Fine structural alterations of muscle fibers in diseases accompanied by myotonia. The authors have reported the results of examination by electron microscopy of two muscle biopsy specimens from cases of myotonia congenita and three cases of myotonia dystrophica. They have stated that "peripheral annular formation" was a frequently observed alteration in the myotonia congenita cases. In the myotonia dystrophica cases there were additionally disorganized myofibrils in the subsarcolemmal region and inclusion body vacuoles morphologically connected with the sarcolemma. The term "peripheral annular formation" refers to the situation in which the peripheral myofibrils of the muscle fiber fracture and the fragments retract and form a helical sheath around the central myofibrils of the same muscle fiber.


The effect of 2,4-D and Dicamba on the growth and yield of garden broad bean (Vicia faba L. var. major). Two experiments were conducted in Egypt to investigate the effect of sublethal concentrations of 2,4-D and Dicamba on the growth and yield of garden broad bean. It was found that 1. as compared to the effects of Dicamba, 2,4-D had a better stimulating effect on the growth characters, the yield, and the yield components of the beans 2. the application at the flowering stage was superior to the earlier application in every respect 3. the optimum rate of 2,4-D and Dicamba that gave the highest increase of the growth, yield, and yield components was 2-5 ppm.


Preliminary study on using fermented skim milk in poultry rations. 80 (4 X 20) four-month-old cockerels were fed the following rations for six weeks: Group 1 = corn and green berseem, group 2 = corn, green berseem, and skim milk, groups 3 and 4 = corn, green berseem, and fermented skim milk. Feeding was ad libitum in groups 1 to 3, and 80% of the group 3 standard in group 4. The live weight increased in all groups during the experimental period. In group 4 it was higher at the end of the experiment than that of groups 1 to 3. But the difference was statistically not significant. The amount of starch units required per unit of live weight increase during the experimental period was 9.76 (group 1) 11.00 (group 2), 10.72 (group 3), and 9.66 (group 4). The visceral fat weights were higher in groups 2 and 3 (not significant). 40 (2 x 20) four-week-old ducklings were fed a commercial ration (group 5) or 65% of this ration supplemented with 35 ml of fermented skim milk (group 6). There were no significant differences in the live weight gains. The amount of starch units required per unit of live weight increase was 2.89 (group 5) and 3.61 (group 6).


Trypsin-activated complex of human factor B with cobra venom factor (CVF), cleaving C3 and C5 and generating a lytic factor for unsensitized guinea pig erythrocytes. I. Generation of the activated complex. A complex formed between cobra venom factor (CVF) and isolated human factor B (B) was found to be converted by trypsin to a stable enzyme, CVF-B which cleaved the third component (C3) and the fifth component (C5) of human complement. The formation of CVF-B by trypsin required divalent cations, whereas the formation of the lytic factor from human serum occurred even in the presence of EDTA. CVF-B purified by gel filtration could initiate the hemolysis of unsensitized guinea pig erythrocytes when incubated with human complement components C5 to C9 in 0.01 M EDTA buffer. C3 was not required for the lysis of guinea pig erythrocytes initiated by CVF-B because of the beta1C precipitation line formed between human serum and anti-beta1C antibody did not inhibit the hemolysis by CVF-B in agarose gel. Treatment of beta1C and beta1F globulins in whole human serum with CVF-B in the presence of 0.01 M EDTA converted them to components with higher mobilities on immunoelectrophoresis.


Trypsin-activated complex of human factor B with cobra venom factor (CVF), cleaving C3 and C5 and generating a lytic factor for unsensitized guinea pig erythrocytes. II. Physico-chemical characterization of the activated complex. A complex, CVF-B, between cobra venom factor (CVF) and human factor B(B) showed weak, short-lived enzymatic activity against the third component of human complement (C3). Once activated with trypsin, it showed strong, stable activity against C3 and C5. CVF-B, an activated form of CVF-B complex, was not affected by the trypsin inhibitor, diisopropylfluorophosphate and neuraminidase. Heating at 56 C for 30 min completely destroyed its activity and heating at 50 C for 30 min destroyed approximately half its activity. The activity of DVF-B decrease markedly at pH 6.0 but was stable at pH 6.5 to 8.5. CVF-B lost 90% of its activity on reduction with 1 mM dithiothreitol, and was completely adsorbed on a cellulose acetate membrane. CVF-B was found to be a complex of CVF and glycine-rich gamma-glycoprotein, with a molecular weight of 340,000. The CVF-B molecule consisted of 4-polypeptide chains, 3 of which were derived from CVF and one from GGG. Hemolytically active CVF-B may be formed from 2 molecules with four-polypeptide chains linked by unknown bonds. Human, rat and guinea pig sera could react with CVF-B to generate a lytic factor. Human and sheep erythrocytes were not sensitive to the lytic factor generated by CVF-B, whereas liposomes prepared from their membrane lipids were equally sensitive to the lytic factor.


The amino acid sequence of Staphylococcus aureus penicillinase. The amino acid sequence of the penicillinase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6) from Staphylococcus aureus strain PC1 was determined. The protein consists of a single polypeptide chain of 257 residues, and the sequence was determined by characterization of tryptic, chymotryptic, peptic and CNBr peptides, with some additional evidence from thermolysin and S. aureus proteinase peptides. A mistake in the preliminary report of the sequence is corrected; residues 113-116 are now thought to be -Lys-Lys-Val-Lys- rather than -Lys-Val-Lys-Lys-. Detailed evidence for the amino acid sequence has been deposited as Supplementary Publication SUP 50056 (91 pages) at the British Library (Lending Division), Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1975) 145, 5.


The preparation of a semisynthetic tritiated insulin with a specific radioactivity of up to 20 Curies per millimole. 1. This paper describes the semisynthesis of [3H]insulin of high specific radioactivity which is indistinguishable from native insulin in its hypoglycaemic activity towards mice. 2. The maximum specific radioactivity so far obtained is 20 Ci/mmol. At this value the recommended scale of preparation is between 1 mCi (30 mug of product) and 10mCi (300 mug of product). Reaction volumes are then of the order of 10 mul. 3. Special problems arise when the techniques of peptide synthesis are applied to the production of such small quantities of material. We describe these problems and discuss the means of overcoming them.


Role of apurinic sites in the resistance of methylated oligodeoxyribonucleotides to degradation by spleen exonuclease. The effect of introducing methyl groups into DNA substrates was studied by using the spleen exonuclease (EC 3.1.4.1), an enzyme which hydrolyses oligonucleotides in a sequential manner by splitting off 3'-phosphomononucleotides starting from the 5'-hydroxyl terminus. Analyses of oligodeoxyribonucleotide 3'-phosphate substrates after reaction in vitro with dimethyl sulphate demonstrated that the resultant methylation pattern differed from the previously found for native DNA, particularly with respect to the relative amounts of 1- and 3-methyladenine produced. Although after treatment with increasing amounts of dimethyl sulphate the substrate became progressively resistant to degradation by the exonuclease, the methylation products themselves were only partially responsible for the observed inhibition of enzyme activity. The incomplete degradation encountered was apparently due to the presence of apurinic sites, which arose as secondary lesions after the spontaneous release of the labile alkyl purines from the methylated substrate. Inhibition of enzyme activity appeared to be competitive, being characterized by constant values for apparent Vmax, and increased values for apparent Km. the interpretation of this, however, is complicated by the complex nature of the substrate, and these aspects are considered in some detail.


Factorization of the Michaelis functions. Each Michaelis function that expresses the concentration of one of the species AL2, AL and A in terms of the concentration of free ligand (or its logarithm) is the product of two functions each of which represents the degree of ligation or de-ligation of a single site. These hypothetical sites have pK values of pK (SEE ARTICLE) where pK and alpha are defined by writing the two molecular pK values as pK +/- log2alpha. The factors are thus real if alpha larger than or equal to 1, i.e. if the binding of L by A is not positively co-operative. The dependence of [AL] on 1n[L] is compared with relations that represent other ligand-dependent equilibria.


Affinity-chromatography purification of alkaline phosphatase from calf intestine. A crude preparation of alkaline phosphatase (EC 3.1.3.1) from calf intestinal mucosa was purified by affinity chromatography on Sepharose-bound derivatives of arsanilic acid, which was found to be a competitive inhibitor of the enzyme. Three biospecific adsorbents were prepared for the chromatography, and the best results were obtained with a tyraminyl-Sepharose derivative coupled with the diazonium salt derived from 4-(p-aminophenylazo)phenylarsonic acid. Alkaline phosphatase was the only enzyme retained by the affinity column in the absence of Pi. The enzyme eluted by phosphate buffer had a specific activity of about 1200 units per mg of protein at pH 10.0, with 5.5mM-p-nitrophenyl phosphate as the substrate.


The nature of experimental error in enzyme kinetic measurments. The nature of experimental error in the determination of initial velocities of enzyme-catalysed reactions was investigated. No support was found for the generalization that such velocities should be homogeneous in variance. Instead the variance increased with the velocity in all of the cases studied. The weighting of sets of replicate observations according to their sample variances was tested in simulated experiments and found to give unacceptable results. It was practicable to decide on the best weighting scheme by examining the variability of the deviations from fitted curves, provided that the number of observations was large enough.


A membrane-associated lipomannan in micrococci. Membranes of Micrococcus lysodeikticus, Micrococcus flavus and Micrococcus sodonensis contain acidic lipomannans. Lipoteichoic acids could not be detected in these organisms, and the suggestion that they are substituted for by the lipomannans is strengthened by the chemical and physical resemblances between the two polymers. The mannans contain glycerol, ester-linked fatty acids and mono-esterified succinic acid residues, giving them both hydrophobic and charged properties. The M. lysodeikticus mannan has a chain of about 60 hexose units with two branch points, and is joined at its reducing end to the 1-position of a glycerol moiety bearing two fatty acid residues. Succinic acid on the mannan enables it to bind Mg2+ efficiently, and the polymer is firmly associated with the cytoplasmic membrane, probably by intercalation of its fatty acids with those of the membrane lipids.


Purification and characterization of kynurenine--2-oxoglutarate aminotransferase from the liver, brain and small intestine of rats. 1. Kynurenine-2-oxoglutarate aminotransferase (isoenzyme 1) was purified to homogeneity from the liver, brain and small intestine of rats by the same procedure. The three enzyme preparations had nearly identical pH optima, substrate specificities and molecular weights. Isoenzyme 1 was active with 2-oxoglutarate but not with pyruvate as amino acceptor, and utilized a wide range of amino acids as amino donors. Amino acids were effective in the following order to activity: L-aspartate greater than L-tyrosine greater than L-phenylalanine greater than L-tryptophan greater than 5-hydroxy-L-tryptophan greater than L-kynurenine. The molecular weight was approximately 88 000 as determined by sucrose-density-gradient centrifugation. The pH optimum was between 8.0 and 8.5. On the basis of substrate specificity, substrate inhibition, subcellular distribution and polyacrylamide-disc-gel electrophoresis, it is suggested that liver, brain and small intestinal kynurenine-2-oxoglutarate aminotransferase (isoenzyme 1) is identical with mitochondrial tyrosine-2-oxoglutarate aminotransferase and also with mitochondrial aspartate-2-oxoglutarate aminotransferase. 2. An additional kynurenine-2-oxoglutarate aminotransferase (isoenzyme 2) was purified from the liver. This enzyme was specific for 2-oxoglutarate and L-kynurenine. Sucrose-density-gradient centrifugation gave a molecular weight of approximately 100 000. The pH optimum was between 6.0 and 6.5. This enzyme was not detected in the brain or small intestine.


Radioimmunoassay of colchicine.

Radioimmunoassay of colchicine. Antibodies to cholchicine were raised in rabbits after injection of N-desacetylthiocolchicine conjugated to bovine serum albumin. Antisera diluted 1:100 bound 50% of 1.6ng of [3H]colchicine. Cross-reaction of the antisera with colchicine derivatives and other drugs was measured and a radioimmunoassay of colchicine in biological fluids was proposed.


Heavy metal-pyrimidine nucleotide interaction: x-ray structure of a cadmium derivative of cytidine 5'-monophosphate. An X-ray crystal-structure determination has shown that the compound [Cd(5'-CMP)(H2O)],H2O has a polymeric structure in which each cadmium atom is bonded to five atoms: to the N(3) position on the base, to a phosphate oxygen from each of three other 5'-CMP groups and to a water molecule.


The copolymeric structure of dermatan sulphate produced by cultured human fibroblasts. Different distribution of iduronic acid and glucuronic acid-containing units in soluble and cell-associated glycans. The structure of dermatan [35S]sulphate-chondroitin [35S]sulphate copolymers synthesized and secreted by fibroblasts in culture was studied. 35S-labelled glycosaminoglycans were isolated from the medium, a trypsin digest of the cells and the cell residue after 72h of 35SO42-incorporation. The galactosaminoglycan component (dermatan sulphatechondroitin sulphate copolymers) was isolated and subjected to various degradation procedures including digestion with testicular hyaluronidase, chondroitinase-AC and-ABC and periodate oxidation followed by alkaline elimination. The galactosaminoglycans from the various sources displayed significant structural differences with regard to the distribution of various repeating units, i.e. IdUA-GalNAc-SO4 (L-iduronic acid-N-acetyl-galactosamine sulphate), GlcUA-GalNAc-SO4 (D-glucuronic acid-N-acetylgalactosamine-sulphate) and IdUA(-SO4)-GalNAc (L-iduronosulphate-N-acetylgalactosamine). The galactosaminoglycans of the cell residue contained larger amounts of IdUA-GalNAc-SO4 than did those isolated from the medium or those released by trypsin. In contrast, the glycans from the latter 2 sources contained large proportions of periodate-resistant repeat periods [GlcUA-GalNAc-SO4 and IdUA(-SO4)-GalNAc]. Periods containing L-iduronic acid sulphate were particularly prominent in copolymers found in the medium. Kinetic studies indicated that the 35S-labelled glycosaminoglycan of the cell residue accumulated radioactivity more slowly than did the glycans of other fractions, indicating that the material remaining with the cells was not exclusively a precursor of the secreted polymers. The presence of copolymers rich in glucuronic acid or iduronic acid sulphate residues in the soluble fractions may be the result of selective secretion from the cells. Alternatively, extracellular, polymer-level modifications such as C-5 inversion of L-iduronic acid to D-glucuronic acid, or sulphate rearrangements, would yield similar results.


Characterization by gas-liquid chromatography-mass spectrometry and proton-magnetic-resonance spectroscopy of pertrimethylsilyl methyl glycosides obtained in the methanolysis of glycoproteins and glycopeptides. The quantitative analysis by gas chromatography of monosaccharides present in glycoproteins and glycopeptides using methanolysis, followed by re-N-acetylation and trimethylsilylation, gives rise to several peaks for each monosaccharide. The identity of these peaks for xylose, fucose, mannose, galactose, glucose, N-acetylglucosamine, N-acetylgalactosamine and N-acetylneuraminic acid was established for alpha- and beta-methyl pyranosides and furanosides by combined g.l.c.-mass spectrometry and proton-magnetic-resonance spectroscopy. These data provide for the unambiguous interpretation of the gas chromatograms obtained in the application of this g.l.c. method, and supply basic information for the further application of mass spectrometry in this field.


Effects of polyamines and methylglyoxal bis(guanylhydrazone) on hepatic nuclear structure and deoxyribonucleic acid template activity. 1. The interaction of polyamines and methylglyoxal bis(guanythydrazone) (1, 1'-[(methylethanediylidene)-dinitrilo]diguanidine) with isolated rat liver nuclei was investigated by electron microscopy. 2. At 4mM, putrescine was without effect; however, spermidine, spermine or methylglyoxal bis(guanythydrazone) resulted in dispersed chromatin and alterations in nucleolar structure. In addition, spermidine or methylglyoxal bis(guanylhydrazone) caused marked aggregation of interchromatin granules. 3. The DNA template property of calf thymus DNA was examined by using DNA polymerases from Escherichia coli, Micrococcus lysodeikticus and calf thymus in the presence of 0-5 mM-amine. 4. In the presence of DNA polymerase, spermine or methylglyoxal bis(guanylhydrazone) inhibited activity, whereas putrescine or spermidine had much less effect or in some cases stimulated [3H]dTMP incorporation. 5. Template activity which was inhibited by spermine or methylglyoxal bis(guanylhydrazone) could be partially restored by additional DNA or enzyme. 6. When mixed with calf thymus DNA, calf thymus histone inhibited template activity as measured with E. coli DNA polymerase. The template activity of such a 'histone-nucleate' could not be restored by putrescine, spermidine, spermine or methylglyoxal bis(guanylhydrazone). 7. DNA template activity of isolated rat liver nuclei was tested by using E. coli DNA polymerase. None of the amines was able to increase the template activity of the nuclear DNA in vitro.


Intramolecular electron transport in human ferroxidase (caeruloplasmin). The oxidation of reduced human ferroxidase by molecular O2 was studied in a stopped-flow spectrophotometer. It was shown that the two type 1 copper atoms behave differently in the absence of iron. The effect of iron on the kinetic parameters was investiagted. A working model for intramolecular electron transport in the enzyme is proposed.


A micro-method for the assay of polyadenylate-containing ribonucleic acid by gel electrophoresis. A micro-method for the determination of the electrophoretic profile of the various poly(A)-containing RNA species in a RNA sample was developed. The method is simple to carry out and allows for great reproducibility. It combines the resolving power of electrophoresis in agarose with the specificity of binding of poly(A) to poly(U)-containing glass-fibre filters. It consists of the following steps. (1) The molecules in an RNA sample are first separated according to their molecular weight by electrophoresis in agarose, at low ionic strength. 2. The molecules thus seperated are then submitted to a second electrophoresis in 'binding buffer' in a direction perpendicular to the first one. In the course of this electrophoresis the poly(A)-containing RNA species are seperated from other RNA species as they bind to a poly(U)-containing glass-fibre filter which is placed across the electrophoresis path. The method was used to determine the electrophoretic profile of Rhynchosciara salivary-gland messenger RNA. It was found that the population of messenger RNA in the gland is dominated by forms moving as 18 and 158 S peaks, but there is also polydisperse RNA with slower mobility.


Isolation and properties of a fragment of human serum albumin demonstrating the absence of a methionine residue from some of the albumin molecules. 1. A fragment designated D was isolated from human serum albumin degraded by CNBr. Its properties show that it is made up of the B and C fragments isolated by McMenamy et al. (1971) (J. Biol. Chem., 246, 4744-4750). 2. Reduction of fragment D gives rise to two chains, one of which consists of the second subfragment of reduced fragment B linked to fragment C by an amino acid different from methionine. It thus demonstrates the existence of albumin molecules from which the second methionine residue located between fragments B and C is missing.


Influence of alanyl ester residues on the binding of magnesium ions to teichoic acids. The binding of Mg2+ to the ribitol teichoic acid of Staphylococcus aureus H walls was examined by equilibrium dialysis in solution and in the intact wall; the influence of alanyl ester groups on binding was determined. In solution the ribitol polymer had a lower affinity than did a glycerol teichoic acid and bound Mg2+ in the ratio Mg2+/P of 1:1. The presence of alanyl ester residues caused a decrease in the amount of cations bound in stoicheiometric proportion to the ratio Ala/P, but the affinity constant was unaltered. It is concluded that in solution the ribitol teichoic acid binds Mg2+ univalently to phosphate groups and univalently to a counter-ion. In the intact wall the binding of Mg2+ was different. The affinity constant was higher and resembled that of a glycerol teichoic acid. It is concluded that Mg2+ forms bridges across phosphate groups in teichoic acid chains lying adjacent to each other in the wall. The effect of alanyl esters was similar to that in solution, but Scatchard plots were not linear at low concentrations of Mg2+ where it was shown that the difference in affinities between walls with and without alanyl ester residues was much greater than it was at higher concentrations of Mg2+. Thus at very low concentrations of Mg2+ effective binding to the wall is markedly improved by loss of alanyl ester residues.


The reaction of choline dehydrogenase with some electron acceptors. 1. The choline dehydrogenase (EC 1.1.99.1) WAS SOLUBILIZED FROM ACETONE-DRIED POWDERS OF RAT LIVER MITOCHONDRIA BY TREATMENT WITH Naja naja venom. 2. The kinetics of the reaction of enzyme with phenazine methosulphate and ubiquinone-2 as electron acceptors were investigated. 3. With both electron acceptors the reaction mechanism appears to involve a free, modified-enzyme intermediate. 4. With some electron acceptors the maximum velocity of the reaction is independent of the nature of the acceptor. With phenazine methosulphate and ubiquinone-2 as acceptors the Km value for choline is also independent of the nature of the acceptor molecule. 5. The mechanism of the Triton X-100-solubilized enzyme is apparently the smae as that for the snake venom solubilized enzyme.


Cellular interactions in the control of granulopoiesis. We have examined several new techniques for studying cellular interactions in the control of granulopoiesis in vitro. Better in vitro growth of mouse bone marrow can be achieved by modifying standard diffusion chamber systems to allow continuous fluid circulation and cell migration. When certain organ fragments are added to such systems, enhanced granulocytic differentiation is observed.


The use of direct current to cause selective block of large fibres in peripheral nerves. The effect of direct current on the propagated compound action potential in a cutaneous branch of the radial nerve of the dog was studied and a convenient method for applying electrical current to a nerve is described. Changes in the flow of blocking current, even when these were made slowly during a period of 5-10 sec, caused stimulation of the nerve. The method was satisfactory for producing differential nerve block within the myelinated fibres. It was confirmed that direct current could be used to eliminate selectively the group II/III potentials. When these potentials had been eliminated for a period of 5 min the mean height of the group IV potentials was reduced to 65% of the control value, and their conduction velocity was decreased by 10%. Relatively small variations in current flow caused a marked change in conduction. In the early stages of block, frequent relatively large reductions in current flow were necessary to produce a constant response and it was impossible to cause a stable effect on conduction until the blocking current had been applied for at least 1 min. Because of nerve damage the method is unsuitable for clinical use.


Differential B and C fibre block by an amide- and an ester-linked local anaesthetic. The relative sensitivity of sympathetic preganglionic and postganglionic axons, B and C fibres, respectively, to two structurally dissimilar local anaesthetics was examined. The concentration of amethocaine (ester-linked tertiary amine) or prilocaine (amide-linked secondary amine) required to reduce the B fibre compound action potential by 50% was one-third of the concentration required to depress the C fibre potential to a similar extent. Both local anaesthetic agents also showed the action potential propagation through B fibres more than through C fibres. Similar results have been reported previously for lignocaine (amide-linked tertiary amine).


Effects of ketamine on central sympathetic discharge and the baroreceptor reflex during mechanical ventilation. In rabbits which were ventilated mechanically, with a background anaesthetic of pentobarbitone or after decerebration, ketamine depressed preganglionic sympathetic activity and arterial pressure. Conduction through central baroreceptor pathways, tested by depressor nerve stimulation, showed a selective inhibition of the heart rate response.


Circulatory responses to ketamine: dependence on respiratory pattern and background anaesthesia in the rabbit. In rabbits which were initially conscious or lightly anaesthetized with pentobarbitone, ketamine respectively increased or did not change arterial pressure, whereas in mechanically ventilated animals there was prolonged depression of both pressure and pregangkioinic sympathetic activity. Although respiratory rate slowed during spontaneous ventilation, blood-gas changes were not responsible for these differences. Following bilateral division of the carotid sinus and aortic nerves, a depressor response to ketamine occurred during spontaneous respiration. When respiratory rate was slowed coincidentally with ketamine injection during mechanical ventilation, the circulatory responses were similar to those during spontaneous respiration; this did not occur after carotid and aortic denervation. These variations in the circulatory effects of ketamine, according to respiratory pattern and background anaesthesia, are discussed.


Species, strain, sex and individual differences in enflurane metabolism. Species, sex and individual differences in serum inorganic fluoride concentrations were demonstrated in mice, guineapigs and rats exposed to either 0.07% or 0.2% enflurane for 35 days, suggesting differences in enflurane biotransformation. Exposure of Fischer 344 rats and Sprague-Dawley rats to 0.2% enflurane for 8 days resulted in enzyme induction as demonstrated by increasing serum inorganic fluoride and cytochrome P-450 concentrations. However, there was no difference in cytochrome P-450 concentrations between the strains despite differences in inorganic fluoride concentration. These results emphasize the multiplicity of factors and the lack of predictability in patterns of enflurane metabolism among species, strains and individuals.


Thrombin-induced disseminated intravascular coagulation. III:Modification by dextran infusion. The cardiorespiratory effects of thrombin-induced disseminated intravascular coagulation (DIC) were studied in two groups of dogs. The main changes were a reduction in cardiac output and arterial pressure, an increase in pulmonary artery pressure and, an increase in pulmonary artery pressure and an increase in venous admixture. In one group of dogs the reduction in cardiac output was diminished by the infusion of dextran 35 ml/kg body weight. This resulted in an increased pulmonary artery pressure but no significant differences in the indices of the efficiency of gas exchange. However, the haemodilution resulted in a lower mixed venous and arterial PO2 in this group of dogs.


The uptake and elimination of halothane in dogs: A two or multicompartment system? II: Evaluation of wash-in and wash-out curves. In 14 mongrel dogs wash-in and wash-out curves for halothane were obtained from measurements of arterial blood, mixed venous blood and end-tidal gas. From a certain point in the wash-in period the halothane concentration of arterial blood can be calculated from the halothane concentration in end-tidal gas and the blood-gas partition coefficient for halothane. Analysis of the curves shows that they are composed of two exponential components suggesting the presence of two body compartments. The question of a two-compartment system versus a multi-compartment system in discussed.


The production of standard atmospheres of volatile anaesthetic agents by a diffusion dilution cell. The diffusion of a vapour into a gas provides a useful method for the preparation of standard atmospheres of the vapour. The construction and use of the apparatus for preparing these standards are described and the relevance of the method to research in anaesthetic practice is discussed.


An expired gas collection and disposal system. An expired gas collection and disposal system based on an independent suction pump is described. The halothane concentration in the atmosphere was measured, with and without the system. The increase of halothane concentration was limited to 1 p.p.m. above the theatre basal value with the system in use, and 5 p.p.m. when no venting was used.


Incidence of suxamethonium apnoea in patients undergoing E.C.T. Plasma cholinesterase variants have been examined in blood samples obtained from 23 patients who, after an intravenous injection of suxamethonium 30 mg before e.c.t., had prolonged apnoea. Attempts have been made to screen the relatives of all patients shown to have an unusual plasma cholinesterase. The present study indicates an increased frequency of the fluoride-resistant variants in those psychiatric patients sensitive to suxamethonium.


Althesin and pancuronium in chronic liver disease. In 32 patients with chronic liver disease, undergoing major abdominal surgery, anaesthesia was induced with either Althesin (alphaxalone and alphadolone acetate) or thiopentone, and maintained with nitrous oxide, oxygen and increments of either pethidine or fentanyl. The patients were ventilated artificially to maintain PaCO, values in the normal range. Pancuronium bromide was used as the muscle relaxant. Liver function tests at 24 hr and 5 day after surgery showed only minor changes compared with findings before operation. There was no significant difference between the Althesin and thiopentone groups. In two patients with severe obstructive jaundice there was difficulty in reversing the effects of pancuronium, but "pancuronium resistance" was observed in all patients. It is concluded that the anaesthetic sequence described, with either Althesin or thiopentone induction, is satisfactory with respect to changes in liver function in patients with chronic liver disease undergoing major surgery.


Althesin as an induction agent for Caesarean section. Thirty patients for elective lower segment Caesarean section were randomly divided into two groups. One group received 50 mulitre/kg of Althesin for induction of anaesthesia and the other, 100 mulitre/kg. The two maternal groups were similar. There was no significant difference in the clinical or biochemical status of the infants except that infants in the low dose group had a significantly higher PO2 in the umbilical venous and arterial blood.


Anaesthesia for fibreoptic bronchoscopy. Fibreoptic bronchoscopy is a useful diagnostic aid but may result in difficulties when associated with endotracheal anaesthesia. As a result, adequate ventilation may be difficult in patients with impaired pulmonary function and, in particular, in female patients because of the smaller size of the laryngeal opening. In a trial of three methods of endotracheal anaesthesia in a series of 39 patients, a direct catheter inflation technique gave satisfactory ventilation without circulatory depression.


Catheter inflation ventilation in tracheal stenosis. Catheter inflation ventilation using simple apparatus is described and its use in a case of tracheal stenosis is reported. The suitability of the method was tested first on a model. Monitoring of blood-gas tensions showed that the patient could be hyperventilated without cardiovascular distubance for a period of 197 min.


Rebreathing in a T-piece: volunteer and theoretical studies of the Jackson-Rees modification of Ayre's T-piece during spontaneous respiration. The Jackson-Rees modification of Ayre's T-piece was examined experimentally and theoretically to see what effects the theoretical restrictions of Onchi, Hayashi and Ueyama (1957) (1:1 I:E ratio, zero deadspace volume) and the square-wave approximation of Mapleson (1958) may have had on the calculated critical fresh-gas flow rate necessary to prevent rebreathing of exhaled alveolar gases. In the experimental examination six conscious alert volunteers breathed through the system as the fresh-gas flow rate was varied in steps, and their ventilation was recorded at each value. Assuming that under rebreathing conditions a normal arterial PCO2 is maintained by hyperventilation,  this experimental situation is identical with one of the two considered theoretically by assuming sine-wave inspiratory and expiratory waveforms, zero longitudinal mixing in deadspace volumes and perfect mixing in the alveoli. Agreement between experimental and theoretical results justifies the assumptions made in the theoretical analysis and the  results indicate that a fresh-gas flow rate of about twice the normal ventilation is necessary to eliminate rebreathing completely from the Jackson-Rees modification of Ayre's T-piece. The exact requirement depends on the deadspace/tidal volume (VD/VT) and I:E ratios. The onset of hyperventilation at lower fresh-gas flow rates is gradual and, in spontaneous breathing with VD/VT approximately equal to 40% and I:E ratio = 1:1.2, is only 10-20% at a fresh-gas flow rate of 1.5 times the normal ventilation.


E.E.G. and multiple unit activity during ketamine and barbiturate anaesthesia. Cortical e.e.g. and multiple unit activity (m.u.a.) of the mesencephalic reticular formation, the anterior hypothalamic area, the basal nuclear group of the amygdala and the dorsal hippocampus were studied before and following i.p. injection of different doses of ketamine hydrochloride and a barbiturate in cats with chronically implanted electrodes. Barbiturate administration resulted in a rapid decrease in m.u.a. in the mesencephalic reticular formation which was accompanied by a significant decrease of activity in the limbic structures. No m.u.a. response was observed to visual, acoutic or somatosensory stimulation or to pain. The m.u.a. of the mesencephalic reticular formation and limbic structures increased gradually following ketamine injection. Intermittent or continuous hypersynchronous activity was characteristic in the cortical e.e.g. During the hypersynchronous activity the responsiveness of m.u.a. in the mesencephalic reticular formation, to visual and acoustic stimuli, was blocked. Somatosensory and painful stimulation, however, resulted in a significant increase in the activity both of the mesencephalic reticular formation and of the limbic neuronal pools.


The effect of enteral oxygen administration on the hepatic circulation during halothane anaesthesia: experimental investigations. An investigation of the hepatic microcirculation and oxygen tension in 20 white rats showed that halothane anaesthesia was associated with a reduction in the diameter of the terminal portal venous branches, sinusoids and central veins, and with a decrease in the hepatic oxygen tension from 28.8+/-4.8 to 22.4+/-3.9 mmHg (mean +/-SEM). Enteral oxygen administration was followed by an increased blood flow in all the observed vessels, by an increase in the number of simultaneously filled sinusoids and also by an increase in the hepatic oxygen tension to 35.2+/-10.1 mm Hg. Subsequently, changes in blood flow in the hepatic artery and portal vein were investigated in 10 cats by cineangiography. During inhalation of halothane the hepatic artery blood flow was observed to increase by 30%, while portal vein blood flow was found to decrease by 57% of the initial value. Thus total hepatic blood flow was reduced by 40%, with the ratio of hepatic artery blood flow to total hepatic blood flow increasing from 19% to 43%. When enteral oxygen was administered, the total hepatic blood flow was restored to 92% of the value before anaesthesia. This resulted from an increase in the portal blood flow fraction only. It is concluded that disturbances in the liver circulation in cats and rats produced by halothane anaesthesia can be modified by the simultaneous administration of enteral oxygen.


The effect of enteral oxygen administration on the hepatic circulation during halothane anaesthesia: clinical observations. A study of the estimated hepatic blood flow (EHBF) using a colloidal gold technique in 28 patients undergoing saphenous vein stripping, showed that the EHBF decreased to 68% of its initial value during the period of halothane anaeshtesia and operation. When enteral oxygen was added EHBF increased to 82% of its initial value. An investigation in 14 other patients under going upper abdominal operations showed that enteral oxygen administration caused the oxygen saturation of the portal blood to increase from 55+/-7.2% (mean +/- SEM) to 80+/-6.2% and, by producing a concomitant decrease in portal pressure, led to a reduction in the portocaval pressure gradient from 74+/-12.5 to 38+/-8.7 mm H2O. It is suggested that the oxygen content of the portal blood per se influences the tone of hepatic presinusoidal sphincters. It is concluded that enteral oxygen administration may minimize disturbances in the hepatic circulation occurring during halothane anaesthesia and surgical operations.


Morphine concentrations in plasma after intramuscular administration. Plasma morphine concentrations were measured by a radioimmunoassay technique following the intramuscular administration of morphine 0.2 mg/kg body weight as a preoperative medication. The highest plasma concentrations were obtained about one hour after the administration of the drug and there was a sevenfold variation in these concentrations between individuals. For 24 hr following a single intramuscular injection, there was measurable quantities of morphine or its metabolites in the plasma. In healthy patients who were undergoing a therapeutic abortion, there was no correlation between pain relief and the plasma concentration of morphine.


Pethidine revisited: plasma concentrations and effects after intramuscular injection. Plasma concentrations of pethidine following i.m. gluteal injection were measured in surgical patients and volunteers. The mean plasma concentrations tended to be higher in the patients than in the volunteers; this may be a result of a slower initial absorption rate. At least 80% of the dose was absorbed from the injection site over the 6-hr period of the study. Fluctuations in plasma pethidine concentration were observed, probably caused by variations in local and systemic blood flow. This effect was more noticeable in the patient group. In general, the time-course of subjective effects in volunteers could be related to maximum plasma pethidine concentrations. However, patients appeared to be less sensitive to these effects at similar plasma drug concentrations, possibly because of catecholamine-mediated stimulus, suggesting that plasma concentrations may be a poor guide to the clinical response in patient-volunteer comparison.


Airway compliance during artificial ventilation. The relationship of anatomical deadspace to transpulmonary pressure was studied in eight subjects awake, breathing spontaneously without endotracheal intubation, and anaesthetized intubated and ventilated artificially. Anatomical deadspace was determined according to the equal area method (Fowler) using carbon dioxide as a tracer gas. Volume measurements were performed using a pneumotachograph. Transpulmonary pressure was measured using an oesophageal balloon and a catheter which was connected to the mouthpiece during spontaneous breathing and inserted into the endotracheal tube during artificial ventilation. Anatomical deadspace was approximately the same during artificial ventilation and spontaneous breathing, despite bypass of the upper airway during anaesthesia. Anatomical deadspace was related linearly to transpulmonary pressure. The regression lines indicated an airway compliance of 3.6 ml/cm H2O during spontaneous breathing and 7.4 ml/cm H2O during artificial ventilation. The alteration in airway compliance caused by artificial ventilation is ascribed to a reduction in bronchial muscle tone.


Maternal and neonatal effects of 1% and 2% mepivacaine for lumbar extradural analgesia. Continuous lumbar extradural analgesia with mepivacaine was administered to two groups of patients in normal labour. One group (26 patients: 1% mepivacaine) received a mean total dose of 342 mg (4.93 mg/kg) per patient, and developed a mean blood concentration of mepivacaine at delivery of 1.82 mug/ml. The neonatal umbilical vein concentration was 0.84 mug/ml. The other group (30 patients: 2% mepivacaine) received a mean total dose of 776 mg (11.65 mg/kg) per patient, and developed a mean blood concentration of mepivacaine at delivery of 3.47 mug/ml. The neonatal umbilical vein concentration was 2.61 mug/ml. Four of the infants of mothers who received 1% mepivacaine were depressed (1-min Apgar score 6 or less), and six of the other group were depressed also. Usually, depression appeared to be related to obstetric factors, rather than to analgesia. Eleven of the 56 infants had umbilical vein mepivacaine concentrations of 3 mug/ml or greater; of these, three were depressed. This does not agree with the concept that the toxic threshold for mepivacaine is 3 mug/ml. In both groups a significant linear correlation was obtained between umbilical vein concentration and total dose of mepivacaine. A maximal dose of 12 mg/kg maternal weight in the non-obese or 12 mg/kg lean body mass in the obese is suggested for continuous extradural analgesia with mepivacaine, although healthy mothers and infants may tolerate much more.


Cardiovascular changes in labour associated with extradural analgesia using bupivacaine. Cardiovascular changes were monitored continuously in 13 women during stimulated labour conducted under extradural analgesia with bupivacaine. Three solutions of bupivacaine (0.5% plain, 0.25% with adrenaline and 0.5% with adrenaline) were administered in a random fashion. The results show that the plain solution of bupivacaine was associated with a decrease in central venous pressure and an increase in maternal heart rate which approached statistical significance 40-45 min after administration. These changes did not occur when solutions containing adrenaline were used. The small number of patients and the random administration of the bupivacaine solutions make it difficult to establish the exact significance of the cardiovascular changes observed and a further within-patient study is required.


A double-blind trial of bupivacaine (Marcain) and etidocaine (Duranest) in extradural block for surgical induction of labour. A double-blind randomized trial was conducted to compare etidocaine, the new local anaesthetic agent, with bupivacaine. One hundred patients were each given a single dose of one of the drugs during the surgical induction of labour. The results showed that etidocaine had a quicker onset of action than bupivacaine, but that its duration of action was shorter, and that it produced a greater degree of muscle weakness. No differences were noted in the side effects of the two drugs.


Effects of pentolinium on blood sugar and serum potassium concentrations during anaesthesia and surgery. Blood surgar and serum potassium (K+) concentrations were measured before, during and 60 min after surgery in two groups of 10 non-diabetic patients during nitrous oxide/halothane/tubocurarine anaesthesia. In the control group the arterial pressure was maintained within the  patients' normal ranges, while in the study group pentolinium was administered i.v. (average 22 mg per patient) to achieve and maintain a mean arterial pressure of 50 mm Hg (+/-10 SEM). In the normotensive group the blood sugar concentration increased markedly and significantly during surgery and in the early postoperative period while the serum K+ concentration was essentially unchanged. In the hypotensive group pentolinium produced a striking modification of the surgery-induced hyperglycaemic response (but not to hypoglycaemic values) as well as a small but significant decrease in serum K+ concentration. The observed increase in the blood sugar concentration may be part of the autonomic response to surgical stress. Two mechanisms can explain the reduction in serum K+ concentration: (1) decreased hepatic glycogenolysis and (2) attenuation of the suppressive effect of adrenaline on insulin release, both effects being secondary to the ganglion-blocking property of pentolinium. These results are in contrast to the widely held belief that ganglion-blocking drugs cause hypoglycaemia.


Influence of ketamine on human plasma cholinesterase. The influence of ketamine upon human plasma cholinesterase (E.C. 3.1.1.8) was determined by means of a colorimetric assay technique at 25 degrees C, pH 7.7 with butyrylthiocholine as substrate. Ketamine caused a reversible inhibition of cholinesterase (pI50= 2.75; apparent Ki=4.94X10(-4) M). The kinetic analysis of the inhibitory action revealed a mixed competitive/non-competitive type of mechanism with a prevalence of the non-competitive component (alpha-value = 4.9). A decrease in cholinesterase activity is thought to be a result of conformational change of the enzyme protein which is induced by a reversible binding of ketamine to anionic side receptors in the vicinity of the active centre.


Unexplained jaundice following non-halothane anaesthesia. A case report. A patient developed unexplained jaundice following repeated anaesthesia. The only inhalation anaesthetic agent used was nitrous oxide. The clinical and laboratory features are very similar to those of the jaundice which has been attributed to halothane anaesthesia.


A case of severely cut throat.

A case of severely cut throat. A 42-year-old man was admitted to hospital with serious neck injuries and partial exposure of the oropharynx. He was sedated and the larynx and trachea were anaesthetized with lignocaine to allow endotracheal intubation. In the course of these procedures, previously unsuspected injuries of the tongue and soft palate were discovered. The contraindications to endotracheal intubation under general anaesthesia in cases of this type are discussed.


An instrument for the accurate and continuous measurement of halothane concentrations in nitrous oxide-oxygen mixtures. An instrument is described which measures continuously both the halothane concentration and the composition of the carrier gas when the vaporizer is situated outside the breathing circuit. The instrument is an adapted katharometer in which the out-of-balance voltage is used to measure the concentration of one compound in a three-component mixture, and the total voltage reduction across the constant-current-supplied bridge is used to indicate the proportions of the other two components. Halothane concentrations can be determined with an inaccuracy of 0.1% for concentrations up to 6%. Nitrous oxide (N2O) concentration in the nitrous oxide-oxygen mixture, serving as carrier gas, can be determined with an accuracy of 1% over the whole range up to 100% N2O. The 99% response time of the instrument is approximately 1 min.


The magnitude of air admixture with a jet device in paediatric anaesthesia. The admixture of air in inspired gas with a paediatric insufflation system based on a gas jet has been investigated. During anaesthesia with spontaneous ventilation 1% of air per kg body weight was found in tracheal gas samples. A venturi effect was virtually absent even at high jet flows, which suggests that artificial ventilation prevents air admixture.


Intraocular pressure and systemic blood pressure in the elderly. The intraocular and systemic blood pressure, height, weight, and haemoglobin were measured in 573 subjects over 60 years old from a general practice population. Intraocular pressure was positively and independently related to systemic blood pressure (P less than 0.0001) and obesity (P less than 0.01) as assessed by the ponderal index. Systolic pressure rather than diastolic or mean pressure was most closely correlated with intraocular pressure and it is suggested that the systolic head of pressure increases the filtrated fraction of aqueous humour to cause a small but sustained rise in intraocular pressure. It is also suggested that obesity may decrease the facility of aqueous outflow.


Vertical ovalness of glaucomatous cupping. Slit-lamp examination and stereoscopic fundus photography were found to be helpful in differentiating between physiological and glaucomatous cupping of the disc. Vertical ovalness of any cup in the disc should raise the suspicion of glaucoma, and the magnitude of the vertical cup: disc ratio is of particular significance.


Pupillary "dilatation lag" in Horner's syndrome. 1. Clinical examination will often fail to identify the presence of a unilateral Horner's syndrome. 2. Confirmation and localization of Horner's syndrome is of clinical prognostic value. 3. Cocaine testing provides confirmation of a Horner's syndrome, but it takes 45 min, is sometimes equivocal, and always delays the localizing hydroxyamphetamine test. 4. "Dilatation lag" is a sensitive and physiological sign of Horner's syndrome, and can be demonstrated by simple Polaroid flash photographs.


Discission needle.

Discission needle. A decision needle suitable for use in cataractous microphthalmic eyes and the principles governing its design are described. It enables extensive microsurgery of the lens capsule to be performed, with minimal loss of aqueous.


A familial syndrome of aniridia and absence of the patella. This is the first report of a syndrome of aniridia and aplasia of the patella. The origin of the defect arises spontaneously in the grandmother of the proband and must be assumed to be a de novo mutation. There is no associated chromosomal abnormality or overt biochemical or other somatic defect. This is an extremely rare mutation exhibiting a dominant autosomal form of inheritance. The gene for aniridia is a dominant gene whose penetrance here is 100%. The combination of aniridia and bone malformations in general is very rare. This linked defect probably represents one of the most rare of human genetic abnormalities. The penetrance of the combined abnormality seems to follow that of the more well-known aniridia gene.


Combined limb deficiencies and cranial nerve dysfunction: report of six cases. Six cases have been presented with combined limb deficiencies and cranial nerve dysfunctions. The major features are congenital disarticulation and congenital amputation associated with various orofacial deficits. Anatomic variations in limb and facial anomalies in these cases, as well as in other cases previously reported; seem to indicate that they are part of a single dysmorphic syndrome rather than a group of distinct clinical syndromes as reported in the past.


Familial presacral teratomas.

Familial presacral teratomas. A tumor complex consisting of presacral teratoma and sacral deformity was described along with its occurrence in 6 kindreds. In addition to the tumor and the sacral defect, some patients have had recurrent abscesses, rectal stenosis and skin dimples as manifestation of the tumor. Urinary tract anomalies have also been found to be associated in some patients. The tumor differed considerably from the usual sacrococcygeal teratoma. Only one of the 19 resected tumors had proved to be malignant, although 2 have recurred in a benign manner. This appears to be inherited as a dominant characteristic.


Leukonychia totalis, multiple sebaceous cysts and renal calculi: a syndrome. We have presented a family of 4 generations demonstrating total leukonychia. Multiple sebaceous cysts and renal calculi are associated features of the syndrome. Inheritance is autosomal dominant. We cannot determine whether renal glycosuria is a component of this syndrome.


Trisomy 14q-.

Trisomy 14q-. Trisomy 14q- syndrome is relatively new and needs further delineation. In comparing our case with other reported cases (Table 1), some similarities are seen. Although the comparison of our case of partial trisomy 14 with the other cases reported in the literature may not be entirely justified (in that the reciprocal translocations are not always identical), it is hoped that by doing so, we can further delineate the common features and prognosis of such individuals.


Alopecia totalis, nail dysplasia and amelogenesis imperfecta. A patient with Turner XO/XX mosaicism is presented who also exhibits alopecia totalis, nail dysplasia and amelogenesis imperfecta. This combination has not been previously reported. What relationship the clinical manifestations have to the chromosome status is also unknown.


Sex chromosome mosaicism of X/XY or X/XY/XYY. To date, we have studied 7 patients with X/XY mosaicism, one of whom showed an X/XY/XYY pattern. Four patients presented as newly born infants because of incomplete male development, ambiguity of external genitalia or Turner syndrome. The other 3 patients presented in midchildhood or early adult life. Bilateral gonadectomy, histologic examination of the gonads for tumor or testicular tissue, and chromosome analysis from blood and gonad specimens (and usually skin) were done in these 7 patients. The Y cell line and mosaicism were always detected in the blood culture although the predominant cell line in the majority of tissues was 45,X. The Y chromosome in one of the patients failed to show the expected bright fluorescence over the long arm, and the Y chromosome of another patient previously reported had a terminal nonfluorescing portion of the long arm. Patients with masculinization showed normal height and, on laparotomy, mixed gonadal dysgenesis. Patients with Turner syndrome showed bilateral streak gonads (2) and, in one 2 1/2-year-old girl, a bilateral gonadoblastoma. All patients with Turner syndrome were less than the third percentile in height. All 7 patients were reared as female, 4 of them requiring surgery to diminish the size of the clitoris. All 7 patients appeared to be developing normally. Nonrecognition or delay of the diagnosis, which still occurs in this condition, appears to be a result of the mild physical abnormalities in some patients and a clinical diagnosis of Turner syndrome supported only by a negative X-chromatin result.


Familial multiforme ventricular extrasystoles with short stature, hyperpigmentation and microcephaly-a new syndrome. A previously undescribed syndrome with ventricular extrasystoles and presumed cardiac syncopy, hyperpigmentation, short stature and microcephaly in a mother and son was presented. Physiologic and pharmacologic studies suggest that the mechanism of the ventricular arrhythmia depends on multiple and reentrant pathways occurring below the bundle of His.


Lethal faciocardiomelic dysplasia- a new autosomal recessive disorder. Three male sibs from consanguienous parents were found to have a strikingly similar pattern of multiple congenital anomalies. The main features were polyhydramnios; low birthweight; dwarfism; epicanthal folds; abnormal ears; microretrognathia; microstomia; microglossia; glossoptosis; webbed neck; severe cardiac defects; radial and ulnar hypoplasia; radial deviation of the hands; brachymetacarpalia; thumb hypoplasia; clinodactyly and hypoplasia of the 5th finger; simian creases; fibular and tibial hypoplasia; talipes varus with hypoplastic heels; wide gap between 1st and 2nd toes; and delayed bone age. Neonatal death occurred in the 3 babies by severe cardiac failure. Differential diagnosis permits one to conclude that this is a new type of faciocardiomelic dysplasia with a probable autosomal recessive inheritance.


[Myelin-like structures in heart muscle cells following exposure to adrenaline]. The state of the muscle cells of the heart was studied experimentally in 36 albino rats the next day after a single administration of adrenaline hydrochloride (3mg/kg), intramuscularly into the hip. Areas of overcontraction and overextension of myofibrills, numerous myelin-like figures not infrequently containing mitochondria and glycogen, drops of lipids were observed by electron microscopy. It is suggested that the affecting action of adrenaline is expressed through the activation of lipolysis which results in dissociation of the protein-lipid components of the mitochondrial membranes, accumulation of fatty acids in the cytoplasm and resynthesis of the new unusual membranous formations.


[Capacity for in vitro growth and the character of synovial fluid cell transformation in rheumatoid arthritis patients]. Investigations carried out permitted to detect the in vitro growth of cells in the synovial fluid of patients suffering from rheumatoid arthritis. Five types of cells (macrophages, polykariocytes, fibroblast-like cells histiocytes and lymphocytes) appeared during transformation. It was revealed that the intensity of the cell growth in the culture depended on the activity of the disease; there was also a significant decrease of this intensity (P less than 0.01) in the treatment of the patients. The growth of the fibroblast-like cells up to the formation of colonies pointed to their possible participation in the genesis of inflammatory processes and sclerosing of the vessels. The observed phenomenon of the cytopathic interaction of the lymphocytes and of the fibroblast-like cells served as an index of an autoimmune conflict in the joint and, possibly, one of the mechanisms of automaintenance of the autoimmune process.


[Changes in the diameter of organ arteriovenous anastomoses during pressor reflexes]. In acute experiments on cats, the diameter changes of the arterio-venous anastomoses in a number of vascular zones and their shunting coefficient were studied under the pressor reflexes; the method of injections of the microspheres was used. In these experiments the shunting capacity of the arterio-venous anastomoses was shown to be decreased in the small intestine, the spleen, the kidney and the gastrocnemius muscle under the pressor synocarotid reflex and the electrical stimulation of the somatic afferents.


[A morphologic analysis of denuding of the villi in the intestinal form of acute radiation sickness]. Light and electron microscopy were applied to the study in sexually mature rats and mice of the areas of the duodenum, jejunum and the ileum 3-4 days after the irradiation in doses of 1000, 1500, 7000 and 15 000 R. Paraffine mucosal sections of the small intestine showed denuding of the stroma of individual villi. However, a study of the thin and semithin epon sections by light microscopy and of the ultrathin ones--by electron microscopy showed the villi to be always covered with enterocytes, whose cytoplasm was overloaded with lipid droplets and almost structureless. Thus, during the enteric form of acute radiation sickness there was no vital denuding of the villi, and the presence of such on paraffine sections served as the result of inadequate treatment of the material.


[Compensatory-adaptive processes in the nervous elements of the intramural plexuses of the small intestine following resection of half of it]. A complicated morphological reconstruction, phasic in character, occurred in the nervous plexuses of the small intestine after resection of half of it. Neurons of both the muscular and the submucosal plexus reacted in a similar way at various stages of the compensatory-adaptive changes in the remaining intestine. The principal form of the morpho-functional normalization of the nerve cells after the development in them of dystrophic changes was apparently the intracellular regeneration.


[An impulse-digital method of measuring blood flow velocity in microvessels]. The photometric trigger method described was used for determining the velocity of erythrocytes. It allows to take continuous erythrocyte velocity and cell flux measurements in the microvessels. Application of the impulse-digital chronometry of the intervals of the erythrocyte transit time ensures direct transformation of the measuring trigger signals into a digital code. The results of testing the device on the microvessels of frog mesentery are given.


[The effect of leukocyte pyrogen on thermosensitive neurons of the anterior hypothalamus]. Impulse activity of neurons of the medial preoptic and septal brain areas of rabbits caused by variations in the local temperature and systemic injections of the leukocytic and bacterial pyrogens was studied. The firing rate of the warmsensitive neurons decreased and that of the cold thermodetectors was activated as a result of pyrogen action. As compared with the bacterial pyrogen, leukocytic pyrogen caused a more rapid decrease of the warmthermodetector activity. Thermoneutral neurons failed to react considerably either to the leukocytic or to the bacterial pyrogen.


[The effects of the pathogenic influence of botulin toxin on different types of spinal motor neurons]. The motor neuron cells of the lumbosacral region were investigated in the spinal cord of cat with the local botulin paralysis. Development of this paralysis was followed by reduction of the membrane potential, of the amplitude of antidromic AP, mono- and polysynaptic EPSP, a fall of the input resistance and by an increase in the level of the critical depolarization of the somatic membrane of the phasic motor neurons of the damaged segments in the spinal cord. Excitation of the tonic motor neurons was not greatly altered in the dynamics of local botulism.


[The neurogenic component of the tone of capacitance vessels in regional arterial hypotension]. It was shown in experiments on rats that lowering of the volume stiffness of the capacitance vessels in the area of the chronic regional arterial hypotension occurred only after their denervation. Experiments on the innervated hind limb showed that the volume stiffness of the capacitance vessels in the area of hypotension failed to differ from the corresponsing indices in control rats.


[Monoaminergic mechanisms of the amygdaloid complex actualizing conditioned reflexes of different biological modality]. Microinjection of dopamine and serotonin into the dorso-medial portions of the amygdalic complex of rats increased the latent period of conditioned defense and motor food reactions, spontaneous motor activity, the number of jerks and the value of the conditioned food reflex. Noradrenaline failed to influence the recorded indices of the conditioned food-procuring reflex, but facilitated the conditioned reaction of avoidance, significantly shortening its latent time. The results obtained pointed to the specificity of the neurochemical mechanisms realizing at the level of the amygdalic complex conditioned reflexes of various biological modality in rats.


[The role of the adrenals in the development of hyperenzymemia in experimental multiple injuries]. The authors studied the activity of acid phosphatase (AP), lactic dehydrogenase (LDH), aspartic and alanine-aminotranspherases (AST and ALT) in the serum of rats with intact and removed adrenal glands after a severe multifocal trauma induced according to Noble-Collip (300 rpt of the drum with the rotation speed of 37 rpt/min). Adrenalectomy showed practically no influence on the dynamics of the LDH and AP activity. An increase in the activity of the AST and especially of the ALT in the serum of adrenalectomized rats after the trauma was considerably less than in the animals with the intact adrenal glands.


[Changes in serum lysozyme activity in terminal states caused by blood loss]. A study was made of the dynamics of the lysozyme activity of the serum in dogs which sustained clinical death on the background of a 2-hour hypovolemic hypotension due to blood loss. There was revealed a progressive increase in the lysozyme activity of the serum during the hypotension and during the first 30 minutes of the postreanimation period. Lysozyme activity of the serum was increased in the course of 4 days after the revival. The significance of the lysozyme activity of the serum as an index of hypoxic injury of the internal organs in terminal conditions is discussed.


[Dynamics of the amino acid composition of the medium during cultivation of isolated liver and kidney by the controlled perfusion method]. The dynamics of the medium amino acid composition was studied during a 6-hour perfusion of dog kidney and liver by a mixture of autogenic plasma and medium 199 (a ratio of 2 : 3). In comparison to the initial level the amount of histidine during 6-hour cultivation of the kidney was found to increase 2.2 times, that of glutamic acid--1.7 times, and of alanine and lysine--1.6 times. At the same time the amount of arginine, serine and asparagic acid became 3.3 times and of glutamine and threonine--2.5 times lower. With the liver perfusion the level of glutaminic acid became 2.9 times, of alanine--2.3 times, of cystine--2 times and of glycine--1.5 times higher. With the liver perfusion the level of arginine decreased so rapidly that none was found in the medium after a 2-hour perfusion. The described method of amino acid analysis during the cultivation of the organs could serve as means for elaborating and correcting the culture media.


[Hepatic chemoluminescence in mice following glucose administration]. The spectral composition of radiation of the liver after intravenous injections of glucose of different concentrations was analyzed. The UV component of the radiation was significant after a 15 mg dose; the doses of 5 and 50 mg gave only visible radiation. These data are considered as an indication of an essential role of unbalanced molecular constellations for the regulation of metabolic process of hepatocytes.


[The effect of cocaine on the central action of noradrenaline]. Cocaine influence on the central action of noradrenaline was studied in experiments on rabbits by the method of impulse summation. Cocaine was shown to increase the noradrenaline action of the central nervous system. Thus, cocaine intensified not only the peripheral effects of noradrenaline (this was known before), but its central action as well.


[A pharmacologic analysis of several adrenomimetic effects of serotonin]. Contractions of the isolated rat vas deferens in response to the addition of serotonin could be explained by the release of catecholamines from the nerve endings. As shown by the use of D-, M- and T-antagonists of serotonin (LSD-25, indocarb, typindole), symatholytic--bretilium, alpha-adrenolytic--droperidol and imipramine, this effect was not associated with the direct activation of serotonin- and adrenoreactive receptors.


[The effect of striatectomy on retraining rats to an avoidance habit in a U-shaped maze]. The capacity of rats to reversal learning changing of the direction of the avoidance response was determined in the Y-shaped maze. Four training sessions--each time in a new direction (to the right or to the left) for running were conducted in the course of one experiment. The results obtained in 4 groups of animals were compared: intact, with bi- and unilateral striatectomy and with bilateral destruction of the parietal cortex. The majority of the intact rats preferred running in the right direction. The character of the preference changed after striectomy: the rats ran more regularly in the direction at the side of which the striatum was injured more. Bilateral striatectomy also led to increase in the number of errors, to the increase in the latency and disturbance of a passive component of the avoidance response.


[The mechanism of nonachlazine on cardiac activity and blood supply]. Nonachlazine (10 mg/kg intravenously) exerted a two-phase influence on the heart activity. The short phase of the weakening of the heart activity gave place to the intensive increase in the cardiac output and the contractility of the myocardium. An increase in the blood supply and heart activity coincided in time with the accumulation of the quantity of noradrenaline and with increase in the phosphorylase "a" activity. Beta-adrenoblockers prevented the development of the effect in question. It is assumed that the efficacy of nonachlazine during ischemic heart disease was connected with its capacity to activate the adrenergic mechanisms of the glycogenolysis regulation leading to the switching of the myocardial metabolism to the anaerobic route of energy release.


[Prevention of cerebrovascular disorders with adrenergic substances]. The author suggests an experimental model of cerebrovascular disorders of the neurogenic (adrenergic) nature following the administration of KCl into the lateral ventricles of the brain of cats or dogs. Surgical desympathization considerably reduced the spasms of the cerebral vessels caused by the central effect of KCl. Dihydroergotoxin, phenoxybenzamine, tropaphene, guanethidine and nialamide produced both the therapeutic and the prophylactic influence under the mentioned experimental disorders of the cerebral circulation.


[The mechanism of the diuretic action of chlorazicin]. Diuretic and natriuretic action of chloracizine in rats was not associated with its direct influence on the kidney and was accompanied by increase in the plasma volume, by a fall of the hematocrite index and of the total plasma proteins. A study of endogenous creatinine and of osmotic-free water clearance showed the diuretic action of chloracizine to be mainly due to the increase of glomerular filtration and to reduction of the relative proximal reabsorption.


[A blocking factor in normal animal sera inhibiting immunologic reactions in vitro]. An extremely thermostable and resistant to some chemical substances factor was found in the sera of Wistar and noninbred rats of different age, male and female. This factor inhibited the action of normal and immune antibodies to rat erythrocytes and rat serum antigens. The blocking factor was relatively specific and more effective in respect to the normal antibodies than to the immune ones. The activity of the blocking factor was connected with the alpha1-globulin.


[Characteristics of a specific antigen of burned skin]. Antisera received by hyperimmunization of rabbits with preparations of the high molecular proteins of burned and normal rat skin were studied in the precipitation reaction before and after the absorption with normal skin and sera proteins. The specific test-system displays a single visual precipitation line. After staining and densitometry the preparations were found to have many components, among which the specific antigen prevailed and other antigen-antibody complexes were present. The specific antigen of the burned skin had relatively weak immunogenic properties.


[Homogenate factor of minks with Aleutian disease]. Antibodies to the factor present in the homogenate of the organs of minks experimentally infected with aleutian disease (AD) were revealed in the sera of minks with AD and also in the sera of humans suffering from systemic lupus erythematosus, hepatitis and cirrhosis, scleroderma and dermatomyositis. Sera of sick minks and humans failed to interact with control homogenates of the organs of healthy minks. In turn, sera of practically healthy minks and humans did not react with the AD-homogenate.


[The carcino-embryonic antigen of experimental tumors of the intestine]. The occurrence of a tumour-specific antigen in the intestinal tumours (induced in 51 albino rats by subcutaneous injection of 1,2-dimethylhydrazine), as well as in the blood serum was studied by double immunodiffusion in agar gel. Intestinal tumours proved to contain a water-soluble antigen absent in other tissues, including the colonic mucosa of control animals. This antigen was found in 70 per cent of the tumour-bearing rats. The antigen is perchloric acid-solubilized and is also present in the embryonic tissues in toto on the 7th and the 9th days of rat gestation. The features of this antigen were analogous with those of the carcino-embryonic antigen in human digestive tract tumours.


[Proliferative activity of Shvetz tumor following single and repeated irradiation]. Autoradiographic study of an experimentally-induced tumour following local irradiation in a dose of 600 rad showed no retardation of the cell cycle 6 to 12 hours after the irradiation. Marked reduction of the mitotic index (MI) and of the labeled nuclei index (LNI) was noted to the 96th hour after the irradiation. In repeated irradiation in a dose of 1200 rad at an interval of 18 hours there was revealed a marked reduction of the MI and of the LNI as a result of the block of the passage of cells from the G1-period into S. However, restoration of the cell proliferation uas noted by the 24th-48th hours. A high MI revealed at all the periods of investigation after repeated tumour irradiation at an interval of 24 hours was possibly caused by an increase in the time of mitosis proper, this also being confirmed by a significant accumulation of the number of late mitotic phases.


[Diurnal changes in the duration of mitosis in rats]. The colchicine method was applied to the study of the 24-hour changes in the duration of mitosis in 45-day rats. The average diurnal duration of mitosis in the pancreatic epithelium, the liver and the epidermis of adult animals was almost half of that in the 7-day-old rats. Diurnal variations of the mitotic index in the investigated tissues could be due both to the variation in the mitotic rate and to that of the duration of mitosis.


[Circadian variations in the response of corneal epithelial cells in mice to the effects of vinblastine]. A drop of a 0.2% vinblastin solution was applied to the eye cornea of mouse at 7 a.m. and at 7 p.m. The cornea of the second eye of the same animal served as control (application of physiological saline). The animals were sacrificed three hours after the application. The results of two analogous experiments showed vinblastin application to cause more expressed statmokinetic reaction in the corneal epithelium in the evening than in the morning hours. The percentage of K-mitoses was also higher in the evening.


[An increase in hypothalamic sensitivity to the inhibiting effects of estrogens caused by use of L-DOPA, diphenine, epithalamin and phenformin in old rats]. Daily treatment of hemicastrated young rats with 0.57 mug of stilbestrol inhibited compensatory ovarian hypertrophy (COH) by 48% in the 3-month animals and by 3% only in the 18-month animals. Administration of L-DOPA, dilantin, epithalamin or phenoformin with the same dose of estrogen to old rats suppressed the COH by 65-98%. L-DOPA and epithalamin were effective when administered into the 3rd cerebral ventricle. A functional nature of the age changes in the hypothalamic sensitivity to the estrogen action is suggested.


[Program of the International Center for Cancer Research: Epidemiological approach]. The development of the International Agency for Research on Cancer is discussed and its programme outlined. The programme of the Agency is largely directed to epidemiological studies which are co-ordinated with laboratory studies. The objective is to make use of geographical variations in cancer incidence as a means of identifying causative factors. The nature, and the difference between analytical and descriptive epidemiology, are discussed. The possible significance of industrial hazards in modern societies is reviewed. The epidemiological approach to the identification of the causation of cancer of the oesophagus and liver is summarized, as is also the possibility of applying epidemiological techniques to the study of host factors.


[Cancer mortality in France. New Aspects of the presentation and analysis of data]. In France mortality statistics are the only complete source of information on cancer. Investigation of the annual figures and the application of statistical methods to their presentation and analysis has facilitated fresh studies of geographical pathology, utilizing methods of analysis with simple and multiple correlations (analysis of correlations). Certain groupings were thus revealed, notably in the case of death from bronchial carcinoma, urinary bladder and gall bladder. Two groups of departements appeared the nearest to the national levels for deaths from cancer for all body sites.


Operative treatment of acromioclavicular dislocations. An operation has been described for the treatment of Type Three acromioclavicular dislocations. It is in this type of case that previous operative procedures have proved to be unreliable, and in which conservative management has resulted in cosmetic deformity and progressive disability. The procedure of coracoacromial ligament transfer has been performed since 1952, and is adaptable for both fresh and chronic dislocations. The technic is simple and direct, and the material needed is both available and almost always uninvolved. The stability produced, after either repair without resection, or repair with resection of the clavicle, leads to a strong, stable shoulder. If there is any doubt as to the integrity of the joint, resection of the clavicle is to be preferred. The results to date have been encouraging, and in the opinion of this author, warrant further trial of this procedure.


[Age at the time of the first birth: a variable with simple, double, or triple significance in breast cancer studies]. I.--The inverse relationship of risk with parity is one of the earliest known features of the epidemiology of human mammary cancer. But recently knowledge of this relationship was refined when Mac Mahon and his colleagues found that the protective effect is actually correlated to the age of the mother at the first birth rather than to the total number of children, so that a woman who has a child before the age of 18 is one third as likely to suffer breast cancer in later life as a woman first delivered at 35. II.--A study was undertaken in the Centre Francois Baclesse on the hypothesis that age at first birth may also be related to the age of the patient at clinical onset of the mammary malignancy. One would expect to find a retardative effect of early delivery since this factor was found to be protective as far as mammary cancer risk is concerned. The conclusions of our investigations are in complete opposition to the original hypothesis: in our series, breast cancer appears to occur significantly earlier in women whose first delivery occurred early. III.--Thus the same process appears to be protective as far as total mammary cancer risk is concerned but accelerating as far as age at tumor onset is concerned. These apparently inconsistent observations led to the hypothesis that both studies might express the same biologic process which, in the case of early delivery, inhibits the mechanism of carcinogenic induction and therefore reduces the total number of cancer but which subsequently quickens the evolution of the inducted disease. Such a conjecture implies that breast cancer should be more severe following early first birth. The analysis of our series, as well as the series of Ontario Cancer Clinics, substantiates this hypothesis. But these conclusions are built on indirect proofs or direct proofs which are still short of statistical significance.


[Preoperative radiotherapy in breast cancer. Description of a clinical trial record and first results]. The protocol of a clinical trial, studying the value of preoperative radiotherapy (RT) in operable breast cancer is described. Results are compared to those of 2 control groups: patients treated either with surgery only or with surgery + postoperative RT. So far, in each of the 3 groups 250 patients have been entered, their total number being expected to reach about 350 per group. Two year results (on 209 evaluable cases) did not reveal any difference in survival between the groups, but a markedly lowered incidence of locally recurrent disease (from 16% to 4%) in the irradiated patients. No increase in mortality or metastasis was noted after RT. Side effects of RT were considered mild and not of such a degree as to necessitate its discontinuation.


Granular cell myoblastoma of the hand: report of three new cases with aggressive behavior in one. Three cases of granular cell tumor of the hand are reported, with locally aggressive behavior in one. Ray amputation in the latter case has so far been successful in controlling the tumor. The literature on recurrent and metastasizing granular cell tumors is reviewed.


[Application of technics for the hybridization between nucleic acids in Oncornavirus research]. The RNA-dependent DNA polymerase of oncornaviruses is a very useful tool for synthesizing DNAs complementary to the viral genomes. These probes have been successfully utilized during the last years to detect viral sequences in the DNA or RNA of virus producing or non-producing cells. The results obtained at the present time lead to a better understanding of the molecular events of virus replication and transformation by oncornaviruses. The same approach has been used to look for the presence of virus-like nucleotide sequences in various human cancers. Although promising results have been obtained, they do not establish that oncornaviruses are directly implicated in etiology of human cancers.


[Oncornaviruses and human leukemias].

[Oncornaviruses and human leukemias]. This is a brief review on current progresses which appeared recently on the isolation of a putative human oncornavirus from human leukemic cells. There are strong arguments in favor of the existence of such an oncornavirus, both indirect (existence of viral nucleotide sequences and viral proteins in human leukemic cells), and direct (isolation of a Type-C virus from in vitro cultures of human leukemic cells).


Motion of the hip joint.

Motion of the hip joint. It has been demonstrated that in the normal hip abduction to adduction motion of the femoral head in the neutral position is equivalent to internal to external rotation of the femoral head in the 90 degree flexed position. For similiar reasons external to internal rotation of the femoral head in the neutral position is equivalent to abduction to adduction motion in the 90 degree flexed position. Due to the architecture of the hip joint, therefore, the hip motion in some pathological conditions can be anticipated and explained.


Study on the surface shape and contours of the femoral head and acetabulum of the human joint. (1) The degree of change and degeneration of the surface of articular cartilage were classified into 6 stages and a distribution chart indicating 6 stages of classification was prepared for each case. (2) The construction of the superficial fine fibrous net-work of the cartilage of the weight-bearing area is different from that of the non-weight-bearing area. (3) The construction of the fiber underneath the surface of the acetabular cartilage is different from that of the surface of femoral head cartilage underneath. (4) When only weight-bearing part was compared, the degeneration at the upper anterior side was least for both femoral head and acetabulum and was most at the slightly posterior part of the upper outer side. (5) The fine fiber of superficial layer of the femoral head and acetabular cartilage were peeling from the periphery toward the center, but no difference of surface roughness was observed by way of measurement directions. (6) Surface roughness of the cartilage increases in proportion to the degree of degeneration and change. (7) The surface roughness of the acetabulum is about twice as large as that of the femoral head cartilage, this being due to the difference in the degree of degeneration. (8) There are 4 kinds of undulations at the surface of the femoral head cartilage. (9) Both femoral head and acetabulum have less waviness of large size at the part bearing large weight. (10) The contour of the femoral head as a whole is slightly ellipsoidal, whose longitudinal axis extends in a craniocaudal direction but the weight-bearing part is nearly circular. (11) The general contour of the acetabulum indicates an ellipsoidal shape with its craniocaudal longitudinal axis slightly inclined forward or backward. The contour of the slightly postero-upper part which is considered to be the maximum weight-bearing part is slightly flat ellipsoidal.


[Study of ventilatory mechanics - its application to artificial ventilation (author's transl)]. Study of ventilatory mechanics implies collection of input variables (stresses estimated by pressures) and output variables (strains), from which the parameters (compliance, resistance, etc.) of a model reproducing the functioning system can be computed. From this point of view, patients under artificial ventilation show a twofold difficulty: the one is the collection of variables, very difficult in consideration of the patients' precarious state, the other the type of  the model: the first order linear model, used for lack of better solution, can be criticized, on the one hand by severe pulmonary changes in these patients, and by the special mode of applying constraints during artificial ventilation on the other. All these facts explain the methodologic and theoretical difficulties encountered in ventilatory mechanics analysis in resuscitation, which actually leads to the expression of one parameter as representative of the pulmonary parenchymal elasticity: the static compliance, and to the determination of the balancing point of the system: the functional residual capacity.


Bone scan in chronic dialysis patients with evidence of secondary hyperparathyroidism and renal osteodystrophy. Bone scans in 13 of 14 patients on chronic dialysis were found to be abnormal. Symmetrical increased activity was noted in the calvarium, mandible, sternum, shoulders, vertebrae, and the distal aspects of the femur and tibia, as well as the patella. The scan abnormality is felt to be most likely the result of secondary hyperparathyroidism because of clinical and laboratory data, and, in four, confirmatory tissue diagnoses. The scan findings support the data of some earlier investigations on bone isotopic accretion in hyperparathyroidism. However, co-existing osteomalacia giving rise to abnormal activity in some of the patients cannot be excluded. Dihydrotachysterol may have minimized the extent of osteomalacia in these patients. Osteoporosis was probably present in some patients, but it appears differently on scan. Osteosclerosis was not detected on radiographic examination. Scan manifestations, especially mandibular activity, were pronounced and appeared earlier than the radiographic changes. The degree and extent of abnormal activity correlated with the length of dialysis and the level of alkaline phosphatase.


Pulmonary infarction complicating the use of Swan-Ganz catheters. Since the introduction of Swan-Ganz (flow-directed balloon-tipped) catheters, in 1970, relatively few serious complications have been reported. This report summarizes three cases of pulmonary infarction secondary to indwelling Swan-Ganz catheters. Two were due to wedging of the catheter and one probably to embolization or extension of thrombus from the tip of the catheter. The radiologist should be aware of this complication, as he is in an excellent position to first make the diagnosis.


Monitoring of ventilation and lung mechanics during automatic ventilation. A new device. A device that allows continuous monitoring and recording of expired minute volume, tidal volume, resistance, compliance, indices of hyperinflation and other measures of ventilation and lung mechanics during automatic ventilation is described. After connection to the ventilator (Servoventilator 900) with one cable it is operating without any calibrations or other measures. The calculation of expired minute volume is done in a new way that eliminates errors due to compression of gas in the connecting lines. Calculations of compliance is made in a way allowing measurements even in patients with hyperinflation. Expiratory and inspiratory resistance values are obtained. The indices of hyperinflation in terms of measured flow and estimated alveolar pressure at the end of an expiration are discussed. The problems and benefits associated with measurements in much obstructive patients are analyzed. A short study of the performance of the calculator is presented.


External radiotherapy and radioiodine in the treatment of 359 thyroid cancers. Between 1943 and 1965, 359 patients with carcinoma of the thyroid were treated by external radiotherapy or radioiodine out of a total number of 560 patients treated during the same period. In 65 of these patients surgery had been satisfactory from a macroscopic point of view. Prophylactic post-operative irradiation was given to 55 and the survival rate was 91 per cent at five years and 85 per cent at ten years. Ten received radioiodine, eight were alive at five years and six at ten years. In 95 patients excision of the tumour had been macroscopically incomplete. Fifty-four were treated by external radiotherapy and the survival rates were 50 per cent at five years and 48 per cent at ten years. For the differentiated carcinoma of this group 68 per cent were surviving at five years and 58 per cent at ten years. Of 41 patients treated with radioiodine, 75 per cent were surviving at five years and 31 per cent at ten years. Eighty-five patients were inoperable. Sixty were treated by external radiotherapy, the survival rates were 17 per cent at five years and 8.5 per cent at ten years. For the differentiated carcinomas of this group the survival rates were 24 per cent and 18 per cent. Twenty-five were treated with radioiodine, 26 per cent were surviving at five years and 4.5 per cent at ten years. The patients treated by external radiotherapy can be divided into two subgroups according to the technique of treatment and dose used. Between 1943 and 1955, patients were treated with conventional X rays (mean applied dose 2,800 rads), between 1956 and 1965 the patients were treated with 60Co (mean applied dose 5,000 rads). For the 45 patients of the first group, the survival rates were 35 per cent at five years and 32 per cent at ten years. For the 124 of the second group the respective survival rates were significantly higher: 60.6 per cent and 53 per cent. The results of external radiotherapy were similar to those of radioiodine at five years and better at ten years. In conclusion, a dose of 5,000 to 6,000 rads delivered by megavoltage external radiotherapy in five to six weeks, is well tolerated and effective mostly in differentiated carcinomas and medullary carcinomas. The survival rates of 64 patients whose metastases were unable to pick up iodine is practically zero at five years. For 68 patients with uptake in their metastases the survival rates were 53 per cent at five years and 23 per cent at ten years. The survival rate in patients with pulmonary metastases was higher than in patients with bony metastases (75 per cent versus 44 per cent at five years and 42 per cent versus 8 per cent at ten years.


[Circulatory and metabolic disturbances in accidental hypothermia (author's transl)]. This work sums up several studies: clinical observation (electrocardiogram, cardiac rhythm, circulatory state), and biology (glycemia, blood oxygenation, acid-base balance) in 24 cases of accidental hypothermia, not related to poisoning by central nervous system depressive agents; haemodynamics in 18 of these cases; pathology of the myocardium in 11 cases; haemodynamics and microscopy of the myocardium in dogs with slowly induced or prolonged hypothermia; finally an electron microscope study in hypothermic rats. Electrocardiographic study and continuous monitoring of cardiac rhythm and tracing show, in addition to well known manifestations (bradycardia, lenghtening of QT, J wave), acute dysrhythmias, particularly circulatory arrests by asystole during or even 72 hours after rewarming. The clinical haemodynamic changes, measurable (cardiac output, mean arterial pressure, central venous pressure), or computable (stroke volume, peripheral resistances) are observed during rewarming. Several haemodynamic developments can be distinguished: --favourable evolution when the initial disturbances (decrease in cardiac output and in stroke volume, increase in peripheral resistances) disappear without any therapeutic support: --haemodynamic developments showing at a certain time evidence of hypovolemia requiring only moderate vascular replacement; --haemodynamic developments showing myocardial damage. In some cases, only hypothermia accounts for these. In circulatory arrests during or after rewarming, these haemodynamic disturbances raise the hypothesis of severe cardiac changes due to hypothermia itself.


Damage and recovery assessment of the mouse jejunum to abdominal X-ray and adriamycin treatment. The influence of adriamycin on the post-irradiation proliferative response of the mouse jejunum was examined. Doses of either 5 or 10 mg/kg of adriamycin administered immediately after abdominal irradiation reduced the LD50/7 days by 300-400 R. Neither dosage of the drug reduced the number of surviving crypts, as measured by the crypt isolation and microcolony techniques, for a given radiation exposure. However, both drug dosages reduced the amount of post-irradiation compensatory hyperplasia, as measured by 3H-thymidine incorporation.


Application of the Weibull distribution to some instances of cell survival; of neoplastic survival, and of ageing. The Weibull distribution has been applied to several processes of survival with either increasing, decreasing or constant hazard rate. In cases of survival where shoulder and exponential segments have been postulated the Weibull distribution seems to fit them.


A simple approach to grey scale echography. The use of grey scale echography may be advantageous in some diagnostic situations, e.g. liver investigations. The effects on the recorded grey scale of different types of signal processing in conjunction with various settings of the brilliance control were investigated using a standard ultrasonic machine. The most satisfactory results were obtained when operating at a high baseline brilliance and modulating the display with signals proportional to the echo amplitude. A series of comparative pictures are shown to demonstrate these effects.


A table for the rapid determination of RET and TDF values. A table has been devised to allow rapid determination of the RET and TDF values for five-day a week therapy schemes which might be included in realistic treatment planning. 2. The table allows easy comparison of the RET and TDF values for different fractionation schemes or, conversely, the devising of equivalent fractionations for similar RET and TDF values. 3. Utilizing the decay tables of Orton and Ellis, it is possible to utilize the table for determining rapidly the total TDF for interrupted or split course treatment regimens. 4. In those departments which treat four days, rather than five days, per week, a table devised on the four-day treatment schedule could easily be devised.


Scintigraphic diagnosis of acoustic neurofibromas. Radioisotope brain scanning gave positive results in 57 out of 68 acoustic neurofibromas in three British neurosurgical centres. Acoustic neurofibromas over 2 cm in diameter may be expected to give a positive scintigraphic result, and tumours of this size also erode the petrous bone. Since most are 3-4 cm in diameter, correlation between the results of petrous radiography and cerebral scintigraphy often permits a specific diagnosis of acoustic neurofibroma to be made. No other radiological investigation may be necessary preoperatively.


Comparison of 125I-labelled fibrinogen uptake and venography in the detection of recent deep-vein thrombosis in the legs. Both techniques were used to examine 72 legs, and agreed about the presence or absence of thrombus in 54 cases (72 per cent). In 41 legs both tests were positive and in 13 legs both tests were negative. In 16 legs the 125I fibrinogen test only was positive, and if the seven legs with clinical conditions known to increase fibrinogen uptake are excluded, there were nine legs (13 per cent) with an increased fibrinogen uptake in the calf and a normal venogram. In two legs the venogram only was positive, and in both cases there was evidence of clot retraction which suggested that the thrombus was more than a week old. The use of radio-opaque markers attached to the skin made it possible to compare the site of thrombosis detected by the two techniques and the results of this comparison indicate that the fibrinogen test underestimated the extent of femoral vein thrombosis in a significant proportion of cases. (p less than 0-001).


Demonstration of abnormalities of the lens by echography. A demonstration of the B-scan echographic appearances of some commonly encountered lens abnormalities is presented. Examples of intumescent, traumatic and calcified cataracts, congenital and traumatic displacements and other abnormalities are shown. The significance of these findings is discussed and the importance of pre-operative ultrasonic examination of the patient for cataract extraction to exclude vitreous or retinal pathology is stressed. The value of echographic examination in traumatic cases, where vitreous haemorrhage has occurred, in the demonstration of intraocular abnormalities, such as retinal detachment or a non-radio-opaque foreign body is also discussed.