Reactive affective cycles and lithium: a caveat. The author has been referred increasing numbers of patients who were inappropriately treated with Lithium for cyclic "depressions" which were in fact reactive-depressive episodes resulting from cyclic patterns of interpersonal behavior. This paper gives two case reports to demonstrate the phenomenon of reactive-affective cycles, their clinical presentations and the problems arising from treatment with medications. The structure of cycles of interpersonal behavior and their presentation in therapy is described and treatment strategies are suggested.


Metaphor as a diagnostic tool.

Metaphor as a diagnostic tool. A case study is reported wherein the patient's frequent use of metaphors was used as presumptive evidence that the patient had been misdiagnosed ten years earlier as having central nervous system disease. The ability to produce metaphors depends upon the capacity to condense several meanings into a word or two, and this in turn implies a rather active associative process. Concretism, not associative richness, characterizes central nervous system disease. The presumption as regards diagnosis was supported by subsequent data including the patient's response to psychotherapy.


Fatal hyperthermia following haloperidol therapy of sedative-hypnotic withdrawal. A 30 year old male, with a history of methalqualone and barbiturate abuse, developed a delirium tremens-like syndrome following discontinuation of the medications. Shortly following high doses of parenteral haloperidol administered for treatment of the withdrawal syndrome, the patient developed severe hyperthermia, with body temperatures reaching as high as 108 degrees F. The hyperthermic episode was followed by cardiovascular collapse, multiple complications, and death. The sequence of events strongly suggests that haloperidol therapy was casually related to the development of fatal hyperthermia. Thus the butyrophenone haloperidol, like the phenothiazine derivatives, can produce clinically important impairment of thermoregulation.


Life threatening self-mutilation of the nose. Potentially life threatening self-mutilation of the nose in a patient with a severe passive aggressive character disorder is described. The phenomenological and psychodynamic features of this case are contrasted with those of schizophrenia and factitious dermatoses with similar excoriations.


Absence of hostility in outpatients after administration of halazepam--a new benzodiazepine. A number of benzodiazepine have been shown to increase hostility and aggression. This study examines whether halazepam, a new benzodiazepine structurally very similar to diazepam, is associated with increases in hostility. Fifty-one adult outpatients in a double blind, 6 week study were randomly assigned either halazepam or placebo. Hostility was measured by changes in response on four different scales, the anger-hostility factor of the Patient Symptom Checklist and three MMPI hostility scales. The results of our study indicated that halazepam does not induce significant changes in hositility.


Evaluation of polysulfone as a potential biomedical material. In the course of preliminary screening of various potential biomaterials, polysulfone (PS) has been found to have good biocompatibility (1,2). This paper describes the detailed results of evaluation of PS by several methods. Although a number of screening programs for biomaterials have been published (3,4,5,6,), we used our own program in this experiment.


The application of experimental design in bioengineering. The use of factorial designs in experimentation and the careful planning of the three basic phases of experimental projects, will maximize the reliable information from the experiment and minimize the cost and effort to the experimentor. The application of the principles of good experimental design are illustrated in a case study of experimentation which investigates a new mode of peritoneal dialysis.


Surface tension measurements on methacrylate monomer solutions, selected solvents, and gel extracts. The surface tensions of selected methacrylate monomer and solvent solutions were measured, and calibration curves were generated. The curves were then used to deduce the amounts of water soluble extractables in methacrylate hydrogels by measuring the surface tension of the extractant. The detectability limit (parts per 10,000) and the overall sensitivity of the method suggests its possible use as an extraction monitor test for related biomaterials.


Structure-function relations in mammalian tendon: the effect of geometrical nonuniformity. The stress-strain relations of mammalian tendon are analyzed in terms of the structure of its constituents. Two observed experimental features are accounted for by the present model: the effect of the elastic fibers on the stress-strain curve in the primary range and the effect of the geometrical diversity of the structural units of the collagen fibers on the nonlinearity of the stress-strain relations. The effect of the matrix-fiber interaction and the bending rigidity of the fiber are neglected. It is shown that the observed nonlinear characteristics of the stress-strain relations in the tendon can be accurately accounted for by the model. It is further shown that on the basis of this model, considerable insight into the structure and mechanics of the tendon's constituents can be obtained from results of simple stress-strain tests.


Instantaneous center of rotation by least square method. In the design of the total replacement of the human joint, the joint center of rotation is often important. This paper describes an analytical technique to study joint kinematics, especially the instantaneous center of rotation. The empirical data for the analysis were obtained by the sonic digitizer system which works acoustically and electronically. As biomechanical applications of the technique, the elbow, the metacarpophalangeal, and wrist joints were studied.


A feasibility study for the use of a silastic gage as an in vivo muscle force transducer. This study investigates the feasibility of utilizing silastic gages for in vivo dynamic muscle force measurement. The gastrocnemius muscle of a fifty-one pound black short hair dog was selected for the test. The study shows that such measurements can be reliably performed in vivo for short durations without interfering with the natural movement of the animal. The durability of the gage appears to be primarily limited by the biological rejection process at the gage site.


An analytical approach to the determination of optimal phasing for external counterpulsation. An inhomogeneous linear one-dimensional mathematical model is constructed as a conceptual approach to the study of the effects of External Counterpulsation (ECP) on the pressure and flow at the root of the aorta. The optimal operation of ECP is defined by two conditions: (1) minimization of the mean systolic pressure; and (b) maximization of the ratio of diastolic area over systolic area under the total pressure curve. The phase shift of the external pressure is determined so as to satisfy these two requirements. It is demonstrated within our approximation that with a given magnitude of external pressure, the phase shifts that satisfy these two requirements are the same. These phase shifts are linear functions of the systolic fraction of the total cardiac period, and depend on the time for the external wave to travel from the site of application up the vascular bed to the root of the aorta, plus the reflection contributions. Even though these results are derived from a simple model far from the complexity of the actual vasculature, the basic concepts would remain valid even if more complex mathematical treatments would have been used.


A self-transmitting surface acoustic wave (SAW) pressure transducer. We have developed a small, pressure-sensitive device using SAW oscillators, which is capable of being implanted and transmitting a signal several hundred feet. This paper presents the device and its prototypes, and data from the laboratory and live subjects.


Limitations of bandwidth compression hearing aids applied to the voiced portion of speech. Numerous speech processing techniques have been applied to assist hearing-impaired subjects with extreme high-frequency hearing losses who can be helped only to a limited degree with conventional hearing aids. The results of providing this class of deaf subjects with a speech encoding hearing aid, which is able to reproduce intelligible speech for their particular needs, have generally been disappointing. There are at least four problems related to bandwidth compression applied to the voiced portion of speech: (1) the problem of pitch extraction in real time; (2) pitch extraction under realistic listening conditions, i.e. when competing speech and noise sources are present; (3) an insufficient data base for successful compression of voiced speech; and (4) the introduction of undesirable spectral energies in the bandwidth-compressed signal, due to the compression process itself. Experiments seem to indicate that voiced speech segments bandwidth limited to f = 1000 Hz, even at a loss of higher formant frequencies, is in most instances superior in intelligibility compared to bandwidth-compressed voiced speech segments of the same bandwidth, even if pitch can be extracted with no error. With the added complexity of real-time pitch extraction which has to function in actual listening conditions, it is doubtful that a speech encoding hearing aid, based on bandwidth compression on the voiced portion of speech, could be successfully implemented. However, if bandwidth compression is applied to the unvoiced portions of speech only, the above limitations can be overcome (1).


An electronic frequency shifting stethoscope for heart sounds. The predominating energy in the normal heart sounds has been found to be at frequencies below the normal hearing threshold. Because it was felt that significant clinical information was likely to be present at those frequencies, an instrument was designed and fabricated which would frequency shift the entire heart sound into the middle of the auditory frequency range. Clinical testing showed that changes were readily detected in a monitoring situation, and that use of the instrument was both simple and easy to learn.


Adsorption of collagen on model hydrophobic surfaces. The change in interfacial tension with time for rat-tail tendon collagen adsorbing at the air, methylene iodide and isooctane interfaces has been followed by the pendant drop technique as a model for hydrophobic biomaterials. It is shown that the surface activity of tropocollagen at these three interfaces is less than that of albumin, gamma-globulin, serum of plasma, so that displacement of a preadsorbed plasma protein layer by tropocollagen molecules is energetically unfavourable and unlikely to occur. It is proposed that this may be one reason for the lack of interaction between hydrophobic soft tissue implants and their tissue capsules. It is then speculated that such interaction may require the development of biomaterials with a specific affinity for connective tissue components.


Calcium and magnesium binding to gamma-carboxyglutamic acid-containing peptides via metal ion nuclear magnetic resonance. The determination of binding constants of metal ions to biomolecules is approachable via many techniques. Metal ion NMR spectroscopy is an alternative to more traditional techniques and is complementary to them, particularly in investigations of the interactions of metal ions with relatively small peptides containing multiple ionizing groups. The method requires relatively small amounts of material, is fairly fast, and is carried out at equilibrium. Our study has been of calcium and magnesium ion binding to gamma-carboxyglutamic acid (Gla)-containing peptides. Dissociation constants of approximately 0.6 mM for the binding of either metal ion to Z-D-Gla-D-Gla-OMe have been obtained. The procedure for determination of these constants via metal ion NMR is discussed.


Identification of two protease inhibitors from bovine cardiac muscle. Low salt extracts from homogenates of bovine cardiac muscle contain two protease inhibitors, one specific for the calcium-activated protease from this tissue and the other for trypsin and chymotrypsin, but no other serine proteases, including plasmin, thrombin, and subtilisin. The former, which can be separated from the protease by chromatography on DEAE-cellulose, is a protein with a molecular weight of 270,000. Its action is not based on the sequestering of calcium, and it is present in large excess over the amount of calcium-activated protease in this tissue. The trypsin inhibitor, which has a molecular weight of 70,000, is estimated to be present at approximately 300 microgram/g, wet weight, of tissue. The identification of inhibitors such as these in the cytoplasm may explain why nonlysosomal proteolytic activity has been thought to be insignificant in the overall turnover of intracellular protein and suggests that a re-evaluation of this possibility is necessary.


Unusual COOH-terminal structure of staphylococcal protease. The extracellular enzyme, staphylococcal protease, carries a COOH-terminal tryptic peptide of 43 amino acid residues most of which are aspartic acid, asparagine, and proline. This peptide might have a function equivalent to that of a similar segment previously observed at the NH2-terminal end of the membrane-bound penicillinase precursor of Bacillus licheniformis (Yamamoto, S., and Lampen, J. O. (1976) Proc. Natl. Acad. Sci. U. S. A. 73, 1457-1461). These observations would suggest that bacterial exoproteins which are secreted in the form of precursors differ from extracellular proteins by the presence of an extra segment at their NH2- and/or COOH-terminal ends.


Kinetic mechanisms of gentamicin acetyltransferase I. Antibiotic-dependent shift from rapid to nonrapid equilibrium random mechanisms. Initial velocity, product, dead-end, and substrate inhibition studies are described for gentamicin acetyltransferase I in the forward reaction. Initial velocity patterns were linear with tobramycin (Km acetyl-CoA = 1.7 micron, Km tobramycin = 1.6 micron), concave upward with sisomicin (V/K.Et = 1.7 X 10(7) M-1 s-1, indicative of nonrapid equilibrium conditions), and showed partial uncompetitive substrate inhibition with gentamicin C1a (Km acetyl-CoA = 1.3 micron, Km gentamicin C1a = 0.12 micron, KI = 6.5 micron). Product inhibition by CoA and acetyltobramycin consists of two competitive and two noncompetitive patterns. Dead-end inhibition by butyryl-CoA and neomycin consists of two competitive and two uncompetitive patterns. However, the uncompetitive pattern between neomycin and acetyl-CoA became noncompetitive when sisomicin rather than tobramycin was the nonvaried substrate. These results are consistent with a Random BiBi mechanism with synergism between binding sites which is nonrapid equilibrium with gentamicin C1a and sisomicin and rapid equilibrium with poor substrates such as tobramycin. The substrate inhibition by gentamicin C1a arises from a reduction in the rate of product (CoA) release which is partially rate-determining under nonrapid equilibrium conditions.


Initiation factor eIF-4B (IF-M3)-dependent recognition and translation of capped versus uncapped eukaryotic mRNAs. Translation of capped and uncapped eukaryotic mRNAs is stimulated by addition of eIF-4B to an mRNA-dependent reticulocyte lysate system. m7G5 ppp inhibits translation of capped but not uncapped mRNAs and reduces translation of capped vaccinia mRNA to the level obtained with uncapped vaccinia mRNA. Exogenous eIF-4B but no other initiation factor reverses inhibition of protein synthesis by m7G5'ppp. Both capped and uncapped mRNAs interact directly with eIF-4B to form a stable complex, which can be detected by a simple nitrocellulose filter binding assay. However, addition of a 5'-cap to beta-eliminated globin mRNA or satellite tobacco necrosis virus RNA (normally uncapped) increased binding affinity of these mRNAs for eIF-4B and causes binding of these mRNAs to become sensitive to inhibition by m7G5'ppp. These results indicate that the role of the mRNA 5'-cap in translation is related specifically to the function of eIF-4B in forming a complex with mRNA (prior to association of mRNA with the 40 S ribosomal subunit) and that both cap and non-cap sequences participate in this process.


Calcium-induced conformational changes in a cyanogen bromide fragment of troponin C that contains one of the binding sites. The increase observed in alpha helix from 20 to 38%, the spectral red shift of the absorption bands of the side chain chromophores, the increase of phenylalanine side chain optical activity and a decrease of cysteinyl side chain reactivity with 5,5'-dithiobis(2-nitrobenzoic acid) are consistent with a coil to helix change in the segment containing Cys-98 and Phe-99 and 102 when the CB9 fragment of troponin C (TnC) with an intact binding site III binds Ca2+. Since similar spectrophotometric observations have been made on the whole molecule the data with CB9 confirm our previous suggestion that binding site III of TnC is one of the strong binding sites for Ca2+. The estimate of the binding constant of Ca2+ for CB9 is about 2 orders of magnitude lower than in whole TnC, indicating further stabilization in the intact molecule.


Quantitation and characterization of antibody binding to tubulin. A goat antiserum, raised to native hog brain tubulin, was characterized by conventional immunological techniques and by employing a method for precipitation of tubulin.anti-tubulin complexes with heat-inactivated Staphylococcus aureus. Antiserum dilution experiments indicated that antibodies to native tubulin were raised, and maximal binding was observed to microtubules fixed with 1 mM glutaraldehyde. Competition experiments, using iodinated fixed microtubules as tracer, demonstrated that equivalent binding occurred with microtubules at protein concentrations 100- to 1000-fold lower than those for monomeric tubulin. A rabbit antiserum raised to sodium dodecyl sulfate-treated axonemal tubulin was also characterized. The serum bound maximally (90%) to either sodium dodecyl sulfate-treated or native iodinated hog brain tubulin, and competition for antibody binding has been observed with tubulin from diverse sources (Tetrahymena pyriformis ciliary axonemes, Lytechinus pictus flagellar axonemes, and mouse neuroblastoma extracts). Using these two antisera, radioimmunoassays are being developed for quantitation of polymeric and total tubulin in cellular systems.


Arginine deiminase from Mycoplasma arthritidis. Properties of the enzyme from log phase cultures. Hydrodynamic, chemical, and optical properties of arginine deiminase (EC 3.5.3.6) from Mycoplasma arthritidis are reported for the enzyme isolated from log phase cells. The S020,w and D020,w values of the enzyme are 5.48 S and 5.87 X 10(-7) cm3/s, respectively; the molecular weight is 87,300. Determination of the amino acid composition shows that about 45% of the residues are nonpolar. Another unique feature of the composition is the presence of 36 half-cystine residues. The state of oxidation of the half-cystines appears to be well established as 16 disulfide and 4 sulfhydryl groups. The reaction of 1 sulfhydryl group with 0.3 mM 5,5'-dithiobis(2-nitrobenzoic acid) has a half-life of about 50 min at pH 8. The modified enzyme retains full activity. Two -SH groups are accessible to this reagent in 2 M guanidine hydrochloride, whereas all 4 -SH groups react immediately in 4 M guanidine hydrochloride. Reduction of disulfide bonds with dithiothreitol occurs only to a limited extent in 8 M urea, but is complete in 4 M guanidine hydrochloride. The enzyme loses activity immediately at pH 2.5, but retains full activity upon standing 8 h at pH 9.5 in several buffers. The large number of cystine residues leads to a complex near ultraviolet circular dichroism spectrum with cystine contributions apparently superimposed on contributions from aromatic residues. The far ultraviolet spectrum suggests that the molecule contains about 18% alpha helix. At pH 2.5, beta conformation and disulfide contributions are dominant. Aromatic and alpha bands are reduced considerably at pH 9.5.


Arginine deiminase from Mycoplasma arthritidis. Structure-activity relationships among  substrates and competitive inhibitors. The arginine deiminase (L-arginine iminohydrolase, EC 3.5.3.6) from Mycoplasma arthritidis catalyzes the irreversible hydrolysis of arginine and related guanidine derivatives to ammonia and the corresponding ureido analog of the substrate. The kinetic constants Km, kcat, and kcat/Km for the arginine deiminase-catalyzed hydrolysis of L-arginine are equal to 4 micron, 29 s-1, and 7.4 X 10(7) M-1 s-1, respectively, at 25 degrees C and pH 7.2. The enzyme also catalyzes the hydrolysis of L-canavanine, Nalpha-methyl-L-argine, D-arginine, L-homoarginine, L-argininic acid, and guanidine, in order of decreasing second order rate constants (kcat/Km); the second order rate constants for these substrates are 10(-3) to 10(-10) smaller than the rate constant for L-arginine. Twenty-two arginine and guanidine analogs were tested for inhibitory capacity. Only 13 are competitive inhibitors having Ki values in the range 3.2 to 40 mM. These results show that binding of ligands to the enzyme is dominated by electrostatic or hydrogen bonding interactions, or both, of the guanidino and alpha-amino group. Neither citrulline nor ornithine, the end product of arginine degradation in M. arthritidis, is an inhibitor of arginine deiminase from this organism.


Human hypoxanthine-guanine phosphoribosyltransferase. Steady state kinetics of the forward and reverse reactions. A steady state kinetic study of the hypoxanthine-guanine phosphoribosyltransferase-catalyzed reaction in the forward and the reverse directions was carried out. The results obtained favor a sequential mechanism where the monomagnesium complexes of IMP and PPi bind to the enzyme in a rapid equilibrium random fashion while products must dissociate from the enzyme in ordered sequence, first the purine base and then the magnesium complex(es) of P-Rib-PP.


Indoleamine 2,3-dioxygenase. Formation of L-kynurenine from L-tryptophan in cultured rabbit fineal gland. The distribution of the indoleamine 2,3-dioxygenase activity was investigated in various parts of the rabbit brain using the supernatant fraction (30,000 X g, 30 min) of homogenates. A low but significant activity was detected in all parts of the brain. The highest activity was associated with the pineal gland and choroid plexus. Specific activities of the supernatant fractions derived from the pineal gland and choroid plexus were 84.8 and 34.2 pmol/h/mg of protein at 37 degrees C, respectively, with L-tryptophan as substrate. When the pineal gland was cultured with L-[methylene-14C]tryptophan, L-[methylene-14C]kynurenine formed by the action of indoleamine 2,3-dioxygenase was found as one of the major products. It was isolated by DEAE-cellulose column chromatography and identified by thin layer chromatography with and without the treatment by kynureninase from a pseudomonad. The amount of kynurenine thus measured accounted for approximately one-third of the total amount of tryptophan metabolites, indicating that the kynurenine pathway is one of the major metabolic pathways of tryptophan in the rabbit pineal gland.


The sugar chain structures of ABO blood group active glycoproteins obtained from human erythrocyte membrane. The glycoproteins of human erythrocyte membrane have two groups of sugar chains with blood type ABH determinants, which are quite distinct in their molecular sizes. A neutral sugar chain and an acidic sugar chain, which belong to the small size group, were isolated from the glycoproteins obtained from the erythrocyte of blood type O individuals, and their structures were elucidated as Fucalpha1 leads to 2Galbeta1 leads to 3N-acetylgalactosaminitol and Fucalpha1 leads to 2Galbeta1 leads to 3(AcNeualpha2 leads to 6)N-acetylgalactosaminitol, respectively. The molecular weight of the large sugar chains with ABH determinants were estimated to be more than 4000. Both large and small neutral sugar chains of membrane glycoproteins obtained from blood type O erythrocyte could serve as acceptors of alpha-N-acetylgalactosaminyltransferases purified from milk of blood type A1 and A2 individuals, producing the same radioactive sugar chain distribution patterns. However, the acidic sugar chain with the H determinant could not serve as an acceptor of these enzymes.


The binding of d-glucosyl-neoglycoproteins to the hepatic asialoglycoprotein receptor. The binding of D-glucosyl-neoglycoproteins and D-galactose-terminated glycoproteins to the hepatic asialoglycoprotein receptor of rabbit liver membranes were characterized and compared. The binding of both types of glycoproteins showed the same dependence on calcium concentration, sensitivity to neuraminidase, and degree of inhibition by various carbohydrate derivatives. These results, along with the observation that the rabbit liver membranes bound both the D-glucosyl- and D-galactosyl-terminated glycoproteins to the same extent, indicated that both types of glycoproteins bound to the same receptor. To confirm this hypothesis, receptors were isolated from rabbit livers by affinity chromatography using D-galactosyl-bovine serum albumin or D-glucosyl-bovine serum albumin immobilized on Sepharose. These receptors were shown to be identical by several chemical and immunological criteria as well as in their ability to bind equal amounts of D-galactosyl- and D-glucosyl-terminated glycoproteins. The conclusion is that the rabbit hepatic asialoglycoprotein receptor cannot discriminate between D-galactosyl and D-glucosyl-terminated glycoproteins and binds both.


Rapid stimulation of hepatic microsomal heme oxygenase in selenium-deficient rats. An effect of phenobarbital. Hepatic microsomal heme oxygenase, the rate-limiting enzyme in heme degradation, is rapidly and markedly stimulated in selenium-deficient rats but not in controls, after a single injection of phenobarbital sodium. This stimulation occurred as early as 2 h and reached an 8- to 10-fold maximum 6 h following the drug. These observations suggest that phenobarbital rapidly and markedly enhances the degradation of hepatic heme in selenium deficiency. The cause for this rapid phenobarbital-mediated stimulation of heme degradation was investigated. It could not be ascribed to either accelerated turnover of cytochrome P-450, or enhanced lipid peroxidation possibly resulting from the concomitant lack of glutathione peroxidase in selenium deficiency. For these reasons, the metabolism of hepatic heme in the selenium-deficient rat liver was further examined during the 6-h period following phenobarbital. These studies indicated that whereas heme was synthesized much faster and to a greater extent in the selenium-deficient rat liver than in the control, its utilization in the formation of hemoproteins such as cytochrome P-450 and tryptophan pyrrolase was apparently impaired in selenium deficiency. Such defective utilization of heme in the 6-h period following phenobarbital could effectively result in a relative excess of unutilized "free" heme; hence the consequent stimulation of microsomal heme oxygenase for its disposal.


Transport of 5-hydroxytryptamine by dense granules from porcine platelets. A method is described for the isolation of a homogeneous preparation of dense granules from procine platelets. The purified dense granule fraction contained approximately 400 nmol of 5-hydroxytryptamine/mg of protein and appeared to be homogeneous when examined by electron microscopy. Isolated dense granules transport exogenously added 5-hydroxytryptamine via two mechanisms: 1) a carrier-mediated process predominating at low substrate concentrations and 2) a diffusion-controlled process predominating at high substrate concentrations. Temperature studies revealed an apparent energy of activation of 14.9 kcal/mol for the carrier-mediated transport. Kinetic data yielded a Km of 3.3 micron and a Vmax of 0.79 nmol/min/mg of protein for the mediated transport process. Steady state uptake was sensitive to changes in medium osmotic pressure and a decline in uptake below 300 mosM was correlated with release of endogenous 5-hydroxytryptamine. The transport was inhibited by a number of structural analogs of 5-hydroxytryptamine. These results demonstrate the existence of a carrier-mediated transport system for 5-hydroxytryptamine in the membranes of the platelet dense granules.


Conversion of rat pre-proalbumin to proalbumin in vitro by ascites membranes. Demonstration by NH2-TERMINAL SEQUENCE ANALYSIS. Rat liver poly(A)-containing RNA was translated in an ascites cell-free system. Labeled protein precipitable by antibody directed against rat serum albumin was identified as pre-proalbumin based on its size and partial NH2-terminal sequence. However, when an ascites membrane fraction was added to the translation reaction, the albumin antibody-precipitable material was smaller than pre-proalbumin. Partial NH2-terminal sequence analysis of this protein revealed that it was proalbumin. Conversion of pre-proalbumin to proalbumin by the ascites membrane fraction was complete and precise--i.e. no serum albumin was observed. Reconstitution in vitro of the processing of pre-proalbumin to its stable intracellular form, proalbumin, provides a method for studying the initial proteloytic event involved in secretion of rat serum albumin.


Cyclic analog of elastin polyhexapeptide exhibits an inverse temperature transition leading to crystallization. The cyclic dodecapeptide analog of the linear polyhexapeptide of tropoelastin crystallizes from water on raising of the temperature and thereby demonstrates an inverse temperature transition implying dominant intermolecular hydrophobic interactions. The temperature profiles of turbidity (TP tau) of the cyclododecapeptide are analogous to those of the polyhexapeptide where increases in concentration lead to translations of the profiles to lower temperature without sharpening of the transition. The demonstration of increase in order with increase in temperature for the cyclododecapeptide in water and the similarity of TPtau's lends credence to the view that increases in temperature lead to increases in order, specifically, for the linear polyhexapeptide and, generally, for the precursor protein of the elastic fiber wherein the repeating hexapeptide occurs.


Reconstitution of hybrid toxin from Fragment A of diphtheria toxin and a subunit of Wistaria floribunda lectin. A hybrid protein was prepared in which Fragment A of diphtheria toxin was linked to a monovalent subunit of the lectin from Wistaria floribunda seeds by a disulfide bridge. The hybrid molecule was reconstituted effectively from a reduced mixture of Fragment A and the lectin subunit by oxidation with o-phenanthroline and CuSO4. The monovalent hybrid protein was partially purified and found to be toxic to L cells. The toxicity of the hybrid protein on the cells was blocked by the addition of either N-acetyl-D-galactosamine, which specifically binds to the lectin, or by anti-Fragment A antibody.


Synthesis of preprolactin and conversion to prolactin in intact cells and a cell-free system. Monolayer cultures of pituitary cells were pulse-labeled with [3H]leucine for several minutes and the incorporated radioactivity was analyzed by immunoprecipitation and electrophoresis on sodium dodecyl sulfate containing polyacrylamide gels. Following a 3-min labeling period, a peak of radioactivity with a mobility similar to that of preprolactin was observed, as well as radioactivity co-migrating with prolactin. Competition with unlabeled prolactin demonstrated the specificity of the immunoprecipitation reaction. After 5 min of pulse-labeling followed by 5-min chase in medium with unlabeled leucine, only a product with the mobility of prolactin remained. Addition of a membrane fraction from dog pancreas to a wheat germ cell-free translation system containing pituitary mRNA resulted in the conversion of preprolactin to prolactin. Partial sequence analysis demonstrated that the processed product contained the correct NH2 terminus of prolactin. Thus, both intact pituitary cells and a cell-free heterologous system are able to synthesize preprolactin and cleave it to prolactin offering strong evidence that preprolactin is the biosynthetic precursor to prolactin.


Actinomycin D prevents nuclear processing of estrogen receptor. This communication describes a novel effect of actinomycin D (AcD) in inhibiting the nuclear processing or turnover of estrogen receptors in the human breast cancer cell line. MCF-7. In the absence of AcD, estradiol treatment results in rapid (5 min) hormone binding and translocation of unfilled cytoplasmic receptors (Rc) and binding of unfilled nuclear receptors (Rn). Thereafter, filled nuclear receptors (RnE) progressively deplete and, by 3 to 5 h, 70% are lost or processed. We now show that 1 to 2 micrometer AcD or chromomycin A3, both of which intercalate at G-C base-pairs on DNA, selectively and completely block RnE processing. In contrast, estrogen binding, translocation of receptor complex, and RnE accumulation in the nucleus are completely insensitive to AcD inhibition. At 1 to 2 micrometer, all other intercalators and inhibitors tested, including other inhibitors of transcription and replication, or inhibitors of translocation or of other functions, fail to prevent binding, translocation, or the nuclear processing step. AcD intranslocation, or the nuclear processing step. AcD inhibition of RnE processing is dependent on dose; at lower doses (100 nM decreasing to 1 nm), progressively greater RnE depletion occurs. AcD completely prevents RnE depletion if given together with or within 30 min after estradiol; at any time between 30 min and 5 h after estradiol, the processing of RnE is stopped instantly by addition of AcD. Because of the complexity of actinomycin action, several mechanisms can be proposed to explain its effect on nuclear ER levels.


Formation of phenylalanine transfer RNA lacking the wye base in Vero cells during methionine starvation. Vero, a cell line derived from African green monkey kidney, normally contains a single species of tRNAPhe (tRNA2Phe), containing a hypermodified base, wye (originally called Y), next to the 3' end of the anticodon. When methionine is removed from the growth medium, there appears a new tRNAPhe species (tRNA1Phe) lacking the wye base and eluting early from reversed phase chromatography columns. Its appearance is not due to the cessation of cell growth. Addition of methionine to cells containing both species of tRNAPhe leads to the disappearance of tRNA1Phe. When [methyl-3H5methionine is added in the presence of actinomycin D, which blocks new RNA synthesis, label appears in the wye base of tRNA2Phe. These results are consistent with the model that tRNA1Phe is an undermodifed precursor of tRNA2Phe and that methionine is required for modification to the mature form.


A photochemically induced dynamic nuclear polarization study of pancreatic phospholipase A2. NMR assignment of some aromatic residues. Application of the photochemically induced dynamic nuclear polarization technique to porcine pancreatic phospholipase A2 and its precursor resulted in the observation of nuclear spin polarization for the single tryptophan and 2 tyrosine residues. Using selectively nitrated enzymes, the tyrosine resonances could be assigned to residues 69 and 123. Both tryptophan-3 and tyrosine-69 are of particular interest because they are part of the lipid binding site.


Production of a covalent flavin linkage in lipoamide dehydrogenase. Reaction with 8-Cl-FAD. A method is described for preparation of apolipoamide dehydrogenase which gives quantitative removal of FAD. Active holoenzyme can be reconstituted by incubation with FAD. Reconstitution of apoenzyme with 8-Cl-FAD results in the fixation of most of the flavin to the protein in a covalently bound form. The portion noncovalently bound was shown to be unmodified 8-Cl-FAD. The covalently bound flavin has an absorption spectrum quite different from that of 8-Cl-FAD. It has a single band in the visible with a maximum at 459 nm (extinction coefficient of 22 mM-1 cm-1) and a shoulder at 480 nm. Model reactions between 8-Cl-Flavin (riboflavin or FAD) and organic thiols (thiophenol, beta-mercaptoethanol, or N-acetylcysteine) give products with spectra which are similar to that of FAD covalently bound to lipoamide dehydrogenase. The products of the model reactions have a single visible band with a maximum at 480 nm (extinction coefficient of 23.6 mM-1 cm-1 to 28.4 mM-1 cm-1) and a shoulder at 460 nm. The products of the model reaction and the covalently bound FAD of lipoamide dehydrogenase appear to be the result of a nucleophilic attack on the carbon at position 8 of the flavin ring by a thiolate anion, displacing the chloride. Thus, the product of the model reaction is 8-(RS)-flavin, and the product of the reaction between 8-Cl-FAD and protein probably has a cysteinyl residue covalently attacked at position 8 of FAD. Reconstitution of apoliopoamide dehydrogenase with 8-Cl-FAD gives two enzyme products which are fractionated by ammonium sulfate. Enzyme fractionating between 20% and 45% ammonium sulfate is monomeric and contains covanently bound FAD. Enzyme fractionating between 55% and 75% ammonium sulfate is dimeric and contains both covalently bound FAD and noncovalently bound 8-Cl-FAD. Both protein fractions contain one FAD per protein subunit and both are active with physiological substrates with Km values for NAD and dihydrolipoamide similar to those of native lipoamide dehydrogenase. The maximum turnover rates differ dramatically. Enzyme fractionating between 55% and 75% ammonium sulfate has a Vmax which is 61 times slower than native enzyme. Enzyme fractionating between 20% and 45% ammonium sulfate has a Vmax which is 7400 times slower than native enzyme. These slower rates are partially explainable by the oxidation-reduction potentials of the modified enzymes. Both covalently bound FAD and noncovalently bound FAD appear to reside in the native flavin binding site of the enzyme. However, once dimerization of the protien has taken place, the noncovalently bound 8-Cl-FAD cannot be induced to form a covalent bond with the protein except under protein denaturing conditions. The implications of these findings are discussed.


Stabilizing effect of various organic solvents on protein. The rate of denaturation of hemaglobin and other proteins by mechanical shaking is strongly affected by organic solvents. A group pf solvents,including alcohols and ketones, was found to stabilize proteins at low concentrations, although these same organic solvents denatured proteins at high concentrations. The stabilizing effect of alcohols increased with increasing chain lenghts. The second group of solvents, including toluene and chloroform, showed only a destabilizing effect, while the third group of solvents such as formamide and pentane had no effect over a wide range of concentrations. Organic solvents may be used to protect or denature a specific protein in solutions containing various proteins.


Structure of the altered oligosaccharide present in glycoproteins from a clone of Chinese hamster ovary cells deficient in N-acetylglucosaminyltransferase activity. Clone 15B cells, derived from Chinese hamster ovary cells and deficient in a specific UDP-N-acetylglucosamine:glycoprotein N-acetylglucosaminyltransferase activity, synthesize glycoproteins with altered oligosaccharide units. Glycopeptides prepared from these glycoproteins contain large quantities of a glycopeptide with the composition (Man)5(GlcNAc)2-Asn whereas parent cells have only small amounts of this glycopeptide. The structure of the glycopeptide was determined by the combination of methylation analysis, acetolysis, Smith periodate degradation, and alpha- and beta-mannosidase digestion. Its complete structure is Manalpha 1 leads to 6[Manalpha1 leads to 3]-Manalpha1 leads to 6[Manalpha 1 leads to 3]-Manbeta1 leads to 4 GlcNAcbeta1 leads to 4 GlcNAc leads to Asn-peptide. The structures of two other glycopeptides found in smaller quantities in clone 15B but not detected in the parent cells were determined and are Manalpha 1 leads to 6 [Manalpha 1 leads to 3]-Manalpha1 leads to 6Manbeta 1 leads to 4 GlcNAcbeta 1 leads to 4GlcNAc-Asn-peptide and Manalpha 1 leads to 3 Manalpha 1 leads to 6[Manalpha 1 leads to 3] Manbeta 1 leads to 4GlcNAcbeta 1 leads to 4GlcNAc-Asn-peptide. It is proposed that the (Man)5(GlcNAc)2-Asn unit is the physiologic acceptor for the particular N-acetylglucosaminyltransferase which is deficient in clone 15B cells and that this reaction is necessary for complex oligosacchari-e biosynthesis.


The dissociation of NO from nitrosylhemoglobin. The reaction between nitrosylhemoglobin and an excess of deoxymyoglobin has been used to study the kinetics of ligand dissociation from Hb4(NO)4 and Hb4(no)1 species. The kinetics of the dissociation of the first NO molecule from Hb4(no)4 was studied by the ligand replacement method. The results indicate that: (a) the ligand dissociation reaction in Hb4(NO)4 is a cooperative process. This is consistent with the results of Moore and Gibson (Moore, E.G., and Gibson, Q.H. (1977) J. Biol. Chem. 251, 2788-2794). (b) alpha and beta chains in the T state formed by adding IHP to Hb4(NO)4 show kinetic heterogeneity. (c) A similar kinetic heterogeneity is shown by alpha and beta chains in the species Hb4NO in the absence of IHP.(d) The value for the NO dissociation rate constant calculated from the slow phases observed in (b) and (c) is similar to that estimated for the R state. These results suggest that the R  to T transition brought about with or without inositol hexaphosphate changes the ligand affinity of one type of the chains much more than of the other. On the basis of IR and EPR studies, it is suggested that alpha chains undergo larger functional changes in R to T transition (or vice versa) in nitrosylhemoglobin. The kinetic parameters for HbNO are compared with those of HbO2 and HbCO and the implications of the results for the reaction mechanism are discussed.


Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits. Cystathionine beta-synthase has been purified from human liver more than 3000-fold by a series of steps including high speed centrifugation, ammonium sulfate fractionation, chromatography on hydroxylapatite and DEAE-cellulose, gel filtration, preparative polyacrylamide gel electrophoresis, and glycerol density gradient centrifugation. The enzyme obtained is homogeneous as judged by polyacrylamide gel electrophoresis in four different systems: native, isoelectric focusing, in sodium dodecyl sulfate, and in 8 M urea. The native enzyme has an estimated molecular weight of 94,000 and is composed of two apparently identical subunits of 48,000. The pure enzyme has a specific activity of 160 units/mg of protein and contains tightly bound cofactor, pyridoxal 5' -phosphate. It is possesses serine sulfhydrase as well as cystathionine synthase activity. It has a broad pH optimum from 8.4 to 9.0, apparent Km values for L-serine of 1.15 mM and for L-homocysteine of 0.59 mM, and a pI of 5.2 The enzyme is stable over a pH range from 6.5 to 8.0 in phosphate buffers and can be stored in 40% glycerol at -15 degrees C for at least 1 month.


Detection and relative quantitation of mRNA for creatine kinase isoenzymes in mRNA from myogenic cell cultures and embryonic chicken tissues. The presence of mRNA coding for creatine kinase M (Mck) and creatine kinase B (B-CK) in RNA from myogenic and fibrogenic cell cultures, embryonic muscle, and embryonic brain tissue was demonstrated by "in vitro" translation in a heterologous cell-free protein-synthesizing system from rabbit reticulocytes. The products were isolated by sensitive immunochemical methods and their identity with isolated M-CK and B-CK was shown by the following criteria: (a) the in vitro synthesized creatine kinases react with the specific antibody against these antigens; (b) the labeled peptides co-migrate with purified creatine kinase on sodium dodecyl sulfate gels in single bands; (c) the labeled peptides form homo- and heterodimers with isolated enzymatically active creatine kinase, thus behaving like authentic creatine kinases. The assay was shown to be reproducible and gave a linear response with increasing amounts of RNA, allowing relative quantitation of mRNA in polysomal RNA for the creatine kinases M and B. MRNA for M-CK was detected in polusomal RAN and total cellular RNA from myogenic cells. It is also present in polysomal RNA from enbryonic muscle and the fraction binding to oligo(dT)-cellulose. mRNA for B-CK could be found in RNA extracted from young myogenic cultures and the fraction of polysomal embryonic brain RNA binding to oligo(dT)-cellulose.


Localization of the arginine tRNA gene to the D segment of T5 bacteriophage DNA. A new procedure for producing duplex DNA fragments. The tRNA genes of bacteriophage T5 are located in four clusters on the continuous heavy DNA strand (Chen, M.-J., Locker, J., and Weiss, S.B. (1976) J. Biol. Chem. 251, 536--547). Three of the four clusters are within the DNA C segment; the fourth cluster, to which only tRNAArg has been localized, maps in a 3.02 kilobase (kb) region of which 1.99 kb are at the right end of the C segment and 1.03 kb at the left end of the D segment. In order to localize the tRNAArg gene further and to define its relationship to the C-D nick, we devised a suitable method for preparing T5 DNA fragments whose ends correspond to the position of the T5 DNA nicks contained in the light DNA strand. In this method, DNA is denatured, partially renatured, and digested with low concentrations of S1 nuclease. Agarose-gel electrophoresis of these digests gives a pattern of bands which correlate in size with the pattern expected from the nicked structure of T5 DNA. Annealing of individual purified T5 [35P]tRNA species to the T5 DNA fragments transferred to nitrocellulose filters shows that tRNAArg hybridizes exclusively to the D fragment and is therefore localized to 1.03 kb at the 5' (left) end of the heavy strand of the D segment. This finding suggests that the promotor for this early gene is to the right of the C-D nick in T5 DNA; hence, the C-D nick does not coincide with this early promotor.


Mutagenesis at a specific position in a DNA sequence. Predefined changes in a known DNA sequence were introduced by a general method. Oligodeoxyribonucleotides complementary to positions 582 to 593 of the viral DNA strand of the bacteriophage phiX174 am3 mutant (pGTATCCTACAAA), and to the wild type sequence in this region (pGTATCCTACAAA), were synthesized and used as specific mutagens. Each of these oligonucleotides was incorporated into a complete circular complementary strand when used as primer on a genetically heterologous viral strand template, by the combined action of subtilisin-treated Escherichia coli DNA polymerase I and T4 DNA ligase. Incomplete duplexes were removed or were inactivated by nuclease S1 and the products were used to transfect spheroplasts of E. coli. Both oligonucleotides induced specific mutations at high efficiency when used with heterologous template (15% mutants among progeny phage). The am phages isolated by this procedure are phenotypically gene E mutants, and contain A at position 587 of the viral strand. They thus appear identical with am3 and provide evidence that the change G leads to A at position 587 is sufficient to produce a defective E function. Since the template for the induction of am mutants carried another genetic marker (sB1), the strains carrying the induced mutations have the new genotype am3 sB1. It should be possible to introduce the am3 mutation into any known mutant strain of phi174 using this same oligonucleotide. Both possible transition mutations were induced in these experiments. In principle, the method could also induce transversions, insertions, and deletions. The method should be applicable to other circular DNAs of similar size, for example recombinant DNA plasmids.


Migration of 40 S ribosomal subunits on messenger RNA in the presence of edeine. The antibiotic edenine induces binding of multiple 40 S ribosomes to reovirus messenger RNAs, producing complexes that sediment rapidly in glycerol gradients. Rapidly sedimenting complexes were also obtained with tobacco mosaic virus RNA and rabbit globin mRNA in the presence of edeine. Following ribonuclease digestion of the heavy complexes, nuclease-resistant 32P-labeled reovirus fragments protected by 40 S ribosomes in the presence of edeine were recovered and fingerprinted. The sequence complexity of the protected material supports the interpretation that 40 S subunits are distributed at many internal sites in each messenger RNA. Additional experiments indicate that binding of the multiple 40 S subunits occurs from a single "entry site" which involves the 5' terminus of the message. This, in turn, implies that in the presence of edeine 40 S ribosomes are able to move along the mRNA chain, attaching initially near the 5' end, then advancing to make room for the next subunit. We suggest that in the absence of antibiotics, also, a 40 S ribosome might bind near the 5' terminus and then advance, stopping where it encounters the first AUG triplet. The effect of edeine might be to interfere with the AUG recognition process, thus allowing the 40 S ribosome to continue unhalted along the message. The present experiments with edeine provide the first direct evidence that 40 S ribosomal subunits are capable of moving along the mRNA chain.


Microporous glassy fillers for dental composites. A microporous filler giving greatly improved finish ability, systemic nontoxic X-ray opacification, low thermal expansion (27.2 x 10(-6)/degrees C), and satisfactory translucencies has been developed for dental composite resin restorations. These fillers are prepared from frits obtained by the low-temperature calcination of gelled inorganic sols followed by a pulsed high-temperature treatment. Composites prepared from these fillers are within the range of commercial products with regard to strength and setting contraction.


The effect of antibiotic additions on the mechanical properties of acrylic cement. Early work on hip prosthesis showed that the metal component would loosen in bone even when screws were used. This practice resulted in the death and resorption of the bone; thus cement was used in orthopedic surgery for firm implantation of prostheses. In recent years antibiotics have been added to the cement as a prophylaxis against infection. This research investigates the effects of antibiotics on the diametral tensile and compression strength of the cement. Samples made with 2 g of antibiotic per surgical packet of bone cement containing the antibiotics gentamicin, keflin, and a combination of the two were tested. These samples were aged at ambient temperature for periods of 1 day and 1, 2, 8, 13, and over 30 weeks. A stastical analysis using a two-way analysis of variance with interaction was conducted. It was concluded that the compression strength was affected by the antibiotic, and not by the aging period, but that there is an antibiotic-aging period interaction. The tensile strength is not affected by either the antibiotic or the aging period, and there is an antibiotic-aging period interaction. Current work being conducted will analyze additional factors and interactions.


Antiinflammatory activities of polymers of o-metacryloyloxybenzoic acid. Antiinflammatory activities of low- and high- molecular-weight polymers of o-methacryloyloxybenzoic acid were compared with the antiinflammatory activity of o-acetoxybenzoic (acetylsalicylic) acid in tests on hind-leg inflammations in rats induced by injection of either Freund's adjuvant or aqueous suspension of kaolin. The antiinflammatory activies of the orally administered polymers cooresponded to 40-90% of the activity of o-acetoxybenzoic acid, and were not substantially dependent on the degree of polymerization.


The effect of surface finish on the anodic polarization of a conventional spherical amalgam. The corrosion of carved, burnished, polished, and burnished--polished samples of a conventional spherical amalgam was studied by anodic polarization in Ringer's solution. The effect of the variation of the mercury content from 40 to 60 wt% on the corrosion of burnished or polished samples was also investigated. It was found that burnished and burnished--polished samples corrode the least and carved samples the most. The current-density peak associated with gamma2 was of greater magnitude in polished specimens than in burnished specimens throughout the range of mercury concentrations investigated. It is hypothesized that lower porosity and more ready passivation of the surface due to a high amount of gamma2 are the reasons that burnished samples corroded less than polished samples in this anodic polarization test.


Experimental infections along subcutaneous conduits. To determine whether progressive infection along percutaneous conduits (PC) usually leads to infection of cardiac assist devices, two PCs each were implanted into the subcutis of 11 dogs. One month later, one end of one conduit was inoculated with either E. coli or S. aureus. The resulting infections in all dogs progressed little during the first two weeks and in 10 of the 11 animals involved less than 40% of the total length of the PC. Bacteriological tests one month after the infecting organisms were introduced showed that they were no longer present at the site of inoculation in 4 of the 11 dogs and no bacteria were found at the opposite end of the inoculated PCs or in the noninoculated PCs. Histological observations confirmed these results and indicated that in all animals encapsulation of the infected area prevented its further enlargement.


Growth and development of the acetabulum in the normal child. Anatomical, histological, and roentgenographic studies. Postmortem studies of ten normal full-term infants and of three children, seven, nine, and fourteen years old, showed that the acetabular cartilage complex is a unit that is triradiate medially and cup-shaped laterally and is interposed between the ilium, ischium, and pubis. This complex is composed of epiphyseal growth-plate cartilage adjacent to these bones, of articular cartilage adjacent to these bones, of articular cartilage around the acetabular cavity, and, for the most part, of hyaline carilage. Interstitial growth within the triradiate part of the cartilage complex causes the hip socket to expand during growth. The concavity of the acetabulum develops in response to the presence of the spherical femoral head. The depth of the acetabulum increased during development as the result of interstitial growth in the acetabular cartilage, of appositional growth at the periphery of this cartilage, and of periosteal new-bone formation at the acetabular margin. At puberty, three secondary centers of ossification appear in the hyaline cartilage surrounding the acetabular cavity. These centers are homologous with other epiphyses in the skeleton. The os acetabuli, which is the epiphysis of the os pubis, forms the anterior wall of the acetabulum. The epiphysis of the ilium, which has been called the acetabular epiphysis, forms a good part of the superior wall of the acetabulum. A small epiphysis of the ischium was seen in the oldest patient, who was fourteen years old. The bone in these epiphyses expands toward the periphery of the acetabulum and thus contributes to its increase in depth.


Morphology of the acetabulum in congenital dislocation of the hip. Gross, histological and roentgenographic studies. At autopsy, the hips of six infants who died soon after birth and had unilateral congenital hip dysplasia were found to have a cartilaginous ridge in the acetabulum which separated the hip socket into two sections. In two of the hips with a moderate degree of dysplasia and in one completely dislocated hip the ridge was formed exclusively by a bulge of acetabular cartilage. In three completely dislocated hips the ridge was formed by a bulge of acetabular cartilage covered by the inverted labrum. The acetabular cartilage showed signs of degeneration whereas the triradiate cartilage was normal. Examination of many newborn infants indicated that hip "clicks" are common and are not diagnostic of hip dysplasia. This diagnosis should be made only when the femoral head slides with a jolt over the acetabular ridge, causing a true positive Ortolani sign. Scattered ossification centers in the acetabular cartilage were seen on the roentgenograms of nearly half of fifty-nine hips with congenital dislocation reduced after the child was two years old, but less frequently in hips reduced at an earlier age.


Computed tomography. Its use in space-occupying lesions of the musculoskeletal system. The value of computed tomography in the diagnosis and management of lesions of the musculoskeletal system is being determined. Illustrative cases including a lipoma of the thigh, osteochondroma of the hip, simple cyst of the ilium, recurrent liposarcoma of the lumbar spine, desmoid tumor in the gluteal region, and postoperative interspace infection of the lumbar spine are presented to indicate the potential value of this procedure in the diagnosis and planning of treatment of musculoskeletal lesions.


Improved fixation of the femoral component after total hip replacement using a methacrylate intramedullary plug. When the distal part of the medullary canal of the femur was plugged with a bolus of methylmethacrylate prior to the insertion of cement and femoral component, fixation of the prosthesis was improved in vitro. A special syringe was devised to introduce the plug at the desired level. When the plug was used, the penetration of the cement into the trabecular bone lining the canal was increased, and subsequent push-out tests showed that the force necessary to disrupt the methacrylate from the bone was significantly greater. Casts of the methacrylate from femora with and without plugged canals showed that the surfaces of the casts made with the canal plugged conformed much more completely with the irregularities of the bone and provided more intimate contact at the cement-bone interface.


The development of a computational stress analysis of the femoral head. Mapping tensile, compressive, and shear stress for the varus and valgus positions. Using a computer-based, two-dimensional finite-element analysis which has wide application to problems involving the hip joint, alterations in the distribution of stress in the femoral head consequent to varus and valgus osteotomy were studied. The mathematical model used in this analysis incorporated experimentally measured spatial variations in the stiffness of the bone of the femoral head and neck. These variations led to patterns of load transmission that were strikingly different from those in a homogeneous material. Because of their lower stiffness, the central region of the head and the medullary region of the neck make very little contribution to weight-bearing, regardless of the orientation of the femoral head. In the neutral configuration (normal neck-shaft angle), the lateral cortex of the neck is in slight tension, while the medial cortex is under strong compression and provides the support for the over-all load on the joint. With increasing valgus angulation, the bending component of the joint load disappears progressively, and when the valgus angulation is 30 degrees in excess of normal essentially equal compressive stresses prevail in both cortices. Varus osteotomy exaggerates the bending component relative to the compressive component of the load. The computed stress patterns in the femoral head and neck for the normal neck-shaft angle show elevations of shear stress where the lateral epiphyseal artery enters and branches within the femoral head. This finding may be significant since this region is the area at risk of infarction in both Legg-Perthes disease in children and idiopathic aseptic necrosis in adults. Since a 30-degree varus angulation induces tensile stresses in the lateral cortex of the neck that are increased fourfold above those for the neutral configuration, it is postulated that force transmitted through the femur when the hip is in abduction could produce shear fractures of the bone in the region of the central branch of the lateral epiphyseal artery and thus occlude this vessel and initiate aseptic necrosis of the femoral head.


The role of mitochondria in growth plate calcification as demonstrated in a rachitic model. In a phosphate-vitamin D-deficiency rachitic model in rats, potassium pyroantimonate was employed as a histochemical stain for calcium at the ultrastructural level in the costochondral growth plates. In the control plates, there was a shift of calcium from an intracellular, mainly mitochondrial location in the top part of the zone of hypertrophic cells to an extracellular, mainly matrix-vesicle location in the bottom part of the zone of hypertrophic cells. In the rachitic plates, mitochondria and cell membranes throughout the bottom of the hypertrophic zone remained heavily loaded with calcium. After treatment with phosphate was started, the mitochondria and cell membranes at the bottom of the hypertrophic zone rapidly lost calcium and matrix calcification began. Thus, in the normal growth plate, matrix calcification begins at the level in the plate where mitochondria lose calcium; in rickets, the matrix does not calcify and mitochondria do not lose calcium; and in healing rickets, calcification begins in the matrix at the bottom of the hypertrophic zone as the mitochondria at that level lose calcium. These findings support the hypothesis that mitochondria play an important role in matrix calcification.


Bilateral total hip-replacement arthroplasty in one stage. We reviewed 122 single-stage bilateral total hip replacements as compared with two other regimens: bilateral total hip replacement performed in stages during the same hospitalization and during separate hospitalizations. When compared with the single procedures, the duration of surgery in the one-stage procedure was not quite doubled while the blood loss was increased by about one-third and the length of stay by about one week. However, the total length of stay in the hospital was reduced by about one-half in comparison with single-admission two-stage replacements and the incidence of local and systemic complications was similar for all three groups, as were the clinical and roentgenographic results. There was one death in the single-stage group due to massive fat embolus.


Skeletal metastases of melanoma.

Skeletal metastases of melanoma. Sixteen hundred and seventy-seven melanoma patients were treated at Duke University Medical Center from 1956 to 1976. Osseous metastases were more common than previously reported and occurred in 116 patients (6.9 per cent), most often in the axial skeleton. Diagnosis was made by roentgenogram, bone scan, or both in the symptomatic patient. Seventy-five patients sustained pathological fractures, most of which were successfully treated conservatively. Nine of the ten patients with neurological symptoms were improved by laminectomy. The grave prognosis for melanoma patients with osseous metastases (mean survival, 3.6 months) led to conservatism even for an impending pathological fracture. Unstable pathological fractures of long bones were treated by internal fixation and irradiation.


Supracondylar fracture of the humerus in children. Seventy-eight supracondylar fractures of the humerus in children were reviewed to compare four kinds of treatment: closed reduction and immobilization in a cast or splint, overhead skeletal traction, side-arm skeletal traction, and Dunlop's skin traction. The skeletal traction device usually used was a winged screw of our own design. The arms treated in overhead traction had significantly less change in carrying angle than those treated in side-arm traction. Significant changes in carrying angle were encountered in three instances of medially impacted so-called non-displaced fractures. There were two instances of significant carrying-angle change due to overgrowth of the lateral aspect of the distal part of the humerus. Overhead traction, utilizing a winged traction screw, was the most effective method of treatment that we found. There were no instances of Volkmann's ischemic contracture.


Surgical treatment of displaced supracondylar fractures of the humerus in children. Analysis of fifty-two cases followed for five to fifteen years. Long-term review of fifty-two displaced supracondylar humeral fractures in children treated by open reduction and crossed Kirschner-wire fixation demonstrated functional results similar to those obtained by closed methods, but fewer and milder cases of cubitus varus deformity (only 25 per cent of patients). The deformity appeared to result from faulty reduction with medial angulation of the distal fragment. Surgical treatment of these fractures may offer, as its principal advantages: reduced hospitalization time, fewer sequelae, more stable fixation, and slightly better anatomical results. No infections or other specific complications (such as myositis ossificans or Volkmann's contracture) were encountered.


In vivo knee stability. A quantitative assessment using an instrumented clinical testing apparatus. Twenty-eight male and twenty-one female subjects with no history of previous injury to their knees were examined using a newly developed clinical testing apparatus designed to record anterior-posterior tibial force versus displacement and varus-valgus moment versus angulation during manual manipulation of the knee. Joint stiffness and laxity were measured from test tracings made with the knee muscles relaxed and tensed. Agreement between these measurements and those made previously on thirty-five fresh cadaver knee specimens was very good. Anterior-posterior laxity averaged 3.7 millimeters in full extension, 5.5 in 20 degrees of flexion, and 4.8 millimeters in 90 degrees of flexion, while the mean varus-valgus laxity was 6.7 degrees in full extension. The common clinical assumption that normal right-left differences are negligible was found to be invalid. Individual right-left differences averaged 26 to 35 per cent for laxity and 19 to 24 per cent for stiffness. There was no discernible tendency for one knee to be more stable than the other; random interchanges of relative stability between the right and left knees were observed for each individual at different knee positions. When requested to tense the knee muscles, these subjects were able to increase their knee stiffness an average of two to four times while knee laxity was reduced to 25 to 50 per cent of the normal value.


The snapping knee of infancy.

The snapping knee of infancy. Three infants with generalized joint laxity and a negative family history had painful episodes of snapping of one or both knees caused by involuntary, momentary lateral subluxation of the tibia. These episodes of subluxation appeared to be due to involuntary contraction of the biceps femoris muscle. Older children learned to produce the phenomenon voluntarily. Treatment should be symptomatic, since the two children who were followed gradually stopped having involuntary subluxations.


The repair of chronic massive ruptures of the rotator cuff of the shoulder by use of a freeze-dried rotator cuff. In sixteen patients with massive tears of the rotator cuff of the shoulder, bridging of the defect with a freeze-dried graft of a rotator cuff from a cadaver produced a satisfactory repair in all cases. A good or excellent functional result was obtained in all but two patients, with a definite decrease or absence of nocturnal pain in all sixteen. The operative technique includes avoidance of a complete acromionectomy and an adequate suture of the deltoid muscle to the acromion after an acromioplasty.


Osseous hydatidosis.

Osseous hydatidosis. Nineteen patients with osseous hydatidosis were treated over a period of thirteen years. There were four deaths. Ten patients became asymptomatic. The treatment used was either curetage or resection, often repeatedly, and protracted lavage of the wound with ethacridine. Five patients received a desensitization treatment (hydatin), but the results in these cases were indeterminate as far as the action of the drug was concerned.


Manchester knee arthroplasty.

Manchester knee arthroplasty. The results of fifty-one Manchester knee arthroplasties in forty-one patients are reviewed and discussed. Excellent and good results were obtained in 85.4 per cent of arthroplasties. Varus and valgus deformity can be corrected and stability preserved or restored. Complications occurred in only twelve patients but resolved in all except one.


The Liverpool Mark II knee prosthesis. A preliminary report. This is a preliminary report of the results of knee joint replacements using the Liverpool Mark II knee joint system which consists of a bicondylar prosthesis and a set of stereotactic instruments. The prosthesis has been developed from Gunston's concept, and the special instruments ensure its accurate insertion through meniscectomy-type incisions placed on either side of the patella. Particular features of the prosthesis are near-normal articulation, and the simplicity of the operation. Sixty-two knee replacements were implanted in forty-two patients between the spring of 1974 and January 1977. After the operation fifty-six knees were painless and four others produced only slight pain. Full extension was obtained in fifty-eight knees, and none showed a valgus or varus deformity. Collateral laxity was absent in all knees. There were two failures. These early results are most encouraging.


The Attenborough total knee replacement. The stabilised gliding knee prosthesis is a compromise between hinged joints and condylar prostheses. It is a two-piece implant designed to allow normal gliding movements of flexion and extension and which, stabilised by a connecting rod between the femoral and tibial components, allows a designed laxity of rotation and lateral movements. A modification of the original femoral component is described. Two hundred and forty-five knee replacement operations have been done between January 1973 and September 1977 and the results are reported. The results using this prosthesis are at least equal to those using hinged or condylar prostheses. So far there has been no case of spontaneous loosening of the components and the implant can be used in patients who, because of severe deformities and instability, are unsuitable for condylar prostheses.


The Stanmore hinged knee arthroplasty.

The Stanmore hinged knee arthroplasty. The Stanmore hinged total knee replacement was introduced in 1969 for severe destructive arthropathy of the knee, and the results of one hundred consecutive operations are presented after an average interval of two and a half years. Insertion of the prosthesis relieved pain in 94 per cent, improved the range of movement in 67 per cent, invariably restored stability and corrected valgus or varus deformity. Gross flexion contractures were improved but not always fully corrected. Serious complications were few, though of three cases of deep infection two came to amputation and one to fibrous ankylosis. There were no mechanical failures of components of the prosthesis.


Arthroplasty of the knee.

Arthroplasty of the knee. Arthrodesis of the knee is a simple and safe operation that ensures stability and freedom from pain. But it is achieved at the expense of movement and occasionally of social acceptability. If arthroplasty is to be recommended, the advantages of arthrodesis must be retained, with the added bonus of a functional arc of movement.


ICLH arthroplasty of the knee: 1968--1977. The essentially satisfactory results from the ICLH implant as used until 1975 were marred by examples of loosening and sinking of the tibial implant, by patellar pain of varying severity, by wear of the tibial implant caused by fragments of cement and by failure consistently to control the alignment of the leg. This report describes the methods now being used to overcome these complications and gives an account of the success so far achieved.


Patellectomy for osteoarthritis. A study of eighty-one patients followed from two to twenty-two years. Eighty-one patients treated by patellectomy for osteoarthritis have been reviewed. Eighty-seven knees were examined with a mean follow-up period of six and a half years. Clinical and radiological assessment was carried out and the results have been analysed. A good result was achieved in 53 per cent, a fair result in 26 per cent and a poor result in 21 per cent. The overall result did not deteriorate significantly with time and the radiological appearance of the tibiofemoral joint deteriorated minimally. Pain before operation, radiological changes at the patellofemoral and tibiofemoral joints and the duration of immobilisation after operation were analysed against the end-result. The only factor before operation that indicated a good prognosis was a minimal radiological change at the tibiofemoral joint. Immobilisation for at least three weeks after operation appeared to be beneficial.


The radiation improvement of polyethylene prostheses. A preliminary study. The radiation crosslinking of high-density polyethylene prostheses was investigated over a wide range of doses in the presence and absence of gaseous crosslinking agents. It was found that in the bulk polymer the crosslinking pattern is completely different from the homogeneous crosslinking that occurs in polymer films. The presence of crosslinking agents causes highly crosslinked polymer to be formed on the surface while the bulk of the polymer is largely unaffected--which is explained in terms of diffusion phenomena. This surface crosslinking has a profound effect on the mechanical properties of the prostheses and restricts cold flow and deformation of the polymer without sacrificing the excellent abrasion-resistance properties of the polyethylene when subjected to high pressures. Based on this research a number of high-density polyethylene knee prostheses have been radiation-crosslinked and the results in vitro appear to be very promising.


The characteristics of acetabular cups worn in the human body. In laboratory tests, the ultra-high molecular weight polyethylene used for the acetabular cups of Charnley hip prostheses has a very low wear rate against steel. In the body radiographic measurements indicate that the polyethylene wears more rapidly. In order to investigate this higher wear rate, the sockets of acetabular cups removed at post-mortem have been examined using optical and electron microscopy. It has been shown that a socket wears predominantly on its superior part and that this is a direct consequence of the orientation of the cup in the body and the direction of loading of the hip. In the worn region the femoral head in effect bores out a new socket for itself, a process which is visible with the naked eye after approximately eight years. Electron microscopy shows that the predominant wear mechanism is adhesion, but after about eight years the appearance of surface cracks suggests that surface fatigue is taking place in addition to this. Laboratory wear tests have shown that pure surface fatigue is not sufficient to account for the high clinical wear rate. Other deformation processes are suggested and discussed with regard to the higher clinical wear rate.


Anterior supracondylar fracture of the humerus (flexion type). A simple technique for closed reduction and fixation in adults and the aged. The management of an anterior supracondylar fracture by closed reduction, traction, percutaneous pinning or open reduction is seldom satisfactory, especially for adults and the aged with a lesser ability to remodel and a slower functional recovery. A new, safe, and simple technique is described in which the condylar mass is pushed posteriorly along the axis of the forearm and the hand is rotated to full supination while the elbow is held in flexion to correct deformities. Fixation is divided into two parts: the circular cast around the upper arm provides a firm buttress onto which the lower fragment is reduced and then the arm is immobilised in a plaster which includes the wrist. Four cases of delayed, comminuted, compound fractures have been fully evaluated clinically and radiologically and the results assessed as good or excellent.


Lower limb arthrodeses in haemophilia.

Lower limb arthrodeses in haemophilia. Sixteen severely haemophilic patients have undergone arthrodesis of one joint of the lower limb in the period 1966 to 1976. There have been nine arthrodeses of the knee and seven of the ankle. The follow-up period was from nine months to eight years. The arthrodeses were secured by internal fixation. The method was not without complications, but a satisfactory bony union resulted in all cases without further surgical intervention.


Triplane osteotomy for severely slipped upper femoral epiphysis. Intertrochanteric osteotomy gives compensatory correction for the severely slipped upper femoral epiphysis without endangering its blood supply. The results of thirty-five such osteotomies carried out over an eighteen-year period are reviewed. The indication for operation was a chronic slip of a third or more of the growth plate in the lateral radiograph. The mean age at operation was fourteen years and the mean follow-up period seven and a half years. The results showed that even a moderate correction of deformity as shown by the radiograph could produce a hip with a functionally satisfactory range of movement. Chondrolysis was the most serious complication and occurred in four hips. The radiological results are discussed in relation to details of operative technique and also to long-term prognosis.


Replacement of the femoral head by open operation in severe adolescent slipping of the upper femoral epiphysis. The stages in adolescent slipping of the upper femoral epiphysis are classified in relation to treatment. The operation of open replacement of the displaced femoral head is described, and the results of a personal series of seventy-three such operations are presented. Open replacement is excellent treatment for severe chronic slipping so long as the growth plate is still open. The greater incidence of avascular necrosis in acute-on-chronic cases is probably due to damage to the blood supply of the head at the time of the acute slip or kinking of the vessels before replacement. Prolonged traction before operation may increase the risk of chondrolysis. Late onset of osteoarthritis when neither avascular necrosis nor chondrolysis has occurred may be due to misfitting of the articular cartilage because of inaccurate reduction.


Halo-pelvic apparatus: peritoneal penetration by pelvic pins. In a series of over 250 patients, four suffered peritoneal penetration by one of the pelvic pins while being put into a halo-pelvic apparatus. In each case a point on the iliac crest two to three centimetres posterior to the anterior superior iliac crest had been used as the anterior landmark for the positioning of the pelvic pin guide. To avoid this complication we advise that the anterior landmark for the guide should be the "tubercle of the crest", five centimetres or more posterior to the anterior superior iliac spine.


Aneurysmal bone cysts of the spine.

Aneurysmal bone cysts of the spine. Aneurysmal bone cysts are uncommon lesions, especially in the spine. Seventy-eight cases have been previously documented in the English literature and an additional fourteen cases are now reported. There is a definite predilection for the lumbar region and the neural arch is the part of the vertebra most commonly affected. It is recommended that treatment should consist of total excision or when this is not possible, curettage. Radiotherapy should be reserved for those few cases where operation is inadvisable.


Congenital spinal extradural cyst (lateral meningocele) simulating acute transverse myelitis. Report of a case. Congenital spinal extradural cysts are rare and may be the cause of acute paraplegia. In their clinical features they closely resemble acute transverse myelitis. Immediate decompression of the spinal cord and removal of the cyst may lead to restoration of normal function. Myelography differentiates these two conditions by showing a cyst in communication with the spinal canal. This investigation must be mandatory.


Familial multiple non-osteogenic fibromata. Three members of a family with a symmetrical distribution of multiple metaphysial lesions presented during childhood with pathological fractures and showed a tendency to spontaneous resolution after maturity. The histological and radiological features suggested multiple non-osteogenic fibromata of bone.


Bone loss in response to long-term immobilisation. The histodynamic response to long-term "non-traumatic" immobilisation was studied in young adult Beagle dogs by means of radiomorphometry and histomorphometry, the right forelimb being encased in plaster and the left forelimb serving as a control. The dogs were killed at two, four, six, eight, twelve, sixteen, twenty, twenty-four, thirty-two and forty weeks and the third metacarpal, radius, ulna and humerus removed for analysis of the contributions of the periosteal, haversian and endosteal envelopes to the bone loss at the mid-diaphysis. The bone mass responded to long-term immobilisation in three stages. First there was a rapid initial loss of bone, reaching its maximum (some 16 per cent of original mass) at six weeks, to which all three bone envelopes, to some extent, contributed. A rapid reversal followed, the bone mass approaching the control values between eight and twelve weeks after immobilisation. A second stage of slower but longer lasting bone loss ended twenty-four to thirty-two weeks after immobilisation; the periosteal envelope was the main contributor (80 to 90 per cent of the total loss). The third stage was characterised by maintenance of the bone mass which had been reduced by some 30 to 50 per cent of original values. This pattern was qualitatively similar in all four bones but the distal bones lost more bone than the proximal bones. The extent of resorption surface and the total histologically "active" periosteal envelope increased parallel to the phases of bone loss. The linear mineralisation rate did not differ significantly between the experimental and control sides.


Hereditary hypophosphataemic rickets with autosomal recessive inheritance and severe osteosclerosis. A report of two cases. We have observed congenital hypophosphataemic rickets in two sons of a marriage between first cousins, their mother being clinically and biochemically normal. Both patients are now approaching middle age. In addition to severe childhood rickets and lifelong hypophosphataemia, their disease is characterised by gross osteosclerosis with extraskeletal ossification, clinically persistent osteomalacia in one and spinal cord compression in the other. The genetics of this disease can be satisfactorily explained only on the basis of autosomal recessive inheritance, a mode which has only once before been reported in the literature. The severity of certain features, which would be expected in a homozygous state, may help our understanding of the more usual X-linked form.


Periosteal resorption of finger phalanges: radial versus ulnar surfaces. Measurement of periosteal resorption (PR) at the radial and ulnar surfaces of the second, third and fourth middle phalanges of one hand in 60 normals and 61 chronic renal failure (CRF) patients showed generally higher involvement at the radial than the ulnar surfaces; however, best diagnostic results were achieved when PR was measured at both radial and ulnar surfaces of the index finger only. With the quantitative method, 31 of 61 CRF patients showed changes, whereas only 22 were identified with the grading method.


Further pitfalls in knee arthrography.

Further pitfalls in knee arthrography. Peripheral separations of the posterior medial meniscus, diagnosed at arthrography, may not be recognized at arthroscopy, arthrotomy or even upon examination of the resected specimen. Arthrographic recognition of an oblique buckethandle meniscal tear may be difficult when the visualized outer fragment maintains a triangular appearance. Articular cartilage defects, out of profile to the x-ray beam, may be suspected at fluoroscopy and confirmed by additional views. There is an icreased incidence of chondromalacia in symptomatic postmeniscectomy knees. Degenerative meniscal changes without arthrographically recognized discrete tears are common, particularly in older individuals. Localized lack of definition of meniscal surfaces may be the only arthrographic finding. Resected specimens invariably show surface irregularities to be more extensive than suggested radiologivally, and frequently there are unsuspected associated horizontal cleavage tears. The clinical implications of degenerated menisci are controversial. A variety of normal synovial folds can simulate the anterior cruciate ligament.


Visualization of vascular structures during routine nephrotomography. Using an immediate nephrotomogram at 30 to 40 seconds, one can show the nephrographic phase and often visualized the renal vein, splenic vein, and portal vein. In a series of 200 consecutive patients, technique was adequate in 169. Some visualization of the renal veins was obtained in 54% and the splenic vein was demonstrated in 25% of the immediate nephrotomograms.


Iatrogenic arterial injuries.

Iatrogenic arterial injuries. A review is presented of patients with an iatrogenic arterial injury treated during the period 1971 through 1976. Twelve patients sustained an arterial injury after diagnostic procedures, eight of them after angiography or heart catheterization. In three cases an injury of the radial artery was caused after puncture or cannulation for monitoring of blood gas values or blood pressure. In seven patients an arterial injury occurred after a therapeutic procedure. In two of them there was a lesion of the external iliac artery after gynaecological operations. Two other cases had an injury of the femoral artery after operation for varicose veins. Not infrequently, arterial injuries after diagnostic as well as after therapeutic procedures are not treated until in a later stage because they are initially overlooked. In only four patients was immediate repair carried out, and in fourteen correction was done later on. In all patients operated upon, the signs and symptoms of the iatrogenic arterial injury were controlled completely and the circulation could restored completely. Some late sequelae of arterial injuries are reviewed. In terms of prevention, the important factors are a sound knowledge of topographical anatomy and improvement of techniques and materials used with diagnostic procedures.


Comparison of expanded PTFE and vein grafts in lower extremity arterial reconstructions. Polytetrafluoroethylene (PTFE) bypasses were used in a series of arterial reconstructions to the popliteal artery (45) and to arteries below that level (11). These were performed in high-risk situations in patients who lacked a suitable saphenous vein. Vein bypasses were performed in a comparable series of high-risk situations in patients having a suitable autologous saphenous vein (45 to the level of the popliteal artery and 11 to an artery below that level). PTFE patency rates at 4-14 months were 43 to 45 (96%) for the femoro-popliteal reconstructions (with a limb salvage rate of 39 to 45 or 87%) and 5 of 11 (45%) for the distal bypasses. Saphenous vein bypass patency rates at 8-14 months were 39 of 45 (87%) for the femoropopliteal reconstructions (with a limb salvage rate of 36 of 45 or 80%) and 5 of 11 (45%) for the distal bypasses. These results justify continued use of PTFE grafts in patients without saphenous veins who require lower extremity arterial reconstructions for limb salvage. The exact place of PTFE grafts in arterial reconstructive surgery of the lower extremity definition based on longer periods of observation.


When can revascularization be limited to the profunda femoris alone? Dealing with lower limbs arteriopathies with combined aorto iliac and superficial femoral occlusive diease and when ischemia leads to operation should an extension bypass to the popliteal or tibial artery be associated every time it is possible? The authors have investigated the results of revascularizing operation above the profunda femoris on 35 limbs (27 patients). On 19 limbs only, has the revascularization been sufficient to cure the distal ischemia. On the other 16 limbs, a second operation was necessary 7 times an extension bypass to the popliteal or tibial artery, once an above knee amputation, twic a below knee amputation. From the comparison of these results with the degree of ischemia and the arteriographic aspect of the profunda femoris, the author's conclusion is that revascularization must extent below the profunda femoris unless the profunda is in good condition and there is no rest ischemia.


EXternal iliac "steal syndrome".

EXternal iliac "steal syndrome". A case of steal syndrome in the external iliac artery characterized by distinct clinical symptoms and by a reversal of blood flow in the internal iliac artery secondary to the closure of the common iliac artery, has been described. The patient reported marked decrease in sexual activity and impariment of erection in addition to intermittent claudication of the corresponding lower extremity. He was able to achieve and maintain an erection only with absolute rest. The erection disapperaed immediately when he moved his lower extremities. Endarterectomy of the common external and internal iliac arteries along with an aortofemoral bypass, resulted in disapperrance of both claudication and his sexual impotence.


True aneurysm of the abdominal aorta due to blunt trauma. This paper presents the case history of a 13-year-old boy who developed a true aneurysm of the abdominal aorta after a blunt abdominal trauma. A few months after the accident the aneurysmm was resected and replaced by a graft. Three previously published cases of abdominal aortic aneurysm after blunt trauma are briefly outlined. In each of these cases, however, a false aneurysm was involved. A traumatic aneurysm can develop after a penetrating or a blunt trauma, with complete or partial lesion of the aortic wall. Consequences of such a partial lesion are described. Operative treatment is required in the presence of an intimal flap or an aneurysm.


Paradoxical embolism.

Paradoxical embolism. Paradoxical embolization of venous thrombus into the abdominal aortic bifurcation has been diagnosed by means of aortography. Lower limb phlebothrombosis accounting for the embolus formation has been demonstrated by phlebography. Arterial embolectomy and venous thrombectomy were successfully performed. Recovery was complete without sequelae.


Positive and negative effects of anticoagulant treatment during and after arterial embolectomy. Eighty-four consecutive patients subjected to arterial embolectomy were studied. Cardiac arrythmia was found in 64% of the cases. The incidence of upper limb embolus was 15%, and lower limb 85%. Our total results are in agreement with most reports--the limb salvage rate of survivors was 84%, and the amputation rate was 16%. The primary mortality, 18%, is a rather low figure considering the high mean age (72 years) of the material. The prognosis after embolectomy was dependent on time from onset of symptoms and on the age of the patient. In the group of patients treated with anticoagulants the primary mortality was 7%, and in the untreated group 26%. The results of this investigation of patients treated with arterial embolectomy indicate: Adequate anticoagulant treatment during the per- and postoperative period decreased the primary mortality significantly, possibly as a result of fewer thromboembolic complications. The anticoagulant treatment was associated with a higher frequency of local complications as postoperative hemorrhage and reocclusions, which increased the frequency of reoperations and amputations. These drawbacks of anticoagulant treatment could possibly be counteracted by proper measures during the operation.


Successful surgical management of a dissecting aneurysm of the ascending and transverse aorta with heart failure due to sudden, severe aortic valve insufficiency. A dissecting aneurysm of the ascending and transverse aorta with heart failure due to sudden severe arotic valve insufficiency in a 47-year-old man has been treated successfully. Vasodilator therapy was done preoperatively, and then hemodynamics was improved markedly. A selective perfusion technique by using separate pumps at pre-determined flow-rates with hypothermia was utilized. The replacement of both the aortic valve and the ascending and transverse aorta involving brachiocephalic artery with a prosthetic valve and expanded polytetra-fluoroethylene coated woven Dacron grafts was performed.


Syringe holder for constant Fogarty balloon catheter inflation. Use of the Fogarty balloon catheter for hemostasis in vascular trauma and difficult vascular dissections requires constant balloon inflation. A syringe holder to maintain balloon inflation without requiring constant attention of an assistant has been designed. Other applications of the syringe holder are discussed, including use with endotracheal tubes, gastrointestinal tubes, and for Fogarty balloon occlusion of pulmonary segments.


Surgical treatment of the "parachute mitral valve" complex in infancy (report of a case). The case is presented of a 15-month-old male, affected by severe mitral valve regurgitation associated to aortic coarctation. The surgical treatment consisted in replacement of the mitral valve by a Hancock prosthesis followed, at a second state, by resection of the coarctation. The mitral insufficiency was secondary to an anomaly of the subvalvular apparatus of the "Parachute Valve" type. The incidence of defects associated to congenital mitral insufficiency is commented. The surgical indications for replacement or repair of these anomalies in infancy are discussed, and the surgical results achieved to data are analysed. Emphasis is made on the convenience, in case the corrective procedure requires valvular replacement, of implanting a low-profile biological prosthesis, which does not require anticoagulant therapy.


Successful repair of left ventricular aneurysm due to blunt trauma. A case report. The authors report the successful surgical treatment of their patient with posttraumatic aneurysm of the left ventricle. On the basis of the data reported in the literature and on their own experience, the authors consider this lesion absolute indication for surgery.


Mitosis in Barbulanympha. I. Spindle structure, formation, and kinetochore engagement. Successful culture of the obligatorily anaerobic symbionts residing in the hindgut of the wood-eating cockroach Cryptocercus punctulatus now permits continuous observation of mitosis in individual Barbulanympha cells. In Part I of this two-part paper, we report methods for culture of the protozoa, preparation of microscope slide cultures in which Barbulanympha survived and divided for up to 3 days, and an optical arrangement which permits observation and through-focus photographic recording of dividing cells, sequentially in differential interference contrast and rectified polarized light microscopy. We describe the following prophase events and structures: development of the astral rays and large extranuclear central spindle from the tips of the elongate-centrioles; the fine structure of spindle fibers and astral rays which were deduced in vivo from polarized light microscopy and seen as a particular array of microtubules in thin-section electron micrographs; formation of chromosomal spindle fibers by dynamic engagement of astral rays to the kinetochores embedded in the persistent nuclear envelope; and repetitive shortening of chromosomal spindle fibers which appear to hoist the nucleus to the spindle surface, cyclically jostle the kinetochores within the nuclear envelope, and churn the prophase chromosomes. The observations described here and in Part II have implications both for the evolution of mitosis and for understanding the mitotic process generally.


Protection of the ischaemic myocardium by glucose-insulin-potassium infusion assessed by ventricular function and electron microscopy. The protective effect of GIK infusion on the ischaemic myocardium was assessed by isovolumic function tests and electron microscopy. There were two control groups, group 1 hearts underwent 2 hours of continous normothermic cross-perfusion and group 2 hearts endured 2 hours of ischaemia. Group 3 hearts were administered GIK solution prior to ischaemic arrest. The group 3 hearts showed less loss of contractile force and contractile velocity from the ischaemic period compared to group 2 hearts, but no benfit was shown in terms of compliance. Electron microscopic examination showed slightly less damage in the group 3 hearts compared to group 2 hearts. Group 1 hearts maintained better function than either of the other two groups. Ultrastructure was not examined in group 1 hearts. A slight protective effect of GIK on the ischaemic myocardium was thus confirmed.