[Repeated sampling of rat polymorphonuclear leucocytes from the pleural cavity. Application for the study of leucocyte chemotaxis (author's transl)]. A method is described for allowing the sampling of a homogeneous population of polymorphonuclear cells (PMN) from the rat pleural cavity a well as a technique involving the use of a phase-contrast microscope and video-recording system to study the necrotaxis of rat PMN towards a single erythrocyte lysed by ruby-laser irradiation. This allows both the speed of the leucocytes and the degree of their chemotactic response to be determined. The advantages and disadvantages of the experimental technique are discussed along with its application to the study of in vitro and in vivo actions of various drugs on rat PMN chemotaxis.


[Morphology and deformability of erythrocytes in muscular dystrophy]. In recent years, the presence of red cell morphological abnormalities in patients with Muscular Dystrophy has made the object of numerous, often contradictory reports. A possible source of such confusion may lie in the fact that human erythrocytes are extremely sensitive to morphologic transformations resulting from various manipulations or environmental conditions in vitro. We have examined the morphology and deformability of erythrocytes from 7 patients with Duchenne and 9 patients with Steinert (myotonic) Muscular Dystrophy. To avoid preparation artifacts, fresh, unwashed red cells suspended in their own plasma were examined under phase contrast microscopy for the presence of either echinocytes and stomatocytes. Deformability was measured by filtration of dilute cell suspensions at constant flow rate through nucleopore membranes (nominal pore diameter = 3 micron). No significant difference was found between the patients' cells and those of 22 healthy volunteer controls. We conclude that previously reported abnormalities may have been the result of preparation artifacts. It appears possible, however, that erythrocytes from Muscular Dystrophy patients may be more sensitive than normal ones to certain stimuli originating from red cell manipulations in vitro.


[Materno-foetal transfer of anti-HLA antibodies. Study by using LDA test (author's transl)]. The LDA test was used to study the materno-foetal transfer of anti-HLA antibodies. The results were compared with those obtained earlier by the complement dependent lymphocytoxicity test (CdL). Although more sensitive than CdL, the LDA test did not demonstrate more maternal antibodies in cord blood when these antibodies corresponded to the child's paternal antigens. Nevertheless LDA demonstrated antibodies did not always behave similarly to those seen by CdL.


Characterization of a cloned ribosomal fragment from mouse which contains the 18S coding region and adjacent spacer sequences. The large EcoRI fragment of mouse ribosomal genes containing parts of the non-transcribed spacer, the external transcribed spacer located at the 5' end of the precursor molecule and about two thirds of the 18S sequence has been cloned in bacteriophage lambda  gtWES. A physical map of the DNA was constructed by cleavage with several restriction endonucleases and hybridization of the restriction fragments of the recombinant DNA with labelled 18S and 45S rRNA. The orientation of the inserted fragment as well as the length of the 18S sequence was determined by electron microscopy of R-loop containing molecules. The absence of hybridization of the cloned fragment to other fragments in the genome shows that the non-transcribed spacer does not have a significant length of sequences in common with other sequences in the genome.


Role of ribothymidine in the thermal stability of transfer RNA as monitored by proton magnetic resonance. In order to elucidate the functional role of the modified uridines at position 54 of tRNA, the 270 MHz high-field proton NMR spectra of methionine tRNAs from E. coli, from a mutant thereof, and from T. thermophilus, containing ribothymidine, uridine and 2-thioribothymidine, respectively, have been measured as a function of temperature. A comparison of the NMR melting profiles of the minor nucleosides from these tRNAs shows that the melting temperature of uridine containing tRNA is 6 degrees C lower than that of the wild type tRNA whereas that of the 2-thioribothymidine tRNA is 7 degrees C higher than that of the wild type tRNA. These results, therefore, demonstrate that these modifications serve for stabilization of the tertiary structure of tRNA.


The binding of tyrosinyl-5'-AMP to tyrosyl-tRNA synthetase (E.coli). The binding between tyrosyl-tRNA synthetase (E.coli) and the alkylanalogue of the aminoacyladenylate, tyrosinyl-5'-AMP, has been investigated by fluorescence titrations and rapid mixing experiments. Tyrosyl-tRNA synthetase has two equivalent and independent binding sites for tyrosinyl-5'-AMP. The intrinsic binding constant is 4 x 10(7)M-1. The binding sites for tRNATyr and tyrosinyl-5'-AMP are independent of each other, the anticooperative mode of tRNA binding being preserved in the presence of tyrosinyl-5-AMP.


The regulatory region of MS2 phage RNA replicase cistron. IV. Functional activity of specific MS2 RNA fragments in formation of the 70 S initiation complex of protein biosynthesis. The initiation region of the MS2 replicase cistron can be isolated as a fragment 59 bases in length protected from RNAase by the binding of the coat protein which serves as a translational repressor. This fragment MS2 R(-53 leads to 6) starts 53 bases before the initiation codon and retains full activity in binding ribosomes. We have investigated the functional activity in initiation of a series of fragments from this region variously shortened from the 5'-end. Ribosome protected fragments starting 17 or 21 bases before the AUG are unable to rebind to ribosomes. The shortest fragment which has this activity was produced by partial S1 nuclease digestion and starts 33 to 35 bases before the AUG. The initiation signal comprises some nucleotides between 21 and 33 bases before the initiation codon and the regulatory region responsible for initiation is longer than that protected by the ribosome in the final initiation complex.


Max-Planck-Institut für Molekulare Genetik, Abteilung Wittmann, Berlin-Dahlem, GFR. It is well established that when E. coli 30S ribosomal subunits are irradiated with ultraviolet light under mild conditions a specific cross-link is formed between protein S7 and the 16S RNA. Methodology is presented for the analysis of the single nucleotide residue concerned in this cross-link. Firstly, the identity of the ribonuclease T1 octanucleotide attached to S7 is confirmed by a new method, which involves isolation and analysis of S7-polynucleotide complexes containing 30 -- 40 nucleotides. Secondly, the isolated S7-octanucleotide complex is digested successively with ribonuclease A, proteinase K and ribonuclease T2, and the nucleotides liberated are identified. The results show unambiguously that uridine residue number 1239 in the 16S RNA sequence is cross-linked to protein S7.


Physical map of the seven ribosomal RNA genes of Escherichia coli. Escherichia coli DNA was digested with restriction endonucleases BamHI, PstI, EcoRI, SalI, HindIII, XhoI, BglII, SmaI, HpaI and with selected double and triple combinations of the same enzymes. The digests were electrophoresed and hybridized with 32P-labelled ribosomal RNA by using the Southern blotting technique. The resulting bands could be arranged into seven groups, and it was possible to construct a unique physical map of the seven rRNA genes (operons) of the bacterial chromosome. Mapping information obtained on several transducing phages and recombinant plasmids carrying rRNA genes, and mapping data published in the literature helped to determine the final map. The results suggest that phage lambda daroE152 carries a "hybrid" rRNA gene which was probably formed by recombination between two different chromosomal rRNA genes.


DNA sequences of the integration sites and inverted repeated structure of transposon Tn3. The nucleotide sequence of the "inverted repeat" structure of the transposon Tn3 was determined by the DNA sequencing procedure developed by Maxam and Gilbert(1). The sequence, 38 base pairs long, is as follows: 5'-GGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAG..(Tn3) 3'-CCCCAGACTGCGAGTCACCTTGCTTTTGAGTGCAATTC.. The integration of Tn3 is associated with a directly repeated sequence of 5 nucleotides appearing at each end of Tn3. The two directly repeated sequences so far determined are not the same. Furthermore, there is no homologous structure around the integration point of Tn3.


Nucleotide sequence of the three major early promoters of bacteriophage T7. I have determined the nucleotide sequences of the three major early promoters of bacteriophage T7 (A1, A2, A3). The sequences confirm the two main homologies found between other known promoters for E. coli RNA polymerase (nucleoside triphosphate:RNA nucleotidyl transferase, E.C. 2. 7. 7. 6). In particular, all three T7 promoters show a very good match with the -35 region homology; the A2 and A3 promoters share a 17 basepair sequence in this region. On the other hand, the match with the Pribnow Box homology is much less pronounced and different for each T7 promoter.


Comparison on the structure and transcriptional capability of growing phase and stationary yeast chromatin: a model for reversible gene activation. We have compared the structure of intra-nuclear and isolated chromatin from logarithmically growing yeast cells to chromatin from cells which had entered the stationary phase and ceased growing. Both chromatins show a similar nucleosomal repeat pattern, 160 bp repeat size, with staphylococcal nuclease and similar variability in repeat sizes within the genome. DNase I produces the same ladder (less than 120 b) and a quite similar extended ladder (120-300 b) which shows that both chromatins have phased nucleosomes. However, the rate of DNase I digestion of growing phase is greater than in stationary. Functionally speaking, growing phase nuclei are 5-20 times as active in the rate of endogenous transcription (all three polymerases are involved). The transcriptional and DNase I susceptibility differences noted in nuclei are maintained in sucrose gradient isolated oligonucleosomes and mononucleosomes from the two states.


Characterization by sedimentation analysis of kinetoplast DNA from Trypanosoma cruzi at different stages of culture. The kinetoplast DNA networks of Trypanosoma cruzi exist under two forms which have been studied by equilibrium density centrifugation in CsCl gradients containing ethidium bromide and by band sedimentation analysis. The relative proportion of the two forms has been measured and varies significantly between the exponential and stationary phase of growth, suggesting that one of these forms is a replicative intermediate. Both forms exhibit very high sedimentation coefficients. The sedimentation velocity ethidium titration was used to measure the superhelix density of the kinetoplast DNA after having established the validity of the method with in vitro closed DNA networks. The superhelix density of the native form of the kinetoplast DNA minicircles is very low and varies according to the physiological state of the trypanosomes. Furthermore, we observed a significant increase of the superhelix density of the kinetoplast DNA of trypanosomes grown in the presence of ethidium.


Cognitive, affective, and transfer of learning consequences of computer-assisted instruction. The effect of computer-assisted instruction (CAI) versus lecture-discussion (LD) on cognitive learning, transfer of learning, and affective behaviors of nurse practitioner students was tested by the following hypotheses: The experimental (E) group will learn, transfer, and demonstrate affective behaviors significantly more than the control (C1 group. Subjects were 31 nurse practioner students at the graduate level. Content taught was the nursing and medical management of hypertensive patients. The 14 E group subjects were taught by means of CAI. The 17 C group subjects were taught by means of LD. Pre- and posttests were done to obtain meassures on cognitive learning and transfer of learning. Demographic data and affective measures were obtained only at the posttest. The hypotheses were tested by means of t test. Pearson's r and MCNemar's Test for Symmetry were done to test the relationship between the variables. Results showed no significant differences between the groups in congitive learning, transfer of learning, or affective behaviors. There were, however, significant differences between the groups in three posttest scores on cognitive learning and transfer of learning, with the E group scoring better. Both groups learned significantly, but only the E group transferred significantly. Implications were made for education of nurse practitioners and staff.


Cholelithiasis. Review of advances in research. Cholelithiasis is now known to result from multiple causes and to have distinct clinical correlates. New knowledge about its pathophysiology and relationship to altered hepatic metabolism, the enterohepatic circulation, and gallbladder function has led to theories of prevention and to medical methods of treatment, including dissolution of stones by bile acid therapy.


Chronic hepatitis.

Chronic hepatitis. Chronic hepatitis may be viral or "lupoid" or may be related to drug use, alcoholism, or Wilson's disease. This article outlines the routine and special laboratory investigations that are indicated when the presence of chronic hepatitis is suspected from symptoms referable to the liver or from biochemical or physical abnormalities in an asymptomatic patient. The importance of needle liver biopsy in diagnosis and in follow-up is emphasized. Special attention is given to the selection of patients for prednisolone therapy.


Primary biliary cirrhosis as a collagen disease. Primary biliary cirrhosis is a disease of the small bile ducts with altered immunologic responsiveness often associated with various collagen diseases. All appear to be mediated by immune complex deposition. They probably are all different clinical manifestations of the same disease with different expressions determined by genetic and acquired factors. Therapy should be directed to the most immediate life-threatening problem.


Amino acid sequence of ATP phosphoribosyltransferase of Salmonella typhimurium. The amino acid sequence of ATP phosphoribosyltransferase [1-(5'-phosphoribosyl)-ATP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.17] of Salmonella typhimurium has been determined. The amino acid sequence analysis was carried out with a combination of manual and automated methods. It was complemented by DNA sequence analysis (done in another laboratory) of the hisG gene, which codes for it. The subunit polypeptide chain contains 299 amino acid residues and has a molecular weight of 33,216. The amino-terminal segment of the protein is relatively basic in character and has limited sequence homologies with the lac repressor and histidinol dehydrogenase. In addition, the protein contains a 40-residue segment that has 13 residues identical with the sequence surrounding the active-site cysteine of glyceraldehyde-3-phosphate dehydrogenase.


Hyperdegradation of proteins in Escherichia coli rho mutants. An Escherichia coli mutant, HDF026, defective for growth of phage T4, has been characterized biochemically and genetically. The mutant displays an elevated level of degradation of abnormal proteins, such as puromycyl polypeptides or canavanine-containing polypeptides. Genetically, HDF026 appears to be an allele of rho, which also encodes the transcription termination factor and RNA-dependent ATPase, Rho. The mutation contransduces by phage PI with ilv, weakly suppresses polar mutations in gal, and permits some growth of lambda N- phage. Temperature sensitive lambda mutants in gene O exhibit a reduced efficiency of plating at intermediate temperature on HDF026 mutants; presumably the lambda Ots protein is rapidly degraded in these strains. The ability of wild-type lambda to grow on HDF026 is also reduced, apparently the result of the lambda N product deficiency. gal escape synthesis, which reflects the level of lambda N activity, is decreased 50-66% in the HDF026 mutant. lambda r32, which requires more N function than wild-type phage, does not grow at all in HDF026. A lon mutation, which decreases protein degradation, partially reverses some of these phenotypes, suggesting that they are related to the protein hyperlability of HDF026.


Replication of an origin-containing derivative of plasmid RK2 dependent on a plasmid function provided in trans. pRK212.2, a derivative of the broad host range plasmid RK2, contains two EcoRI cleavage fragments, A and B, neither of which can replicate by itself in Escherichia coli. Fragment A (41.7 kilobases), but not fragment B (14.4 kilobases), can be cloned by insertion into the unrelated plasmids mini-F and ColE1. Fragment B contains the origin of replication and the ampicillin-resistance determinant of RK2. Transformation of E. coli cells containing the mini-F-fragment A hybrid plasmid with fragment B DNA results in the recircularization and replication of fragment B as a nonmobilizable plasmid (pRK2067) with the copy number and incompatibility properties of RK2. Fragment B cannot be cloned in the absence of fragment A because the latter fragment suppresses a function, specified by fragment B, that results in loss of host cell viability. A small segment (2.4 kilobases) of fragment B that contains the RK2 origin of replication but no longer affects host cell growth in the absence of fragment A had been cloned previously by insertion into a ColE1 plasmid. This hybrid plasmid, designated pRK256, will replicate in E. coli polA mutants only when a fragment A-bearing helper plasmid is present. These results demonstrate that the potentially lethal function specified by fragment B of RK2 is not necessary for replication and that at least one trans-acting function is directly involved in RK2 replication.


Nucleotide sequence of the ribosomal protein gene cluster adjacent to the gene for RNA polymerase subunit beta in Escherichia coli. The 3072-nucleotide-long sequence of a segment from the 88-min region of the Escherichia coli chromosome has been determined. The sequence covers the genes for ribosomal proteins L11 (rplK), LI (rplA), L10 (rplJ), and L7/L12 ((rplL), and the 5' end of the gene for the beta subunit of RNA polymerase (rpoB), along with the presumed regulatory regions for these genes. The probable locations of the promoter for the first two genes (the L11 operon) and the promoter for the latter three genes (the proximal part of the beta operon) have been identified. We have also found that the four ribosomal protein genes preferentially use codons that are recognized efficiently by the most abundant tRNA species. These and other features of the sequence results are discussed in relation to available information obtained from both in vitro and in vivo experiments on the expression of these ribosomal and RNA polymerase subunit genes.


Further studies on the mode of action of the heme-controlled translational inhibitor. We have isolated [de Haro, C. & Ochoa, S. (1978) Proc. Natl. Acad. Sci. USA 75, 2713-2716] a protein factor (eIF-2 stimulating protein, ESP) that is essential for formation of ternary and 40S initiation complexes by the eukaryotic polypeptide chain initiation factor 2 (eIF-2) at the low concentrations of eIF-2 present in reticulocyte lysates. The fact that stimulation of complex formation by ESP is virtually abolished when the small (38,000 daltons) subunit of eIF-2 is phosphorylated by ATP in the presence of eIF-2 kinase (heme-controlled inhibitor, HCI) is consistent with the notion that HCI inhibits translation in lysates by blocking the interaction of eIF-2 with ESP. Our present work, with highly purified eIF-2 and ESP, has additionally established that, unlike phosphorylation of the small subunit, phosphorylation of the middle (52,000 daltons) subunit of eIF-2, which does not lead to translational inhibition in lysates, does not affect eIF-2-ESP interaction. This provides further support for our model of translational inhibition by HCI.


Direct chemical method for sequencing RNA. Four different base-specific chemical reactions generate a means of directly sequencing RNA terminally labeled with 32P. After a partial, specific modification of each kind of RNA base, an amine-catalyzed strand scission generates labeled fragments whose lengths determine the position of each nucleotide in the sequence. Dimethyl sulfate modifies guanosine. Diethyl pyrocarbonate attacks primarily adenosine. Hydrazine attacks uridine and cytidine, but salt suppresses the reaction with uridine. In all cases, aniline induces a subsequent strand scission. The electrophoretic fractionation of the labeled fragments on a polyacrylamide gel, followed by autoradiography, determines the RNA sequence. RNA labeled at the 3' end yields clean cleavage patterns for each purine and pyrimidine and allows a determination of the entire RNA sequence out to 100-200 bases from the labeled terminus.


Greatly decreased susceptibility of nonmetabolizing cells towards detergents. The addition of different detergents to Chlorella cells that had previously accumulated 6-deoxyglucose causes a rapid release of the hexose analogue into the medium. This effect is independent of the nature of the detergent and is observed only when the cells are in an energized state. Thus, in the presence of the uncoupler p-trifluoromethoxycarbonylcyanide phenylhydrazone or of inhibitors such as N-ethylmaleimide, the cells show a greatly reduced susceptibility towards detergents. Similarly, the detergent-induced loss of accumulated alpha-aminoisobutyric acid from Saccharomyces cerevisiae and of potassium from Escherichia coli is also strongly affected by the energy state of the cells. The differential susceptibility of energized and nonenergized cells was observed at all detergent concentrations tested. Measurements of substrate efflux at different concentrations of Triton indicated that only Triton monomers are responsible for the increase in permeability. The absorption of [14C]Triton X-100 by Chlorella and the binding of detergent to the cells were measured in the presence of metabolic inhibitors. Again, nonenergized cells bound a significantly lower amount of Triton X-100. The amphiphilic antibiotic nystatin produced effects on cell permeability similar to those of detergents, whereas toluene, which is apolar, gave opposite results.


Role of Thy-1 antigen in the in vitro differentiation of a rat mammary cell line. A line of rat mammary cells, LA7, undergoes differentiation into domes or ridges or projections under partial medium control. Immunofluorescent studies show that at the time of dome formation the LA7 cultures express the Thy-1 antigen at the borders between cells. Exposure of the cultures to certain monoclonal anti-Thy-1.1 sera prevents formation of new domes and causes disappearance of preexisting ones; antisera to whole cells produce no visible effect. Cultures exposed to anti-Thy-1 sera at effective concentrations of antibody against domes show morphological changes and ridge formation. It seems that the specific interactions of these antisera with the Thy-1 antigen redirects the differentiation program of the cells.


Secretion and cell-surface growth are blocked in a temperature-sensitive mutant of Saccharomyces cerevisiae. Saccharomyces cerevisiae cells contain a small internal pool of the secretory enzymes invertase and acid phosphatase. This pool increases up to 8-fold at 37 degrees C in a temperature-sensitive, secretion-defective mutant strain (sec 1-1). Cell division and incorporation of a sulfate permease activity stop abruptly at the restrictive temperature, while protein synthesis continues for several hours. Electron microscopy of mutant cells incubated at 37 degrees C reveals a large increase in the number of intracellular membrane-bound vesicles, which are shown by histochemical staining to contain the accumulated acid phosphatase. The vesicles are removed and the accumulated enzymes are secreted when cells are returned to a permissive temperature in the presence or absence of cycloheximide. These results are consistent with a vesicle intermediate in the yeast secretory pathway and suggest that exocytosis may contribute to cell-surface growth.


Monovalent ionophores inhibit secretion of procollagen and fibronectin from cultured human fibroblasts. Procollagen and fibronectin are major products of confluent fibroblasts in culture and both are released from the cells. Procollagen is secreted by known pathways, while the mechanism of fibronectin release is controversial. We find that the secretion of both these proteins can be reduced to 20% by low concentrations (0.1-1 muM) of ionophores that have affinity for monovalent cations. In contrast, little effect upon secretion was found for similar concentrations of an ionophore that binds divalent cations. Electron microscopy showed that the inhibition of secretion is accompanied by accumulation of membranous vacuoles. We believe that the ionophores impede secretion by acting on the secretory structures rather than on the proteins themselves. Biochemical studies supported this interpretation because no changes were detected in hydroxylation or glycosylation of procollagen or glycosylation of fibronectin, nor were significant changes in cellular amino acid incorporation observed. Pulse-chase studies indicated that the rates of secretion were impaired by the ionophore without enhancing intracellular degradation. The decreased secretory rates accounted for the lower levels of procollagen and fibronectin in the culture medium; no evidence for increased catabolism of the secreted proteins was found. Secretion could be readily restored by removing the ionophore from the culture medium. The results indicate that procollagen and fibronectin may be simultaneously secreted, possibly utilizing a common pathway for secretion; the ionophores effectively interfere with cellular secretory pathways without impairing protein synthesis or protein glycosylation or altering protein catabolism.


Inhibitors of membrane transport reduce lysosomal enzyme secretion from dogfish phagocytes and their killing of sea urchin eggs. Blood phagocytes of the dogfish Mustelus canis attack oocytes of the sea urchin Arbacia punctulata, first provoking a surrogate fertilization response and then killing the eggs. To test the hypothesis that secretion of lysosomal contents is critical in this model of phagocyte-mediated cell injury, we studied effects of agents that modify lysosomal enzyme secretion. Inhibitors of membrane transport (>0.1 mM) inhibited postphagocytic secretion of lysosomal beta-glucuronidase from dogfish phagocytes: phloretin > ethacrynate > furosemide > 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid >> pyridoxal phosphate > ouabain. The same order of activity was found for inhibition by these agents of killing of Arbacia eggs by phagocytes. Cell activation (fertilization response) and cytotoxicity were quantitated both morphologically and by measurements of enzyme (beta-glucuronidase, catalase) release. The agents neither inhibited fertilization responses of eggs to calcium ionophore A23187 nor impaired their viability. Vital staining demonstrated that ethacrynate prevented phagocytes from degranulating upon contact with zymosan particles. The data not only suggest that agents primarily known for their capacity to inhibit membrane transport systems can inhibit lysosomal enzyme secretion from phagocytes but also support the hypothesis that secretion of lysosomal contents mediates activation and killing of target cells in phagocyte-mediated tissue injury.


Construction of an artificial blood vessel wall from cultured endothelial and smooth muscle cells. Cloned bovine endothelial cells were grown on a preformed layer of cultured rat smooth muscle cells that contained large amounts of connective tissue proteins. The successful growth of the endothelial cells was dependent upon the addition of more than 2.5 x 10(4) cells per cm2, and the final density reached was approximately 2.5 times higher than that obtained for the same cells growing on plastic. The endothelial cells anchored more firmly to the smooth muscle cells than to plastic, and electron microscopy showed the existence of an irregular, dense, basal lamina-like structure between the two cell types. Biochemical analysis of the lamina produced by the endothelial cells in isolation demonstrated the presence of collagen and two fucosylated glycoproteins. The structure produced, which has some of the characteristics of a blood vessel wall, was stable for several months in culture and has many potential applications.


Tropomyosin synthesis accompanies formation of actin filaments in embryonal carcinoma cells induced to differentiate by hexamethylene bisacetamide. Hexamethylene bisacetamide (HMBA) induces in vitro the cytodifferentiation of PCC3/A/1 mouse embryonal carcinoma (EC) cells. In EC cells, actin is associated with surface structures but microfilament bundles are not seen. After 2 days of HMBA treatment, rounded EC cells are converted to flat adhesive ones with a developed cytoskeleton containing actin and tropomyosin. The ratio of actin to total proteins is constant in EC cells and their HMBA derivatives; but a striking difference is observed for one of the newly synthesized proteins (Mr 34,000) identified as tropomyosin. Synthesis of tropomyosin is followed by its association with actin microfilament bundles, as revealed by indirect immunofluorescence microscopy with specific antibodies.


Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Addition of arachidonic acid and the divalent cation ionophore A23187 to a suspension of human peripheral blood polymorphonuclear leukocytes led to the formation of (5S)-hydroxy-6,8,11,14-icosatetraenoic acid, (15S)-hydroxy-5,8,11,13-icosatetraenoic acid, and (5S,12R)-dihydroxy-6,8,10,14-icosatetraenoic acid. A method based on high-pressure liquid chromatography has been developed for assay of these metabolites. The addition of arachidonic acid to human polymorphonuclear leukocytes always resulted in formation of the isomeric monohydroxy acids. However, cells prepared from blood of different subjects were found to vary with respect to formation of the 5,12-dihydroxy acid. Addition of the ionophore alone strongly stimulated the formation of the 5-monohydroxy acid and more specifically the 5,12-dihydroxy acid from endogenous arachidonic acid. In all experiments performed the formation of the 5-hydroxy acid and the 5,12-dihydroxy acid was maximally stimulated when both arachidonic acid and the ionophore were added to the incubation mixture. Under these conditions, stimulation of 40-fold or more of the formation of both compounds was observed. The data demonstrate that, in addition to causing release of endogenous substrate, the ionophore also activated the enzymatic system involved in the further transformations of arachidonic acid. This finding raises the possibility that this pathway of arachidonic acid metabolism is involved in the biological response (e.g., release of lysosomal enzymes, the slow reacting substance of anaphylaxis, and chemotactic factors) of leukocytes to A23187 and other stimuli.


Neuroactive drugs inhibit trypsin and outer membrane protein processing in Escherichia coli K-12. Previous studies demonstrated that a cloned 2-megadalton (MDal) fragment of Escherichia coli DNA contained the structural gene for major outer membrane protein a (also known as 3b or M2 (40 kDal). The present study demonstrates that M2 is synthesized from a 42-kDal precursor that also is present in the outer membrane. The conversion of the 42-kDal precursor to M2 is inhibited by a number of different local anesthetics (procaine, piperocaine, lidocaine, cocaine), by the neuroactive drug atropine, and by the classical trypsin inhibitors N alpha-tosyllysine chloromethyl ketone (TLCK) and benzamidine. Our kinetic studies demonstrate that the amidase action of pure trypsin is inhibited competitively by the local anesthetics tested (excluding lidocaine) as well as by atropine and neostigmine. A mechanism of action for local anesthetics as well as atropine in E. coli may to be inhibit trypsinlike proteases, in a competitive manner, in the region of the outer membrane. The mechanism of action of these compounds in regulating nerve conduction in man have certain features in common with the mechanism proposed in E. coli.


Glutathione-dependent hydrogen donor system for calf thymus ribonucleoside-diphosphate reductase. Purified calf thymus ribonucleoside-diphosphate reductase (2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1), showed an absolute requirement for a dithiol as hydrogen donor, whereas the natural monothiol glutathione (GSH) was inactive per se. However, a protein partially purified from thymus coupled the oxidation of GSH to the formation of deoxyribonucleotides by ribonucleotide reductase. In analogy with the ribonucleotide reductase system of Escherichia coli this protein was called glutaredoxin [Holmgren, A. (1976) Proc. Natl. Acad. Sci. USA 73, 2275-2279]. Thymus glutaredoxin had the following properties: (i) its molecular weight determined by gel chromatography was about 12,000; (ii) it was active iwth ribonucleotide reductase in the presence of GSH, NADPH, and glutathione reductase but had no activity with NADPH and thioredoxin reductase; and (iii) it was immunologically different from thioredoxin because it did not bind to antithioredoxin immunoadsorbents. Experiments on the crossreactivity of thymus and E. coli ribonucleotide reductases and the corresponding thioredoxin and glutaredoxin systems showed essentially no specificity for the homologous thioredoxin but a high species specificity for the homologous glutaredoxin.


Cloning in Escherichia coli and physical structure of hepatitis B virion DNA. A restriction map of hepatitis B virion DNA was established after cloning of the whole viral genome in Escherichia coli. By use of EcoRI, Xho I, Bgl II, Xba I, BamHI, HincII, and Hae III endonucleases, a total of 28 restriction sites were mapped. The single-stranded region was localized on the restriction map and 5' end of the short strand was mapped at a fixed position.


Interaction of the cheC and cheZ gene products is required for chemotactic behavior in Escherichia coli. Previous work has shown that the cheC gene product of Escherichia coli plays a key role in regulating the direction of flagellar rotation during chemotactic responses. An attempt was made to identify other stimulus transduction elements that interact with the cheC component by examining cheC revertants for functional suppressors. Approximately two-thirds of the revertants studied appeared to be due to back mutation or to second-site mutations near or within the cheC structural gene. The remainder of the revertants carried suppressor mutations that mapped at the cheZ locus. Half of these suppressors impaired chemotaxis in a cheC+ background and were shown by complementation analysis to be defective in cheZ function. These suppressors corrected cheC defects in an allele-specific pattern, suggesting that the cheC and cheZ proteins are in direct contact and are mutually corrective due to protein-protein interaction. Observation of swimming patterns and flagellar rotation in cheC cheZ mutants demonstrated that the interaction of these two gene products influences both the spontaneous frequency of flagellar reversals and the ability of the rotational machinery to respond to chemotactic stimuli. A model of this interaction and its possible role in chemotaxis are discussed.


Septum formation, cell division, and sporulation in mutants of yeast deficient in proteinase B. Mutants of Saccharomyces cerevisiae that carry lesions in the structural gene for proteinase B, prb1, have been isolated. Proteinase B was thought to be involved in activation of chitin synthase zymogen to allow septum formation during budding and to be involved in sporulation. The prb1 mutants are able to grow and divide and they form apparently normal septa that contain chitin. Most diploids homozygous for prb1 mutations are unable to complete sporulation.


Platelet storage by temperature cycling. The following summarizes our observations on in vitro viability and function and ultrastructure of platelets stored at 4 degrees, 22 degrees, and by temperature cycling: 1) Continuous 4 degrees storage for 24 hours resulted in irreversible loss of discoid shape and eliminated platelet capability for microtubule reassembly. 2) Abnormal in vitro platelet function (aggregation) and significant decreases in viability (recovery from hypotonic shock) occurred concomitantly with losses in microtubule reassembly capabilities. 3) Platelets demonstrating a capability for microtubule reassembly during 4 degrees storage (temperature cycled) produced normal aggregation responses and gave enhanced viability scores. 4) Platelets stored by temperature cycling for 96 hours produced viability scores equal to those produced after storage at 4 degrees for 24 hours or those kept at 22 degrees for 72 hours.


Platelet behavior and aging in the circulation. This review of the development of knowledge concerning the fate and function of circulating platelets and our recent experiments with a radioisotope label for platelet surface glycoproteins support the hypothesis that platelets are continualy involved in reversible contact interactions for the support of endothelial integrity. These encounters result in the loss of pieces of the platelet surface membrane and could contribute to the structural and functional changes of platelet senescence. The concepts of continuous involvement of platelets in hemostatic encounters and a fixed circulating lifespan are not mutually exclusive phenomena: platelet hemostatic encounters could preferentially involve younger platelets and be mostly reversible while the metabolic machinery which determines platelet survival deteriorates in a manner unrelated to these platelet-surface interactions. Obviously the nature of platelet behavior and aging in the circulation requires much more precise definition.


The free iliac flap: a lateral modification of the free groin flap. A lateral modification of the free groin flap, called the free iliac flap, is presented. By moving the outline of the free groin flap laterally, so that the medial margin lies lateral to the underlying femoral triangle, a flap is obtained which is uniformly slender and which has a long vascular pedicle. The anatomical findings, a method for safe dissection of the superficial circumflex iliac vessels, and the results of 18 clinical cases are presented.


Patterns of vascular anastomoses vs. success of free groin flap transfers. A series of 40 free groin flap transfers is reviewed and analyzed with regard to the factors influencing success or failure. Emphasis is placed on the patterns of venous anastomosis used, and the use of autogenous vein grafts in the arterial limb. The series was too small to establish that any one of the 4 types of venous hookups was superior to the others. However, we would suggest that the superficial venous conduit in the flap, if there is one, be connected to a vein in the recipient area and not to the deep venous system of the flap.


Healing of microvascular arterial anastomoses, as seen on corrosion casts by scanning electron microscopy. We made 44 microsurgical anastomoses in the femoral artery in rats. The healing was studied from one day to 4 months, by making an acrylic cast of the lumen of the femoral artery and the surrounding vessels, and examining the cast by scanning electron microscopy. The method proved to be easy and relatively quick, and it limited the possibility of artifacts. The high depth of focus permitted simultaneous study of the main lumen and of the perivascular structures after microvascular anastomoses.


An analysis, from photographs, of the results of four approaches to elongating the columella after repair of bilateral cleft lip. A system for subjective and objective clinical analysis of the lower third of the nose before and after lengthening the columella was devised, and used the study of photographs of 77 patients who had had lengthening done by one of 4 approaches. It was found that each method was equally effective in lengthening the columella and in restoring a normal relationship between the structures in the tip of triangle (the basal view of the nose). However, there were certain peculiar advantages and disadvantages of each surgical technique, and these are discussed.


Punch hair grafting under split-skin grafts on scalps. A method is presented for punch hair grafting under split-skin grafts and under very thin, scarred, bald skin. When used, the grafts have had a 100 percent survival, and almost 100 percent of the follicles survived as well.


Successful reattachment of an almost totally avulsed ear; use of the fluorescein test. The advent of sophisticated techniques, including microvascular surgery and the "pocket principle," should not always preclude a simple suturing reattachment of an almost totally avulsed ear. Confirmation of adequate perfusion of the ear by the fluorescein test may be a strong factor in the decision.


The effects of gravity on delayed and transplanted delayed tubed flaps. Altering the position (elevated or dependent) had no immediate effect on the blood supply of delayed or transplanted delayed tubed flaps. However, after 72 hours the mean survival length in the dependent tubes was less than that in the elevated tubes. (This difference was only significant in the delayed untransplanted flaps, and not so in the delayed transplanted flaps). All of the dependent tubes had a significant increase in water content (compared to the elevated tubes). This increase was greater in the transplanted delayed tubed flaps. The tissue pCO2 levels were significantly increased after 24 hours in the dependent transplanted tubes, reflecting poor circulation and ischemia in them. The rate of clearance of subcutaneously injected technetium-99m was significantly increased in the dependent transplanted tubes after 72 hours, while in the elevated tubes the clearance rate was similar to that in normal skin. The morphological appearance of the vessels in these flaps complemented the results of the functional study.


Results of phalloplasty.

Results of phalloplasty. We present our experience with a method of phalloplasty which can be applied by reconstructive surgeons to cases of penile loss from diverse etiologies. The complications with this method have been frequent, but not life-threatening. Achievement of the stated objectives is obtained in a sufficiently high proportion of cases to make this a method whorthwhile to use until a clearly superior method can be demonstrated.


Combined report of problems and complications in 793 craniofacial operations. We report the experiences in 6 major craniofacial centers, with similar teams but in different parts of the world, in a total of 793 craniofacial operations. The mortality rate was 1.6%. Complications developed in 16.5% of the cases (including infections in 4.4%). This surgery has many potential advantages, not least of which is its psychosocial effects on previously disfigured patients. Certain problems seem inherent, however, for there are not yet any satisfactory solutions to them. Some of the factors that reduce morbidity and improve results include the use of hypotensive anesthesia, a reduction in operating time, rigid stabilization of the mobilized bones at the end of the operation, a diminution in the number of incisions, and extensive antibiotic therapy.


Treatment of Peyronie's disease by dermal grafting. We describe our experience with dermal grafting for the treatment of Peyronie's disease in 27 patients over a 3-year period. With the various nonsurgical treatments, a significant number of patients remain handicapped by the disease. For this unresponsive group, we recommend surgical excision of the penile plaque with dermal grafting. The proper selection of patients for this operation is of paramount importance, and this can be facilitated by a preoperative psychological evaluation in doubtful cases.


Alternatives to subcutaneous mastectomy. It is our belief that subcutaneous mastectomy often leads to complications, with poor results. In addition, because a considerable amount of breast tissue may be left behind, its value as a prophylactic operation must be questioned. Two alternatives are presented. In our experience, these lead to fewer complications with a more thorough removal of the mammary gland, and achieve a better appearance. The alternatives are (1) simple mastectomy with secondary reconstruction; (2) the type of mastectomy described by Spira--with primary reconstruction using a subpectoral silicone prosthesis covered by muscle and an inferiorly-based dermal flap.


Metabolic adaptations in delayed skin flaps. Glucose utilization and hexokinase activity. The distribution of glucose and hexokinase activity was determined in the epithelial tissue of delayed bipedicled skin flaps in guinea pigs. The periods of "delay" were 1, 3, 7, 14, or 21 days. The flap survival was maximal (100% of the flap) when the flap elevation was performed either 7 or 14 days following the "delay" procedure. When the flap elevation was performed 1, 3, or 21 days following the "delay" procedure, the result was partial necrosis. A differential distribution of epithelial glucose was found within the bipedicled flaps. The lowest glucose level (30% of normal) was at a distance of 2 to 3.5 cm from the end of the caudal pedicle during the first day after the "delay" procedure. This decreased glucose content recovered toward normal levels during the later part of the "delay" period. The bipedicled flaps exhibited increased hexokinase activity during the 3-week period of the "delay," and the responses of hexokinase activity and tissue glucose levels to the "delay" procedure were reciprocal in the caudal half of the flaps.


Transfer of a free lateral thoracic flap in a child. We believe the axillary (lateral thoracic) flap should be one of the free flaps of choice in children, because it has vessels of 1.5 mm or more in diameter--thus making it possible for the donor and recipient vessels to be approximately the same diameters. This makes the suturing easier and helps to ensure a good result. The patency rate increases as the diameter of the vessels to be anastomosed increases. We present a successful case in which this flap was used in an 8-year-old boy.


[Herzberge - a chapter in the history of psychiatry in Berlin]. This paper gives an outline of the work done at the insane asylum at Herzberge, Berlin, from 1893, the year when the asylum was established, through to World War 1. The then concept of therapy includes many basic principles that are now embraced in the term sociotherapy.


[Fundamentals of fixation of cytological preparations (author's transl)]. Short description of the technique of fixing material--obtained by percutaneous fine needle biopsy--for cytology. A well experienced cytopathologist is mandatory for interpretation of the specimen.


Resolution, sensitivity, and contrast in gamma-camera design: a critical review. The performance of present-day gamma-cameras is examined from a historical perspective and the prospects for further improvements assessed. The author attempts to show quantitatively that spatial resolution of 25-cm field-of view cameras has reached a point where further advances can bring only diminishing returns clinically, unless improvements in sensitivity, or alternatively, in photon yield of the clinical procedure, are also realized. However, better image contrast due to developments in display technology and emission computed tomography may improve lesion detectability more directly than would an increase in resolution.


Long-term radiographic-pathologic follow-up of patients treated with visceral transcatheter occlusion using isobutyl 2-cyanoacrylate (Bucrylate). Visceral transcatheter occlusive therapy was performed with isobutyl 2-cyanoacrylate (Bucrylate) in 14 patients. Of 10 patients who subsequently died, postmortem examination in 6, performed 2--196 days post-embolization, showed only a mild histiocytic foreign body giant cell reaction to Bucrylate. The reaction was confined to the vessel lumina and did not involve the vessel walls or contiguous parenchymal tissues. Clinical and radiographic follow-up in the other 4 patients (range = 30--180 days) showed no evidence of untoward reaction to Bucrylate. No ischemic or inflammatory complications were observed in any of the peripheral organs.


Clinical evaluation of the modified Makari skin test in minimal residual malignant disease. The results of a double-blind controlled study of the modified Makari skin test in urological malignancy are described. The study suggests that the test will be useful in the monitoring of primary treatment and in the detection of recurrent malignancy and thus indicates a role for the Makari skin test in minimal residual malignant disease.


Treatment of rheumatoid arthritis with a single daily dose of benoxaprofen. A single daily dose of 600 mg of henoxaprofen has been shown to be more effective than a previously reported dosage regime in patients with rheumatoid arthritis. Increased total daily dosage was not associated with a greater incidence of side-effects. The drug worked slowly reaching a plateau after eight days of treatment. It was usually well tolerated especially by the gastro-intestinal tract.


A double-blind cross-over evaluation of ketoprofen (Orudis) and ibuprofen in the management of rheumatoid arthritis. In a multi-centre double-blind cross-over trial using the double-placebo technique, 55 patients with rheumatoid arthritis were treated for 10 days for each trial drug with ketoprofen (200 mg/day) and ibuprofen (1200 mg/day). Both drugs induced a clinically and statistically significant improvement of all the symptoms studied, except for pain at night during ibuprofen administration. Ketoprofen displayed a therapeutic efficacy significantly superior to ibuprofen in five of the eight symptoms studied. Side-effects were recorded in 10 patients receiving ketoprofen (one patient withdrew because of heartburn) and in nine patients receiving ibuprofen.


Clinical comparative evaluation of choline magnesium trisalicylate and acetylsalicylic acid in rheumatoid arthritis. A multicentre double-blind comparison of choline magnesium trisalicylate (CMT) and acetylsalicylic acid (ACSA) compared the two medications for seven weeks in rheumatoid arthritis patients. Investigators measured the number of painful and swollen joints and the duration of morning stiffness, and assessed the overall condition of each patient. Both medications were highly effective in significantly reducing the severity of symptoms flaring after interruption of prior therapy. CMT achieved a greater reduction in the number of swollen joints than did ACSA  (P less than 0.05). The incidence of adverse side-effects per patient was significantly less with CMT (P less than 0.05) (ACSA 32.1%; CMT, 16.3%. A larger percentage of ACSA patients (50.8%) reported adverse side-effects than did CMT patients 28.4%) (P less than 0.02).


Selective examination of the large branches of the arch of the aorta with the help of a new triiodinated angiographic contrast material (iodamide 420). The selective angiography of the large branches of the arch of the aorta was performed on 25 patients using Iodamide 420 as contrast medium. In 24 cases the quality of the recordings was excallent, in one case it was qualified assessable. The contrast medium caused no complication. According to the experience gathered so far, the method and the contrast material can be safely applied to the mapping of congenital anomalies, post-traumatic injuries, and the degenerative processes, as well as to the detection of the relationship between large vessels and tumours.


Lessons learnt from 2,409 burn patients operated by early excision. During the last 12 years early excision of burns followed by immediate grafting has been the standard procedure at the Burns Unit in Ljubljana. The results, although greatly superior to the classical approach, show that the early removal of burned tissue before the 5th postburn day does not solve the problem in all cases. No problems were observed in deep dermal and subdermal burns not exceeding 40% of the body surface in the average healthy young individual. These cases can be helped and fully rehabilitated in 6 weeks with less disfigurement and functional disability. In burns exceeding 40% of the body surface or in smaller burns affecting patients in unfavorable age and health groups, the above method is not so easy to apply because of problems involving a number of factors: the timing and the selection of the area to be excised, the availability of grafts, blood loss, and coagulation problems, the indications for the use of tourniquet, the problem of excision of infected areas, etc. It is important to work out a strategy for each individual case. The authors show that the improvement of diagnosis and understanding of the deep dermal burn will lead to better results.


[Lithium salts in the treatment of cluster headache]. After analysing personal results and the data in the literature concerning the therapeutic effects of Lithium salts in cluster headache, the Authors discuss some of the pathogenetic problems related to this particular form of idiopathic headache. The results obtained seem very favourable however the therapeutic efficiency of Lithium salts, also observed in neuralgic-vasomotor syndromes (Charlin, Sluder) and in some forms of chronic headache, seems to indicate a relatively unspecific mechanism of action. The Authors suggest therefore an intervention in the stabilization of the membrane at the CNS level, with increasing efficiency of "antinociceptive" system.


Acute excision or exposure treatment? Results of a randomized controlled clinical trial. An evaluation of a total of 2,460 patients treated with exposure during the period 1962-1971, marked that the exposure method showed satisfactory results, but also that there are clear upper limits for the possibilities of this method. The approach of treatment was reconsidered and consequently very severely burned patients were excised acutely in the years 1972-1975. It was proved plausible, permissable and practically possible. On May 1, 1976, a randomized, controlled clinical trial commenced: Patients admitted for fresh burns were divided into groups: one group was unsuited for trail (U), (e.g. small children, electric burns etc.); of the remaining patients every even was treated with acute excision (A), (i.e. operation within 24 hours post burn), every odd patient according to the classical exposure method (E), employed by our unit: exposure followed by excision and transplantation of all unhealed burned areas no later than day 14 post burn. The results concerning mortality in the first 2-year material are presented. In the first year, which began a few months after moving from a 115 year old hospital into a quite new university hospital, the mortality is found to be twice as high as that found the second year. The reasons are the difficulties caused as a result of moving to new larger buildings, needing an increase of staff with two thirds, all of which are inexperienced in the care of burned patients. The mortality is exactly the same in the group treated with acute excision (A) as the group treated with exposure (E). The trial must continue and results of studies concerning morbidity will be published later.


Early necrectomy in deep burns of aesthetically and functionally important areas. Deep burns of aesthetically and functionally important body areas in children may in their later growth and development have a decisive role. Of the total number (2743) of hospitalized children at the Burns Department of the Pediatric Surgery in Zagreb in the last ten years, deep burns of some aesthetically and functionally important body areas were separated and the results of the application of the early necrectomy and immediate grafting method, as recommended by Janzekovic, are analysed. It is concluded that the results, due to the strict and minute application of the method (considered are individual technically important details and solutions) are good in aesthetic and even more so in the functional sense. Very fast recovery of the functions as well as the fact that up till now no surgical corrections for functional disorders were necessary in analyzed areas, along with already known advantages of the early surgical treatment, undoubtfully speak for its application.


Severity and prognosis after early excisions from one to twenty percent of the body surface area. The authors review 101 small and medium early excisions with immediate grafting. They study several parameters concerning the severity of the burn, the time and the duration of the surgical procedure, the blood losses, the effect on the protidemia during the shock period, the duration of the hospital care, the septicemic risk, the mortality, and the functional and cosmetic results. They come to the conclusion that, under 15% of the body surface area, early excision can be done at one single operation with hardly any risk, and that it is better to perform it as soon as possible (before 12 hours if possible). With a good splinting and a daily rehabilitation, the cosmetic and functional results are very satisfactory.


Rebuilding the burned face.

Rebuilding the burned face. Many of the methods and techniques used throughout the whole field of reconstructive plastic surgery owe their origins to problems first encountered in the severely burned patient. Gillies first used the tubed pedicle flap in reconstructing the face of a naval seaman burned in World War I. Axial pattern flaps such as the deltopectoral are widely used in the treatment of head and neck cancer and the one-stage free flap obviously has an exciting future. In many burned patients such flaps cannot be utilised owing to the non-availability of suitable vessels in either donor or recipient areas. Random pattern flaps such as the tube pedicle must therefore continue to play an important role in treating these cases. The plastic surgeon who undertakes the repair of the burned face must have wide experience of all methods of tissue replacement, whether by free graft or flap transfer. In resurfacing the nose the author has used Wolfe grafts when the cartilages are not involved or a tubed flap from the arm if this is not so. A long tubed pedicle flap from the back is preferred for resurfacing the chin and upper neck providing contour as well as excellent skin cover. Some extremely deep burns such as occur in epileptics or alcoholics may need bone-grafting, and the help of a good prosthetics department will be needed when the orbit has been destroyed.


Prospective randomized treatments for burned hands: nonoperative vs. operative. Preliminary report. It has been suggested that deep partial-thickness burns of the hand which remain unhealed by 14 days should be excised and totally resurfaced. Controlled data supporting this suggestion is not available. Therefore, a prospective randomized study was performed on 222 burns of the hand to evaluate if excision and skin grafting had any advantage over conservative management. Full-thickness burns were eliminated from the series by excision and grafting them as soon as possible after the diagnosis had been made. To eliminate the very superficial burns, randomization did not take place until the wound had remained unhealed for ten days and would not heal for at least another week. In the two groups, the first ten days were managed similarly with topical antibacterials, escharotomies when necessary, and splinting in the "safe" position. Conservatively managed hands were treated with scarlet red gauze dressing as soon as all eschar had been removed. Those cases randomized into the excision and grafting group were operated upon approximately day 14. Physical therapy was the same in both groups except for the immediate period after grafting. Results were recorded by active and passive joint measurements and photographs on predetermined days throughout the study. In this study, spontaneous healing, taking as much as five weeks, gave acceptable results, comparable to excision and grafting performed at two weeks. The use of range of motion exercises, accurate splinting and pressure allowed optimal healing and prevented stiffness and contractures in both groups. There was no significant difference between the two treatment modalities.


Late results following treatment of deep burns of the hands. During a 10-year period, 467 patients with burns involving the hands have been treated, 290 of whom during the past 5 years. Two groups of patients were examined: the first were those who had received treatment between 1967 and 1971 using the exposure method and the reconstruction with skin grafts only after the spontaneous separation of the eschars, and the second, using the closed method and early or late excision of the necrotic tissue followed by covering with split-thickness grafts. In this second group are included also those patients whose burns can be classified as medium depth at the time of admission but in whom experience has shown that one is dealing with lesions with a tendency to become deeper during the post-burn period. For these cases a dermabrasion of the lesions was performed without covering with free grafts. In the cases subjected to surgery using the technique of tangential excision and dermabrasion in order to reach the more difficult areas such as the interdigital spaces, dermabrasion was only performed between the 2nd and the 28th day. The removal of the burned tissue was followed by covering with free grafts, except in those cases in which the depth was in doubt. The results obtained have demonstrated that in the first group the scars have led to serious invalidating consequences which have necessitated long and complex surgical reconstruction programmes. In the second group almost complete function has been restored with the aid of only minimal surgical correction, most often in the interdigital spaces. We would like to emphasize the usefulness of surgery in those cases on the borderline between medium and full thickness. The tendency of these lesions to become deeper has often led to scars which are very similar to those following the deep lesions.


Temporary skin substitutes and evaporative water loss. The authors worked out a simple method, which enables an orientative evaluation of different skin substitutes as to their effectiveness in preventing gross evaporative water loss from decorticated dermis. The method is based on the loss of weight of decorticated dermis samples (covered by different materials) incubated in a thermostat for 1, 2, 3 and 4 hours at 37 degrees C. Following skin substitutes were tested: Lyofoam; Epigard; collagen foil; freeze dried amniotic membrane; freeze dried porcine xenografts; deep frozen porcine xenografts; and fresh porcine xenografts. Controls lost during 4 hours incubation at 37 degrees C 61.34% of the original weight (similarly as samples covered by synthetic skin substitutes or amniotic membrane). Samples covered by freeze dried xenografts lost only 33.07%, samples covered by deep frozen xenografts 13.20% and by fresh xenografts, 6.06%.


Long-term therapy of second and third degree burns in children using Jobst-compression suits. Thirteen children, aged between 2 1/2 and 14 years, with full-thickness burns are presented. These children were treated with compression suits according to the method developed by the Jobst Institute in Toledo, Ohio. The material manufactured in Switzerland is described and the advantages and disadvantages of this material are discussed. Group I comprised 8 children who were fitted out with the suit directly after the burns had healed. These were all scalds covering 11 to 30% of the body surface and necessitating Thiersch grafts. Group 2 comprised 5 children who were only fitted with this suit 3 months to 2 years after the original accident. By that time they had all developed massive, hypertrophied scars, limiting flexion and extension of the joints. In the first group the skin colour rapidly returned to normal, the development of hypertrophic scars was not marked and these scars had a definite tendency to regress. Nine of ten affected joints either became normal or showed a considerable improvement in function. In the second group, 19 of 25 affected joints had become normal one year after the suits had been fitted and four showed definite improvement. Here the scars regressed, although admittedly slower than in the first group. The children appeared to wear the suits without discomfort or trouble.


The influence of burn trauma on the hypothalamus-pituitary axis in normal female subjects. In 5 severely burned women (greater than 25% TBS, II degrees and III degrees burns) the following hormones were investigated by RIA. (1) LH-releasing hormone test in the initial phase of burn shock with 100 gamma 3 LH-RH. (2). Follow-up controls of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (HPRL), oestradiol (E2), progesterone (P) and testosterone (T) in the catabolic and healing phase of burn disease. All women were before onset of burn trauma regularly ovulating. The following preliminary results can be presented: If the burn trauma occurs in the preovulatory phase of the menstrual cycle, there was no ovulation during the time of observation. As a sign of the normal function of the anterior lobe of the pituitary gland all subjects responded with an increase of plasma LH to the stimulation with LH-releasing hormone. The burn trauma interferes with the female endocrine equilibrium by involving hypothalamic centres. Negative feedback mechanisms by the secretion of adrenal hormones and temporary hyperprolactinemic states as a further result are discussed.


Warm dry air treatment of 345 patients with burns exceeding 20 per cent of the body surface. Two groups of patients with burns covering more than 20% of the body surface treated in a warm dry environment in two Burn Units in Sweden have been compared. The methods of treatment of the 345 patients were almost identical, using plasma and crystalloid solutions during the period of early intense therapy, use of frequent bathing and early debridement of the necrotic burned tissue and application of homo- or heterograft skin prior to the transplantation of autograft skin. The percentage mortalities in the two groups of patients (15.7% and 20.2%) were not significantly different, neither were the causes of the burn or the cause of death. Combination of the results and probit analysis did however show that treatment in a warm dry environment was associated with a lower rate of mortality in patients with very extensive burns than found in other studies not using these environmental conditions in Sweden prior to 1968 (by the same authors) in the United Kingdom and in the United States of America.


The prevention of wound infections in burn patients. To investigate the necessity of "protective isolation" and/or gastrointestinal tract decontamination in the prevention of infections in burn patients treated under ward conditions, a bacteriological inventory of burn sites, oropharynx and faeces was made 3 times a week. The origin of bacteria isolated from the lesions was determined by typing. In addition, the effect of local protection by topical application of silver-sulphadiazine or nitrofuralum was investigated. Of potentially pathogenic bacteria known to cause infections in burn, St. aureus was found to be almost exclusively exogenous in origin. Str. pyogenes, on the other hand, appeared either to be strongly inhibited by topical treatment or else to have colonized the wounds only from endogenous sources. Endogenous (gi-tract) Enterobacteriaceae biotype-positive samples were restricted to burn sites near the mouth and the anus. Enterobacteriaceae biotypes of exogenous origin appeared to colonize wounds of about one third of the patients. It is concluded that topical protection is insufficient in the prevention of bacterial colonization of the lesions. Therefore, protective isolation (St. aureus, etc.) and selective gastrointestinal decontamination are to be considered for infection prevention.


Humoral antibodies against skin allografts. Using the collodion agglutination method the authors studied antibody formation against skin allografts in severely burned patients. They succeeded in detecting antibodies which start appearing on the third day following transplantation at the earliest. Later their titers increase reaching the maximum a few days before first signs of graft rejection. High titers persist for relatively long periods after graft rejection. Antibodies were not detected if the grafts were taken from an identical twin. In this case the grafts were not rejected. These results could be used for the determination of the optimal time for debridement of adhering allografts before the onset of rejection.


Parenteral administration of ketoprofen in osteoarthritis: a double-blind trial versus the N-methyl-d-glucamine salt of indomethacin. In a double-blind trial 40 patients with ostheoarthritis were treated for relief of pain with ketoprofen or with the N-methyl-d-glucamine salt of indomethacin, both drugs being administered i.m. at the dosage of 100 mg/day for 12 days. Ketroprofen and the indomethacin salt significantly improved pain, functional capacity and walking distance, while only the former reduced the knee size in the patients with gonarthritis. The two drugs showed roughly the same latency period and the same duration of activity. Ketoprofen was perfectly tolerated: on the contrary, in one patient treated with the indomethacin salt, the treatment was stopped because of vascular hypotension and cutaneous rash. A significant increase of blood urea nitrogen was observed only in the group of patients treated with the indomethacin salt.


Clinical comparison of fenbufen and aspirin in osteoarthritis. The objective of the study was to compare efficacy and safety of Fenbufen and Aspirin in osteoarthritis. The study was a double-blind, randomized trial with crossover. The test subjects were treated for 4 weeks with 600 mg Fenbufen and for 4 weeks with 3.6 g Aspirin per day. 35 patients with osteoarthritis of the knee and 18 patients with osteoarthritis of the hip participated in the study. The physical measurements of osteoarthritis activity showed significant improvement with both Fenbufen and Aspirin. The drugs were comparable with respect to: 1) improvement of physical m-easurements, 2) investigator's assessments, and 3) patients' assessments. A smaller number of patients reported drug-related side effects with Fenbufen than with Aspirin. 57% of the patients reported side effects during treatment with Aspirin and 40% during treatment with Fenbufen. There were no abnormalities discovered in haematologic or biochemical tests performed during the course of the trial.


The use of penicillamine in the treatment of rheumatoid arthritis and scleroderma. The use of penicillamine in the treatment of rheumatoid arthritis and scheroderma is reviewed. Much of the worlds literature was collected including both open studies and control studies. Both types with over 1,300 patients in the open trials and as one would expect, a smaller group in the control trials, showed about 64 percent of the patients having good results. Side effects range from one quarter to one third of the treated patients. This seems to show penicillamine as an effective drug for the treatment of rheumatoid arthritis though with a multiplicity of side effects. Its use in the treatment of scleroderma is still uncertain. Because of the rarity of the disease the number of patients treated has been small and the data is conflicting.


Deposits of immunoglobulins and complement in skin of patients with rheumatoid arthritis. Influence of anti-rheumatic treatment. Immunopathological studies on skin biopsies from 88 patients with rheumatoid arthritis showed that one-third of them had deposits of IgM and/or C3 in the walls of small vessels immediately underneath the dermal-epidermal junction. The deposits in the vessel walls which may reflect subclinical immune complex vasculitis could be correlated to the occurrence of IgG-rheumatoid factor in the serum, but not to IgM-rheumatoid factor, other extra-articular manifestations, or to the occurrence of circulating immune complexes demonstrated by the complement consumption test or the thrombocyte aggregation test. Two untreated patients had granular deposits in the dermal-epidermal junction. Five out of 50 patients developed deposits in the dermal-epidermal junction during treatment with levamisole, penicillamine, or azathioprine, as observed by serial skin biopsies.


Enzyme-linked immunosorbent assay for determination of IgM rheumatoid factor. A semi-automated enzyme-linked immunosorbent assay (ELISA) for determination of IgM rheumatoid factor was established. Human gammaglobulin (Cohn fraction II) was used as an antigen on a solid phase of polystyrene microtitre trays. The results were read on a spectrophotometer. ELISA and the sheep cell agglutination test were compared in a study of sera from 400 blood donors, 53 patients with active rheumatoid arthritis and of 200 sera received for routine determination of rheumatoid factor. The results of the two tests correlated well. The ELISA procedure was precise, objective, inexpensive and well suited for quantitative routine determination of IgM rheumatoid factor.


A double-blind study of erbium169 synoviorthesis in rheumatoid digital joints. Results after one year. A double-blind study was made on the effectivenss of erbium169 synoviorthesis in the digital joints of 7 patients with erosive, seropositive rheumatoid arthritis. The study involved 70 joints observed over a 12-month period: 20 pairs of metacarpophalangeal joints (MCP) and 15 pairs of proximal interphalangeal joints (PIP) were injected with erbium169 in one joint and saline in the other one. All joints had radiological lesions corresponding to State I and II of the Steinbroker classification. Six months after synoviorthesis, good and excellent results were observed in 71% of the articulations treated with erbium169 and in only 40% of those injected with saline (placebo) (p less than 0.01). Good and excellent results were noted in 79% of the joints treated with the isotope after one year, compared with only 50% injected with the placebo (p less than 0.05). The beneficial effect of erbium169 synoviorthesis on the pain and inflammatory phenomena of rheumatoid digital joints is therefore proven. Occasionally the isotope causes a slight decrease in the range of movement of the treated joint.


Predominance of cells with T-markers in the lymphocytic infiltrates of synovial tissue in psoriatic arthritis. Synovial tissue from 8 patients with psoriatic arthritis (PSA) were investigated by direct immunofluorescence technique with FITC-conjugated anti-F(ab')2 antiserum, and with a specific rabbit anti-human T-lymphocyte antiserum by indirect immunofluorescence method with FITC-conjugated goat-anti-rabbit Ig antiserum as the second layer. The majority of the lymphocytes in the tissue displayed membrane fluorescence with the anti-T antiserum. Staining with the conjugated anti-F(ab')2 antiserum revealed both intra- and extracellular immunoglobulins. These results indicate that the majority of the lymphocytes in the synovial tissue of PSA are T-lymphocytes, and that a minor number of the cells belong to the B-cell line.


The effect of penicillamine on blood pressure and vascular disease in mice with infarct-kidney hypertension. Treatment with penicillamine was capable of bringing down the elevated systemic arterial pressure in the thymus-dependent phase of infarct-kidney hypertension in mice; a marked improvement in the clinical condition of the treated animals was observed as compared with untreated hypertensive mice. No pathological changes in either kidney or heart could be attributed to toxic side effects of penicillamine either in normotensive or in hypertensive mice treated for several months with penicillamine. It is concluded that penicillamine may have an effect on thymus-dependent reactions, such as the increased blood pressure in the chronic phase of infarct-kidney hypertension in mice. In mice, the treatment can be extended over a considerable part of the animal's life span without apparently giving rise to toxic side effects on vital organs.


[Renal artery stenosis following kidney transplantation -- an avoidable complication?]. Many etiologies have been proposed for renal artery stenosis following renal transplantation. Incorrect operative technique is the most frequent cause, but the condition is often due to vascular parietal lesions resulting from traction on the vessels during removal of kidneys, which causes dislocation of arterial parietal structures. Such traction is inevitable if kidneys are removed separately due to difficulties arising during deep mobilization of the kidneys. Furthermore, this technique involves direct flushing into the renal artery, and this may cause damage to the intima due to the canula. Canula and traction are the major causes of stenosis. The authors present their own cases and propose that kidneys be removed "en bloc". This is the only way to prevent traction on vessels, and it permits flushing through the aorta for cooling.


An extrinsic membrane polypeptide associated with high-molecular-weight protein aggregates in human cataract. A 43,000-dalton polypeptide has been isolated from the high-molecular-weight disulfide-rich fraction of the water-insoluble protein of human cataractous lenses. On the basis of immunochemical reactivity and fluorescent antibody binding, this polypeptide is localized in the membrane region of the lens cell. This observation suggests an interaction between the soluble lens proteins and membrane-associated polypeptides in the formation of large protein aggregates which may cause cataract.


DNA organization of Methanobacterium thermoautotrophicum. The organism Methanobacterium thermoautotrophicum, an archaebacterium, is envolutionarily very distant from both traditional prokaryotes and eukaryotes. Its genome (DNA) has physical characteristics typical of most prokaryotes except that it is quite small (about 10(9) daltons, less than half the size of the genome of Escherichia coli) and contains a significant amount (6 percent) DNA which renatures extremely rapidly.


Human macrophage migration inhibition factor: evidence for subunit structure. Macrophage migration inhibition factor (MIF) derived from human lymphoid cell lines was found to lose biologic activity on dialysis. Although activity was not recovered in the dialyzate, mixing experiments demonstrated that the components in the retentate and dialyzate could reassociate to restore activity. The fragment of larger molecular weight (less than 10,000) could inhibit the activity of intact MIF, whereas the smaller molecular weight fragment (5,000 to 10,000) could not. These findings suggest that human MIF is composed of at least two noncovalently linked subunits. In analogy to the situation for certain bacterial toxins, one of these may represent an attachment piece for a target cell membrane receptor.


Cadmium: in vivo measurement in smokers and nonsmokers. Absolute amounts of cadmium (in milligrams) in the left kidney and concentrations of cadmium (micrograms per gram) in the liver were measured in vivo in 20 healthy adult male volunteers. Organ cadmium levels of smokers were significantly elevated above those of nonsmokers. No relationship was evident between body stores of cadmium (liver and kidney) and cadmium or beta 2-microglobulin in urine or blood. The average total body burden of cadmium in man at age 50 is estimated to be 19.3 milligrams for nonsmokers and 35.5 milligrams for smokers (38.7 pack-year smoking history). Biological half-time for the whole body was, on average, 15.7 years (10- to 33-year range). Dietary absorption was 2.7 micrograms per day. Cigarette smoking resulted in the absorption of 1.9 micrograms per pack.


Permeability of the cell-to-cell membrane channels in mammalian cell juncton. The channels in the junctions of various mammalian cell types--primary cultures and lines--were probed with a series of linear fluorescent amino acid and peptide molecules of different size and charge. Permeability is limited by probe size and electronegativity, these two factors apparently being related reciprocally. In respect to both factors, mammalian junctional channels are more restrictive than insect channels; hence the mammalian channels are narrower, more polar, or both. The channels of the various mammalian cell types differed slightly from each other; in some types the serum of the culture medium affected the channel permeability.


Induction of luteolysis in the human with a long-acting analog of luteinizing hormone-releasing factor. Subcutaneous injection of 50 micrograms of a long-acting analog of luteinizing hormone-releasing factor on each of two successive days during mid-luteal phase in normally cycling women induced a short luteal phase and premature menstruation. These events were associated with luteolysis, as evidenced by the consistent and parallel premature decline of progesterone and estradiol levels compared with those in control cycles. This finding may prove to be useful in the prevention or interception of implantation.


Heparin neutralization of PGI2: effects upon platelets. Heparin neutralizes the inhibitory effect of prostacyclin (PGI2) on platelet aggregation. The PGI2-induced enhancement of platelet cyclic adenosine monophosphate levels is also inhibited. The mechanism appears to involve a direct interaction in which heparin neutralizes the inhibitory effects of PGI2 on platelet aggregation but, at the same time, does not lose its own anticoagulant activity. These findings may explain instances in which heparin infusions have been reported to produce hyperaggregation of platelets, thrombotic episodes, and thrombocytopenia in patients.


A relationship between DNA helix stability and recognition sites for RNA polymerase. The RNA polymerase binding sites on the DNA of (i) the aroE-trkA-spc segment of the Escherichia coli genome, (ii) transposon Tn3, (iii) plasmid ColE1, and (iv) coliphage lambda were mapped by electron microscopy, with the use of the BAC technique; these maps were compared with the maps of the early-melting regions for the same genomes. The results indicate that in all these cases the binding sites for the E. coli RNA polymerase lie preferentially in the early melting regions of DNA. These data indicate that helix stability may be an important feature of the multipartite nature of the promoter structure.


Toxaphene, a complex mixture of polychloroterpenes and a major insecticide, is mutagenic. Toxaphene, the most widely used chlorinated insecticide, is mutagenic in the Salmonella test without requiring liver homogenate for activity. This insecticide is a complex mixture (more than 177 polychloroterpenes) with carcinogenic activity in rodents. Some but not all of the mutagenic components are easily separated from the insecticidal ingredients.


Human growth hormone: complementary DNA cloning and expression in bacteria. The nucleotide sequence of a DNA complementary to human growth hormone messenger RNA was cloned; it contains 29 nucleotides in its 5' untranslated region, the 651 nucleotides coding for the prehormone, and the entire 3' untranslated region (108 nucleotides). The data reported predict the previously unknown sequence of the signal peptide of human growth hormone and, by comparison with the previously determined sequences of rat growth hormone and human chorionic somatomammotropin, strengthens the hypothesis that these genes evolved by gene duplication from a common ancestral sequence. The human growth hormone gene sequences have been linked in phase to a fragment of the trp D gene of Escherichia coli in a plasmid vehicle, and a fusion protein is synthesized at high level (approximately 3 percent of bacterial protein) under the control of the regulatory region of the trp operon. This fusion protein (70 percent of whose amino acids are coded for by the human growth hormone gene) reacts specifically with antibodies to human growth hormone and is stable in E. coli.


Recent therapeutic advances in thrombotic thrombocytopenic purpura. Whole plasma infusion, in our experience, has been highly effective in the management of patients with thrombotic thrombocytopenic purpura. The effectiveness of plasma infusion in the treatment of this severe disorder implies the deficiency of a factor in the patient's plasma. Furthermore, we have observed that when platelets are suspended in plasma obtained during active, untreated thrombotic purpura, aggregation occurs. This effect is neutralized by preincubation of the thrombotic thrombocytopenic purpura plasma with normal plasma. Thus, there is both a correlation with the clinical pathogenic mechanism, disseminated platelet aggregation, and with the therapeutic response to plasma infusion. Based upon our experience and the concept that thrombotic thrombocytopenic purpura is a plasma factor deficiency state, we recommend initial infusion of a full plasma volume equivalent over the first 24 hours. This should be done under an intensive care setting. After this initial plasma infusion, we advise the infusion of 3 units of plasma daily until a full remission is obtained. When the clinical situation has stabilized, we stop the daily plasma infusions and cautiously observe for recurrence of the manifestations of thrombotic thrombocytopenic purpura. If there is a recurrence, plasma is again infused in substantial quantity during the first 24 hours and then 3 units daily until a full remission is again evident. Whether the plasma requirement might be attenuated or the course of the disease shortened by the concomitant use of antiplatelet agents, corticosteroids or other means remains to be determined.


Drowning and near-drowning: current concepts and neutrophil function studies. A near-drowning by a young man in an indoor pool is reported, and the current concepts of therapy are discussed. Laboratory studies of the patient's neutrophil function and chemotactic response were performed on the day of admission and on hospital days 2 and 4. Neutrophil function and chemotaxis were equal to control values, indicating no effect of near-drowning on these aspects of the host immune system. Hospital admission and supportive therapy including intubation, positive end-expiratory pressure, steroids, and antibiotics are recommended, if necessary, in management of the nearly drowned patient.


Legal implications of patient records.

Legal implications of patient records. Significant changes have been made by the courts and legislatures on the rights of patients to review or acquire their own medical records. There are great dangers in writing any personal, unscientific comments into the record which could embarrass the physician in court. Attempts to prevent the patient from gaining access to his record is fraught with grave consequences.


Metabolic alkalosis complicating weaning from mechanical ventilation. Metabolic alkalosis was identified and confirmed as a precipitator of acute hypercapnea. As a result, weaning from mechanical ventilator therapy was delayed. Correction of alkalosis followed by reduction of PCO2 confirmed the compensatory mechanism during alkalosis, and weaning from intermittent mandatory ventilation then proceeded at an appropriate rate.


Pain clinics: their value to the general practitioner. Physicians in general practice frequently encounter patients with chronic pain; such patients pose a difficult management problem. A new approach to treatment is offered by the Pain Center at the University of Tennessee Center for the Health Sciences. The Pain Center, with a staff drawn from a number of medical and allied health specialties, offers a multidisciplinary approach to the treatment of patients with chronic pain. We describe the facilities and the therapeutic programs available at the UTCHS Pain Center, and the methods and goals of treatment.


Paecilomyces cellulitis in a renal transplant patient: successful treatment with intravenous miconazole. We report an immunosuppressed host with an unusual fungal infection which resolved during intravenous therapy with a new antifungal agent. This agent, miconazole, appears to have minimal side effects and a broad antifungal spectrum, and it deserves consideration for treatment of susceptible organisms.


A double-blind trial of loperamide in the treatment of chronic diarrhoea. A new antidiarrhoeal compound, loperamide (Imodium; (Janssen) Ethnor) has been evaluated in the treatment of patients with chronic nonspecific diarrhoea. In a double-blind trial its effect was compared with that of a placebo. The results of this trial indicate that loperamide is an effective antidiarrhoeal compound.


A comparison of the antibacterial activity of sulphonamide-trimethoprim combinations. Sensitivity patterns of 326 clinical isolates toward sulphonamide/trimethoprim combinations were tested in vitro. The relative merits of the different combinations are discussed in their pharmacological and bacteriological contexts. It is concluded that organisms sensitive to cotrimoxazole as judged by in vitro sensitivity tests performed at 37 degrees C are also sensitive to sulphamoxole/trimethoprim.


The distribution in mice of intravenously administered labelled Candida albicans. The time dependence of the distribution of intravenously injected radiolabelled Candida albicans in the body of mice was studied. The Candida cells were labelled by cultivating them 7 days at 28 degrees C in a medium containing one of the following radionuclides: 46Sc, 95Nb, 59Fe, 144ce, 89Sr, 60Co, 65Zn, 54Mn, 45Ca, 51Cr and 91Y, which are listed in decreasing order in respect to amount bound. The labelled cells were killed by heating them 120 min at 60 degrees C, without loss of immunologic properties. Owing to the amount and strength of binding, 144Ce labelled Candida, together with 14C labelled cells was used in animal kinetic study. A rapid disappearance of the labelled cells from blood, interrupted by a small peak, was paralleled by a transient uptake in lungs and followed by a long lasting accumulation in the liver. The kidneys and spleen revealed only small uptakes of the labelled material.


The effect of nystatin on the morphology of Candida albicans. The effect of nystatin on Candida albicans was observed by light and scanning electron microscopy; it caused abnormal growth. Some cells had deep depressions in the cell walls; budding and germ tube formation were reduced.


Wood fiber contamination of reusable cotton laparotomy pads. If the thesis that disposable fabrics are responsible for granulomatous peritonitis is correct, surgeons who operate within the abdominal cavity and use these products would be reporting instances of granulomatous peritonitis in epidemic proportions. Such is not so. Consequently, there can be valid concern expressed as to implied medicolegal problems. While the observations and conclusions were made in obvious good faith, nevertheless, there appears to be sufficient grounds for questioning this apparent cause and effect conclusion and for focusing interest on a more important consideration, the indiscriminate collection, sorting and laundering of the reusable cotton laparotomy pad. Certainly, attention should be directed to the more rigidly controlled use and disposition of these pads by the individual hospital.


The Kraske operation for carcinoma of the rectum. Kraske's methodology was classic: develop the operation in the laboratory, try it initially on patients as a last resort and, if it works, expand its use to patients with less severe disease. His operation immediately gained acceptance and was popular for the next quarter of a century. It was subsequently modified by Hochenagg, Billroth and Rydygier. These men merely altered the amount or manner of sacral removal. The operation was largely abandoned after Miles (3) showed that the lymphatic spread from carcinoma of the rectum is toward the liver. Kraske's procedure, however, stands as a landmark in preantibiotic operations on the colon. Combined with abdominal exploration, this type of procedure can be used to preserve the anus in certain instances of carcinoma of the rectum today.


Principles and practice of antibiotic therapy for post-traumatic abdominal injuries. Improved surgical techniques, the use of modern antibiotics and better understanding of the microbiologic characteristics of abdominal sepsis have lead to a satisfying clinical outcome in instances of abdominal trauma which once meant almost certain death. Yet many questions remain unanswered. Future development of several newer antibiotics may further improve the rate of complications. A study of host defense mechanisms may provide additional clues to prevent long term morbidity. Hopefully, future studies will encourage the use of a single antibiotic in the treatment of abdominal trauma. While the newer antibiotics are being investigated, certain older antibiotics, such as penicillin, chloramphenicol and tetracycline, merit additional evaluation under controlled, prospective, randomized, comparative clinical trials.


Considerations in the choice of surgical needles. Bodily tissues of varying consistency, thickness, penetrability, location and weave are encountered by the surgeon. Correspondingly, he should choose surgical needles that will introduce sutures through these tissues in the most precise and rapid manner, ideally creating a wound just large enough to draw the suture material into and through the tissue. Manipulation of the needle is aided by selecting one appropriate to the specific wound site and by the choice of a needle holder that is most ideally suited to the particular needle. Although the primary reason for appropriate choice of needle and needle holder is better patient care, an extremely important secondary reason is greater comfort and satisfaction for the surgeon in using ideal instruments.


The effects of transient candidemia on the brain: preliminary observations on a rodent model for experimental deep candidosis. Deep candidosis was established in healthy uncompromised Wistar rats by injecting Candida albicans into the right internal carotid artery. Death of these animals could be produced within seven days by injecting 10(7) yeasts. The kidneys were most severely infected, and the entire brain was involved. No animal demonstrated leptomeningitis. Within one to two days microabscesses developed, subsiding into a histiocytic response in five to seven days. By seven days, chronic inflammation with noncaseating granulomas was seen. Throughout the study, cerebrospinal fluid and blood cultures failed to demonstrate the fungus. This rodent model is similar to human cerebral candidosis.


Renovascular hypertension in childhood: successful treatment by renal autotransplantation. Five cases of renal autotransplantation for renovascular hypertension in children are described. Hypertension in these cases was managed temporarily with medications until the patients grew to a size that made an operative procedure feasible. Following operation the blood pressure returned to normal in three patients without any antihypertensive medication during the period of follow-up (8 months to 6 years). In the other two patients, small doses of antihypertensive medications still were needed, despite correction of the stenosis. The results of this series demonstrate that autotransplantation is a safe and effective procedure in childhood renovascular hypertension in contrast to other forms of vascular reconstruction, which carry a high rate of failure in this age group.


Parenteral antibiotics in elective colon surgery? A prospective, controlled clinical study. The addition of perioperative gentamicin and clindamycin to an oral antibiotic bowel preparation was studied in a prospective, randomized, double-blind series of patients undergoing elective colectomy. Fifty-nine patients completed the study, with all receiving mechanical preparation of the colon and oral neomycin and erythromycin base. Thirty-one of these patients also received a preoperative and postoperative intravenous dose of gentamicin and clindamycin, while 28 received placebos. The two groups of patients were similar in age, both habitus, pathologic diagnosis, concomitant disease, operative procedures, operative time, blood loss, and adequacy of mechanical preparation of the colon. The incidence of infectious complications related to colectomy was 1% (three of 28) in the placebo group and 7% (two of 31) in the group receiving intravenous gentamicin and clindamycin. There were no wound infections directly related to colectomy in either group. There was no statistically significant reduction of infectious complications with the addition of intravenous gentamicin and clindamycin to oral neomycin and erythromycin-base bowel preparation.


Enhancement of rat renal allografts with monoclonal antibody. Treatment of rat allograft recipients before grafting with donor spleen cells and whole, pooled antidonor alloimmune serum results in indefinite renal allograft survival. The enhancement is immunologically specific. In these experiments a monoclonal, homogenous anti-BN antibody was produced by a hybridoma clone created by fusing the mouse-P3 myeloma with spleen cells from Lewis rats immunized with BN lymphoid cells. The hybridoma supernatent enhanced survival of LBN renal allografts in Lewis recipients as effectively as whole Lewis anti-BN antiserum. Dilution of the hybridoma supernatent by tenfold or a hundredfold abrogated the enhancement effect.