAS treatment effectively prevented the development of hypertension in the SH rats, it did not influence the development of left ventricular hypertrophy as reflected by increases in left ventricular mass, RNA, DNA, and hydroxyproline content. The data suggest that the development of myocardial hypertrophy and myocardial dysfunction in the SH rat is in part independent of hypertension and plasma renin activity.


Target organ damage in black hypertensives.

A representative sample of black hypertensives has been appraised to determine candidacy for hypertension treatment. A total of 1759 black residents were successfully screened at home. Forty-one percent of the males and 33% of the females had diastolic blood pressures of 95 mm Hg or greater. They were invited for secondary screening along with those hypertensives controlled on therapy. Clinical and laboratory evidence of cardiovascular disease was common among examined patients who were studied to determine their eligibility for therapy based on criteria of elevated blood pressure (greater than 104 mm Hg) at two visits, or evidence of end organ damage at lowere blood pressure levels. Of patients previously aware of their hypertension but not on therapy, 88% of the males and 67% of the females were considered candidates for therapy. Of patients not previously aware of their elevated blood pressure, 72% of the males and 67% of the females were considered candidates.


Cardiac, skeletal and ophthalmologic abnormalities in relatives of patients with the Marfan syndrome.

Nine patients with the Marfan syndrome and 40 of their first degree relatives were evaluated for the presence of cardiac, skeletal and ophthalmologic abnormalities. Aortic root dilatation and mitral valve prolapse were sought by echocardiography, and the metacarpal index was calculated from hand X-rays. Abnormalities of all the tests performed were present in all nine index cases, except for one normal eye exam. Mitral prolapse was present in thirteen relatives (33%) and aortic root dilatation in seven (18%). At least one cardiac abnormality was present in nineteen (47%) relatives. Aortic root dilatation was more common in male relatives; the incidence of mitral prolapse was approximately equal in the two sexes. Abnormal metacarpal index (greater than 8.0) occurred in fifteen of twenty-six relatives examined (58%). Ophthalmologic abnormalities were found in only four relatives. Two relatives had abnormalities of all three organ systems evaluated, five others had abnormalities of two systems, and fourteen had abnormalities of one system. We conclude that cardiac and skeletal abnormalities are demonstrable in a high percentage of first degree relatives of patients with the Marfan syndrome.


Plasma androgens in women with hyperprolactinaemic amenorrhoea.

Cortisol, androstenedione, testosterone, dehydroepiandrosterone sulphate (DHAS) and free dehydroepiandrosterone (DHA) were measured in plasma of ten women affected by amenorrhoea with hyperprolactinaemia and eleven women affected by secondary hypothalamic amenorrhoea; twelve normal women at the second day of the menstrual cycle were used as controls. All subjects were hospitalized and 17-ketosteroids, 17OH-corticosteroids and total dehydroepiandrosterone were also measured in urine. Plasma DHAS was increased in all subjects affected by amenorrhoea with hyperprolactinaemia, while plasma DHA and urinary DHA were significantly increased in this group in comparison to other groups. Plasma cortisol, androstenedione and testosterone and urinary 17-oxosteroids and 17OH-corticosteroids were not significantly differnt in the three groups. In subjects affected by amenorrhoea with hyperprolactinaemia treated with bromocriptine a clear decrease of DHAS correlating with a decrease of plasma prolactin was observed. Since in wome DHAS sems to be almost exclusively secreted by the adrenal gland and most of the circulating DHA is dervied from adrenal secretion, these data suggest that human prolactin can stimulate DHAS production by the adrenal cortex.


Enhanced DNA synthesis in isolated calf lymph node lymphocyte cultures.

Calf sub-mandibular lymph node lymphocytes and human peripheral blood lymphocytes were oxidized by NaIO4. In liquid cell cultures, both types of cells were transformed with enhanced DNA synthesis. In mixed lymphocyte cultures, untreated human lymphocytes were transformed by irradiated-oxidized human cells. However, untreated calf lymphocytes were not transformed by irradiated-oxidized calf cells. Either human or calf lymphocytes were isolated from cell-cell interaction in agarose on slides. After 2-3 days of culture, cells were pulsed with tritiated thymidine. Autoradiography indicated greater numbers of cells with active DNA synthesis in NaIO4-oxidized calf cells and in calf cells incubated with Phaseolus vulgaris E-PHA compared to untreated lymphocytes. Similarly treated human cells did not show any increase in the numbers of cells with active DNA synthesis. No enhancement of DNA synthesis was seen in oxidized calf cells which were reduced with NaBH4 or cultured with hydroxyurea. In these restricted in vitro systems, calf cells are 'transformed' independent of cell-cell interaction, while human cells are not.


Confounding factors in HLA-DW 2 typing of human leucocytes.

Three healthy HLA-B7 homozygous subjects were found with similar but not identical HLA-D antigens; one was DW 2 homozygous according to independent typing results. This could be an expression of "long" and "short" HLA-D antigens or be due to differences in weak antigens outside the HLA-D region. Two further healthy HLA-B7 homozygous subjects were studied; one was apparently heterozygous for DW 2, the other apparently carried no DW 2 antigen. Both could discriminate between different DW 2 homozygous test cells. Two such test cells--one from a patient with multiple sclerosis (MS) and the other from a man with two children with MS--gave variable and absurb reactions with cells from the two subjects in question. It is tentatively suggested that genes exist which, when present in both moities in a mixed leucocyte reaction (MLR), can impair the MLR and give false "typing" reactions. This might be more common among patients with MS and perhaps also some other diseases (certain arthritides, e.g. rheumatoid arthritis) than among healthy subjects and can complicate or make impossible the interpretation of HLA-D typing data. It could also explain the previously-described impaired MLR between cells from patients with these diseases.


Generation of T-cell function in organ culture of foetal mouse thymus. II. Mixed lymphocyte culture reactivity.

The generation of MLC reactive cells in organ cultures of embryonic mouse thymus is described. At least 4 days in culture are required before MLC reactive thymocytes are detectable in this system, which is in marked contrast to the short incubation period required for the expression of Thy-1 on T-cell precursors in other systems. Our data demonstrates the generation of T-cell subsets independent of influences from peripheral lymphoid organs, and in the absence of B cells or their products. One very important application of this technique is in the investigation of the mechanism of T-cell tolerance to self.


Resolution of hypoxic changes in the heart and pulmonary arterioles of rats during intermittent correction of hypoxia.

1. Rats kept in a hypoxic chamber (10% O2) for 3 or more weeks developed right ventricular hypertrophy, muscularization of pulmonary arterioles and polycythaemia. These changes resemble those found in human hypoxic disease and, in particular, in patients dying from chronic airways obstruction. 2. Resolution of these changes was studied in a normal environment and in an intermittently normal, intermittently hypoxic environment. The latter regimen modelled the situation of patients with cor pulmonale receiving long-term intermittent oxygen therapy. 3. In a normal environment right ventricular hypertrophy and polycythaemia were resolved in 6 weeks but vessel changes were not resolved in 12 weeks. 4. In the intermittently normoxic environment (40 or 80 h in air per week) there was some resolution of right ventricular hypertrophy in 6 weeks but no significant reduction in vessel thickening or in polycythaemia in 12 weeks.


Plasma glucose, non-esterified fatty acids and amino acids in Huntington's chorea.

1. The metabolic responses to an oral glucose tolerance test (100 g) and an intravenous insulin provocation test (0-1 i.u./kg) were studied in nine control subjects and nine patients with Huntington's chorea. 2. Plasma glucose responses to these stimuli were identical in both groups. 3. High fasting concentrations of non-esterified fatty acid (NEFA) were recorded in the choreic patients when compared with control subjects. This difference was maintained under hypoglycaemic conditions. However, during hyperglycaemia the differences in NEFA concentrations between the groups was abolished. 4. Total plasma tryptophan concentrations were equal in the two groups. Free plasma tryptophan, however, was markedly reduced in the choreic group, and this appeared to be a result of a disturbed relationship between free tryptophan and NEFA concentrations. The abnormalities in free tryptophan values were sensitive to plasma glucose concentrations, as hyperglycaemic conditions markedly reduced the differences between the choreic and control group. 5. Patients with Huntington's chorea showed reduced fasting plasma concentrations of leucine, isoleucine and valine.


Legislation on prevention of occupational dermatoses.

Legislation is one way to eliminate sensitizers and irritants. Purity requirements, declaration and labelling, industrial health codes and pre-employment occupational aptitude examinations are useful in combating occupational and contact dermatitis by drugs and products of daily use. Chromium compounds, turpentine, balsam of Peru, benzocaine and other can be eliminated by administration and legislation.


Allergic paraben and benzyl alcohol hypersensitivity relationship of the "delayed" and "immediate" varieties.

From a review of the literature, and the results of scratch, intracutaneous and subcutaneous injections of patients with parbens and benzyl alcohol sensitivity of the delayed type characterized by allergic contact dermatitis and strongly positive patch patch tests, it would appear that such sensitivity is not usually accompanied by the immediate urticarial type of allergic sensitivity. This communication concerns itself with results of testing patients with clinical sensitivity and positive patch test reactions to the parabens or benzyl alcohol with scratch, intracutaneous and subcutaneous injections of these preservatives in order to determine the relationship of the "delayed" type of allergic hypersensitivity to the parabens and benzyl alcohol with the "immediate" variety of hypersensitivity. The parabens and benzyl alcohol are widely employed as preservatives for many allergenic extracts used in scratch and intracutaneous testing. In addition, these preservatives are used in injectable corticosteroid medicaments and in local anesthetic solutions. In order to determine whether the presence of these preservatives in allergenic extracts would produce false positive scratch or intracutaneous tests or might produce an immediate, urticarial or anaphylactic reaction in patients with allergic contact dermatitis and positive patch test reactions to these preservatives, two patients with positive patch test reactions and allergic contact dermatitis to the parabens and two with similar benzyl alcohol sensitivity were tested in the manner detailed in the following case reports.


Contact dermatitis from pyrrolnitrin (an antimycotic agent).

Two cases are described of acute contact dermatitis from an antifungal cream, containing pyrrolnitrin, employed for the treatment of tinea cruris. Positive reactions to pyrrolnitrin and to a chemically related substance, 1-chlor-2,4dinitrobenzene, were put into evidence.


Occupational contact dermatitis from Cichorium (chicory, endive) and Lactuca (lettuce).

In two cases, occupational contact dermatitis was found to be due to chicory (Cichorium) used as a salad plant. In one of the two cases, contact sensitivity to letuce (Lactuca) was also observed. The sesquiterpene lactones of the plant may be the allergens.


Occupational pigmented contact dermatitis from Naphthol AS.

Hyper-pigmentation as a manifestation of contact sensitivity to optical brighteners has previously been reported. In 1973 we observed an epidemic of pigmented contact dermatitis occurring in a textile mill in connection with the manufacture of drill fabrics impregnated with a recently introduced azo dye coupling component Naphthol AS. Of the 53 workers included in the study, 12 presented a spotted pattern of hyperpigmentation mainly affecting the exposed areas, but without pruritus, 18 were pigmented to a lesser degree, and in 21 it was not possible to discern any well-defined discoloration; some of the patients in the last group, however, complained of slight pruritus. The last two patients who were fair-skinned showed a reddish-brown pigmentation and a well pronounced pruritus. Hyper-pigmentation was most pronounced in individuals with dark complexions, whereas fair-skinned patient also showed "classical" eczematous symptoms including pruritus. A field study demonstrated direct exposure to the chemical. All 53 patients were patch-tested with Naphthol AS 5% in water, and 24 were found to be positive. Histological features were melanocyte proliferation, incontinence of pigment, and various degrees of damage to the basal layer.


Sensitivity to epoxy resins and triethylenetetramine.

The present studies concerned 31 work sites in eight factories at which 422 persons were employed. In the course of seven years there were 126 cases of dermatitis, 99 of whom were patch-tested. Positive reactions to epoxy resin and/or to triethylenetetramine were found in 65.7% of the subjects. The aetiology of the other cases is discussed. Some of the patients who were positive to epoxy resin were tested with Bisphenol A and modified resins with blocked epoxy groups. The latency period of dermatitis and the localization were recorded, as well as the influence of the season and of certain working conditions on the occurrence of sensitization. Of the 80 patients who changed their occupation, there were relapses in 50 within one year. Relapses were more frequent in persons who continued to work with epoxy resins for more than three months after the appearance of dermatitis and in those simultaneously sensitive to allergens in the standard series.


Contact dermatitis due to Nyloprint.

The Nyloprint process is becoming more frequently used in Great Britain. We report a case of contact dermatitis in a 60-year-old man who was employed in the production of Nyloprint formes. The process is described in detail. Patch tests showed him to be very sensitive to an acrylamide derivative, which is used as a monomer in this process.


Allergic contact dermatits and conjunctivitis from epinephrine.

A patient with chronic open-angle glaucoma was suspected of having allergic dermatitis and conjunctivitis to epinephrine. He was tested with epinephrine and other active substances, the preservatives and antioxidants usually used in the preparation of eye drops. He was also tested with other possible contactants with which he had had contact. The patient showed positive allergic patch test reactions to the chloride solution of epinephrine. The patient showed an unexpected positive reaction when tested with di-isopropyl fluorophosphate (DFP). The importance of routine patch testing in ophthalmic practice to detect sensitizers in cases of contact allergy is stressed.


Cinnamon dermatitis from an ointment.

Six patients are reported who had an allergic contact dermatitis from the use of a proprietary antiseptic ointment containing oil of cinnamon. Three were positive and three negative to balsam of Peru; two of these and one other also reacted to cinnamic aldehyde. The history and usage of cinnamon is briefly reviewed.


Irritant dermatitis from diallylglycol carbonate monomer in the optical industry: clinical and experimental studies of cutaneous tolerance and chemical investigations.

The diallylglycol carbonate monomer causes dermatitis due to irritation in the optical industry. Cutaneous intolerance may effect as many as 70% of the exposed persons employed. Almost all control subjects who where patch-tested showed irritation at a 2% concentration. The histological effects were an acute oedema with inflammation of the papillary dermis, and diapedesis of neutrophil polymorphonuclear leukocytes. Experiments on animals confirmed the irritant nature of the product; in the rabbit, a single application produced irritation, but to a lesser degree than in humans. Tests for possible sensitizing effects in the guinea pig have given negative results. Chemical analysis of the monomer revealed the presence of diallyl carbonate and acrolein. Allyl alcohol was detected in only one case. Patch tests were carried out in a group of control subjects with acrolein, diallyl carbonate and allyl alcohol. The histological appearance of the lesions caused by acrolein was quite different from that due to diallyglycol carbonate. It is probable that the irritant is the diallylglycol carbonate monomer itself.


Allergic contact response to vitamin A acid.

Three patients treated daily with vitamin A acid cream experienced after one week, seven weeks and 14 weeks respectively sudden redness and itching at the treated sites. Patch testing with the cream (containing 0.05% vitamin A acid) and with vitamin A acid 0.05% in absolute alcohol produced strongly positive reactions in the patients but only slight erythema in some of the controls. Since patch testing with vitamin A acid 0.005% in absolute alcohol elicited no response in controls but positive reactions in the three patients, it is probable that these latter reactions were due to contact allergy. Histologically the test reaction showed intact epidermis and dense dermal infiltration by mononuclear cells, and thus resembled a response of the tuberculin type.


Occupational dermatosis due to a soil fumigant.

D-D mixture is a preplant soil fumigant. It contains dichloropropanes and dichloropropenes, epichlorohydrin and is known as a primary irritant. Three cases of untoward reaction to D-D are reported. By patch testing, the existence of a contact allergic sensitivity to D-D could be proved in one patient. The other two cases reacted negatively; they were probably of a primary irritant origin. Patch tests with compounds related to D-D suggest that the cause of contact allergy must be sought in the propene(s) fraction of D-D. In future cases of untoward reactions to D-D, patch testing appears to be necessary in order to differentiate between a contact allergic and a primary irritant reaction.


Occupational eczema from N-isopropyl -N'-phenylparaphenylenediamine (IPPD) and N-dimethy-1,3 butyl-N'-phenylparaphenylenediamine (DMPPD) in tyres.

Forty-two cases of contact sensitivity to N-isopropyl-N'-phenylparaphenylenediamine (IPPD), an amine antiozonant used in rubber manufacture, were collated from several firms and plants dealing with tyres. Ten motor car tyres manufactured by eight different firms all induce sensitivity reactions in seven subjects allergic to IPPD. Clinical cross-reaction tests show that 100% of the subjects sensitive to IPPD are also sensitive to N-phenyl-N'-cyclohexy-paraphenylenediamine (CPPD), another amine antiozonant, and 37% to paraphenylenediamine (PPD). The various types of tyres were analyzed by gas chromatography and then by infra-red and thin-layer chromatography where necessary. None of the 12 tyres examined was found to be free from aromatic amines. Test reactions carried out with various automobile accessories on subjects allergic to IPPD in tyres gave positive results precisely in those cases where the articles contained IPPD. The authors then studied occupational sensitivity to N-dimethyl-1,3 butyl-N'-phenylparaphenylenediamine (DMPPD), a rubber antiozonant purported to be non-sensitizing and marketed in the United States. The The DMPPD tests were positive for all the IPPD-allergic patients tested; there is no doubt as to the allergenic nature of DMPPD. The irritant and sensitizing potentials of the four amines in question were tested in laboratory animals: PPD proved to be the most allergenic product, IPPD the least allergenic, and DMPPD and CPPD seem to give identical results. All these products produce positive cross-reactions in varying degrees of severity.


Occupational dermatitis from Lactuca sativa (lettuce) and Cichorium (endive). Simultaneous occurrence of immediate and delayed allergy as a cause of contact dermatitis.

Four patients with occupational contact dermatitis to Lactuca sativa had cross-sensitivity to Cichorium endivia. One of the patients also had contact urticaria to Lactuca and Cichorium, and another reacted positively to scratch tests with these plants as a sign of immediate allergy. In two cases such immediate allergy was considered the cause of a vesicular, intense itching eruption within a few minutes of contact with fresh leaves of Lactuca on previously eczematous skin. The severe chronic dermatitis of the hands of these patients is ascribed to combined delayed and immediate allergy.


Temperature dependent primary irritant dermatitis from lemon perfume.

In a recent outbreak of hand eczema amongst cleaning personnel after the introduction of a new, lemon-scented detergent, it was noted that the patients complained of a burning, stinging sensation when their hands were submerged in hot detergent solutions. Since routine patch testing with the Standard Series and perfume components was of no help in pinpointing the responsible agent, testing with selected perfume components was repeated at higher temperatures. Identical tests were placed on both forearms for 20 min, one arm being exposed to 43 degrees C, the other to 23-25 degrees C. Little or no reaction was seen on the "cold" arm, whereas the lemon perfume component Citral proved to be a strong primary irritant at higher temperatures. Histological examination of the test sites showed the reaction to be of a toxic (primary irritant) nature. Surprisingly, the toxic character could still be recongized in biopsies taken as late as 48 h after exposure. It is suggested that: 1. Heat plays an important part in the outbreak of primary irritant (toxic) dermatitis and can be used as an accelerating factor when testing for primary irritants. 2. It is important to be sure that detergents and detergent perfumes do not contain substances which act as irritants at the temperatures at which they are habitually used (45-50 degrees C). 3. We probably ought to use lukewarm rather than hot water for manual dishwashing and cleaning whenever it is possible.


Selective blockage of the Na+ transport path by Bay g 2821.

A series of transport and electrophysiological experiments were carried out on rat salivery duct epithelium to study the mechanism of action of Bay g 2821 on electrolyte transport at the cellular level. On the basis of the reported data it is suggested that Bay g 2821 blocks Na+ entry into the cell at the luminal rather than at the intersitial membrane of the duct cell.


Use of Buf-Puf and mild cleansing bar in acne.

As a result of this clinical study with the Buf cleansing system, I believe that it offers several advantages:(1) it is effective with minimal daily use; and (2) patients report that their skin feels smoother and they are easily able to control the irritative potential by experimentally titrating their own levels of application. Based on this sampling of acne patient, I conclude that the buf cleansing system is a useful addition to the treatment modalities now available for acne.


Detection of left ventricular failure in patients with adult respiratory distress syndrome.

Fourteen patients with adult respiratory distress syndrome were admitted to the medical intensive care unit and received bedside heart catheterization with the use of a balloon-tipped, flow directed catheter. Four of the 14 (29 percent) were found to have left ventricular failure (LVF), defined as a pulmonary artery wedge pressure greater than 12 mm Hg. Analysis of the standard clinical and laboratory data demonstrated no criteria which could differentiate those patients with LVF from those without. Three of the four patients indentified as having LVF responded to therapy directed toward LVF with substantial clinical improvement.


Ventricular inversion associated with normally related great vessels.

A patient with ventricular inversion with normally related great vessels and double inlet left ventricle is presented. the patient also showed features of Down's syndrome. Association of ventricular inversion with normally related great vessels is rare and leads to a basic functional state like that of complete transposition of great vessels derived from the connections between the ventricles and great vessels. The association of ventricular inversion with Down's syndrome observed in the case reported represents a rarity.


Choroid plexus papilloma. II. Ultrastructure and ultracytochemical localization of Na-K-ATPase.

An electron-microscopic study of a choroid plexus papilloma from the lateral ventricle of a child revealed fine structural features typical of normal choroid plexus tissue. Utilizing the Ernst technique for demonstrating ouabain-sensitive, potassium-dependent phosphatase activity, Na-K-ATPase was localized along the basal and lateral plasmalemmas of the tumor epithelium but not along the ventricular surface (apical plasmalemma). This localization is similar to that found in normal choroid plexus epithelium of all species studied to date.


[The possibility of oral rehabilitation of the handicapped under anesthesia].

In addition to technical and personnel requirements, clinical experience is necessary for oral rehabilitation of handicapped patients under general anesthesia. As our investigation has shown, the dental measures conceivable under legal aspects and theoretically feasible under general anesthesia, are almost exclusively limited to uncompromising, dental surgical reconstruction, if possible in one session. Conservative measures show a lasting success in few cases only, especially in occlusal acrylic and amalgam fillings of handicapped persons of sufficient intelligence and personal oral hygiene. Treatment under general anesthesia is inevitably indicated in imbeciles, the feeble-minded, spastics, epileptics, and sometimes in mongoloids. The patient's wish or that of his companion are not sufficient, nor the lack of will or obstinacy. Only after all other means failed, should oral rehabilitation be performed under general anesthesia.


Enzymatic responses of transplanted tumour cells towards estrogen, progesterone and testosterone.

The influence of estrogen, progesterone and testosterone on the activities of alkaline and acid phosphatases, adenosine triphosphatase and succinate dehydrogenase were determined by cytochemical methods in sarcoma 180 and Ehrlich's carcinoma cells transplanted in male and female Swiss mice. The results revealed differential effects of the sex hormones on different enzymes which seemed to depend on the type of tumour cell studied and the sex of the host mice.


Ca-linked phosphorylation of a light chain of vertebrate smooth-muscle myosin.

In vertebrate smooth muscle actomyosin and myofibrils a myosin light chain of molecular weight about 20,000 becomes phosphorylated at the same Ca2+ concentration as required to stimulate the actin-activated ATPase activity of myosin. Further, the degree of phosphorylation in the preparations as well as in various reconstituted actomyosins is proportional to their measured Ca2+ sensitivity. The phosphorylation process is very rapid and is essentially completed before the rise in ATPase activity. The enzyme responsible for the observed myosin phosphoylation is a specific myosin light chain kinase which is routinely co-purified with myosin. This kinase is normally present in actomyosin and its removal together with tropomyosin leads to a complete loss of the actin-activated ATPase activity. It is suggested that the Ca-dependent phosphorylation of the light chain via the light chain kinase represents the initial step in the activation of myosin that leads to contraction. Relaxation is probably effected by an as yet uncharacterised light chain phosphatase.


Inhibition of human mixed lymphocyte culture stimulation by anti-HLA-D-associated antisera: studies with primed responding cells.

The inhibitory effects of HLA-D-associated antisera on stimulating lymphocytes when cultured together with allogeneic primed responding lymphocytes were investigated. The responding lymphocytes were primed for either the HLA-Dw2 or Dw3 determinants. The presence of HLA-D-associated (Ia-like) antibodies during the culture period specifically inhibited the stimulatory capability of lymphocytes possessing the HLA-D determinants with which the antisera were apparently reacting, as long as the stimulating cells carried the determinant for which the responding cells were primed. HLA-D-associated antisera of other specificities caused no decrease in the stimulatory capability. These antisera, therefore, apparently contain antibodies which are reactive with determinants closely associated or identical to the HLA-D determinants and may be human analogues to the mouse Ia antigens.


Selective activation of human suppressor cells by a nonproliferative stimulus.

The eliciting of suppressor cell activity by heat-treated stimulating cells demonstrates that suppression can be induced by an antigenic but non-effective mixed lymphocyte culture (MLC) stimulus in vitro. Simultaneous or prior MLC or cytotoxic T lymphocyte activity is not required for alloantigen-induced suppressor cell activation.


Monoamine and GABA metabolism and the anticonvulsant action of di-n-propylacetate and ethanolamine-O-sulphate.

The time course of changes in behaviour, seizure response and cerebral monoamine and gamma-aminobutyric acid (GABA) metabolism has been studied in relation to the anticonvulsant actions of di-n-propylacetic acid (DPA) and ethanolamine-O-sulphate (EOS) on sound-induced seizures in DBA/2 mice. Changes in cerebral monoamine metabolism after EOS (75 or 150 mug, intracerebroventricularly) were not related to its anticonvulsant action. The primary effect was GABA-transaminase inhibition (by 50-70%) leading to a 2-4 fold increase in cerebral GABA concentration. Increases in brain GABA concentration (maximally 36%), 5-hydroxyindoleacetic acid (5HIAA, maximally 134%) and homovanillic acid (HVA, maximally 183%) were seen after DPA (400-600 mg/kg, i.p.). The time course of the increases in HVA and 5HIAA did not correlate with the anticonvulsant effect. Elimination of these increases by the use of inhibitors of monoamine synthesis (alpha-methyl-p-tyrosine and p-chlorophenyl-alanine) did not alter the anticonvulsant effect of DPA. Experiments using probenecid suggested that the increases in 5HIAA and HVA after DPA result from inhibition of their active transport out of the brain.


Effects of levodopa and dopamine of plasma glucose concentration in mice.

In nialamide-treated, fasted mice levodopa produced a dose-dependent hypoglycaemic response. The response was also seen in pargyline-treated mice but not in animals which were not treated with a monoamine oxidase inhibitor. Dopamine did not affect plasma glucose under these conditons. In doses which were ineffective when injected i.v., both levodopa and dopamine produced hypoglycemia when injected intracerebroventriculary (i.c.v.). The hypoglycaemic response to levodopa was prevented by the dopamine antagonists, haloperidol and pimozide. The possible involvement of 5HT in the hypoglycaemic response to levodopa was suggested by the blockade of the response by cyproheptadine and methysergide together with the observations that hypoglycaemia is produced by 5HTP and by i.c.v. 5HT. p-Chlorophenylalanine (PCPA) also reduced the response to levodopa but the usefulness of PCPA as an inhibitor of 5HT synthesis in these experiments in doubtful since it also inhibited the hypoglycaemic effects of 5HTP and i.c.v. 5HT. Hypoglycaemia produced by levodopa did not appear to involve stimulation of insulin secretion since plasma IRI levels were not increased by levodopa and the hypoglycaemia was accompanied by a elevation of plasma FFA and no significant change in the liver glycogen content. It is suggested that the hypoglycaemic effect of levodopa is mediated through dopamine acting in the brain, although the involvement of 5HT in the response and the mechanisms involved remain to be determined.


Synaptosomal adenosine triphosphatase (ATPase) inhibition by organophosphates.

Chicken spinal cord adenosine triphosphatases (both Na+, K+ stimulated and ouabain insensitive) were inhibited by tri-o-tolyl phosphate (TOTP, a neurotoxic organophosphate which is not a cholinesterase inhibitor) and mevinphos (a non-neurotoxic compound but inhibitor of cholinesterases). The inhibition was concentration and time dependent, with an initial rapid drop in activity followed by a gradual exponential decline.


[Vectorcardiographic contribution to the differential semeiology of cardiomyopathies (author's transl)].

The electro-vectorcardiographic findings of 59 patients with idiopathic cardiomyopathies, divided by means of hemodynamic and angiographic study into dilated (38 cases), hypertrophic obstructive (10 cases) and hypertrophic non obstructive (11 cases), were compared with those of a control group of 17 patients with left ventricular hypertrophy of known etiology. The statistical vectorial analysis of the 4 groups, excluding the patients with intraventricular conduction disturbances and patients below 10 years of age (46 cases), showed low voltage of the first vectors, especially at 0,01 sec., in the obstructive compared with the non obstructive type. On the basis of the data from the literature on histological findings in cardiomyopathies, these differences can be interpreted as due to a different myofibrillar arrangement in the free wall of the left ventricle.


[Peripartum cardiomyopathy (author's transl)].

Three cases of peripartum cardiomyopathy (CMP PP) are presented. In our opinion this term is more correct than post-partum cardiomyopathy. The study was performed both clinically and hemodynamically; patients were followed up for a long period (in one case up to 14 years). Although there were consistent differences in the rise and development of the disease, the clinical and laboratory results could be put together clearly. In the light of this clinical experience, a wide revision of the literature on the topic was carried out, using the hypotrophic-hypokinetic forms of cardiomyopathy (congestive) as a comparison with peripartum cardiomyopathy, which seem to be clinically correlated.


Effect of chemical carcinogens on pancreatic DNA synthesis in vivo.

The effect of dimethylnitrosamine (DMN), ethionine, streptozotocin, N-methyl-N-nitrosourethan (MNUT), N-bis(2-hydroxypropyl)nitrosamine (DHPN), azaserine, and 4-hydorxyaminoquinoline 1-oxide (4-HAQO) on DNA synthesis after partial pancreatectomy was studied. Its results indicates that DNA synthesis of the residual pancreas occurred and reached the maximum value at 3 days and returned to the control value 12 days after the operation. DNA synthesis, which was inhibited 96.7% by hydroxyurea 3 days after the operation, indicated that semi-conservative DNA synthesis had occurred in the residual pancreas. DMN and ethionine, non-pancreatic carcinogens, did not inhibit while DHPN, MNUT, azaserine, and 4-HAQO, pancreatic non-endocrine carcinogens, inhibited DNA synthesis in the rat pancreas by 57.9, 76.4, 71.7, and 82.1%, respectively. The effect of streptozotocin, pancreatic endocrine carcinogen, on DNA synthesis was not clear from the present experiment. Further effect on the inhibition of DNA synthesis by these carcinogens was obtained by dose-response studies and its results indicated that there was a correlation between pancreatic carcinogens and the inhibition of DNA synthesis after partial pancreatectomy in rats.


[Spontaneous aortic dissection. Diagnostic experience with 32 patients].

Of 48 patients in whom angiography was carried out on the clinical suspicion of spontaneous aortic dissection, the diagnosis could be confirmed in 18 cases only. On the other hand, aortic dissection was discovered incidentally in 14 patients on whom angiography was being carried out for other reasons. The high incidence of incorrect diagnosis is due to the variety of clinical symptoms caused by various types of dissection combined with the non-specific radiological findings on chest radiographs. Unlike plain films, aortography, provided a suitable technique is employed with an understanding of the possible sources of error, gives a high degree of diagnostic certainty with little risk. It is therefore always indicated when the demonstration or exclusion of an aortic dissection is likely to influence treatment.


[The segmental early relaxation phenomenon; its incidence and angiographic appearance (author's transl)].

Amongst one hundred patients examined radiographically, segmental early relaxation (SERP) of the antero-lateral wall of the left ventricle was observed in 21 cases; in 17 cases this was associated with a significant stenosis of the anterior descending branch of the left coronary artery. The reversibility of this phenomenon produced by vaso-dilators or by aorto-coronary by-pass operations with consequent increase in oxygen supply, as well as the frequency of this phenomenon in coronary disease suggests that it is due to mild, local hypoxia. On this view, SERP has clinical significance as an angiographic indicator of local oxygen deficit. Other possible causes are discussed and the findings compared with those reported in the literature.


[Coronary fistulae (author's transl)].

Three patients with coronary fistulae are described, including one patient with a rare coronary-pulmonary double fistula. The clinical features, diagnostic aspects and radiological signs are reviewed.


[Intraosseous angiography in the elucidation of the pathogenesis of juvenile bone cysts (author's transl)].

The results of intraosseous angiography in juvenile bone cysts suggest that their development is related to an anomaly of early metaphyseal vessels, although it is not established whether one is dealing with a primary ectasia or arteriovenous anastomoses. Juvenile bone cysts therefore belong to the category of congenital diseases. Intraosseous angiography also helps in distinguishing osteolytic processes from fibromas, myxomas, chondromas and osteoblastomas. None of the above-mentioned tumours consists of communicating chambers, such as have been demonstrated in cysts. The treatment consists of complete currettage followed by spongiosa tamponade.


[Morphometry of primary varicose veins (author's transl)].

Morphometric investigations into the perforating veins in cases of primary varicosities have revealed typical, so far unrecognized, features of insufficiency. A significant difference was found in the diameters of central and peripheral parts of the vein amounting to a ratio of 1.5:1 with single, and 1.8:1 with paired incompetent perforators. These perforators therefore act in producing a jet. The pathophysiological and diagnostic significance of this jet phenomenon is discussed. Variations in the pattern and frequency of incompetent perforators were found between the medial and lateral aspects of the calf. Evidence concerning the mode of incompetent perforators is discussed.


[New therapeutic possibilities in the diagnosis of congenital cystic bile duct dilatations (author's transl)].

The case of a 30-year-old woman with intra- and extrahepatic biliary dilatations (Caroli's disease) is reported. The features of the disease and its differential diagnosis are discussed. Special reference is given to the diagnostic approach by endoscopic retrograde cholangiography and to treatment with Chenodeoxy-cholicacid.


[Transjugular puncture of the portal vein. Portography and selective phlebography of abdominal organs. An experimental study in dogs (author's transl)].

Transjugular transhepatic portography is a new method for catheterising the portal vein and its tributaries. In order to gather experience of the method before applying it clinically, the transvenous approach was studied in six dogs. Transjugular portography has the following advantages as compared with umbilical vein catheterization and percutaneous, transhepatic portal vein catherterisation: 1. Because of the relative positions of the jugular veins, vena cava and portal vein, manipulation of the catheter for selective phlebography is simpler. 2. There is no risk of a haemoperitoneum or bile peritonitis if a correct technique is used since the liver capsule remains intact. 3. In the presence of portal hypertension, it may be possible in future to create an intrahepatic portocaval shunt by the transjugular approach without a major operation. Sclerosis of oesophageal varices is possible, as it is with the other procedures.


[Renovascular hypertension in neurofibromatosis. Simultaneous occurrence of multiple abdominal and cerebral vascular abnormalities (author's transl)].

Vascular involvement in von Recklinghausen's neurofibromatosis has been known since the work of Reubi (1944, 1946). We found 72 cases of neurofibromatosis with renovascular hypertension reported in the literature. We have observed three female patients, of whom two had unilateral renal artery abnormalities consisting of stensoses and small aneurysms. The third patient, who had a right-sided nephrectomy for probable occlusion of the renal artery, had a coarctation of the abdominal aorta and complete occlusion of the left renal artery and of the coeliac-mesenteric trunk. There were, in addition, large, bilateral aneurysms in the circle of Willis.


Radiologic aspects of Ask-Upmark kidney.

Radiologic work-up in a young girl suffering from severe hypertension revealed a small right kidney. In the pathological examination of the surgical removed right kidney segmental hypoplasia was found--Ask Upmark kidney. A detailed radiologic description of this entity is presented.


[The ultrasound appearances of thrombosis of the inferior vena cava due to renal tumours (author's transl)].

The findings of ultra-sound in four cases of thrombosis of the inferior vena cava due to malignant renal tumours are described. In three patients the cava was occluded by tumour, twice by infiltration and once by a mobile tumour mass in the vessel. The advantages of rapid imaging of normal and abnormal vascular structures are described. The method can demonstrate the occluding material in the vessel as well as showing the extent of local tumour infiltration around the cava, information which cannot be provided by cavography in the presence of complete occlusion.


[Ultrasound progress control of retroperitoneal tumours during chemotherapy (author's transl)].

In a retrospective study the chemotherapeutic response of retroperitoneal tumours was controlled by means of ultrasound and lymphangiography 34 patients. It could be demonstrated that ultrasound is a reliable tool for the evaluation of bulky retroperitoneal tumours, frequently undetectable by lymphangiography. The reliability was better than 90%.


[The value of quantitative functional scintigraphy of the kidneys in urology (author's transl)].

The results (in 221 cases) of quantitative functional scintigraphy (Q.F.S) using 125I-hipuran (sequential scintigraphy ROI-nephrography, unilateral clearance studies) were compared with the radiological, laboratory, surgical, histological and clinical findings. Clearance measurements were superior to estimates of blood urea and/or creatinin levels. The width of parenchyma in the urogram or the secretion value did not provide sufficiently valuable evidence regarding renal function. Agreement between the above findings and those on Q.F.S. was observed in 85.7%. In the absence of agreement, Q.F.S. proved the more sensitive method and was more frequently correct. Additional information was obtained in 78.8% and treatment influenced in 18 to 65%, depending on the underlying disease. Q.F.S, had a determining role in the choice of treatment (nephrectomy, preservation of the kidney, conservative treatment) in relation to the estimate of function of the other kidney and is of considerable value to the urologist in pre-operative diagnosis.


[Role of renal function and calcemia in demonstration of kidneys in 99mTc-diphosphonate skeletal scintigrams (author's transl)].

Normally, in 99mTc-diphosphonate-skeletal scintigrams the kidneys are delineated with the same intensity as the lumbar spine; This is not the case in patients with reduced renal function. In a series of 20 patients with varying degrees of renal insufficiency, a continuous decrease in the renal intensity with increasing serum creatinine was seen: clearly recognizable decreased renal intensity in patients with serum creatinine over 2 mg%, and no visualization of the kidneys in patients with serum creatinine over 8 mg%. This effect is intensified through a simultaneously existing hypercalcemia has the opposite effect, i.e., the intensity decrease is partially prevented. In patients with normal renal function a hypercalcemia even leads to an increased renal intensity. As a further cause for excessive renal intensity, an increased parenchymal transit time was found in the radionephrography in 5 out of 11 patients with normal serum creatinine in whom the increased renal intensity in the skeletal scintigram was a chance finding.


[Sources of error in the interpretation of bone scans with 99mTc-diphosphonate (author's transl)].

Errors in the interpretation of bone scans with 99mTc-diphosphonate may be due to summation of radio-activity from superimposition of various bone structures. Lesions with increased bone turn-over as well as reactive hyperaemia result in increased uptake. The possibility of extraosseous uptake of diphosphonate must be borne in mind during the evaluation of bone scans. The kidneys and lower urinary tract must be considered. Absent or slight uptake by the kidneys with good demonstration of bone suggests increased diphosphonate uptake by the bones. Special attention should also be paid to zones of decreased uptake, since these are also due to abnormalities in the bone.


[Comparative investigations of osteotropic radionucleides. IV. The dynamics of uptake in normal and abnormal bone (author's transl)].

The dynamics of uptake of osteotropic radionucleides in normal and abnormal bone were studied by means of sequential and functional scans. Various phosphate and phosphonate complexes were compared in vivo and in vitro. Only phosphonates were considered as suitable for bone scanning. In normal bones in beagles, radioactivity after HEDP fell to 65% after two hours, but was 105% with 18F. In relation to healing fractures, the curves differ quantitatively and qualitatively. In this situation, functional curves derived from dynamic scans provide a better parallel with histological findings than does static scintigraphy with an uptake quotient. Sequential and functional scanning are able to document the therapeutic effect of irradiation of bone metastases.


[Pharmacokinetics and plasma albumen binding of iotroxic acid (Biliscopin), iodoxic acid (Endomirabil) and ioglycamine (Biligram) (author's transl)].

Pharmacokinetic data after injection of the new cholegraphic contrast medium iotroxic acid (Biliscopin) in man are reported and compared with the results of injections of ioglycamate and iodoxic acid. Iotroxic acid is less completely bound to plasma proteins than ioglycamate, but significancy more so than iodoxamate. Plasma protein binding depends on contrast concentration in the plasma, as does excretion in the urine. Biliary transport rate and maximal iodine concentration in the gall bladder are higher after injections of iotroxinate and iodoxamate than after ioglycamate.