Selective suppression of autoantibody responses in NZB/NZW mice treated with long-term cyclophosphamide. Autoimmune responses were assayed in 80 cyclophosphamide-treated and control NZB/NZW mice over a period of 1 year. Fluctuation between positive and negative immunofluorescent heterogeneous ANA tests and daily alterations of ANA titers were detected in young mice of both sexes. Although high-dose cyclophosphamide therapy (8 mg/kg/day) failed to prevent the spontaneous appearance of ANA, titered ANA values were partially suppressed in high-dose treated mice. This study permitted sequential comparisons between ANA titers and anti-DNA as useful indices of cyclophosphamide-induced suppression of autoimmune disease. ANA titers were relatively resistant to cyclophosphamide therapy. Antibodies directed specifically against DNA were suppressed mice receiving high-dose cyclophosphamide. In treated animals, decreased anti-DNA levels were associated with protection from severe glomerulonephritis and renal vasculitis. Treatment with low-dose cyclophosphamide (1 mg/kg/day) appeared paradoxically to stimulate autoantibody production and renal disease/vasculitis.


[Treatment of inflammatory complications of permanent implanted pacemakers]. The Authors report an experience of 165 patients who underwent to implantation of artificial pacemaker from January 1973 to December 1974 and report 16 cases of infection. They consider many surgical and biologic factors that can have caused uprinsing of infection. The Authors report the therapeutic treatment the patients underwent and conclude that the best treatment is the implantation, to another seat, of new pacemaker.


[Clinical significance of changes in tryptophan metabolism]. The Authors describe the various anomalies of the metabolism of tryptophan that are observed in various diseases. The oxidative pathway is most important of the metabolic pathway of the amino acid; the degredation of tryptophan is particularly influenced by steroid hormones and vitamins' want. The metabolic anomalies are demonstrable both in malignant tumors (mostly in bladder cancer and Hodgkin's disease), both during psychiatric diseases (such as depression and schizophrenia) and in the diseases of connective tissue in addition to congenital errors of the degradation of tryptophan (such as Hartnup's disease, tryptophanuria and 3-hydroxychinureninuria). The metabolic pictures are manifest after amino acid's in the diseases of connective tissue but are independent for clinical seriousness and, in any case, less significant than those observed in other pathological pictures, mostly in Hodgkin's disease. The existence of anomalies of tryptophan's metabolism is certainly shown in many diseases, however the true physiopathogenetic meaning of these metabolic alterations is not yet specified. Particularly it is not definite if these alterations are the cause of diseases, which they appear in, or if they are secondary alterations.


[Solute charge in milk feeding of babies with diarrhea]. In each one of the samples, investigation of osmolarity, concentration of sodium chloride and proteins and bacteria was carried out. With these data, concentration of solutes in milks was estimated, together with a calculation of renal charge they represented. The most outstanding results showed that mothers offer whole and half skimmed milks at concentrations less than normal dilutions; thus, the solute charge was found in most cases, far below figures reported as average. In a good number of milks, osmolarity showed to very high, specially in those added with corn syrup. Only in 9 of the formulas germs were not identified; in the rest, E. coli predominated and there was high index of contamination.


Contribution of cardiac pacing to our understanding of the Wolff-Parkinson-White syndrome. This review discusses the information which can be obtained by cardiac pacing in patients with the Wolff-Parkinson-White syndrome. Programmed electrical stimulation when combined with the recording of intracardiac electrograms and surface electrocardiograph leads, can be extremely useful in the following areas. 1) Determining the type of the accessory atrioventricular connexions; 2) determining the electrophysiological properties of the accessory atrioventricular pathway; 3) localizing the position of the accessory atrioventricular pathway; 4) determining the mechanisms of any tachycardia; 5) assessing effect of drugs; 6) identifying patients likely to be at high risk; and 7)evaluating postoperative conduction.


Death during operation.

Death during operation. Although deaths that take place during the course of an operation are commonly called "Death under the Anaesthetic", they did occur before the advent of anaesthesia and in 1824 Dupuytren listed seven posssible causes. Thirty-three reported cases are mentioned and compared with Dupuytren's list. Air embolism was the commonest cause. The last survey in 1956 suggested that anaesthesia was entirely responsible for about 60 per cent of cases and surgery for 10 per cent.


A comparison of methods for the measurement of cardiac output and blood oxygen content. A comparison has been made between the recently introduced thermal dilution method for measurement of cardiac output and the standard dye dilution technique. Two relatively new methods of measurement of blood oxygen content, one involving the measurement of oxygen tension after release of oxygen by carbon monoxide, and the other the measurement of current flow upon reduction of oxygen in a galvanic cell, have been compared with a standard indirect method of measurement of blood oxygen content. All three new methods fulfilled the criteria of accuracy and simplicity and compared favourably with the standard methods. Of the two new methods for measurement of oxygen content, that involving reduction of oxygen in a galvanic cell was superior by virtue of compactness and speed of operation.


Recovery and skills related to driving after intravenous sedation: dose-response relationship with diazepam. Skills related to driving, the ability to discriminate the fusion of flickering light, and hand and foot proprioception, were measured double-blind in 34 healthy volunteers before and after three doses of i.v. diazepam. The effects of diazepam were most harmful to co-ordination. With 0.15 mg/kg, 0.30 mg/kg and 0.45 mg/kg of diazepam the impairment of co-ordinative skills was statistically significant (P less than 0.05) up to 2, 6 and 8 hr respectively. No impairment of performance on any test was measurable at 6 hr after 0.15 mg/kg or at 10 hr after 0.30 or 0.45 mg/kg of diazepam. There were large interindividual variations in serum concentrations of diazepam within each dose level. The increases in serum concentrations of diazepam after the intake of food support the concept of an enterohepatic cycle for diazepam. It was concluded that patients should not drive or operate machinery for at least 6 hr after 0.15 mg/kg of i.v. diazepam and at least 10 hr after 0.30 mg/kg and 0.45 mg/kg.


A controlled trail of doxapram in acute respiratory failure. The efficacy of a respiratory stimulant (doxapram) in antagonizing carbon dioxide retention associated with controlled oxygen therapy (28 per cent) in acute-on-chronic respiratory failure was assessed by a double-blind crossover trial in eight patients. PaCO2 rose in egery case during the placebo in the initial treatment period (mean increase 10 mm Hg). In those patients receiving doxapram initially PaCO2 fell in three and rose in one (mean decrease 4 mm Hg). All who has shown a rise in PaCO2 during the initial period on placebo showed a fall in the subsequent period on doxapram. In the six patients who completed the study, mean PaCO2 at the end of the doxapram period was significantly lower than the end of the placebo period (60 mm Hg against 67 mm M Hg). In three patients the rise in PaCO2 was accompanied by significant impairment in the level of consciousness which was reversed during the doxapram period. PaCO2 was not significantly different during either treatment period. No serious unwanted effects were encountered.


An operation for restoration of urinary continence following total loss of the urethra. Twenty-three patients with urethral loss have been treated by the simple creation ofa "spout" from the bladder wall. The procedure is suggested for the surgical treatment of lymphopathia venereum and for consideration in certain other conditions when urinary diversion is unacceptable.


The paretic pupil: its incidence and aetiology after keratoplasty for keratoconus. The present study reveals that pupillary abnormalities are common after keratoplasty for keratoconus and that, in addition to the fixed dilated pupils which we have found in 7.8 per cent. of eyes, varying degrees of partially dilated pupil frequently occur after operation. In our experience, glaucoma is not a sequel to the simple paretic pupil, a finding which confirms the results of the smaller series of Alberth and Schnitzler (1971); glaucoma thus seems to be no more a special complication of keratoplasty for keratoconus than it is of keratoplasty for any other corneal pathology. The paretic pupils can be explained on the basis of ischaemic atrophy of the sphincter pupillae muscle secondary to an iris strangulation phenomenon occurring during surgery in the manner we have discussed. The relative frequency of a dilated pupil, together with the common finding of focal iris atrophy after minimal surgical trauma to the iris in cases of keratoconus, forces one to conclude that the pathology in this condition is not confined to the cornea but probably extends to the iris and possibly to the scleral envelope as well.


Intravitreal hyaluronic acid injection. A long-term clinical evaluation. Healon-H was used in the treatment of seven cases of complicated retinal detachment. A permanent re-attachment was achieved in two cases. No serious ocular complications have been encountered after a follow-up of 4 1/2 years.


Essential thiols of yeast hexokinase: alkylation by a substrate-like reagent. It is demonstrated that N-bromoacetyl-D-galactosamine acts as a substrate-like reagent for yeast hexokinases A and B, producing affinity labeling. At the order of 10(-3) M reagent concentrations, rapid inactivation of the enzyme is produced: the kinetics are consistent with dependence upon a reversible inhibitor-enzyme initial complex, with a dissociation constant of 3.8 x 10(-3) M for hexokinase B at 35 degrees, pH 8.5. The glucose analog is 30-fold less effective, presumably due to self-protection. The inactivating reaction is an order of magnitude faster than that with bromoacetate. All the alkylation of hexokinase B was shown to occur at two thiol groups per subunit, associated stoichiometrically with inactivation. Unlike the reaction there of simple alkylators, two nonessential thiols per subunit are left unattacked when this inactivation reaction is complete. Protection against the affinity alkylation is exerted by the substrates glucose, mannose, fructose, glucose 6-phosphate, fructose 6-phosphate, ATP-Mg, and ADP-Mg, in proportion to their affinities for the active center. Free ATP also protects. Mg2+ alone has no influence, and Mn2+ gives a slight acceleration, when correction is made for a slow inactivation that occurs when the enzyme is incubated at 35 degrees with Mn2+ alone. Galactose, virtually a nonsubstrate, has no influence on the affinity alkylation, but N-acetylgalactosamine, a nonsubstrate and a weak inhibitor of the enzymic reaction, has an accelerating effect. An interpretation is made in terms of binding to a site that influences the active center. This affinity label should provide a means of isolating a peptide containing active-center-related groups.


Partial purification and properties of an enzyme from Escherichia coli that catalyzes the conversion of glutamic acid and 10-formyltetrahydropteroylglutamic acid to 10-formyltetrahydropterol-gamma-glutamyglutamic acid. An enzyme that catalyzes the conversion of L-glutamic acid and 10-formyl-H4folic acid (also known as 10-formyl-H4pteroylglutamic acid) to 10-formyl-H4pteroyl-gamma-glutamylglutamic acid has been purified by 74-fold from extracts of Escherichia coli. ATP, Mg-2+, and a monovalent cation (K+ or NH-4, but not Na+) are required for the enzyme to function. Radioactive and bioautographic analyses revealed the formation of a single product. This product was identified as 10-formyl-H-4pteroyl-gamma-glutamylglutamic acid from its spectral characteristics, its ability to be used effectively as a growth faster for Lactobacillus casei 7469, and from radioactive analysis that indicated the incorporation into the product of 1 mol glutamate/mol of 10-formyl-H-4pteroylglutamic acid utilized. The enzyme functions optimally at pH 9.0-9.8 and at 50 degrees. Its molecular weight is estimated at 42,000-43,000. The Km values are 180 muM for L-glutamic acid and less than 2 muM for (-) 10-formyl-H-4pteroylglutamic acid. The only other naturally occurring folate compounds with significant activity as substrate are H-4pteroylglutamic acid and 5,10-methylene-H-4pteroylglutamic acid; however, these compounds are not used as effectively (K-m values are 10-12 mu-M) as 10-formyl-H-4pteroylglutamic acid.


The structure of the globin genes in chromatin. The distribution of proteins in the neighborhood of the globin genes of duck reticulocyte chromatin has been studied. This chromatin is first shown to be an active template for transcription in vitro of globin messenger-like RNA. The chromatin is then treated with staphylococcal nuclease and the DNA fragments protected from nuclease attack ("covered DNA") are isolated. Alternatively, the chromatin is titrated with poly-D-lysine, and by successive treatment with Pronase and nuclease, the DNA regions accessible to polylysine are isolated (open "DNA"). In order to determine the distribution of globin gene sequences in open and covered DNA, these two fractions are annealed to globin cDNA (globin probe). It is found that while all globin gene sequences are represented in covered DNA, a specific portion of the globin gene is missing from open DNA, corresponding to about 20% of the gene length. It is concluded that specific regions of the globin genes of reticulocyte chromatin are partly covered by proteins in such a way as to render them in accessible to polylysine. In contrast, no difference is observed in the annealing properties of open and covered regions to globin probe using DNA isolated from erythrocyte chromatin, which is a poor templete in vitro for production of globin message. The annealing of open and covered DNA to each other has also been studied. It is found that open and covered DNA have identical sequence populations. Thus, in contrast to the special arrangement of proteins in the neighborhood of the globin gene, there does not appear to be any sequence-specific arrangement of the bulk of the chromatin proteins on chromatin DNA.


Iodination of Escherichia coli lac repressor. Effect of tyrosine modification on repressor activity. Treatment of Escherichia coli lac repressor with iodine (Kl3) at 4 degrees and pH 7.5 resulted in the rapid loss of repressor DNA binding activity. At a 30-fold molar excess of iodine to repressor, inactivation was complete within 15 sec. Inducer binding under the same conditions was only slightly affected. Iodinated repressor remained tetrameric, indicating that no gross structural alteration of the protein has taken place. Control experiments demonstrated that side products of the reaction did not contribute to the observed activity loss. Moreover, no restoration of binding activity was observed when iodinated repressor was assayed under a variety of assay conditions. Incubation of repressor with lac operator containing gamma plac DNA during the iodination reaction resulted in approximately 50% protection of binding activity. This protective effect was only partially operator specific, as gammaDNA lacking the operator binding site afforded roughly 25% protection under the same conditions. Incubation with either inducer and anti-inducer molecules during the iodination reaction did not protect repressor DNA binding activity. Iodination with K-131I-3 demonstrated that at complete inactivation virtually all of the bound iodine was recovered as iodotyrosine. A minor amount of cysteine oxidation to cysteinesulfonic acid was also detected. This oxidation encompassed no more than 30% of a single cysteine residue )tentatively identified as cysteine-107). Unstable intermediate oxidation products of cysteine did not appear to be involved in the loss of DNA binding activity. Modification of amino acids other than tyrosine and cysteine was not observed. Tryptic digestion of -131I-labeled repressor suggested that approximately 90% of the incorporated radioactivity was located in the repressor N-terminal tryptic peptide. Automated sequence analysis of iodinated repressor confirmed that at roughly 0.5 bound iodine atoms per repressor subunit (corresponding to approximately 5-10% activity loss) tyrosine residues 7, 12, and 17 were labeled in the ratios 1.0:0.5:0.8. Doubling the amount of bound iodine to 1.0 atom per subunit (corresponding to approximately 50-60% activity loss) did not significantly change the pattern of incorporation.


A comparison of the fluorescence of the Y base of yeast tRNA-Phe in solution and in crystals. The fluorescence properties of the Y base of yeast tRNA-Phe are known to be quite sensitive to the environment. The fluorescence lifetime of the Y base in yeast tRNA-Phe is identical in orthorhombic crystals and in the mother liquor from which these crystals are grown. It is 10% higher than the lifetime observed in dilute solutions of tRNA. This small change is a solvent effect due to isopropyl alcohol in the crystallization medium. Isopropyl alcohol does not change the accessibility of the chromophore of the Y base as measured by iodide quenching rates in solution. The accessibility in intact tRNA-Phe is much less than in a ribonuclease digest. Thus, within the limits of the sensitivity of the method, the Y chromophore occupies the same environment in solution and in the crystal and it must be at least partially buried.


Polyglycerophosphatide metabolism in Escherichia coli. When Escherichia coli B cells were labelled with [14-C] glycerol and chased, there was a marked sparing of the phosphatidyl moiety compared to the nonacylated glycerol moiety of phosphatidylglycerol. When energy-depleted cells were restored to an energy-rich medium there resulted a conversion of 32-P-labelled cardiolipin to phosphatidylglycerol, a lack of phosphatidic acid accumulation and no loss in total polyglycerophosphatide counts. In cell-free extracts, phosphatidic acid produced from 32-P-labelled cardiolipin by the action of Escherichia coli phosphalipase D, was readily recycled to form poly-glycerophosphatide. In the presence of glycerol, such extracts displayed traansphosphatidylase activity by degrading cardiolipin to phosphatidyglycerol mainly. The results as a whole indicate that the enzyme synthesizing cardiolipin together with cardiolipin-hydrolyzing phospholipase D constitute a cycle which is normally involved in the turnover of polyglycerophosphatides in Escherichia coli.


Movement of calcium through artificial lipid membranes and the effects of ionophores. The calcium efflux from multi-layered vesicles (liposomes) of different lipid composition has been studied. Liposomes composed of lipids extracted from cattle retinas are compared with liposomes which consist of phosphatidylcholine or a 1:1 phosphatidylcholine/phosphatidylserine mixture. The percentages of 45-Ca capture by these three types of liposomes are 10, 1 and 4% respectively; The efflux rates are 2.5-10- minus 6, 2-10- minus 6 and 4-10- minus 5 S- minus 1 respectively. The semilogarithmic efflux curves for phosphatidylcholine and phosphatidylcholine/phosphatidylserine liposomes are linear with time, but those for the retinal lipid liposomes are discontinuous. The activation energy for the calcium efflux from the latter liposomes is about 10.5 kcal/mol, both before and after the discontinuity. The ionophores X537A and A23187 enhance the calcium leakage from retinal lipid liposomes, the latter ionophore being much more effective than the former. At high concentrations both ionophores seem to transport calcium as a 1: 2 Ca-ionophore complex. At low ionophore concentrations, however, X537A appears to transport calcium as a 1:1 complex, but A23187 as a 2:1 complex.


Membrane reconstitution in chl-r mutants of Escherichia coli K 12. VIII. Purification and properties of the FA factor, the product of the chl B gene. The isolation and purification of the product of the chl B gene of Escherichia coli K 12 from the chl A mutant have been attempted. The purified protein gives a single band in 10% sodium dodecylsulfate/polyacrylamide gel electrophoresis. The molecular weight is estimated to be 35 000. This protein, that we have named "FA factor", does not contain any lipid, has a strong tendency to lose its activity by polymerizing but can be kept in an active state when stored in buffer containing NaCl. The addition of purified FA protein to a soluble extract from the chl B mutant strain grown under anaerobiosis in the presence of nitrate initiates the "complementation reaction", i.e. the reconstitution of the nitrate reductase activity and the formation of particulate material similar to the native membrane with respect to the structure and enzymatic function. FA protein acts both on the rate of reconstitution and on the total amount of reconstituted enzyme. The complementation leads to the reconstitution of nonsedimentable nitrate reductase and to the formation of three types of particles of different buoyant densities (1.10, 1.18 and 1.23) the two lightest of which contain nitrate reductase. It is shown that FA factor is incorporated only into the particles of intermediate density. In vivo, this factor is located in the native membranes of chl A, chl C, chl D and wild-type strains, whatever the growth conditions, aerobiosis or anaerobiosis, and in the presence or absence of nitrate. Protein FA can be released from either of these membranes (native or reconstituted) by removing Mg-2+ or by subjecting Kaback's vesicles to mechanical treatments; in the case of 1.18-reconstituted particles and wild-type membranes, the release of FA protein does not exert any effect on the level of the nitrate reductase activity.


Membrane reconstitution in chl-r mutants of Escherichia coli K 12. IX. Part played by phospholipids in the complementation process. The supernatant extracts of the chl A and chl B mutants of Escherichia coli K 12, the phospholipids of which are labeled by growth in 32 P or [2- 3H]glycerol media, contain 20 times more radioactivity than the supernatant extract of the wild-type strain grown under the same conditions. We have observed that, after complementation, 80% of the radioactivity previously contained by Extracts A and B is incorporated into reconstituted particles. The chromatography of 3H-labeled Extract B on DEAE-cellulose and followed by gel filtration of radioactive fractions on Sephadex G-200 has shown that the phospholipids of Extract B are only bound to soluble proteins and not to fragments of membranes; it can be assumed that they have been solubilized in the form of a lipid-protein complex by cell breakage. When Extracts A and B are treated by phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) before being mixed together, an inhibition of the reconstitution of nitrate reductase activity which is proportional to the phospholipase C concentration and the length of treatment is observed. The analysis of lipids and phospholipids of particles (Peak I, Peak II and Peak III) formed during complementation and reconstituted nitrate reductase shows that their phospholipid contents (phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylserine) and especially that of Peak II (d equals 1.18) are closely related to that of native particles from the wild-type strain. These results allow one to propose a hypothesis explaining the mechanism involved in complementation.


Lipid phase transitions in cytoplasmic and outer membranes of Escherichia coli. The cytoplasmic and outer membranes containing either trans-delta-9-octadecenoate, trans-delta-9-hexadecenoate or cis-delta-9-octadecenoate as predominant unsaturated fatty acid residues in the phospholipids were prepared from a fatty acid auxotroph, Escherichia coli strain K1062. Order-disorder transitions of the phospholipids were revealed in both fractions of the cell envelope by fluorescent probing or wide angle X-ray diffraction. The mid-transition temperatures, Tt, and the range of the transition, delta-T, are similar in the outer and cytoplasmic membrane. Relative to the corresponding extracted lipids, 60-80% of the hydrocarbon chains take part in the transition in the cytoplasmic membrane whereas in the outer membrane only 25-40% of the chains become ordered. The results suggest that in the outer membrane part of the lipids form fluid domains in the form of mono- and/or bilayers.


Comparison of the myoglobin of the zebra (Equus burchelli) with that of the horse (Equus caballus). The tryptic and peptic peptides from the myoglobin of the zebra (Equus burchelli) have been compared with those obtained from the myoglobin of the horse (Equus caballus). No differences in the myoglobin were found between these two species.


The myoglobin of primates. VII. Perodicticus potto edwarsi (potto). The primary structure of the myoglobin of the prosimian Lorisidae Perodictius potto edwarsi (potto) was studied. Tryptic, chymotryptic, peptic, subtilisin and thermolysin peptides were aligned against the sequence of human myoglobin. Sixteen differences were found which were confirmed by sequential analysis. On comparison of the West African potto with two other prosimian myoglobins known so far, there were 12 differences between the potto and the galago (East African) and 18 differences between the potto and the sportive lemur (Madagascar).


High affinity phlorizin receptor sites and their relation to the glucose transport mechanism in the proximal tubule of dog kidney. A set of high affinity phlorizin receptors in a brush border membrane preparation from dog kidney cortex is described. The dissociation constant, Kd is approximately equal to 0.3 muM (20 mM Tris-HCl, 150 mM Na-+, 5mM EDTA pH 7.45, 37 degree C). The number of receptor sites is approximately equal to 12-10- minus 12 mol/mg membrane protein. Preincubation with sugar substrates shows that the high affinity phlorizin binding is completely abolished by D-glucose (100 mM), 3-deoxy-30fluoro-D-glucose (125 mM) and alpha-methyl-D-glucopyranoside (125 mM), while 40-50% inhibition is observed with glucose concentrations as low as 5 mM. D-Galactose adn beta-methyl-D-galactopyranoside inhibit 20-40% at 125 mM while 2-deoxy-D-glucose and 2-deoxy-D-galactose inhibit minimally (approximately equal to 25%) at the same concentration. L-glucose, D-mannose, D-xylose, myoinositol, D-fructose and 3-O-methyl-D-glucose do not inhibit significantly in concentrations up to 600 mM. Unlabelled phlorizin (1 muM) and D-glucose (125 mM) completely wash off bound [3-H] phlorizin from the high affinity site. In contrast, phloretin (100 muM) is only about 50% as effective in displacing bound [3-H] phlorizin. Binding decreases with decreasing sodium concentration and is abolished by N-ethylmaleimide (7 mM). No inhibition is observed with ouabain (0.125 mM), cytochalasin B (0.1- 42 muM) and concanavalin A (10-10 000 mug/ml). The specificity of inhibition of phlorizin binding in vivo to the luminal membrane of the proximal tubule in dog kidney has also been investigated. Alpha-methyl-D-glucopyranoside completely washes off bound [3-H] phlorizin. D-galactose is only about 10% as effective at equivalent doses. There is no observable wash off of bound [3-H] phlorizin with D-fructose, myoinositol, D-mannose or 2-deoxy-D-glucose. The relative affinity of monosaccharides for the glucose transport receptor at the brush border was investigated in vivo using the multiple indicator dilution technique to determine their fractional reabsorption under identical conditions of phlorizin blockade. The relative affinities are in the order D-glucose approximately equal to alpha-methyl-D-glucopyranoside greater than D-galactose greater than 2-deoxy-D-glucose greater than D-fructose approximately equal to myoinositol. It is concluded (i) that phlorizin receptors on the brush border of the proximal tubule in vivo are identical to the high affinity phlorizin binding sites in the brush border membrane fraction in vitro and (ii) that these phlorizin receptor sites are either in close proximity, or identical, to the glucose transport receptor.


Phospholipase activity plays no role in the action of colicin K. 1. A mutant lacking both detergent-resistant and detergent-sensitive phospholipase A activities is fully sensitive to colicin  K. 2. In the absence of cellular phospholipases A, colicin K does not promote hydrolysis of phosphatidylethanolamine. 3. Cells of the colicin-treated mutant lacking lysophosphatidylethanolamine are as abnormally permeable to Co-2+ as the wind type is. 4. Increased levels of lysophosphatidylethanolamine in colicin-treated cells are not necessary for the increased sensitivity to sodium dodecylsulfate.


NMR investigation of the effect of selective modifications in the anticodon loop on the conformation of yeast transfer RNA-Phe. Changes in the 300 MHz proton NMR spectrum of yeast tRNA-Phe induced by the removal of the Y-base from the anticodon loop are reversed when the dye proflavine is incorporated in its place. These observations correlate with our earlier interpretation of the NMR data that removal of the Y-base causes a change in the conformation of the anticodon stem. Such changes in stem conformation may in part be responsible for the differences in the biochemical properties of tRNA-Phe, tRNA-PhePF and tRNA-Phe-Y.


The isolation of large polysomes in high yield from unfractionated tissue homogenates. It was found that if large quantities of both exogenous RNA and Mg-2+ were present during gentle tissue homogenization, the subsequent addition of deoxycholate to the whole homogenate produced a viscous mass from which polysomes could be isolated in large yields. These polysomes were substantially less degraded than those isolated by previous methods. In the case of rat liver, 15 ribosomes per mRNA was the species present in highest concentration. The parameters of this method were investigated and optimized. About 80 percent of the rRNA in the homogenates was recovered in the polysomes. Omission of deoxycholate permitted the isolation of less-degraded free polysomes as well. In the liver of fed rats these represented one-fourth of the total polysomes, in good agreement with results obtained by an independent approach. Using the method to isolate polysomes from the liver of starving rats, it was found that only about one percent of the large amount of monomers and dimers present resulted from polysome breakdown during isolation. It was further shown that random RNAase hydrolysis of polysomes could not produce the patterns of liver polysomes seen during starvation. Polysomes isolated by this procedure were quite stable in solution and were very active in cell-free protein synthesis. Application of this method without adaptation to eight other tissues also permitted the isolation of large polysomes in high yields.


Regulation of RNA synthesis in Escherichia coli during a shift-up transition. These experiments investigate two aspects of RNA synthesis in Escherichia coli ML30 during the transition from a relatively slow rate of growth to a more rapid one: (1) the number of growing RNA molecules per cell, and (2) the average time required for addition of a nucleotide onto a growing RNA chain. Cells were grown at 30 degrees C in a glucose-minimal salts medium and shifted-up by the addition of Casamino acids. Measurements were made of the rates of incorporation over short intervals (e.g. 5,8,12, and 16 s) of [3-H]guanine into the internal and 3'-terminal nucleotides of RNA. After correction for the specific activities of the intracellular GTP pools, and for the rate of [3-H]guanine accumulation at the 3'-terminus of non-growing RNA, the rates of chain elongation were calculated. It was found that cells growing at a rate of 0.9 generations/h contain approx. 4800 RNA molecules, growing at a rate of 28 nucleotides/s per chain. Cells growing exponentially at the postshift-up rate (1.2 generations/h) contain 7000 RNA molecules per unit equivalent cell mass, which are growing at a rate of 32 nucleotides/s per molecule. Three min after shift-up, cells contain the same number or slightly fewer (10%) growing RNA molecules than cells prior to shift-up, 4300, and these are being elongated at a rate of about 32 nucleotides per s. The results are consistent with the view that in the range of growth rates studied, the total rate of RNA synthesis is regulated through a limitation in the number of functioning RNA polymerase molecules, each working at a relatively constant, presumably maximal, average rate.


Ribosomal and non-ribosomal RNA synthesis in vitro. The synthesis of total and ribosomal RNA using nucleoids of Escherichia coli as template was measured; of the total RNA synthesized by endogenous RNA polymerase which only completes chains, and added RNA polymerase which initiates new chains, 50-70 and 3-5%, repectively, was rRNA. Total RNA synthesis by added enzyme, however, was 10-20 times higher than endogenous RNA synthesis; thus rRNA was synthesized at the same rate by the endogenous and the added enzyme. We conclude that the percentage rRNA in vitro is no measure of the rate of rRNA synthesis. Furthermore, it follows that the added enzyme, like the endogenous one, is packed at the physical limit on the ribosomal cistrons. Consequently, initiation of ribosomal cistrons by added enzyme was at or near the maximal rate possible for this system in which the elongation rate is 10-20% of that in vitro. When RNA synthesis was assayed at various ratios of RNA polymerase to phenol-extracted DNA, the amount of rRNA made per DNA, which is a measure of the frequency of transcription of ribosomal cistrons, varied. The ratio of rRNA synthesis relative to total RNA synthesis also varied, but in a different way, again leading to the conclusion that this ratio, as determined in vitro, does not reflect the efficiency of transcription of the ribosomal cistrons.


Quinone induced stringent control. Accumulation of ppGpp and inhibition of RNA synthesis in stringent Escherichia coli by 5,8-dioxo-6-amino-7-chloroquinoline. The mode of action of a synthetic cytostatic quinone was studied in Escherichia coli. 1. At concentrations of 1.5-6 mug/ml, 5,8-dioxo-6-amino-7-chloroquinoline rapidly inhibits growth and protein synthesis in E. coli. The synthesis of RNA is immediately affected in E. coli rel+ whereas in E. coli rel- the accumulation of RNA can proceed on addition of the quinone. This indicates that the inhibition of RNA synthesis in the stringent strain is a consequence of the regulatory phenomenon governed by the rel gene. 2. Chloramphenicol, known to abolish the stringent control mechanism, added simultaneously with the quinone allows the accumulation of RNA to proceed in the stringent strain. 3. Guanosine tetraphosphate accumulates in quinone-treated E. coli rel+ but not in the relaxed mutant strain. 4. Addition of amino acids reverses all inhibitory effects observed in quinone treated stringent and relaxed cells. 5. It is concluded that the bacteriostatic effect of 5,8-dioxo-6-amino-7-chloroquinoline on E. coli is caused by an apparent intracellular amino acid starvation.


Affinity-labelling of Escherichia coli ribosomes by a derivative of phenylalanyl-tRNA. A critical test for the specificity. Under nonenzymatic binding conditions p-nitrophenoxycarbonyl-phenylalanyl-tRNA can be bound to the donor as well as the acceptor site on the Escherichia coli ribosome. Precharging ribosomes with phenylalanyl-tRNA in the presence of elongation factor Tu and GTP blocks both the donor- and the acceptor site against affinity labelling by p-nitrophenoxycarbonyl-phenylalanyl-tRNA.


Some effects of calcium and magnesium ions on the activity of bovine pancreatic deoxyribonuclease A. Bovine pancreatic deoxyribonuclease requires divalent metal cations for hydrolysis of DNA. The effects of calcium and magnesium, alone and combined, on the rate and kinetics of the reaction were examined. Divalent metal salts of DNA were used as substrates. The ratio of either Ca-2+ or Mg-2+ to DNA-P in these salts was 1:2. The Mg-2+ salt of DNA was found to have sufficient Mg-2+ for optimal DNAase activity. Addition of MgCl-2 to a large excess of Mg-2+ over DNA-P had no effect on the rate. Km for the hydrolysis of Mg-2+-DNA was 1.76 mM. Km for the hydrolysis of Ca-2+-DNA was too low to measure by our  methods of assay, indicating a high affinity of enzyme for substrate. The rate of hydrolysis of Ca-2+-DNA, however, is slow compared to that of Mg-2+-DNA. By mixing the Ca-2+ and Mg-2+ salts of DNA, a synergistic effect on the activity of DNAase was observed. On the basis of kinetic studies the synergistic effect is attributed to an increased affinity of DNAase for DNA (Km equals 0.34 mM for the mixed Ca-2+, Mg-2+ salt of DNA). A 2-fold increase in DNAase activity was observed when DNAase was incubated in CaCl-2 before assay. This 2-fold stimulation was not related to the synergistic effect. DNAase I is inactive against the sodium salt of DNA. In experiments with mixed Na+ and Mg-2+ salts of DNA, Na+-DNA was found to be a competitive inhibitor of the action of DNAase against Mg-2+-DNA.


[Ribosome stability of Escherichia coli cells in amino acid starvation]. The dissociation of ribosomes from two isogenic pairs of Escherichia coli strains was studied during exponential growth, under amino acid starvation and subsequent chloramphenicol treatment. There were no significant differences in Mg2+-dependent dissociation of ribosomes from exponentially growing rel+ and rel- minus strains. The differences in dissociation of the ribosomes from rel+ and rel- minus cells were observed only upon amino acid starvation of these cultures. The dissociation of ribosomes from starved rel+ cells was more complete. After chloramphenicol treatment isolated ribosomes were more resistant to dissociation into subunits. Alterations of dissociation of the ribosomes in vitro correlated both with the amount of polysomes and the level of RNA synthesis in cells. It is proposed that rRNA synthesis in bacteria depends on the ratio of programmed and deprogrammed ribosomes.


[2 phosphotransferase systems that control the second stage of phosphoenolpyruvate-dependent glucose phosphorylation in E. coli]. Analysis of E. coli W mutants defective in glucose transport suggests an existence of two enzyme systems which carry out the second step of phosphoenolpyruvate (PEP)-dependent glucose phosphorylation, thus controlling the glucose transport into E. coli cells. One system (PTS-glu-alpha) controls phosphorylation and transport of both glucose and alpha-methylglucoside, the other system (PTS-glu-beta) controls phosphorylation and transport of glucose only. PTS-glu-alpha system is damaged in the mutants studied, but PTS-glu-beta system is intact. On account of this fact the mutants do not uptake 14-C-alpha-methylglucoside and their extracts are practically incapable of its phosphorylation, phosphoenolpyruvate being used as phosphate donor. At the same time the mutants are capable of 14-C-glucose uptake and PEP-dependent 14-C-glucose phosphorylation. In one of the strain, having the intact PTS-glu-alpha system, the uptake of glucose and alpha-methylglucoside was stimulated by the addiction of glucose in the cultural medium. No such effect was observed in bacteria with the disturbed PTS-glu-alpha system and the intact PTS-glu-beta system. Probably, the PTS-glu-alpha system can be inducible, in contrast with the PTS-glu-beta system. The damage of the PTS-glu-alpha system results in resistance of bacteria to glucose-induced inhibition of the enzyme synthesis.


Comparative symptomatological and evoked potential studies with d-amphetamine, thioridazine, and placebo in hyperkinetic children. In a double-blind study, 62 hyperkinetic children were randomly assigned to 8 weeks of treatment with either placebo, thioridazine, or d-amphetamine. The overall clinical symptomatology improved with all three substances, although d-amphetamine was significantly superior to placebo and thioridazine. Out of eight symptom clusters rated by the parents, two improved significantly with placebo, one with thioridazine, and six with d-amphetamine. The d-amphetamine was superior to placebo in reducing muscular tension and superior to thioridazine in decreasing hyperactive-impulsive behavior, psychosomatic problems, and muscular tension. Out of four teachers' symptom clusters, inattentive-passive behavior was significantly improved by thioridazine (which was also superior to placebo), while hyperactivity was reduced by d-amphetamine. Quantitative evaluation of visual evoked potentials (VEPs) revealed an increase in latencies and decrease in amplitudes during thioridazine treatment. Paradoxically, d-amphetamine also increased latencies, while tending to augment amplitudes. Regression and correlation analysis of clinical symptomatology with VEP variables showed that the shorter the pretreatment latencies and the higher the amplitudes, the more disturbed was the child. Short latencies and small amplitudes in the pretreatment period were predictors of good therapeutic outcome with subsequent thioridazine treatment, while short latencies and high amplitudes were indicative of such with d-amphetamine treatment. During therapy, the greater the drug-induced augmentation of latencies, the greater the clinical improvement. Finally, VEP differences between therapy-responsive and -resistant patients were explored and discussed.


Phenethylamine in normal urine: failure to verify high values. The phenethylamine (PEA) level in daytime urine samples of 18 normal subjects was measured by an isotope dilution technique. Purification of PEA from other urinary substance, after the addition of 1-14C-PEA to urine samples, was achieved by the sequence: thin-layer chromatography (TLC), derivatization, TLC, and finally, gas chromatography (electron capture). The estimated mean daily output of PEA was 10.3 mug/day. A circadian rhythm was not evident on the basis of analyses of 24-hr urine collections from four normal subjects. Three acute schizophrenics had levels within the normal means.


[Purification of microbial asparaginases by the aid of affinity chromatography]. Asparaginases from Escherichia coli and Erwinia caratovora were isolated and purified by column chromatography with a specific sorbent (sepharose, covalently bound to N-alpha-(6-aminohexyl)-D-asparagine). Homogenous asparaginase from E. coli was isolated by one-step procedure, while the enzyme from Er. carotovara was 50-60-fold purified. Asparaginase from Mycobacterium n. sp. was found not to bind with the specific sorbent.


[Binding of ribosomal RNAs with ribosomal proteins covalently bound to polymer carriers]. Conditions for covalent binding of ribosome proteins from Escherichia coli with insoluble polymers are found. A number of polymer carriers and several methods of protein binding to them were tested, the best one being the fixation of ribosome proteins on cyanogen bromide-activated Sepharose. Binding is studied with fixed on the polymer total 30S and 50S proteins, with individual S7 and S20 proteins, 16S and 23S RNAs in conditions optimal for the reconstruction of 30S subunits in vitro. It is found that at least some of ribosome proteins, being bound with polymer carrier, retain the ability to recognize their specific sites on RNA.


Comparative evaluation of artificial ventricles in the United States. A cooperative, comparative evaluation of nine artificial ventricles was performed on two standardized mock circulations. The ventricles included five air-driven diaphragm types, three sack types and a mechanically driven type. The slopes of the ventricular output curves varied from 0.04 to 0.88 at 0 to 5 Torr filling pressure and the maximum ventricular output varied from 3.8 to 11.9 liters/min at 100 Torr outflow pressure. All ventricles had decreased output with increased outflow pressures (70 to 130 Torr). Hemolysis index ratio (HI test/HI std) for HI std equals 0.024 plus or minus .005 (plus or minus 1 SD) g/100 liters (N equals 12), was +21.5 and +6.9 for a Dacron cloth and fibril heart, respectively, +2.0 to +2.86 for three sack ventricles, and +3.2 for a smooth diaphragm ventricle. The mechanical ventricle with a sinusoidal driving waveform and smooth surface had the lowest hemolysis, HI equals 0.008 plus or minus 0.003 (plus or minus 1 SD) (N equals 6). Sack ventricles caused marked hemolysis if the walls touched during systole. Ventricular dimensions varied: weight 116 to 700 g, length 9.2 to 18.7 cm, and volume 235 to 430 ml. Performance data was returned to each individual laboratory which resulted in modification of ventricular design in at least three instances. Comparative, standardized testing of artificial ventricles may shorten development time and provide performance criteria for application in man.


Mediterranean macrothrombocytopenia.

Mediterranean macrothrombocytopenia. Platelet count, platelet size, and circulating platelet biomass concentration estimates made with an erythrocyte-calibrated electronic sizing system on EDTA-anticoagulated blood samples gave population medians and 95% ranges for 145 asymptomatic Mediterranean and 200 healthy Northern European subjects. The Mediterraneans had lower platelet counts [161,000 (89,000-290,000)/mul compared with 219,000 (148,000-323,000)/mul] and higher arithmetic mean volumes [17.8 (10.8-29.2) cu mum compared with 12.4 (9.9-15.6) cu mum], while the individual lognormal platelet size distribution profiles were comparable [geomatric standard deviations of 1.78 (1.60-1.98) against 1.70 (1.54-1.88)]; and the platelet biomass concentrations, given by count per microliter times mean volume times 10- minus 7 and expressed as a volumetric percentage of whole blood, were almost identical [0.286% (0.216%-0.379%) against 0.272% (0.201%-0.367%)]. Mediterranean macrothrombocytopenia is, therefore, considered a benign morphologic variant that requires differentiation from thrombocytopenias in which the circulating platelet biomass concentration is decreased.


Selected list of books and journals for the small medical library. This revised list of 446 books and 137 journals is intended as a selection guide for small or medium-sized hospital libraries or for the small medical library serving a specified clientele. Books and journals are categorized by subject, with the books being followed by an author index and the journals by an alphabetical title listing. Items suggested for initial purchase by smaller libraries are indicated by an asterisk. To purchase the entire collection of books and to pay for annual subscriptions to all the journals would require an expenditure for about $14,500. The cost of only the asterisked items recommended for first purchase totals approximately $4,100.


Science-specialty literatures their legendary contemporary polarity, based on the transmission of information between generations. Each of fifteen scientific specialty fields was represented by a journal and the percent of "legendary" papers (those with at least one reference twenty-five or more years old) was calculated for each field. Non-legendary papers were designated as "contemporary". A historical divergence was uncovered when the highly legendary field, physiology, was compared with the highly contemporary field, microbiology, both fields being moderately contemporary in 1922. The legendary contemporary field characteristics of a field are useful for estimating libraries' requirements for back holdings and for appraising literature searches.


Past presidents I have known.

Past presidents I have known. This paper is an account of the accomplishments of some of the early past presidents of the Medical Library Association known personally to the author in his career as a medical librarian. It demonstrates the qualities that made these librarians leaders of our profession and also indicates their personal attributes that contributed to the advancement of medical librarianship. It is hoped that the historical presentation of some of the giants of our profession will inspire present and future presidents and other medical librarians with an understanding of some of the qualities necessary to the continuing success of our profession.


Comparison of skin erythemas under two different fractionation schemes. This paper reports the results of a prospective clinical trial comparing 200 rads daily five times weekly for four weeks with 400 rads twice weekly for four weeks. Total dose in the first case was 4,000 rads and in the second 3,200 rads. Thirty patients threated palliatively for bronchial carcinoma are involved in this report. Treatment was given at 220 kV and the intensity of skin erythema at the end of the treatment was the measure of comparison. Generally 200 rads daily five times weekly for four weeks produced more intense erythema than the other scheme used.


Whole body potassium in patients with ureterosigmoid anastomoses. Total body potassium was measured by whole body counting in 11 patients with uretero-sigmoid anastomoses who had undergone cystectomy 4 months to 13 years previously. The measured total body potassium was not significantly different in any of the patients from the "normal" value for the individual patients, predicted from height and age. It was only significantly different from that predicted from height, age and weight in 1 patient. In the series as a whole, the measured values of whole body potassium were not significantly different from the "normal" values estimated by either relationship. From measurements of skinfold thickness, the lean body mass of each patient was estimated. The mean potassium content, 62-0 mEg/kg LBM in the male patients was within the normal range. The absence of potassium depletion may derive from the successful abolition of hyperchloraemic acidosis by long-term alkali therapy.


Oestrogen therapy and serum cortisol in carcinoma of the prostate. Patients with prostatic cancer, receiving oestrogen therapy were found to have elevated serum cortisol levels and lymphopenia. Oestrogens are known to have a profound effect on the immune system; the possibility that this effect is mediated through the adrenal cortex is discussed. The significance of these findings, however, remains to be determined.


Serial Fluorine-18 bone scans in the follow-up of carcinoma of the prostate. 74 patients with prostatic cancer were studied annually by combined radiological and fluorine-18 scan survey over a 5-year period. The results of the long term follow-up of bone cans is reported. At the time of the initial diagnosis 71-5% of the patients had advanced disease and 56% had radiological or scan evidence of metastases. A critical evaluation of the scans resulted in the detection of early bone lesions in 25% of patients with no radiological evidence of metastases. Follow-up of these patients has shown that scan abnormalities preceded radiological changes from between 1 to 4 years and there was good correlation proven histologically by bone biopsy or autopsy in more than half of the patients. In patients with a positive bone scan and positive X-rays the scan abnormalities were more extensive than the corresponding X-ray lesions. When bone healing occurred with endocrine treatment this was more readily apparent on the X-rays. False negative scans were not seen with fluorine-18 which allows for greater accuracy in the detection of skeletal metastases. Bone scanning has enabled correct staging to be carried out. This study confirms the high incidence of cardiac and vascular complications in patients treated with oestrogens.


The concentration of sulphamethoxazole and trimethoprim in human prostate gland. Sulphamethoxazole and trimethoprim concentrations were measured in 19 enucleated human prostate glands. Good concentrations of sulphamethoxazole were found after 4 days of treatment: the ratio of plasma concentration to that of prostate varied from 1-25 to 3-29. The trimethoprim concentrations were 2 to 3 times higher in the prostate than in the plasma. These high concentrations were reached very rapidly after the first dose of trimethoprim. The results are compared with date from the literature. The combination sulphamethoxazole-trimethoprim should be of value in the treatment of bacterial prostatitis.


Vas anastomosis: a return to simplicity. Vas anastomosis is successful in restoring sperm to the ejaculate in 80 to 90% of cases. A simple, end-to-end, mucosa-to-mucosa anastomosis performed with non-absorbable, monofilament sutures is, in the author's opinion, the best procedure. Pregnancies follow in about one-third of the cases.


Ampicillin, carbenicillin indanyl ester, and nifuratel in the treatment of urinary infection in domiciliary practice. A total of 120 patients, including 53 pregnant women with significant bacteriuria, received 163 7-day courses of oral antimicrobial agents allocated in a randomised manner. The cure rates after 6 weeks' follow-up ranged from 73% to 86%, and there was no statistical difference between preparations of ampicillin, carbenicillin indanyl easter, and 2 different formulations of nifuratel. Side-effects occurred in 30% to 40% of the courses of penicillin drugs, but in under 15% of the course of nifuratel. It is concluded that the new oral preparation of carbenicillin is a useful addition to the list of antimicrobial agents which are effective in the treatment of urinary infections in domiciliary patients. Furthermore, nifuratel has been confirmed as a highly active non-toxic drug which is valuable in the treatment of urinary infections.


Intra-arterial infusion of Solcoseryl: a clinical trial of a method of treatment for pre-gangrene of the lower limb. A randomized double blind trial of the drug Solcoseryl given by intra-arterial infusion was carried out on 57 patients with pre-gangrene of the lower limb. A sequential analysis was carried out and the trial stopped when the results showed a statistically significant result in favour of the active drug.


The construction of a skin-lined hemithorax in pigs. The feasibility of creating a skin-lined hemithorax was tested in 6 pigs. All the pigs survived intrapleural skin grafting, and within 3 weeks they doubled their mean initial weight from 16-3 plus or minus 1-6 kg to 32-4 plus or minus 2-6 kg. In 4 (out of 4) pigs the skin-lined cavity was opened successfully to the exterior; it had reproduced closely the contour of the hemithorax. It is concluded that it is feasible to construct a skin-lined hemithorax with a mean volume of 276-3 plus or minus 19-6 ml in pigs, whose mean body weigh was 37-5 plus or minus 2.5 kg. This confirms earlier work in the rat.


Diagnosis, clinical course and treatment of acute dermal gangrene. Twenty patients with acute dermal gangrene following surgery, trauma or sepsis are described. In 12 the skin became gangrenous secondary to a necrotizing process affecting the subdermal fascia, and in 8 the condition arose primarily in the skin. In the first group mortality was high unless radical excision of the necrotic fascia was performed at an early stage; in 3 of the recent patients the overlying skin was removed, defatted and stored for later grafting. In the second group, incision and adequate drainage combined with antibiotics seemed to suffice. Hyperbaric oxygen was of dubious value in the first group but appeared to contribute to arrest of the lesion in the second group.


Wound infections due to Bacteroides fragilis following intestinal surgery. Ninety-six wound infections due to Bacteroides fragilis occurring after intestinal surgery are described. Most infections followed appendicectomy or colectomy for diverticulitis. B. fragilis was isolated in pure growth from 47 per cent of infections, and in mixed culture the other common bacteria were Klebsiella spp., Escherichia coli and Enterobacter spp. Fifty-three per cent of the infections responded rapidly to either non-specific measures or antibiotic therapy, but 47 per cent of patients developed complications, usually abscess formation. The successful isolation of bacteroides from clinical material requires special precautions. The specimen for bacteriological examination must be sent to the laboratory in a transport medium which maintains an anaerobic environment and the culture techniques must include a selective agar for the isolation of anaerobic bacteria. The role of antibiotic therapy in preventing postoperative wound infection after intestinal surgery is discussed. Bacteroides has an unusualy pattern of antibiotic susceptibility and it is essential that an effective antibiotic such as lincomycin is included in the treatment of infection originating from the intestinal tract.


"Topical nephropathy" and "tropical extramembranous glomerulonephritis" of unknown aetiology in Senegal. A study of renal biopsy specimens obtained in Senegal from 24 children and six adults with nephrotic syndrome showed two unusual varieties of nephropathy--namely, an extramembranous glomerulonephritis associated with hypocomplementaemia (four cases), a combination previously described only in systemic lupus erythematosus, and a "tropical nephropathy" (16 cases). The latter, though lacking the diffuse glomerular deposits of immunoglobulin described in quartan malarial nephropathy (Q.M.N.), showed a curious progressive and segmental glomerulosclerosis, characterized by a "flaking" or fibrillary splitting of the glomerular capillary wall, seen in Q.M.N. Serological evidence of malaria was lacking in a third of the childhood cases.


Mitigation of amphotericin B nephrotoxicity by mannitol. Renal transplant recipients are susceptible to a number of fungal infections amenable to therapy with amphotericin B, but azotaemia is an almost invariable sequel to the use of this agent. As intravenous mannitol has been shown to minimize nephrotoxicity induced by amphotericin B in dogs we treated four kidney transplant recipients who had systemic fungal infections with mannitol and amphotericin B. None showed significant reduction in renal function though a mild metabolic acidosis did develop.


First results of a randomized clinical trial of fast neutrons compared with X or gamma rays in treatment of advanced tumours of the head and neck. Report to the Medical Research Council. Results of the first randomized clinical trial to compare the effects of fast neutrons and those of x or gamma rays (photons) in treating patients with advanced tumours of the head and neck are reported. In 37 out of 52 patients treated with neutrons and 16 out of 50 treated with photons the local tumour completely regressed; the tumour later recurred in nine of the 16 photon patients but in none of the 37 neutron patients. The advantages to the neutron-treated patients were seen in tumours of well and poorly differentiated histology and in each site. Complications after treatment did not differ significantly between the groups. Despite these substantial differences in local control of the tumour there were no significant differences in mortality between the series. A detailed study of the effective doses and the response of tumours and normal tissue in each series indicated that the improved results from neutron therapy were due to differences in the biological quality of the beam and not to the rather higher average effective dose in the neutron series. To assess the long-term effects of neutron treatment patients in earlier stages of disease and with smaller tumours should be included in the next phase of the trial.


Use of computer program for diagnosing jaundice in district hospitals and specialized liver unit. A computer-assisted model for diagnosing jaundice has been adapted for use on the University of London C.D.C. 7600 computer via an on-line terminal at King's College Hospital to provide a rapid turn-round time. The model was used prospectively in the diagnosis of 219 patients--135 seen in a specialized liver unit and 84 seen in one of four district hospitals in south-east London--with an overall accuracy in distinguishing among 11 different causes of jaundice of 69% and 62% respectively. These figures rose to 77% and 88% respectively when only those patients in whom the final diagnosis reached a "certain" probability were considered. When used to distinguish between a medical and a surgical cause of jaundice the accuracy was 86% in the liver unit and 77% in the district hospitals, rising to 95% in both series for those with a diagnosis of certain probability. The proposed improvements to the model--namely, the use of two deparate data bases and more diagnoses within the matrix--should be improve the accuracy even further. In practice the rapid feedback to the clinicians looking after patients provided help in managing difficult cases.


Use of biochemical profile in children's hospital: results of two controlled trials. Two controlled trials of the use of a biochemical profile were conducted in a childern's hospital to see whether the profile led to diagnoses which would not otherwise [have been made and to see what effect it had on the number of extra  requests for pathololgical investigations and the length of stay in hospital]. Altogether 2816 children were examined and 13 new diagnoses made. There was a significant increases in the total number of pathorequests but the profile did not alter the length of stay in hospital. We conclude that the profile mad only a small contribtuion to the overall care of the pateints.


Diagnosis of gastric cancer.

Diagnosis of gastric cancer. A prospective comparison was made of the accuracy of different diagnostic methods for gastric cancer. The basis of the study was a consecutive series of 113 patients thought to have gastric pathology; cancer was the final diagnosis in 32. Endoscopy and radiology were the most accurate investigations, whereas biopsy, cytology, and clinical examination gave disappointing results. A wide range of clinical features and laboratory investigations were studied in all patients in an attempt to identify criteria suggestive of malignancy. Multifactorial computer analysis of these investigations failed to improve upon the radiological diagnosis. A systemic approach designed to make optimal use of limited endoscopic and histopathological resources in the diagnosis of gastric lesions is presented.


Comparative trial of nafoxidine and ethinyloestradiol in advanced breast cancer: an E.O.R.T.C. study. A randomized clinical trial of nafoxidine, a non-steroidal oestrogen antagonist, and ethinyloestradiol in postmenopausal patients with advanced breast cancer produced objective remissions in 31% of 49 women receiving nafoxidine and in 14% of 49 receiving ethinyloestradiol. The differences in remission rates was almost significant (0.05 less than P less than 0.10). Life-threatening complications were more frequent with ethinyloestradiol than with nafoxidine but the latter produced specific toxic reactions on skin and hair that may limit its practical usefulness. Synthetic oestrogen antagonists may occupy a privileged place in the treatment of breast cancer, and other representatives of this new class of compounds should be accurately assessed in randomized clinical trials.


Controlled clinical trial of L-dopa and nafoxidine in advanced breast cancer: an E.O.R.T.C. study. L-Dopa lowers plasma prolactin levels, and there have been reports that patients with advanced breast cancer have been successfully treated with L-dopa. To test the potential value of L-dopa in this disease a randomized clinical trial of L-dopa and nafoxidine (as the reference compound) was conducted in postmenopausal women with advanced breast cancer. Objective remissions were obtained in sever out of 36 patients (19%) treated with nafoxidine but in none out of 40 patients treated with L-dopa. L-Dopa in the dose schedule used seems to be ineffective in advanced breast cancer.


Duration of treatment for urinary tract infections in children. In a double-blind trial 45 children aged 6 months to 14 years with Escherichia coli infections of the urinary tract were given co-trimoxazole for two weeks and then allotted at random to one of two treatment groups for the remainder of six months; one continued with the active drug and the other with dummy tablets of identical appearance. Of the 24 children who took co-trimoxazole for two weeks and the 21 who took it for six months, 11 and 10, respectively, remained without further infections for at least a year. Over 90% of the reinfections occurred within five months of stopping the antibiotics, and the longer treatment did not cause any delay in their appearance. Thus probably a six-month course of treatment is no more likely to achieve a cure than a two-week course; nevertheless, no infection occurred during treatment, and there may be an advantage in continuing with antibiotics in small dosage.


Indomethacin--aspirin interaction: a clinical appraisal. Plasma profiles of indomethacin after a 50-mg oral dose were constructed in six healthy volunteers before and after a week of aspirin treatment. Aspirin did not interfere with indomethacin plasma levels. To examine the clinical effect of concurrent indomethacin and aspirin treatment 20 patients with seropositive rheumatoid arthritis were given indomethacin 100 mg/day, aspirin soluble 4 g/day, and the two drugs taken together in random order. Analysis of the clinical indices of inflammation--articular index and mean pain score--and of the efficacy of each treatment showed no significant differences between the three treatment groups. With the proliferation in the number of anti-rheumatic drugs available, the case for giving two or more nonsteroidal anti-inflammatory drugs concurrently remains unproved.


Prophylactic fluoride treatment and aged bones. In a double-blind trial with monofluorophosphate (25 mg fluoride per day) given to 460 aged persons (237 treated, 233 control) for eight months no difference was observed in height, admission to hospital, or mortality. Fractures and exacerbation of arthrosis were more frequent in the fluoride group. Vertebral x-ray films showed no difference. The free ionized fluoride levels in the plasma of the fluoride-treated group were still twice as high two months after treatment ended. Fluoride treatment in the prophylaxis of osteoporosis is not recommended unless there is simultaneous measurement of plasma ionized fluoride levels.


Cryptococcal meningoencephalitis.

Cryptococcal meningoencephalitis. A patient was admitted to hospital with an apparent psychiatric disturbance. When she became stuporous the cerebrospinal fluid was cultured but proved sterile. The latex test showed that serum was positive for cryptococcal antigens, and cryptococcal meningoencephalitis was diagnosed. Amphotericin B was given but when she developed a toxic reaction it was replaced by flucytosine. She responded well to flucytosine alone and no side effects appeared on continued treatment. Cryptococcal meningitis may present as a psychiatric disturbance, and serological tests are invaluable aids to diagnosis.


Use of clomiphene and luteinizing hormone/follicle stimulating hormone-releasing hormone in investigation of ovulatory failure. A luteinizing hormone/follicle-stimulating hormone-releasing hormone (LH/FSH-RH) test was performed in 70 women with amenorrhoea or anovulatory infertility, or both, and a clomiphene stimulation test was also performed in 24 of these patients. Most patients responded to LH/FSH-RH with significant increases in LH and FSH. In women with gonadal dysgenesis or premature ovarian failure exaggerated responses were observed after LH/FSH-RH and there was no change in high basal LH levels after clomiphene. Patients with absent or impaired responses to LH/FSH-RH failed to respond to clomiphene. All patients with anovulatory menstrual cycles responded to both LH/FSH-RH and clomiphene, while seven out of 13 amenorrhoeic patients with a normal LH/FSH-RH response showed an early LH rise during clomiphene treatment and six were unresponsive. These results suggest a difference between the two groups at hypothalamic level with consequent therapeutic implications.


A study of yaws among pygmies in Cameroon and Zaire. In a survey of 333 pygmies in the Cameroon 4.5 percent. were found to have clinical evidence of yaws. This was also found in 10 per cent. of the inhabitants of camps in Zaire. The results of VDRL and FTA-ABS tests on a sample of the population are presented. These provide evidence of a very high incidence of treponemal disease, 80 to 90 percent. of the population showing serological evidence of infection. Active transmission is taking place in both areas but more frequently in Zaire.


Failure to infect gnotobiotic colostrum-deprived, and normal piglets with Treponema pallidum (Nichols). Normal piglets kept at 16 degrees C. and gnotobiotic piglets kept at 32 degrees C. rapidly destroyed Treponema pallidum, while gnotobiotic piglets kept at 26 degrees C. showed slightly slower clearance. No infections were established. The high body temperature of the piglets has an important influence on the survival of T. pallidum.


Non-specific urethritis and the tetracyclines. The possible aetiological factors in non-gonococcal and non-specific urethritis are reviewed. The response of NSU to various courses of different tetracycline drugs is assessed. Prolonged courses of treatment did not give better results than shorter courses. When reviewing the infective aetiology of non-gonococcal urethritis, it was noted that more than one organism (or potential pathogen) would be present in many cases. It is therefore surmised that there may be at times a mixed aetiology and at other times a truly non-specific aetiology. Isolations by different workers have indicated that the following organisms might be expected: Chlamydia 40 per cent.; Mycoplasma-M. hominis 20 per cent., T-strain over 60 per cent.; Trichomonas 15 per cent.; Candida possibly over 5 per cent. Truly non-specific urethritis may account for 25 to 30 per cent. of cases.


An additional silver impregnation method for demonstration of degenerating nerve cells and processes in the central nervous system. A new silver impregnation technique for frozen and paraffin sections of formalin-fixed nervous tissue has been devised by modifying the Fink-Heimer14 and De Olmos-Ingram6 methods. The modified versions have been combined into a single staining procedure. Cobalt or lead nitrate are substituted for uranyl nitrate. Silver nitrate in the impregnating solution is replaced by silver lactate or protargol. This procedure results in a preferential impregnation of degenerating perikarya, dendrites, axons and synaptic endings. It affords a more complete impregnation of 'preterminal' axonal arborizations than previous methods. The method is effective for the demonstration of degenerating terminals in the rat cerebellar cortex. Emphasis has been laid on the usefulness of the method for the study of drug-induced CNS lesions.


A method for prevention of cardiovascular reactions to laryngoscopy and intubation. A technique of nebulizing lidocaine in the upper airways was developed and its effectiveness in preventing cardiovascular responses to laryngoscopy and intubation was documented. In ten pre-treated patients the average percentage-rise in systolic blood pressure was 10.3 per cent and there were no arrhythmias. The pulse rate increased by 16.8 per cent. In ten control patients, the systolic blood pressure increased by 56 per cent and the incidence of arrhythmias was 40 per cent. The pulse rate increased by 38.8 per cent. The significance and application of these results is discussed and compared to other available methods. The opinion is expressed that the effect of the aerosol, especially as it relates to the suppression of arrhythmias, is partly due to systemic absorption of lidocaine.


The effects of continuous positive pressure ventilation on pulmonary oedema, gas exchange and lung mechanics. The effect of continuous positive pressure ventilation was studied in 23 dogs in whom pulmonary oedema was induced by rapid intravenous infusion of dextran 40. CPPV slowed but did not prevent the formation of oedema. CPPV prevented or reversed the formation of liver-like areas in the dependent lobes, maintaining the oedematous lung compliant and aerated. This led to a reduction of shunt and an increase in PaO2. The use of CPPV decreased cardiac output and body oxygen consumption. Mixed venous oxygen tension was higher in dogs ventilated by CPPV and these dogs tolerated fulminant frothy oedema without distress.


Serum free fatty acid and blood sugar levels in children under halothane, thiopentone and ketamine anaesthesia (comparative study). Serum free fatty acid and blood glucose levels were determined in 30 children under halothane, thiopentone and ketamine anaesthesia. Blood sugar is increased above baseline values by halothane 54.75 per cent (+++), thiopentone 71.7 per cent (++++) and ketamine 12.2 per cent (+) anaesthesia. Serum free fatty acid was increased during halothane 58.7 per cent (+++) and thiopentone 34.4 per cent (++) anaesthesia, but was decreased with ketamine anaesthesia 13.4 per cent (-). It is assumed that several factors contribute to these changes and are related either to the sympathetic nervous system or basal metabolism and to the specific actions of each drug.


Post-operative epidural analgesia: effects on lung volumes. A study was undertaken to assess the role of post-operative pain in reducing Functional Residual Capacity (FRC) and Vital Capacity (VC). The efficacy of post-operative epidural analgesia in reversing these changes was measured in eight subjects after upper abdominal operations. With pain, FRC and VC were 78 per cent and 37 per cent of control respectively. Following epidural analgesia, the values were 84 per cent and 55 per cent. These figures indicate the pain component in the post-operative reduction of these two lung capacities. This partial restoration may be of value in the prevention of post-operative pulmonary complications by avoiding closure of small airways during tidal breathing and by increasing the effectiveness of deep breathing and coughing in the removal of secretions and the reversal of atelectasis.


Poly IC therapy in aleutian disease of mink. Twenty-four virgin female aleutian mink were infected with aleutian disease agent and after 24 hours, 12 of these were treated with a course of polyinosinic acid-polycytidilic acid (Poly IC) injections. After six weeks the gammaglobulin level was significantly lower in the treated group but at 12 weeks this difference was no longer present. Four of the treated mink had normal target organ histology when killed at 20 weeks. The untreated group all showed moderate to marked changes but this difference was not statistically significant. There was a marked increase in the reactive lymphocyte blastogenesis index during the first weeks of infection and the phytohaemagglutinin response was seen to fall progressively. The antiglobulin reaction usually became positive after infection but neither antinuclear nor antierythrocyte antibodies were found. Precipitating antibodies to several polynucleotides were frequently present and were unrelated to infection or to Poly IC treatment.


Evacuated blood-collection tubes--the backflow hazard. Five cases of nosocomial infection caused by Serratia marcescens were traced to backflow of blood from nonsterile evacuated blood-collection tubes. The mechanism of backflow was investigated theoretically and the conditions were determined under which backflow can occur. The theory was confirmed by experiments conducted on a simulated venous system and by measurements of the venous pressure in the brachial vein of a patient during application and removal of a tourniquet. Various possible solutions to the backflow hazard include strict adherence to correct venipuncture technique, sterilization of all blood-collection tubes, improvement of the vacuum in the tubes and incorporation of a check valve into the system.


Beclomethasone dipropionate in asthma.

Beclomethasone dipropionate in asthma. Beclomethasone dipropionate aerosol therapy can replace or diminish systemic corticosteroid therapy in the majority of asthmatics. In a clinical trial of 41 patients with perennial asthma, the 10 who had not required long-term corticosteroid therapy improved symptomatically and in pulmonary function. Of the 31 who had required prolonged systemic corticosteroid therapy 12 were able to discontinue oral prednisone therapy, 15 were able to decrease the maintenance dose of prednisone and only 4 were unable to decrease the dose; all maintained satisfactory lung function and some showed improvement. Discontinuation of systemic corticosteroid therapy was accomplished more readily in patients whose daily maintenance dose was less than 15 mg and who had been taking the drug for less than 3 years. Side effects consisted of a "dry throat" in seven patients, two of whom had throat infections with Candida albicans. Recurrence of rhinitis after discontinuation or reduction of systemic corticosteroid therapy was noted in 11 patients.


The permanent Tenckhoff catheter for chronic peritoneal dialysis. Over a 3 1/2-year period the permanent Tenckhoff catheter was used in 66 patients (32 men and 34 women) maintained on chronic peritoneal dialysis for periods from 2 1/2 to 36 1/2 months; 57 patients had dialysis in hospital for 20 to 24 hours twice a week and the other 9 had dialysis at home for 10 to 12 hours four times a week. While the Tenckhoff catheter was in place 14 patients received a renal transplant; for 13 who required peritoneal dialysis during the post-transplant phase the Tenckhoff catheter was used. In nine patients abdominal surgery did not interfere with the continuation of peritoneal dialysis via the Tenckhoff catheter. From a total of 5067 dialyses 40 positive cultures were reported (0.8%). Peritonitis was clinically evident on only 14 occasions (0.28%). Permanent catheter obstruction developed in 16 patients, in 11 of whom it was related to peritonitis. With the introduction of the permanent Tenckhoff catheter long-term peritoneal dialysis has become a simple, safe and painless procedure, suitable for virtually all patients who require maintenance dialysis.


Compartments and cell flows within the mouse haemopoietic system. II. Estimated rates of interchange. Part-body irradiated CBA mice were injected with CBA-T6 bone marrow. In this way a predominantly donor population was established in the femora while the marrow of the humeri remained largely (average 94%) of host origin. In animals examined cytologically up to 2 years later, no tendency was observed for the proportion of donor cells in the humeri to increase. Splenectomy had no effect on this. When femoral bone marrow from the experimental mice was injected into lethally (whole-body) irradiated recipients, cells originating from the primary host repopulated the lymph nodes to a disproportionate extent. Equilibration between the cell populations of femora and humeri occurred after re-exposure to 600 rad whole-body irradiation, but not after 100 rad or 350 rad; thus, regeneration of damaged bone marrow involved a significant contribution from extrinsic stem cells only after the highest dose of radiation. The data are compatible with an inflow of at most ten effective stem cells per humerus per day from the blood, and suggest a much lower figure. This means that few if any of the stem cells of peripheral blood enter the bone marrow and found haemopoietic clones. Evidence is adduced for the existence of a proliferating lymphoid sub-population in the bone marrow, contributing some 5-10% of the observed mitoses. The mitotic cells in the lymph nodes are replaced from marrow-derived progenitors at an estimated rate of 4-5%/day. The relevant data for the thymus are more variable, but suggest an average figure of 8-11%/day. Earlier data from mouse parabionts suggest a lower rate of inflow to the thymus.


Recognition sequences of repressor and polymerase in the operators of bacteriophage lambda. Nucleotide sequences in two wild-type and six mutant operators in the DNA of phage lambda are compared. Strikingly similar 17 base pair units are found which we identify as the repressor binding sites. Each operator contains multiple repressor binding sites separated by A-T rich spacers. Elements of 2 fold rotational symmetry are present in each of the sites. Superimposed on each operator is an E. coli RNA polymerase recognition site (promoter). Similarities in the sequences of the two lambda promoters, a lac promoter, and an E. coli RNA polymerase recognition site in SV40 DNA are noted.


Effect of 5-bromodeoxyuridine on the transcriptional properties of the genome in WI-38 human diploid fibroblasts. Growth of WI-38 diploid fibroblasts in a medium containing 5-bromodeoxyuridine (BrdU) resulted in an increased GMP and a decreased AMP incorporation into the RNA synthesised in vitro on a chromatin template. This effect was similar to that previously reported using 3T6 mouse fibroblasts-1. Substitution of thymidine by BrdU in DNA, also altered the characteristics of the DNA template itself, since the increased incorporation of guanine and decreased incorporation of adenine into RNA were evident also when purified, isolated DNA was used as template. The extent of replacement of AMP by GMP was proportional to the extent of replacement of thymidine by BrdU. Although there are variations in the base composition of RNA transcribed from BrdU-containing DNA templates, there are no significant difference in overall template activity or in the number of available chromatin binding sites for E. coli RNA polymerase. Confluent monolayers of BrdU-treated WI-38 fibroblasts are still able to respond with cell proliferation to a change of medium, as evidenced by an increased incorporation of (-3H)thymidine and an increase in chromatin template activity. The length of the prereplicative phase is similar in both BrdU-treated and untreated cells, although the magnitude of the increase of (-3H)thymidine incorporation is reduced by approximately 30% after BrdU treatment. The increase in chromatin template activity is associated with an increase in the number of chromatin binding sites for E. COLI RNA polymerase, suggesting that the presence of BrdU does not interfere with the availability of initiation sites or alter the actual rate of transcription.


The interaction of natural tetra-azacyclopentazulene dyes with DNA and their effects on the DNA and RNA polymerase reactions. The interaction of two natural tetra-azacyclopentazulene dyes with native calf thymus DNA was studied by means of microcalorimetric, viscosimetric, and spectroscopic measurements. The results are consistent with the hypothesis of an intercalative-binding. However, comparison of calorimetric studies shows that the changes in enthalpy associated with the interaction of these compounds with DNA are, in absolute value, significantly lower than those found with known intercalating agnets (daunomycin, ethidium bromide).  The influence of these dyes on the template capacity of DNA in the in vitro synthesis of nucleic acids was also determined.  Under the conditions used, these compounds selectively inhibited DNA synthesis.  No appreciable inhibitory effect upon E. coli RNA polymerase was observed.  Both compounds had greater inhibitory effect on rat liver high molecular weight DNA polymerase than E. coli DNA polymerase I.  Zoanthoxanthin was a more effective inhibitor than 3-norzoanthoxanthin.


The effect of intracoronary injection of contrast medium upon coronary blood flow. The changes in coronary blood flow in response to intracoronary injection of 3 ml of 76% Renografin were studied in 47 patients using the thermodilution technique for continuous measurement of coronary sinus blood flow. Within seconds after left coronary injection, an increase in coronary sinus flow began which peaked at an average of 53% above control in 5-10 seconds. There was a corresponding decrease in coronary resistance. Flow returned to control level in almost all patients within one minute of injection. Twenty-four of 35 patients had no change in coronary sinus flow in response to right coronary injection. This can be explained by the fact that most of the venous flow from the right coronary artery returns in such a way that it cannot be measured by the coronary sinus catheter. Of the eleven patients who did show an increase, seven had angiographically documented right to left collaterals, suggesting that the increase in flow was the result of vasodilatation of the left coronary bed by contrast arriving via the right to left collaterals. The percent changes in flow and resistance in response to left coronary injection were isgnificantly greater in the 13 normals than in the 34 with obstructive disease of the left coronary artery (P lessthan 0.01). Flow rose 70 plus or minus 27% (mean plus or minus standard deviation) in the normals versus 46 plus or minus 25% in the patients with coronary artery disease, while resistance fell 44 plus or minus 9% versus 33 plus or minus 11%. The differences, however, were not sufficient for these changes to be of value in the assessment of the degree of impairment of the coronary arterial bed in the individual patient.


Treatment of nasal polyps with intranasal beclomethasone dipropionate aerosol. In a double-blind trial thirty-five patients with moderately-severe nasal polyposis were treated with intranasal beclomethasone dipropionate aerosol for 3 weeks. The dose given (400 mug/day) had only local effect on the symptoms. Judged by diary card scores the nasal symptoms were reduced to 52% of the pre-trial level for the whole group. Corrected for the placebo effect the percentage was 68. The reduction of symptoms was equally apportioned to the three symptoms, sneezing, nasal secretion and blockage. The treatment was tolerated well, and it is concluded that intranasal treatment with beclomethasone dipropionate aerosol offers most patients with nasal polyps a good response without any risk of systemic steroid side-effects.


Incidence of serum anti-DNA precipitins in patients with systemic lupus erythematosus by counterimmunoelectrophoresis. The technique of counterimmunoelectrophoresis (CIE) has been adapted for detection of serum precipitins to calf thymus (CT) DNA in patients with SLE, discoid LE, miscellaneous connective tissue and infectious diseases, and control populations. Of seventy-eight LE patients, 58% demonstrated anti-ss DNA precipitins, and 20% exhibited anti-ds DNA precipitins. Good correlation was noted between the presence of ss DNA precipitins and ss DNA binding values determined by the more sensitive ammonium sulphate precipitation assay. Depressed total serum haemolytic complement activity in CH50 mu/ml was noted in 64% of sera exhibiting ss DNA precipitins and 38% of those with negative ss DNA precipitins. There was a strong association, however, between ds DNA precipitins and depressed serum complement levels. Although less sensitive than primary binding assays, CIE can be used as a rapid and simple screening test for detection of circulating anti-native and denatured CT DNA precipitins. CT DNA serum precipitins are present in a significantly higher percentage of SLE patients when compared with other disease states and normal control populations.


Investigations of allergic status and blood counts in Chinese patients receiving daily or intermittent rifampicin in Hong Kong. In a controlled trial in Hong Bong, 575 Chinese patients with pulmonary tuberculosis whose treatment with first-line regimens had failed were allocated at random to the following retreatment regimens of chemotherapy. (1) Rifampicin plus ethambutol daily (ER7). (2) Rifampicin plus ethambutol twice a week (ER2). (3) Rifampicin plus ethambutol once a week (ER1). (4) Rifampicin plus ethambutol daily for 2 months and then once a week (ER7ER1). (5) Ethionamide plus pyrazinamide plus cycloserine daily for 6 months and then ethionamide plus pyrazinamide daily (EtZC), as a control regimen. Answers to a questionnaire on allergic disease, the results of prick tests with standard allergens, ABO blood grouping, size of tuberculin response during chemotherapy, and a rifampicin patch test showed no associations with the occurrence of adverse reactions to daily or intermittent rifampicin. Mantoux testing during chemotherapy provided no evidence of an immunosuppressive effect of rifampicin. Mean platelet counts at 12 months were significantly lower than those at 3 months on the two once-weekly regimens (ER1, ER7ER1) and on the control regimen (EtZC), although still within normal limits. At 3 months, but not at 12 months, mean platelet counts on the two once-weekly regimens were significantly lower 6 hr after a dose of the regimen than they were before the dose.


A computer-oriented linkage analysis scheme. A comprehensive, computer-oriented scheme for genetic linkage analysis is described. It computes the likelihood of a complex pedigree allowing for many non-standard features including multiple alleles (up to four per locus), multiple mates, more than one mating in the eldest generation, consanguinity, missing or partially tested persons, and different recombination fractions between males and females. The program works by computing weighted likelihoods in a vertical, descending fashion. First, the set of possible genotypes for the members of the eldest generation is determined and prior probabilities assigned to these states of nature (based on gene frequency calculations). Phenotypic information is used to modify these probabilities in the standard manner. Then, for a particular set of genotypes, the conditional likelihood of the remainder of the pedigree is computed. This calculation may itself be many-branched and therefore a computer is necessary to keep track of the stages of the process. When the youngest generation has been taken into account, a final likelihood is determined, reflecting all information in the pedigree. The current version of the program successfully calculates the exact likelihood of a complex pedigree which was designed to exploit the non-standard features of the program. It has also computed likelihoods for a published pedigree, and the results are essentially equal to those obtained by the other authors using a previously available computer scheme for linkage analysis.


Serum proteins as indicators of poor dietary intake in patients with chronic renal failure. A study of serum proteins in patients on regular hemodialysis has shown that many have low serum transferrin levels but near normal serum albumin and normal or raised pre-albumin levels. Hemoglobin values were related to transferrin levels. Low transferrin levels also occurred in patients with advanced osteitis fibrosa. Deficient protein intake seems the likely explanation. Measurement of pre-albumin does not reflect low protein intake in chronic renal failure; reasons for this discussed.


Effect of equivalent antihypertensive doses of mefruside and cyclopenthiazide on serum electrolytes, uric acid and glucose tolerance in hypertensive patients. 1. A comparative cross-over trial of mefruside and cyclopenthiazide, each drug being given for 6 weeks, was conducted on thirty hypertensive patients with diabetes mellitus or impaired glucose tolerance. Other antihypertensive therapy, any antidiabetic therapy and potassium supplementation were kept constant throughout the trial. Dosages of mefruside and cyclopenthiazide were adjusted to give approximately equal blood pressure levels in the two drug periods. 2. There was no significant difference in the following parameters studied during the sixth week of each of the two periods of drug therapy: serum electrolytes, total CO2, chloride, urea, amylase, haemoglobin, erythrocyte sedimentation rate, platelet and white blood cell counts, lying and standing blood pressure and pulse rate, weight, fasting and 2-h glucose and insulin levels and five-value glucose and insulin curve areas, fasting calcium and phosphate. 3. Serum creatinine and uric acid showed a small but significant fall during mefruside therapy.


A comparative evaluation of three high efficiency disposable dialyzers. Until recently all disposable dialyzers have had a poorer overall performance than the best non-disposable dialyzer, the Meltec multipoint. The three disposables considered here (Gambro Lundia Nova, Cordis HFAK 4 and Rhone Poulenc RP 5) all have clearance of small molecules close to or, for the HFAK 4, just above that of the multipoint though their middle molecular clearance is not quite as good as the multipoint. The HFAK 4 has a better basal ultranfiltration rate but a poorer maximum ultrafiltration capacity. The RP 5 has a higher residual blood volume than the multipoint. In other respects the dialyzers are almost interchangeable and are reasonable alternatives to the multipoint in those centers which can afford single use disposable dialyzers.


Rejection episodes and patient and graft survival after renal transplantation. The occurrence of acute rejection episodes following renal transplantation was correlated with one-year patient mortality and graft failure rates in a series of 102 consecutive transplant recipients. Twenty-one patients had two or more rejection episodes in the first two months post transplantation; 17 of these expired or lost their kidney compared to only 5 of 28 patients with no rejection episodes in this time period. Similarly, of the 14 patients who developed a second rejection episode 2--6 months post transplantation, 8 died or lost the graft compared to only 2 of 21 patients who had no rejection episodes in this time period. Thus, the development of a second rejection episode early after transplantation necessitating treatment with high dose prednisone therapy carries an ominous prognosis and suggests that serious consideration must be given to graft removal and subsequent retransplantation.


5-Fluorocytosine treatment of candidiasis on a patient receiving regular hemodialysis. A patient developed a severe urinary infection with Candida albicans following a cadaveric renal transplant operation. It was necessary to remove the graft and return the patient to regular hemodialysis treatment. The fungi infection was successfully eradicated by a single oral dose of 5-Fluorocytosine (20 mg/kg) after each dialysis treatment. Pharmacokinetic studies revealed that the drug had a dialyzate clearance ratio of 0.66 when compared with creatinine; the drug was not metabolized and there was no other route of elimination.


Amniocentesis.

Amniocentesis. The indications, technique, and potential complications of the now commonly used obstetric procedure, amniocentesis, have been reviewed. Although amniocentesis is considered by many a routine and a very safe procedure, there are potential complications, especially for the fetus, but for the mother as well. The frequency of these complications can be reduced by meticulous attention to technique and especially by preliminary placental localization. The latter is probably best accomplished by the ultrasound B scan. Because there are potential complications, the indications and timing of amniocentesis must always be carefully weighed before it is carried out.


Tumors of the hand.

Tumors of the hand. A review of 129 hand tumors suggests that diagnosis of a swelling in the hand is often uncertain because of the close proximity of many different tissues in a small volume. Histologic diagnosis is necessary to assure appropriate treatment; excisional biopsy should be done whenever possible; if the lesion is benign, treatment has been completed; in the event the lesion is malignant, further treatment will not have been materially compromised. The margin of normal tissue around malignant lesions often precludes treatment of such tumors of the hand by ray resection or wide local excision because adequate wide excision will frequently leave nothing functional. Attempts at wide local excision are ofter compromised by the surgeon's natural desire to preserve function; this frequently results in incomplete removal of the tumor. The function preserved will be of little benefit to a patient with widespread metastases.


Somatomedin.

Somatomedin. Somatomedin is a peptide component of serum which has been postulated to mediate the action of growth hormone on skeletal tissue. Direct effects on cartilage include stimulation of the synthesis of mucopolysacharide, protein, and nucleic acids. Insulin-like effects on non-skeletal tissues and cells have been described, and a relationship to NSILA-S and MSA has been suggested. The liver may be an important source. Non-specificity of bioassays is a problem. Growth hormone deficiency, malnutrition, therapy with corticosteroids or estrogens, and a type of dwarfism characterized by high serum growth hormone are associated with decreased somatomedin. An unexplained phenomenon is the normal somatomedin with low or undetectable growth hormone in certain cases of craniopharyngioma or other tumors involving the hypothalamus. Somatomedin is increased in acromegaly.


Immunology of cartilage in septic arthritis. Septic arthritis in one knee joint was produced in 18 rabbits, the contralateral knee being left intact. Sections stained with fluorescein conjugated anti-IgG and with fluorescein conjugated anti-IgM showed layers of immunoglobulins on the articular cartilage in 16 out of 17 injected joints, and 10 out of 17 supposedly "normal" knee joints. Concurrent tests for circulating anti-staphylococcal alpha-lysin gave negative results. Cultures of synovial fluids were negative. These observations suggest that articular cartilage may act as an auto-antigen; immunological mechanisms involved may be due to the combined activity of both cell-bound and humoral antibodies. There are 2 components to a septic arthritis, the primary being a bacterial and the secondary immunologic in nature.