[Hydration of the left spiral of the poly-L-proline type. Study by the Monte Carlo method]. The paper exhibits results of hydration shell Monte Carlo calculations in poly-L-proline II and extended helix conformation and in alpha-helical and beta-structural conformations for comparison. It was found that left-handed helix of poly-L-proline II type as well as epsilon-helix are characterized by very favorable hydration. Therefore this conformation has preference as compared to other standard conformations of the main polypeptide chain. This determined inevitability of cold denaturation of protein.


[A new approach to the thermodynamic role of imino acids in collagen. Solution of a thermodynamic paradox]. The dependence of denaturation transition thermodynamic parameters in various collagens from imino acid compositions has been analysed. Computational and experimental data suggest independence of the collagen molecule hydration on imino acid composition and sequence in the polypeptide chain. The continuous net of hydrogen bonds is interrupted, if imino acid residues occur in the sequence of amino acid residues, as follows from Monte Carlo computations, because the hydrogen of NH-group plays sufficient role in water shell formation for this conformation. As a consequence, entropy of denatured collagen-water system increases hand by hand with increasing imino acid content and therefore delta S increases. The increase of enthalpy of transition from imino acid content is determined by favorable Van der Waals interactions of pyrrolidine rings in native triple helical collagen structure. It was pointed out that proline role is determined by decreasing hydration in the single stranded polypeptide chain in Polyproline II conformation that leads to an increase of entropy of the polypeptide-water system. Thus, the collagen structure formation by imino acids is promoted in the water media due to single chain left-helical conformation being unfavorable for proline residues as well as due to the enthalpy nature of the triple helix stabilization.


[Inhibition of psoralen sensitized photohemolysis by a marigold (Bidentis tripartita) extract]. Hemolysis induced by psoralen and UV-A radiation (PUVA-hemolysis) was significantly inhibited by the addition of Bidentia tripartita extract. The rate of hemolysis was reduced both when the extract was present during irradiation, or added after PUVA-treatment. The inhibition effect was more pronounced when the extract was present during irradiation.


[Dark and photosensitized hemolysis of erythrocytes in the presence of dithranol]. Ditranol (1,8-dihydroxy-9-antrone) induced dark lysis of erythrocytes. After irradiation of the cells with UV-light (366 nm UV-A light) in the presence of ditranol (DUVA-effect) the hemolytic effect increases. It has been found that antioxidant butylated hydroxytoluene BHT in the concentration 10(-7) M did not affect the dark lysis, while with increased BHT concentration up to 10(-5) M the hemolytic effect of ditranol was intensified. The presence of BHT in the above concentration under DUVA-effect did not change the velocity of cell lysis. Sodium aside did not affect the dark hemolysis of ditranol, but it inhibited photosensitized hemolysis.


Modification of dry 1,2-dipalmitoylphosphatidylcholine phase behavior with synthetic membrane-bound stabilizing carbohydrates. Carbohydrates, particularly disaccharides, have been shown to accumulate in organisms as protective solutes during periods of stress such as freezing and desiccation. Cholesterol and lipid derivatives containing the protective carbohydrates galactose or maltose, O-[11-(1-beta-D-galactosyloxy)-3,6,9-trioxaundecanyl]ol (TEC-GAL), O-[11-(1-beta-D-maltosyloxy)-3,6,9-trioxaundecanyl]ol (TEC-MAL), and 14-(galactosyloxy)-N,N-dimethyl-O-(dipalmitoylphosphatidyl)- 6,9,12-trioxa-3- azoniatetradecanol (DP-GAL), have been synthesized to investigate the interaction of a protective carbohydrate moiety tethered to the 1,2-dipalmitoylphosphatidylcholine (DPPC) bilayer surface. Toward this goal, we have investigated the calorimetric and infrared spectroscopic behavior of mixtures of DPPC codried with these glycolipids. The synthetic glycolipids are shown to decrease significantly the main transition temperature (max Cp) of dry DPPC with a concomitant reduction in the cooperativity of the transition, as evidenced by a decrease in the enthalpy with increasing glycolipid. The decrease in transition temperature is shown to be related to chain melting monitored by the CH2 symmetric stretch frequency through the transition using FTIR. We also present evidence that the glycolipids interact with the interfacial region of DPPC, as shown by the decrease in the phosphate symmetric stretch intensity with increasing concentration of glycolipid. These observed effects are similar to the action of bulk protective sugars with DPPC; however, the concentration of glycolipid and the associated carbohydrate concentration needed to effect the observed changes are reduced compared to the quantity of bulk carbohydrate previously shown to give similar results with DPPC.


Coupling of DTPA to proteins: a critical analysis of the cyclic dianhydride method in the case of insulin modification. The reaction between the cyclic dianhydride of diethylenetriaminepentaacetic acid (DTPA), a bifunctional reagent, and proteins under various conditions was studied using porcine insulin as a model protein. The reaction was compared with that between citraconic anhydride, a monofunctional reagent, and insulin. Products were characterized chromatographically and electrophoretically before and after deesterification by hydroxylamine. A DTPA-conjugated product was further characterized by proteolytic fragmentation. The reaction with citraconic anhydride yielded the expected number of products exclusively acylated on amino groups. In contrast, the reaction with the cyclic dianhydride of DTPA under all conditions examined yielded a much higher number of products than expected. Among the products formed were O-acylated ones and products of intermolecular cross-linking. It is concluded that the use of the cyclic dianhydride of DTPA does not allow the reliable preparation of proteins or other macromolecules conjugated with a high number of DTPA molecules in which each molecule of DTPA is linked to one amino group of the macromolecule through a single amide bond.


Characterization of mercapturic acid and glutathionyl conjugates of benzo[a]pyrene-7,8-dione by two-dimensional NMR. Non-K-region polycyclic aromatic hydrocarbon (PAH) o-quinones represent alternative metabolites of PAH trans-dihydro diol proximate carcinogens. These PAH o-quinones react readily with glutathione and N-acetyl-L-cysteine, and these adducts may be responsible for their detoxication. Reactions between benzo[a]pyrene-7,8-dione and either N-acetyl-L-cysteine or glutathione gave three predominant products which were purified by semipreparative reverse-phase high-pressure liquid chromatography and characterized by homonuclear two-dimensional correlation spectroscopy (COSY). The first product corresponded to a Michael type, 1,4-addition product isolated at the level of quinone oxidation. The second product converted to the first and is a presumptive 1,4-addition product isolated at the level of hydroquinone oxidation. The third product was 7,8-dihydroxybenzo[a]pyrene (a hydroquinone) and was formed as a result of the reductive potential of the thiol. Additional proof for the catechol structure was obtained by its conversion to its diacetate and its identity with authentic 7,8-diacetoxybenzo[a]pyrene. The structures of these adducts and intermediates confirm that thiol addition involves formation of the ketol and rearrangement to give a catechol followed by oxidation to yield the quinone adduct. No evidence was obtained for the formation of either bisphenol or bisglutathionyl adducts. The COSY spectra provide the first complete structure of a benzo[a]pyrenyl-peptide conjugate.


A novel galactose- and arabinose-specific lectin from the sponge Pellina semitubulosa: isolation, characterization and immunobiological properties. A new lectin from the sponge Pellina semitubulosa is derived which was extracted and purified to homogeneity. The purified lectin is probably a hexamer of polypeptide chains (each M(r) 34,000) which are covalently linked via disulfide linkages; the isoelectric point is 6.1. The lectin displays the following specificities: D-galactose (50% inhibition of hemagglutination at 0.2 mM) = L-arabinose (0.2 mM) greater than D-fucose (1.5 mM) greater than D-glucose (3.0 mM). It precipitates human erythrocytes (A1, A2, A1B, B, and O) with a titer between 2(8) and 2(11) and erythrocytes from sheep and rabbits with a titer between 2(5) and 2(10). The Pellina lectin displays a strong mitogenic effect on spleen lymphocytes from mice. Immunochemical analyses revealed that both murine T- and B-lymphocytes display a capping of the lectin receptors on their cell surfaces after lectin treatment. Murine macrophages were found to endocytose the lectin. Pellina lectin at concentrations between 0.3 and 10.0 micrograms/ml potently enhances interleukin 1 (IL-1) release from mouse peritoneal macrophages and interleukin 2 (IL-2) production in mixed murine lymphocyte cultures.


Effect of different binding proteins on the detection limits and sensitivity of assays based on biotinylated adenosine deaminase. The properties of binding proteins that control the nature and magnitude of inhibition of the enzyme-ligand conjugates in homogeneous enzyme-linked competitive binding assays were investigated. An assay for biotin that employed adenosine deaminase as the enzyme-label was used as a model system because of the availability of several biotin-specific binders with different characteristics. It was found that the association constant between the ligand and the binding protein, as well as the depth of the binding pocket, affect the response characteristics of the assay. In addition, the reported data suggest that steric-hindrance effects also contribute toward the sensitivity and detection-limit capabilities of the assay.


Characterization of an aromatic amino acid aminotransferase from Rhizobium leguminosarum biovar trifolii. The most abundant aromatic amino acid aminotransferase of Rhizobium leguminosarum biovar trifolii was partially purified. The molecular mass of the enzyme was estimated to be 53 kDa by gel filtration. The enzyme transaminated aromatic amino acids and histidine. It used aromatic keto acids and alpha-ketoglutaric and oxalacetic acids as amino-group acceptors. The optimum temperature was 35 degrees C. Using phenylalanine and alpha-ketoglutaric acid as substrates the activation energy was 46.2 kJ.mol-1 and for the couple tryptophan:alpha-ketoglutaric acid it was 70.3 kJ.mol-1. The optimum pH was different for each substrate: 7.3 for phenylalanine, 7.9 for histidine and 8.7 for tryptophan.


Molecular probes for muscarinic receptors: derivatives of the M1-antagonist telenzepine. Functionalized congeners of the M1-selective muscarinic antagonist telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H- thieno[3,4-b][1,5]benzodiazepin-10-one) were developed and found to bind to the receptor with affinities (Ki values) in approximately the nanomolar range. The derivatives contain a 10-aminodecyl group, which provides a nucleophilic functionality for further derivatization. The attachment of a spacer chain to the distal piperazinyl nitrogen was based on previous findings of enhanced affinity at muscarinic receptors in an analogous series of alkylamino derivatives of pirenzepine [J. Med. Chem. (1991) 34, 2133-2145]. The telenzepine derivatives contain prosthetic groups for radioiodination, protein cross-linking, photoaffinity labeling, and fluorescent labeling and biotin for avidin complexation. The affinity for muscarinic receptors in rat forebrain (mainly m1 subtype) was determined in competitive binding assays vs [3H]-N-methylscopolamine. A (p-aminophenyl)-acetyl derivative for photoaffinity labeling had a Ki value of 0.29 nM at forebrain muscarinic receptors (16-fold higher affinity than telenzepine). A biotin conjugate displayed a Ki value of 0.60 nM at m2-receptors and a 5-fold selectivity versus forebrain. The high affinity of these derivatives makes them suitable for the characterization of muscarinic receptors in pharmacological and spectroscopic studies, for peptide mapping, and for histochemical studies.


Modulation by dexamethasone of insulin binding and insulin receptor mRNA levels in U-937 human promonocytic cells. Treatment with 5 x 10(-6) M dexamethasone stimulated insulin binding in human promonocytic U-937 cells. When curvilinear Scatchard plots were examined according to the one-site model, only changes in affinity, but not in receptor numbers, were observed. However, when the two-site model was applied, an increase in both the affinity and the number of the high affinity-low capacity sites was observed, with maximum values at 15 h. By contrast, the low affinity-high capacity sites did not undergo significant alterations. Northern blot assays revealed two insulin receptor-related mRNAs of approximately 11 and 7 kb in size. Dexamethasone increased the levels of these RNAs, following similar kinetics to those of high affinity receptor expression. This suggests that the 11 and 7 kb species carry information for high affinity insulin receptors, and that in U-937 cells the expression of this receptor subclass is primarily regulated at the mRNA level.


Carboranyl peptide-antibody conjugates for neutron-capture therapy: preparation, characterization, and in vivo evaluation. Two model peptides rich in boron and prepared by Merrifield syntheses, dansyl.(nido-CB)2, (1) and dansyl.(nido-CB)10.Lys.Ac (2), where nido-CB represents the alpha-amino acid [nido-7-CH3-8-(CH2)3CH-(NH2)COOH-7,8-C2B9H10]-, were conjugated with the anti-CEA mAb T84.66 using peptide active ester reagents. The dansyl groups provided a means of fluorimetric analysis of mAb conjugates which was augmented by conventional amino acid analyses for nido-CB. The conjugate of 1 contained an average of 63 B atoms per mAb molecule. The mAb conjugate of 2 was chromatographically separated into a strongly fluorescent high molecular weight aggregated fraction (HMW) and a less intensely fluorescent monomeric fraction. Both fractions retained immunoreactivity. The HMW species contained an average of ca. 490 B atoms/mAb molecule, as determined by amino acid analysis. Biodistribution data were collected using nude mice bearing LS174T xenografts and 125I-labeled mAb conjugates. While the lightly B-loaded dipeptide conjugate gave biodistribution results which resembled those of native T84.66 mAb, the undecapeptide conjugate displayed greatly enhanced liver uptake and decreased tumor accretion. These results suggest that as the boron-containing burden on the supporting immunoprotein is greatly increased, as in the case of the T84.66-2 conjugate, loss of circulating conjugate to liver effectively competes with the desired tumor localization. Means which might be taken to circumvent this difficulty have been described elsewhere (ref 15).


New chelating agent for attaching indium-111 to monoclonal antibodies: in vitro and in vivo evaluation. 111In possesses excellent radiophysical properties suitable for use in immunoscintigraphy of cancerous tissues when attached to an antitumor antibody. However, 111In has a tendency to accumulate in normal tissues such as liver. Instability of the linkage between 111In and antibody may contribute to this problem. To avoid this, we developed a new bifunctional chelating agent, 1,3-bis[N-[N-(2-aminoethyl)-2-aminoethyl]-2-aminoacetamido]-2-(4- isothiocyanatobenzyl)propane-N,N,N',N'',N''',N'''',N''''',N'''''- octaacetic acid (LiLo), that forms a kinetically stable chelate with metal ions such as indium. Using LiLo, indium-111 was conjugated to a human monoclonal antibody, 16.88. Competitive binding analysis revealed that the 16.88-LiLo conjugate is as immunoreactive as the unconjugated native antibody. This conjugate was compared with 111In-16.88, where diethylenetriaminepentaacetic acid dianhydride (DTPAa) was used as the chelating agent. In vitro stability studies showed that 111In was more stably bound to 16.88-LiLo than to 16.88-DTPA. Biodistribution studies in athymic mice bearing colorectal tumor xenografts indicated less liver retention with 16.88-LiLo than with 16.88-DTPA. These results demonstrate that LiLo is superior to DTPAa for attachment of 111In to the monoclonal antibodies.


Influence of dietary cholesterol on polyunsaturated fatty acid composition, fluidity and membrane-bound enzymes in liver microsomes of rats fed olive and fish oil. Male rats were fed diets containing olive or marine fish oils (10% w/w) with or without added cholesterol (1% w/w). After six weeks of feeding, the major fatty acid composition, fluidity, fatty acid desaturating and cholesterol biosynthesis/esterification related enzymes of liver microsomes were determined. Both olive oil and marine fish oil diets, without added cholesterol, enriched content of oleic and docosahexaenoic acids, respectively, of rat liver microsomes. The results were consistent with reduction in delta 6 and delta 5 desaturation of n-6 essential fatty acids and higher fluidity in the marine origin oil group. Inclusion of cholesterol into diets resulted in decreased membrane arachidonic acid content, with concomitant increase in linoleic acid content. Cholesterol feeding also decreased delta 6 and delta 5 desaturase activities, as well as membrane fluidity. Furthermore, the activity of acyl-CoA:cholesterol acyltransferase decreased, whereas the activity of hydroxymethylglutaryl-CoA reductase increased, in liver microsomes from both cholesterol-fat groups.


Essential arginines in mercuric reductase isolated from Yersinia enterocolitica 138A14. The mercuric reductase from Yersinia enterocolitica 138A14 was inactivated by the arginine modifying reagents 2,3-butanedione and phenylglyoxal. The inactivation by 2,3-butanedione exhibited second order kinetics with rate constant of 32 min-1 M-1. In the case of phenylglyoxal, biphasic kinetics were observed. The oxidized coenzyme (NADP+) prevented inactivation of the enzyme by the alpha-dicarbonyl reagents, whereas the reduced coenzyme (NADPH) enhanced the inactivation rate. The loss of enzyme activity was related to the incorporation of [2-14C] phenylglyoxal; when two arginines per subunit were modified the enzyme was completely inactivated.


New strategy in glycopolymer synthesis. Preparation of antigenic water-soluble poly(acrylamide-co-p-acrylamidophenyl beta-lactoside). Stereospecific phase-transfer-catalyzed glycosidation of acetobromolactose 3 with p-nitrophenoxide gave the peracetylated 1,2-trans-beta-D-4-nitrophenyl lactoside 4. Functionalization of 4 into an N-acryloyl monomer was achieved by catalytic transfer hydrogenation of the nitro group, followed by N-acryloylation of the resulting amino group, on both O-acetyl-protected and unprotected disaccharides. Copolymerization of 4-acrylamidophenyl beta-lactoside (9) with acrylamide, initiated by ammonium persulfate, afforded a water-soluble carbohydrate copolymer (glycopolymer). The antigenicity of the new polymer was demonstrated by agar gel diffusion with Arachis hypogaea (peanut) and Ricinus communis (castor bean) lectins. Quantitative precipitation and enzyme linked lectin assays (ELLA) were also performed with peanut lectin.


In vitro digestion of dystrophin by calcium-dependent proteases, calpains I and II. Dystrophin is a cytoskeletal protein which is thought to play an important role in membrane physiology since its absence (due to gene deficiency) leads to the symptoms of Duchenne muscular dystrophy (DMD). Some disruption in the regulation of intracellular free Ca2+ levels could lead to DMD-like symptoms. In this study, calpains, which are very active calcium-dependent proteases, were examined for their capacity to hydrolyse dystrophin in vitro. The results show that calpains are able to split dystrophin and produce breakdown products of different sizes (the degree of cleavage being dependent on the incubation time with proteases). The time-course of protease degradation was examined by Western immunoblot using three polyclonal sera which were characterized as being specific to the central (residues 1173-1728) and two distal parts of the molecule ie specific to the N-terminal (residues 43-760) or the C-terminal (residues 3357-3660) extremities of the dystrophin molecule. The cleavage patterns of dystrophin showed an accumulation of some major protease-resistant fragments of high relative molecular mass (250-370 kDa). These observations demonstrate that calpains digest dystrophin very rapidly when the calcium concentration is compatible with their activation. For instance, it is clear that calpains first give rise to large dystrophin products in which the C-terminal region is lacking. These observations suggest that dystrophin antibodies specific to the central domain of the molecule should be used to detect dystrophin for diagnostic purposes and before any conclusion as to the presence or absence of dystrophin can be deduced from results obtained using immunoanalyses of muscle biopsies.


Evolutionary divergence plots of homologous proteins. A simple and efficient method is described for analyzing quantitatively multiple protein sequence alignments and finding the most conserved blocks as well as the maxima of divergence within the set of aligned sequences. It consists of calculating the mean distance and the root-mean-square distance in each column of the multiple alignment, averaging the values in a window of defined length and plotting the results as a function of the position of the window. Due attention is paid to the presence of gaps in the columns. Several examples are provided, using the sequences of several cytochromes c, serine proteases, lysozymes and globins. Two distance matrices are compared, namely the matrix derived by Gribskov and Burgess from the Dayhoff matrix, and the Risler Structural Superposition Matrix. In each case, the divergence plots effectively point to the specific residues which are known to be essential for the catalytic activity of the proteins. In addition, the regions of maximum divergence are clearly delineated. Interestingly, they are generally observed in positions immediately flanking the most conserved blocks. The method should therefore be useful for delineating the peptide segments which will be good candidates for site-directed mutagenesis and for visualizing the evolutionary constraints along homologous polypeptide chains.


Overproduction and purification of lysyl-tRNA synthetase encoded by the herC gene of E coli. Lysyl-tRNA synthetases are synthesized from two distinct genes in E coli, lysS and lysU, but neither gene product has been purified distinctively by using overproducing systems. The lysS gene has been identified by a herC mutation which restores maintenance of the mutant ColE1 replicon. The herC gene product was overproduced by using a tac promoter fusion and purified to homogeneity. The purified HerC protein possesses a lysyl-tRNA synthetase activity as predicted by the sequence identity of herC to lysS. The procedure is useful for rapid mass-scale purification of lysyl-tRNA synthetase.


A comparison of case retrieval times: film versus picture archiving and communications systems. One of the advantages that a picture archiving and communications system (PACS) is supposed to provide over a film-based operation is improved performance in retrieving images. Although it seems self-evident that this should be so, this experiment was intended to verify this and to provide some time comparisons for the two methods. The experiment consisted of randomly selecting ultrasound and computed tomography cases and determining how long it took to retrieve files at a PACS workstation or in person from the file room. To simulate actual retrieval volumes, a total of 40 cases from current to 6 months old, 20 cases from the past year, and 10 cases more than 1 year old was selected. Results indicate that PACS retrieval can indeed be faster than file room retrieval. However, the difference is less for recent cases than for older cases. For cases 6 or fewer months old, the workstation retrieval was approximately 2.5 minutes faster per case than the film file room. This time difference increased markedly when extended to the 1-year and older-than-1-year groups. This report details the results of this study and provides information about the reliability of the two archives.


Design of a high-speed, high-resolution teleradiology network. A teleradiology system acquires radiographic images from one location and transmits them to one or more distant sites where they are displayed and/or converted to hard-copy film recordings. The long-term goal of teleradiology research is to show that teleradiology systems can provide diagnostically equivalent results when compared with conventional radiographic film interpretation. If this hypothesis is proven, provision of the following radiology services will be improved: (1) providing for primary interpretation of radiological images for patients in underserved areas as well as in other medical facilities; (2) integration of radiological services for multihospital/clinic health care provider consortiums; (3) improving emergency service and intensive care unit coverage; (4) offering consulting-at-a-distance with subspecialty radiologists; and (5) providing radiologists in the community or in rural areas with immediate access to large academic centers for help in the interpretation of difficult and problematic cases. We are designing a high-speed, high-resolution teleradiology network that will communicate between our level 3 medical center and several outlying medical centers within the metropolitan area. Computed tomography (CT), magnetic resonance (MR), and screen-film examinations will be digitized to 2,000 x 2,000 or 4,000 x 4,000 pixels at the remote sites, transmitted to the central referral facility, and sent to a laser film printer, replicating the original film. This film may then be used for primary diagnosis, overreading/consultative purposes, or for emergency department preparation. Inherently digital modality data (eg, MR and CT) can be sent without digitization of the multiformat film if desired.


Teleradiology via narrow-band integrated services digital network (N-ISDN) and Joint Photographic Experts Group (JPEG) image compression. The importance of remote access to both radiological images and medical information has stimulated many demonstration projects that use a variety of telecommunications providers' offerings. Teleradiology, through modest cost channels, can achieve adequate response times using a combination of narrow-band integrated services digital network (N-ISDN) and data compression. A demonstration project, developed in collaboration with Southwestern Bell Technology Resources, Inc, uses the aggregate bandwidth of two B channels (achieving a rate of 120 kilobits per second) and a block-oriented discrete cosine transform compression/decompression implementation based on the Joint Photographic Experts Group Standard for Still Image Compression. System response measurements for an Inquiry and Display Station accessing the Mallinckrodt Institute of Radiology's Radiology Image and Information Management Testbed via the N-ISDN connection show response times to be within 20 seconds. Viewing applications have been shown at sites within St Louis and at Radiological Society of North America, 1990, in Chicago.


Quality monitoring of soft-copy displays for medical radiography. As presentation of medical radiographic images on soft-copy displays (cathode ray tubes) becomes increasingly prevalent in electronic radiography, methods of quality assurance must be developed to ensure that radiologists can effectively transfer film-based reading skills. Luminance measurements provide the basis for evaluating the state of soft-copy displays. An integrated approach has been implemented at Mallinckrodt Institute of Radiology (MIR, Washington University, St Louis, MO) that facilitates measurement of geographically distributed soft-copy displays with centralized data logging, performance tracking, and calibration. MIR's central radiology image manager exercises the display station that drives the monitor, harvests the measurement data, stores the results, and submits the resulting data for additional processing. The luminance measurements are collected by a small, portable, photometric instrument designed at MIR that includes a serial port that is accessed via local area terminal service supported by the radiology image manager. The design details of the photometric instrument and example luminance characteristics of several soft-copy displays used at MIR are presented in this report.


Compressed radiological images and workstation viewing. The viewing of radiological images on workstations has peculiarities that must be taken into account in the design of a compression technique. The images may be manipulated on a workstation to change the contrast, to change the center of the brightness levels that are viewed, and even to invert the images. Because of the possible consequences of losing information in a medical application, bit-preserving compression is used for the images used for diagnosis. However, for archiving, the images may be compressed to 10% of their original size. A compression technique based on the discrete cosine transform takes the viewing factors into account by compressing the changes in the local brightness levels. The compression technique is a variation of the Consultive Committee on International Telephony and Telegraphy Joint Photograph Experts Group compression that suppresses the blocking of the discrete cosine transform except in areas of very high contrast.


Portable image-manipulation software: what is the extra development cost? A hospital-wide picture archiving and communication system (PACS) project is currently under development at the University Hospital of Geneva. The visualization and manipulation of images provided by different imaging modalities constitutes one of the most challenging component of a PACS. It was necessary to provide this visualization software on a number of types of workstations because of the varying requirements imposed by the range of clinical uses it must serve. The user interface must be the same, independent of the underlying workstation. In addition to a standard set of image-manipulation and processing tools, there is a need for more specific clinical tools that can be easily adapted to specific medical requirements. To achieve this goal, it was elected to develop a modular and portable software called OSIRIS. This software is available on two different operating systems (the UNIX standard X-11/OSF-Motif based workstations and the Macintosh family) and can be easily ported to other systems. The extra effort required to design such software in a modular and portable way was worthwhile because it resulted in a platform that can be easily expanded and adapted to a variety of specific clinical applications. Its portability allows users to benefit from the rapidly evolving workstation technology and to adapt the performance to suit their needs.


Orientation correction for chest images. This report presents an automatic procedure that determines the orientation of computed radiography (CR) chest images and rotates them to a standard position to be viewed by radiologists. As an input, CR images of a normalized size of 1,000 x 1,000 or 2,000 x 2,000 pixels are used. The analysis is performed in three steps. First, the orientation of the spine within the image is determined. Then, a function searches for upper extremities and the subdiaphragm. Finally, the lungs are extracted and their areas are compared. This indicates whether the image needs to be y-axis flipped. These three steps set the value of three parameters on the basis of which the final rotation angle is determined. The procedure has been implemented in the clinics at UCLA. The rate of correctly rotated images is 95.4%.


Recognition of chest radiograph orientation for picture archiving and communications systems display using neural networks. A neural network classification scheme was developed that enables a picture archiving and communications system workstation to determine the correct orientation of posteroanterior or anteroposterior chest images. This technique permits thoracic images to be displayed conventionally when called up on the workstation, and therefore reduces the need for reorientation of the image by the observer. Feature data were extracted from 1,000 digitized chest radiographs and used to train a two-layer neural network designed to classify the image into one of the eight possible orientations for a posteroanterior chest image. Once trained, the neural network identified the correct image orientation in 888 of 1,000 images that had not previously been seen by the neural network. Of the 112 images that were incorrectly classified, 106 were mirror images of the correct orientation, whereas only 6 actually had the caudal-cranial axis aligned incorrectly. The causes for misalignment are discussed.


Potential of digital flashing tomosynthesis for angiocardiographic evaluation. A system for digital flashing tomosynthesis (DFTS) consists of four electrocardiogram-gated and simultaneously flashed x-ray tubes, a 14" image intensifier, a unit for digital subtraction angiography (DSA), a personal computer-hosted transputer network for three-dimensional (3D) reconstruction as well as for quantitative coronary angiography and ventriculography, a display unit and an individual digital archive. DFTS-tomoangiograms may be presented in single slice mode or as multiple slices of arbitrary thickness, using rotating and stereographic presentation of 3D images. DFTS represents a configuration for standardized digital angiocardiography with digital archiving and assures optimal reproducibility and safety. This angiographic configuration is feasible for both ambulatory angiography to allow high volume cardiovascular angiographic screening and for the quantitative assessment of natural progression or potential regression of coronary artery disease resulting from interventional or pharmacological therapy.


[Dietetic and pharmacologic treatment of hypercholesterolemia. Study of 32 patients over 14 months]. The aim of the study was to evaluate the effectiveness of dietetic-behavioural and pharmacological treatment on 32 patients with high level hypercholesterolemia (LDL-c greater than 160 mg/dl) over 14 months. Clinical and laboratory tests were performed at time 0 (enrollment), at time 1 (after 2 months dietetic-behavioural treatment only), at time 2 and time 3 (after 6 and 12 months respectively of combined dietetic-behavioural and pharmacological treatment). The dietetic-behavioural treatment consist of reduced intake of saturated fatty acids, cholesterol and rapidly absorbed glycid; increased intake of omega-3 fatty acids and fiber; reduced overall calorie intake. The patients were also advised to take light daily exercise. The pharmacological treatment (sinivastatin 20 mg/die) was given to patients whose total cholesterol levels were over 250 mg/dl after 60 days of dietetic-behavioural only treatment and then continued for the whole study. The result showed an average reduction of 20% (p less than 0.01) in LDL-c in all patients after dietetic-behavioural only treatment and a further 20% (p less than 0.01) reduction after 12 months of combined treatment. There was therefore confirmation of the validity of dietetic-behavioural and pharmacological treatment during our study.


[Fecal chymotrypsin and steatorrhea in chronic pancreatitis]. The aim of the present study was to evaluate in 56 patients (48 M, 8 F) with chronic pancreatitis: a) the diagnostic validity of fecal chymotrypsin (FCT) assay, performed both on random samples and from previously homogenized samples collected over 3 days; b) the correlation between chymotrypsin and fecal fat excretion. CTF was measured using Kaspar's colorimetric method and fecal fats using the Van de Kamer method. Mean values of chymotrypsin measured on random samples were very similar to those measured on previously homogenized feces, 17.9 +/- 16.7 U/g vs 17.1 +/- 15.3 U/g respectively. There was a highly significant correlation between these values (r = 0.77 p less than 0.0003) and a highly significant inverse correlation between fecal fat and chymotrypsin excretion, both when the latter was measured on random and on previously homogenized samples (p less than 0.0001). FCT assay was fairly good sensitive (54%) for the whole group of patients with chronic pancreatitis, but very good (91%) for the group of patients with steatorrhea. The results show that the fecal chymotrypsin assay on random fecal samples is as valid as that carried out on homogenized feces and that there is a good correlation between fecal chymotrypsin values and steatorrhea of pancreatic origin.


[Polyps of the proximal colon: rightward shift, malignancy potential and symptomatology]. To evaluate the neoplastic risk of polyps of the right hemicolon we assigned 202 polyps larger than 4 mm, consecutively resected, to two groups according to their location, proximal or distal to the splenic flexure. We compared sex and age of the patients and the following characteristics of the polyps: size 10 mm and over, adenomatous and villous component, presence of severe dysplasia and absence of a stalk. We found that polyps in the proximal colon were less frequently dysplastic and smaller; on the other side fewer of them had a stalk. A significant rightward shift was observed in the male patients over 65 years old. Apparently right hemicolon polyps are less prone to overt clinical bleeding.


Hepatotoxicity of hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors. The first clinical studies on hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reported a low incidence of liver toxicity. The personal observation of a case of simvastatin-induced acute cholestatic hepatitis prompted us to evaluate the true incidence of hepatic side effects of these drugs in a large Italian population. One hundred patients taking simvastatin and ninety patients treated with pravastatin were followed-up six months with periodical evaluation of serum lipid levels and liver function test. In 5% of simvastatin-treated patients and 4.5% of pravastatin-treated patients significant liver toxicity was observed, which required drug discontinuation. The mechanism of liver damage was direct, idiosyncratic, but immunological features of drug toxicity could be hypothesized in one patient.


[Assessment of gallbladder motility in patients with alcoholic hepatic cirrhosis after a fatty meal. A real-time ultrasonography study]. Gallbladder emptying after fatty meal administration was investigated by real-time ultrasonography in 10 patients with alcoholic cirrhosis of the liver, and 10 normal controls. Gallbladder volume was measured using the sum of cylinders method before and 5', 15', 20', 30', 60', 90', and 120' after fatty meal administration. Patients with liver cirrhosis presented the gallbladder volume significantly increased after 15' and 20', and significantly reduced after 60' and 90' in respect to controls. A significant difference was found between the groups in the two curves, patients showing a retarded contraction of gallbladder. The mechanism for sluggish gallbladder emptying in liver cirrhosis is unknown, however impaired emptying with bile stasis provides a potential pathophysiology basis for the high frequency of cholelithiasis in this disease.


Toxoplasmic encephalitis in AIDS.

Toxoplasmic encephalitis in AIDS. Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV). Symptoms range from lethargy and apathy to coma, incoordination and ataxia to hemiparesis, loss of memory to severe dementia, and focal to major motor seizures. Involvement may be closely associated with HIV infection per se, as in the AIDS dementia complex, but is frequently caused by opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans or malignancies such as primary lymphoma of the CNS. The clinical presentations of attendant and direct CNS involvement are remarkably non-specific and overlapping, yet a correct diagnosis is critical to successful intervention. Toxoplasmic encephalitis is one of the most common and most treatable causes of AIDS-associated pathology of the CNS. A great deal has been learned in the last 10 years about its unique presentation in the HIV-infected patient with advanced disease. Drs. Benjamin J. Luft of the State University of New York at Stony Brook and Jack S. Remington of the Stanford University School of Medicine and Palo Alto Medical Foundation's Research Institute have studied T. gondii for many years and are two of the leading experts in the field. This commentary comprises an update of their initial review (J Infect Dis 1988;157:1-6) and a presentation of the current approaches to diagnosing and managing toxoplasmic encephalitis in HIV-infected patients.


Parasiticidal effect of chemotherapy in alveolar hydatid disease: review of experience with mebendazole and albendazole in Alaskan Eskimos. Evidence that the larval stage of Echinococcus multilocularis in humans is killed by chemotherapy is presented in a review of our 17-year experience with treatment of alveolar hydatid disease in Alaska. The efficacy of chemotherapy was assessed with use of an in vivo assay of parasite viability by means of inoculation of voles, immunohistochemical tests, and histopathologic findings. Of 14 tests performed for nine patients, 12 in vivo assays (86%) were negative after chemotherapy, while only two (17%) of 12 vole tests for seven untreated patients were negative. Regression of arrest of growth of metastatic and primary hepatic lesions, together with their partial-to-complete calcification and prolonged survival times has been observed among patients treated with the benzimidazole compounds. For six who received appropriate chemotherapy, treatment has been discontinued for an average of 4.6 years (range, 3-7 years) without an increase lesion size or other evidence of reactivation.


Two cases of endocarditis due to Lactobacillus species: antimicrobial susceptibility, review, and discussion of therapy. Endocarditis caused by lactobacilli may lead to death or to relapse of infection, despite antimicrobial treatment. We report two cases of lactobacillus endocarditis in individuals with native bicuspid aortic valves who survived without relapse and review the 39 other cases reported in the literature. In only 15 previously reported cases have patients been cured with medical therapy alone. One of our patients, who was infected with Lactobacillus acidophilus, was cured by medical therapy alone, and our other patient, who was infected with Lactobacillus casei subspecies rhamnosus, required surgical replacement of his aortic valve. L. acidophilus was tolerant and L. casei subspecies rhamnosus was resistant to many antibiotics tested. Combinations of penicillin or daptomycin and gentamicin were synergistic by time-kill assay. Synergistic therapy with a penicillin and an aminoglycoside was effective clinically and appears to provide optimal medical treatment on the basis of microbiological data.


[Metastasis to the penis from carcinoma of the rectum. A clinical case]. Penile metastases are extremely uncommon, with less than 300 reported cases. The primary sites of the responsible carcinoma have been bladder, rectum, prostate, kidney, testis, lung, nasopharynx and melanoma in that order. We report a case confirming the same data: no therapy has been shown to be helpful, the prognosis is very poor, with an average survival of less than one year. On the other hand we pointed out the importance of CT scan as a diagnostic tool for assessing the spread of neoplasm.


Measures of capillary permeability in acute falciparum malaria: relation to severity of infection and treatment. Capillary permeability was investigated in 32 Thai patients aged 14-49 years who had acute falciparum malaria with use of three distinct techniques: quantitation of the urinary albumin/creatinine ratio (ACR), estimation of the transcapillary escape rate of radiolabeled albumin (TER), and retinal photography/fluorescein angiography. Fourteen patients had uncomplicated infections and 18 were severe cases. The severely ill patients had significantly higher ACRs (median, 4.8 mg/mmol; 95% confidence limits, 2.4-19.9 mg/mmol) and TERs (median, 8.3%/h; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 1.0-8.8 mg/mmol; TER: median, 5.9%/h; 95% confidence limits, 3.8-10.6%/h; P = .014 and .042). Both variables were significantly associated with biochemical indices of disease severity including total serum bilirubin levels (rs greater than or equal to 0.398, P less than .025 in each case), but there were no significant differences between ACRs and TERs among comatose and noncomatose patients with severe infections (P greater than or equal to .08). Retinopathy (hemorrhages, cotton-wool spots, capillary nonperfusion, and/or extravasation of fluorescein) was found in eight severely ill patients and in two uncomplicated cases. Fluorescein leakage was evident in six patients. Although fluorescein leakage had the strongest parametric correlation with the presence of coma relative to both ACR and TER in the full patient series (r = 0.58, P less than .01), multiple linear regression analysis indicated that concentrations of plasma lactate (t = 2.998, P = .006) and serum creatinine (t = 2.200, P = .036) were the factors responsible for this association. These data do not support a role for tissue edema in the pathogenesis of cerebral malaria but reveal an association between markers of disease severity and a generalized increase in systemic capillary permeability.


[Comparison between a diet with mainly vegetal protein content and a diet with mainly animal protein content in hepatic cirrhosis]. Eight cirrhotic patients were studied in a randomized crossover single blind study in order to compare the effects of two isocaloric, and with equal amount of protein diets on nitrogen balance and on the portal systemic index. One diet was 2:3 vegetable protein to total protein content (diet V) and the other 2:3 animal protein to total protein content (diet A). Each diet was changed every three weeks. Five patients followed the VAV scheme and three the AVA scheme. The mean values of the porto systemic index were almost the same with the two diets while the value of the nitrogen balance was less negative with the diet A than with the diet V, showing an increasing trend, more marked with the diet A, at every consecutive time of observation. The variance analysis was not significant for any of the two diets. Diet V was well tolerated.


Toxoplasmosis in bone marrow-transplant recipients: report of seven cases and review. We report seven cases of cerebral or disseminated toxoplasmosis that occurred following bone marrow transplantation (BMT) and review the other 24 cases described in the literature. For all the cases, toxoplasmosis occurred within 6 months of BMT, with the highest incidence in the second and third months. Twenty-four of 26 recipients tested serologically before BMT were positive for Toxoplasma gondii, a finding that supports the view that such cases result from reactivation of latent infection. At the onset of clinical symptoms, IgG antibody titers were unchanged or decreased in 23 of 25 documented cases, and IgM antibodies were detected in two cases. Antemortem diagnosis was made in 16 cases and was based on the response to specific therapy in six cases and/or the demonstration of the parasite in body fluids or tissues in 10 cases. Autopsy was performed in 19 cases and revealed that infection was not restricted to the brain but either involved lung or heart tissue or was disseminated in 14 cases.


Vibrio vulnificus infection in Taiwan: report of 28 cases and review of clinical manifestations and treatment. From May 1985 through July 1990, 28 episodes of Vibrio vulnificus infection in 27 patients were encountered in five major hospitals in Taiwan. The ages of patients ranged from 19 to 76 years; the ratio of male to female patients was 2:1. Eighteen episodes manifested as bacteremia and eight as wound infections alone. One patient each developed gastroenteritis and pneumonia after nearly drowning. Twenty-three patients exhibited skin manifestations. Twenty patients had underlying diseases. All patients were treated with antibiotics, and 14 also underwent some form of surgical treatment (incision and drainage, fasciotomy, debridement, or amputation). Thirteen of the 28 episodes were preceded by precipitating factors; most were due to ingestion of seafood or exposure of abraded skin to salt water. Ten of the 18 septicemic patients died--most within 48 hours of hospitalization. One patient without bacteremia who had a wound infection died. Results of in vitro susceptibility studies suggested that ampicillin or a third-generation cephalosporin would be effective. Susceptibility to aminoglycosides was observed for greater than 90% of isolates. We recommend combined therapy with a third-generation cephalosporin or ampicillin and an aminoglycoside along with appropriate surgical therapy for the treatment of V. vulnificus infection.


Clusters of invasive group A streptococcal infections in family, hospital, and nursing home settings. The spread of group A streptococcal infection to close contacts of infected persons is well recognized. With the resurgence of invasive group A streptococcal infections, there is an increased potential for clusters of patients with invasive disease. We reviewed data collected since December 1988 at the Centers for Disease Control (Atlanta) to identify clusters of infection in which one or more patients had invasive disease. Twelve family clusters were identified. Infection in index cases included the toxic shock-like syndrome and septicemia. Infection in family contacts included invasive infections, pharyngitis, or asymptomatic carriage. Most invasive disease occurred in adults, while the majority of noninvasive infections were in children. Five nosocomial clusters with spread of infection from patients to hospital personnel were documented. All index patients had the toxic shock-like syndrome; secondary infections included the toxic shock-like syndrome, pneumonia, bullous cellulitis, lymphangitis, and pharyngitis. Clusters of invasive infections also were identified in five nursing homes. Pneumonia, cutaneous infections, and the toxic shock-like syndrome occurred most commonly. Clustering by nursing home unit occurred in three outbreaks. In hospitals and nursing homes, improved infection control will likely decrease secondary spread; in families, spread of disease may be prevented by identifying and treating those harboring the organism or by chemoprophylaxis. Studies that characterize the rate of secondary infection are needed before definitive recommendations can be made.


Chronic arthritis after rubella vaccination. In August 1991 the Institute of Medicine released a report entitled "Adverse Effects of Pertussis and Rubella Vaccines" that examined, among other relations, the relation between immunization with the RA 27/3 rubella vaccine strain and chronic arthritis. The committee spent 20 months reviewing a wide range of information sources including case series and individual case reports published in peer-reviewed journals and reported by vaccine manufacturers; unpublished case reports from physicians, parents, and other concerned persons; epidemiological studies; and laboratory studies. There were no animal studies available. The committee found that the evidence is consistent with a causal relation between the RA 27/3 rubella vaccine strain and chronic arthritis in adult women, although the evidence is limited in scope. Proving that rubella vaccination can cause chronic arthritis will require a better understanding of pathogenetic mechanisms and additional well-designed studies. We briefly describe the committee's evaluative methods and present the evidence underlying its conclusion.


Superantigens, T cells, and microbes.

Superantigens, T cells, and microbes. It is well recognized that toxins of Staphylococcus aureus and Streptococcus pyogenes are responsible for a wide range of clinical conditions, although their precise mode of action remains unclear. Recently, there has been a resurgence of interest in these toxins, now grouped with superantigens, because they cause profound alterations in the immune system homeostasis. Superantigens are molecules, including endogenous retroviral gene products and microbial toxins, that share a unique set of characteristics. They bind with high affinity to major histocompatibility complex class II at regions distinct from the conventional antigen binding groove and cause prolific activation or anergy of T cells with certain T cell receptor variable-region gene families. Whilst most of the superantigens described to date are products of bacteria or viruses, the presence of superantigens in parasites and their role in disease pathogenesis remain to be defined. It is probable that associations are present between superantigen-induced proliferation or anergy of peripheral blood T cells and clinical manifestations of human infectious diseases. The identification of these may pave the way toward a better understanding of disease pathogenesis and the possible development of newer immunotherapeutic regimes. This review summarizes the current thinking on microbial superantigens, their association with human T cells, and speculations about their significance.


Pleural infection caused by Capnocytophaga canimorsus, formerly CDC group DF-2. An 80-year-old man with Waldenström's macroglobulinemia developed pneumonia and empyema due to Capnocytophaga canimorsus (formerly CDC group DF-2). No growth was detected in blood cultures, but the organism was identified from cultures of pleural fluid. The infection responded well to antibiotics and drainage via a chest tube. To our knowledge, this is the first report of a clinical isolate of C. canimorsus from a pulmonary source. The absence of concurrent bacteremia raises the possibility that the lower respiratory tract can be the site of primary infection with this organism.


Endocarditis due to Neisseria mucosa: two case reports and review. Two cases of endocarditis caused by Neisseria mucosa are reported, and the literature on N. mucosa endocarditis is reviewed. N. mucosa is a rare but serious cause of endocarditis that is associated with a high rate of embolic complications and high mortality and is not always highly sensitive to benzylpenicillin. Most patients with N. mucosa endocarditis have been treated with combined therapy with penicillin and an aminoglycoside, although the optimal regimen has not been defined.


Severe pneumococcal sepsis and meningitis in human immunodeficiency virus-infected adults with sickle cell disease. Pneumococcal infection is frequent in children with sickle-cell disease (SCD) but is less common in adults. Infection due to human immunodeficiency virus (HIV) is also a risk factor for pneumococcal infection. The purpose of this study was to determine the clinical course of HIV infection in adults with SCD. During a 6-year period, 283 adults suffering from SCD were screened for HIV type 1 and HIV type 2 infections. The clinical course of HIV infections in these patients was retrospectively analyzed at the term of the study. HIV type 1 infection was detected in eight patients. The mean follow-up period after diagnosis of HIV infection was 4.6 years. None of the patients had AIDS. Five episodes of severe pneumococcal infection were observed in four of these eight patients (septic shock in two patients and three episodes of meningitis in two patients); two patients died of meningitis. Only one severe pneumococcal infection (meningitis) was observed in the 275 non-HIV-infected patients with SCD (P = .000001). Our results show that pneumococcal infection appears to occur frequently and is often serious in HIV-infected adults with SCD.


Epidemiology and clinical significance of nontuberculous mycobacteria in patients negative for human immunodeficiency virus in Switzerland. Over the last decades, the rate of isolation of tubercle bacilli has declined in the developed countries, while the incidence of infection with nontuberculous mycobacteria (NTM) has increased. In a retrospective study, we analyzed all cases of patients negative for human immunodeficiency virus (HIV) and from whom NTM were isolated in the Zurich area of Switzerland from 1983 to 1988. During the 6-year study period, 513 patients infected with NTM were identified, 34 of whom had clinically significant disease. The presentation of mycobacteriosis was found to be lung disease in 23 cases, soft-tissue disease in 10 cases, and disseminated disease in one case. The highest attack rate of pulmonary mycobacteriosis was 0.49% and was found in the group of patients 41-50 years old. During the 6-year period, the incidence of tuberculosis declined from 16.2 to 13.2 per 100,000 population, while the incidence of mycobacteriosis increased from 0.4 to 0.9 per 100,000 population. Clinically nonsignificant NTM isolates were found more frequently in patients with chronic lung diseases (P less than .01) and especially in patients with a history of tuberculosis (P less than .001).


Implications of viral resistance to amantadine in control of influenza A. Antiviral agents are valuable adjuncts to vaccine in the control of type A influenza. Amantadine has been available for many years for prophylaxis and therapy, but there have been concerns about side effects, particularly in the elderly. Thus, the anticipated licensure of rimantadine, an antiviral with the same efficacy as amantadine but with fewer side effects, has been viewed as a major advance. Rimantadine has thus far remained unlicensed, and attention has become focused on antiviral resistance to these drugs, an issue previously recognized but not considered important in decisions concerning drug use. The major implications of antiviral resistance relate to questions of whether there are differences in pathogenicity and transmissibility of resistant influenza type A viruses in comparison with sensitive ones. Resistant viruses have not been found to be more virulent than sensitive ones. The extent to which they may be transmitted or perpetuated has not been established. In light of this situation, it is suggested that drug use not be sharply restricted and that recommendations be periodically reviewed as more definitive data become available. As with any infectious disease, attempts should be made to limit exposure of uninfected individuals to those infected with the influenza A virus, regardless of whether they are receiving an antiviral drug.


Bacterial brain abscesses: factors influencing mortality and sequelae. Thirty-nine cases of brain abscess diagnosed since the advent of the computed tomographic (CT) scan were analyzed for factors influencing the outcome. The mortality rate was 13%, and severe sequelae were present in 22% of the survivors. The mean delay between occurrence of the first symptoms and hospitalization was significantly shorter for the 12 patients with poor outcome (death or severe sequelae) than for the 25 who recovered (fully or with moderate sequelae). Moreover, severely impaired mental status and neurological impairment at admission were associated with a poor outcome in terms of both mortality and sequelae. In all cases with fatal outcome or severe sequelae, the diagnosis was made and treatment was initiated within 24 hours of admission. There was no apparent correlation between the outcome and the presence or type of predisposing factors, the radiological, biological, or microbiological findings, or the treatment modalities. Thus, with the advent of the CT scan and the possibility of early diagnosis and treatment, the prognosis of brain abscess appears to be mainly determined by the rapidity of progression of the disease before hospitalization and the patient's mental status on admission.


Septic arthritis and bacteremia due to Mycoplasma resistant to antimicrobial therapy in a patient with systemic lupus erythematosus. We report a case of septic arthritis caused by Mycoplasma hominis in a patient with systemic lupus erythematosus. The infection started as monarthritis but spread to at least four joints despite apparently suitable therapy with various antimicrobial agents, including doxycycline, clindamycin, and ciprofloxacin; subsequent bacteremia was documented. Control was ultimately achieved with use of the experimental fluoroquinolone temafloxacin in combination with doxycycline administration, arthroscopic drainage of a persistently infected joint, several intravenous infusions of immunoglobulins (which led to increases in levels of antibodies specific to M. hominis), and discontinuation of corticosteroid therapy. Antimicrobial susceptibility testing of various mycoplasmal isolates showed the presence of the tetM gene, disparity between susceptibility to tetracycline and doxycycline, and increasing resistance to most antimicrobial agents used (including to fluoroquinolones before clinical use), although the patient ultimately had a favorable clinical response to treatment with combined modalities.


Imported malaria in pregnancy: report of four cases and review of management. Malaria is a common infection worldwide. Increased travel by pregnant women makes it likely that physicians in the United States will see cases of malaria in this population. We observed four cases of malaria during pregnancy over an 8-month period at a general hospital in the United States. These cases illustrate the association between pregnancy and severe malaria in the mother and congenital infection in the newborn. We also noted delays in diagnosis because malaria was mistaken for other common illnesses. Therapy was complicated by concerns about the safety of antimalarial agents for the fetus and newborn as well as drug resistance. While chloroquine is safe for use in pregnancy, drug resistance is now common, especially when the etiologic organism is Plasmodium falciparum. There are concerns about the safety of administering other antimalarial agents during pregnancy (e.g., mefloquine). Concerns about the safety and availability of these agents limit options for prophylaxis.


Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Demographic information, risk factors, therapy, and outcome for all patients who had candidemia at Barnes Hospital, St. Louis, between 1 September 1988 and 1 September 1989 were retrospectively reviewed. One hundred six candidemic patients were identified, representing 0.5% of all medical and surgical discharges and 0.33% of total patient discharges. These percentages represent a 20-fold increase in the incidence of candidemia at our hospital in comparison with that during 1976-1979. Candida albicans was the most frequently isolated species (63%), followed by Candida tropicalis (17%), Candida glabrata (13%), Candida parapsilosis (6.5%), and Candida krusei (0.9%). Overall mortality was 57%, and 14 (23%) of 60 deaths occurred within 48 hours of the detection of candidemia. Mortality was associated with higher APACHE II scores (25 for nonsurvivors vs. 16 for survivors; P = .0001), the presence of a rapidly fatal underlying illness (P = .0009), and sustained positivity of blood cultures (P = .02). In cases of sustained candidemia, the isolation of non-albicans Candida species also correlated with increased mortality (8 of 8 vs. 10 of 21; P = .005). Thirty candidemic patients (28%) did not receive any antifungal therapy, and 19 (63%) of these untreated patients died. Eleven untreated patients (37%) survived without sequelae. There has been a marked increase in the incidence of candidemia in our institution that is associated with a high overall mortality. Candidemia lasting less than 24 hours was associated with a lower mortality than was that of longer duration. Severity of illness and duration of candidemia should be used as stratifying factors in prospective studies to determine optimum therapy.


Plasma and whole blood exchange in meningococcal sepsis. The present study describes the effect of plasma exchange or whole blood exchange (PEBE) on the survival rate among patients with fulminant meningococcal sepsis and on the level of circulating endotoxin. Since 1989 all patients with meningococcal disease and hypotension who were admitted to our intensive care unit were treated with PEBE. Results for our patients were compared with those for a historical control group conventionally treated between 1984 and 1989 (n = 10; mortality rate, 60%); the expected mortality rate, which was based on the Niklasson prognostic score and was calculated for seven patients in this control group, was 73%. A total of 15 patients were treated with PEBE, three (20%) of whom died, whereas the prognostic score (calculated for 14 patients) for this group was 62%. In two of the fatal cases, PEBE was started after a delay of greater than or equal to 40 hours. In the remaining 13 patients, PEBE was started within 5-30 hours after the first hospital admission. The mortality rate among this group was 8% (one of 13 patients); this rate was significantly different from that among the control group (P = .025). For seven patients treated with PEBE, plasma endotoxin concentrations were sequentially measured. The overall half-life (+/- SEM) of endotoxin was 181 +/- 18 minutes. This is approximately the same as reported values for patients who were not treated with PEBE. It is concluded that early initiation of PEBE may improve the rate of survival among patients with meningococcal infection and hypotension but that the mechanism of the beneficial effect is most likely not based on the elimination of endotoxin.


Fatal septicemia due to Mycoplasma arginini: a new human zoonosis. A 64-year-old slaughterhouse worker with advanced non-Hodgkin's lymphoma developed septicemia and pneumonia. Mycoplasma arginini, a wall-free prokaryote found in a variety of domestic animal hosts, was repeatedly isolated from blood and bronchial washings from the patient. Immunosuppression, in part caused by hypogammaglobulinemia, probably played a key role in predisposing the patient to a fatal infection. This case suggests that animal mycoplasmas should be considered in the list of infectious agents acquired by immunosuppressed hosts.


Rocky Mountain "spotless" and "almost spotless" fever: a wolf in sheep's clothing. In 10 (10.8%) of 93 laboratory-confirmed or probable cases of Rocky Mountain spotted fever seen at Duke University Medical Center from 1969 to 1991, illness without rash or fleeting or atypical skin eruptions were noted. Data from these 10 cases and 33 similar previously reported cases of Rocky Mountain "spotless" or "almost spotless" fever support the premise that human Rickettsia rickettsii infection has a broader spectrum than that indicated by its classic description. Sixty-one percent of patients with Rocky Mountain spotless or almost spotless fever have been men. Two-thirds have been black. Although in some cases the absence of rash may be due to the prompt institution of therapy with chloramphenicol or tetracycline, in others long delays in recognition of the disease and treatment occurred, resulting in the deaths of 53% of patients. On the basis of outcome in the cases reviewed, empirical administration of chloramphenicol or a tetracycline to selected patients is justifiable (including those patients with severe organ dysfunction), even if they have no rash, a transient rash, or a rash of unusual distribution. Indeed, without such therapy, patients with spotless or almost spotless fever may die. Recognizing such atypical cases is analogous to seeing a wolf in sheep's clothing--intuition, experience, knowledge, and a high index of suspicion are required.


Epidemiology of Aeromonas infections in California. In May 1988, California became the first state to make aeromonas infection a reportable condition, thereby permitting the first population-based study of the epidemiology of infection caused by Aeromonas organisms. Case investigations were carried out on 219 of the 280 patients whose infections were reported during the first year of notification. The overall incidence rate for Aeromonas isolation was 10.6 cases per 1 million population. The gastrointestinal tract was the most commonly reported site from which Aeromonas was isolated (81%), with wounds being the next most common source (9%). Five (2%) of the 219 patients died; all five had serious underlying medical conditions apart from aeromonas infection. No common-source enteric outbreaks were reported. The high rate of gastrointestinal symptoms and isolation of organisms from medically vulnerable patients and the fact that other bacterial enteric pathogens were rarely isolated from symptomatic patients support evidence from previous studies that Aeromonas is an enteric pathogen. The evidence from these case reports in California suggests that aeromonas infections are not an important public health problem and are largely nonpreventable. Thus, public health surveillance is not necessary and mandatory reporting has been discontinued.


Infections due to Nocardia transvalensis: clinical spectrum and antimicrobial therapy. Nocardia transvalensis, a rare Nocardia species, has previously been recognized as a cause of actinomycotic mycetoma. In a retrospective review of N. transvalensis isolates referred to the Centers for Disease Control (Atlanta) during the period January 1981 through January 1990, we identified 15 patient isolates. Four N. transvalensis isolates originated from one Australian reference laboratory; one patient's isolate that was identified by the Australian laboratory but that was not received at the Centers for Disease Control was also included in our study. A review of the cases of these 16 patients found that N. transvalensis caused infection in 10 patients and colonization in two patients. Six (75%) of eight patients with primary pulmonary or disseminated N. transvalensis infections had an underlying immunologic disorder or were receiving immunosuppressive therapy; three patients with disseminated infection died. All nine infected patients for whom specific antimicrobial therapy was prescribed received trimethoprim-sulfamethoxazole. Results of in vitro antimicrobial susceptibility tests of 11 N. transvalensis isolates revealed increased antimicrobial resistance to amikacin and other drugs when compared with that of other Nocardia species. Severely immunocompromised patients are predisposed to N. transvalensis pneumonia or disseminated infection, and the lung may be the portal of entry.


Diloxanide furoate for treating asymptomatic Entamoeba histolytica cyst passers: 14 years' experience in the United States. Diloxanide furoate is used for treating asymptomatic or mildly symptomatic persons who are passing cysts of Entamoeba histolytica. The Centers for Disease Control (Atlanta) released this drug for 4,371 treatment courses from 1977 through 1990. Of the 2,815 report forms (64%) returned, 656 adverse effects were reported for 390 treatment courses (14%); they included flatulence (260), diarrhea or cramping (100), nausea (93), headache (17), disorientation or dizziness (9), and diplopia (4). During 1984-1990 uniform collection of data allowed more detailed analysis of toxicity and efficacy; fewer adverse effects were reported for persons aged 20 months to 10 years than for persons aged greater than 10 years (6 of 206 [3%] vs. 89 of 763 [12%], relative risk = 0.27, 95% confidence interval = 0.12 less than relative risk less than 0.61). Parasitological cures were achieved during 497 (86%) of the 575 treatment courses (52%) administered to asymptomatic persons who were passing cysts, who had received a full 10-day treatment course, and for whom results of a follow-up stool examination (greater than or equal to 14 days post-treatment) were available. Diloxanide furoate is safe and effective for treating asymptomatic persons who are passing E. histolytica cysts and may be particularly well tolerated in children.


Disseminated Nocardia brasiliensis infection with septic arthritis. An unusual case of disseminated Nocardia brasiliensis infection is presented. The patient, who had been receiving chronic dexamethasone therapy for 4 years, had pneumonia and septic arthritis of the left knee due to N. brasiliensis. To our knowledge, this is the first report from the United States of a synovial joint infection with this organism. Disseminated disease due to N. brasiliensis is infrequently reported; it is most often seen in the immunocompromised patient and is often unresponsive to therapy.


Evaluation of eight serological tests in the diagnosis of human echinococcosis and follow-up. The ELISA with use of IgG, IgA, and IgE, latex agglutination, indirect hemagglutination (IHA), total IgE, the radioallergosorbent test (RAST), and immunoelectrophoresis (IEP) were carried out to determine the preoperative diagnosis of infection due to Echinococcus granulosus in 131 patients. Eighty-nine patients received follow-up care for 42 +/- 22 months (mean +/- SD); 72 were treated surgically and 17 with mebendazole only. We analyzed 5 +/- 2 serum samples per patient and analyzed each serum sample using the eight tests. IgG ELISA was the most sensitive (up to 94%) and specific (up to 99%) test for the majority of cyst locations in the patient. IEP was positive in only 73% of cases. The combination of IgG ELISA, IHA, and IgA ELISA allowed us to achieve a sensitivity of 81% in cases of pulmonary echinococcosis. IgE and IgA were both responsible for most nonspecific reactions, the former in patients with parasitic diseases other than echinococcosis and the latter in patients with cirrhosis of the liver and malignancies. IgG ELISA and IHA were the most adequate tests for postsurgical follow-up. In patients with favorable clinical outcome, the specific IgG level decreased early toward the end of the first year, although serological positivity could persist beyond 6 years. A rise of IgG level 2 or 3 years after treatment suggested persistent active infection. In patients with mebendazole-associated cure, only tests with total or specific IgE detection seemed to exhibit a strong association with decreasing levels or with negative results.


Bactericidal activity of antibiotics alone and in combination against Enterococcus faecalis in a pharmacodynamic model. We evaluated the bactericidal kinetics of teicoplanin, mezlocillin, netilmicin, and ciprofloxacin alone and in dual combinations against strains of Enterococcus faecalis susceptible or resistant to ampicillin in a pharmacodynamic model reproducing in bacterial culture in active human plasma or Mueller-Hinton broth the serum kinetics of these antibiotics in humans. Killing was not different in cultures grown in plasma and those grown in broth. Antibiotics used alone had no or low bactericidal activity except for high-dose ciprofloxacin (600 mg intravenously [iv] twice daily or 750 mg orally twice daily), which achieved a 3- to 4-log reduction in colony-forming units (cfu). Netilmicin was equally active at 6 mg/kg once a day or 2 mg/kg three times daily in all combinations. No major increase in bactericidal activity was detected in any combination that included mezlocillin. Maximal synergistic killing was observed for the combination of teicoplanin plus netilmicin (both at three-times daily and once-daily dosing), which sterilized the bacterial cultures (initial inoculum, 10(6) cfu/mL). Combinations of ciprofloxacin at 600 mg iv twice daily and 750 mg orally twice daily plus either teicoplanin or netilmicin were less synergistic but equally effective in total killing as a result of the high bactericidal activity of ciprofloxacin alone.


Mechanisms of resistance to growth inhibition and killing by beta-lactam antibiotics in enterococci. Enterococci are characterized by an intrinsic resistance to growth inhibition by beta-lactam antibiotics. The low susceptibility of enterococci to beta-lactam antibiotics is associated with the synthesis of a particular penicillin-binding protein (PBP) that has a low affinity for beta-lactam agents. This protein appears to be capable of taking over the function of the other PBPs when they are saturated with beta-lactam molecules or inactivated by mutations. A quantitative correlation can be established between the binding of several beta-lactam molecules to the low-affinity PBP and the minimal inhibitory concentration for enterococcal strains. In contrast, the mechanism of enterococcal resistance to the bactericidal activity of beta-lactam agents that inhibit growth at relatively low concentrations appears to be associated with an alteration in the pattern of autolytic enzyme activity. In particular, lack of or poor activity of an autolytic enzyme appears to be responsible for the paradoxical bactericidal response often exhibited by clinical isolates of Enterococcus faecalis in the presence of penicillin.


Antibiotic resistance of clinical isolates of Enterococcus in Italy. Alarming reports from various parts of the world of an increase in multiple-drug resistance among enterococci have prompted the Italian Association of Clinical Microbiologists to sponsor a nationwide study aimed at assessing the magnitude of this problem in Italy. During the last 3 months of 1988, technicians from a total of 162 general and teaching hospitals, in 16 of the 20 Italian regions and covering 89,061 beds, isolated 58,886 bacterial strains from inpatients and outpatients. Enterococci (4,879) represented 8.3% of all microorganisms identified, with Enterococcus faecalis accounting for 4,554 strains and Enterococcus faecium for the remaining 316 (6.5% of all enterococci analyzed). Enterococci were recovered most frequently from urine (62.5%) and genitourinary samples (13.7%). Only 58 strains (1.2%) were associated with bacteremia. The in vitro susceptibility of these organisms to 21 commonly used antibiotics is reported and compared with the susceptibility of isolates from a smaller epidemiologic study conducted in Italy in 1986 as well as with more recent findings from individual laboratories.


Resistance of enterococci to aminoglycosides and glycopeptides. High-level resistance to aminoglycosides in enterococci often is mediated by aminoglycoside-modifying enzymes, and the corresponding genes generally are located on self-transferable plasmids. These enzymes are similar to those in staphylococci but differ from the modifying enzymes of gram-negative bacteria. Three classes of enzymes are distinguished, depending upon the reaction catalyzed. All but amikacin and netilmicin confer high-level resistance to the antibiotics that are modified in vitro. However, the synergistic activity of these last two antibiotics in combination with beta-lactam agents can be suppressed, as has always been found in relation to high-level resistance to the aminoglycosides. Acquisition of glycopeptide resistance by enterococci recently was reported. Strains of two phenotypes have been distinguished: those that are resistant to high levels of vancomycin and teicoplanin and those that are inducibly resistant to low levels of vancomycin and susceptible to teicoplanin. In strains of Enterococcus faecium highly resistant to glycopeptides, we have characterized plasmids ranging from 34 to 40 kilobases that are often self-transferable to other gram-positive organisms. The resistance gene vanA has been cloned, and its nucleotide sequence has been determined. Hybridization experiments showed that this resistance determinant is present in all of our enterococcal strains that are highly resistant to glycopeptides. The vanA gene is part of a cluster of plasmid genes responsible for synthesis of peptidoglycan precursors containing a depsipeptide instead of the usual D-alanyl-D-alanine terminus. Reduced affinity of glycopeptides to these precursors confers resistance to the antibiotics.


Modulation of host defenses by cytokines: evolving adjuncts in prevention and treatment of serious infections in immunocompromised hosts. Traditional management of infectious complications, especially in immunocompromised hosts, has depended on the prompt initiation of therapy with broad-spectrum antibiotics. During the past several years, however, a number of cytokines (interleukins, hematopoietic growth factors, interferons) have been developed and produced by recombinant DNA technology, and preclinical and clinical studies of cytokines in immunocompromised hosts have begun. The data being generated suggest that certain cytokines can accelerate neutrophil and monocyte/macrophage production, enhance their function, and potentially decrease infectious complications. The role of these agents in both the prevention and treatment of infectious diseases represents an important research challenge and offers new approaches to the prevention and treatment of infection in immunocompromised hosts.


Group A Streptococcus septicemia and an infected, ruptured abdominal aortic aneurysm associated with pharyngitis. A 65-year-old man had a 3-day history of sore throat, fever, rigors, back pain, abdominal discomfort, nausea, vomiting, and diarrhea. The patient's daughter had group A streptococcus pharyngitis. The patient was found to have a ruptured abdominal aortic aneurysm. He underwent resection of the aneurysm and right axillary femoro-femoral bypass graft. The patient died 40 hours after admission. Gram stain of the aneurysm showed numerous gram-positive cocci. Group A streptococcus grew from cultures of blood, throat, and aneurysm. The group A streptococcus was M type 3, T type 3 and produced streptococcal pyrogenic exotoxin A. This case is a very rare fatal complication of group A streptococcus pharyngitis.


Fever of unknown origin after Angelchik antireflux prosthesis implantation. The Angelchik device is a silicone collar placed at the gastroesophageal junction for preventing reflux. Many complications associated with the use of this device have been reported, including disruption, migration, and erosion into the gastrointestinal tract. We report another complication of the device, that of abscess formation presenting as fever of unknown origin. This complication emphasizes the need for careful investigation of any implanted foreign body in the evaluation of a patient who has fever of unknown origin.


Kingella kingae intervertebral diskitis in an adult. Kingella kingae rarely causes infection and is mainly associated with endocarditis and septic arthritis in adults. The organism is also capable of causing intervertebral diskitis in children, but thus far, no reports of this infection occurring in adults have been published. A case of diskitis due to K. kingae in an adult is reported for the first time, and the literature on this infection in children is reviewed.


Impact of human immunodeficiency virus infection on the epidemiology, clinical features, management, and control of tuberculosis. After years of decreasing prevalence and increasing hope that tuberculosis, like smallpox, could be eliminated, the disease has resurfaced as a major public health problem in the United States. Particularly ominous are the appearance of multiple-drug-resistant strains and their impact on patients and health care workers who are infected with the human immunodeficiency virus, among whom mortality rates reach 80% 2-3 months postdiagnosis. To respond effectively to this new threat, it is critical that we reorient our thinking about tuberculosis and redirect health care resources to programs for tuberculosis control. We need to reinstitute screening of high-risk populations and ensure proper isolation of patients with the disease. Diagnosing tuberculosis at the earliest possible stage is obviously of the utmost importance. High priority must be given to the development of rapid diagnostic tests and techniques that screen for drug resistance. We must implement and adequately fund drug-discovery programs to develop new therapeutic agents that are effective against multiple-drug-resistant strains of Mycobacterium tuberculosis. Effective programs for monitoring the treatment of patients with tuberculosis must also be implemented. Failure to adequately support such programs has probably led to the recent upswing in multiple-drug-resistant tuberculosis, especially in large cities along the eastern seaboard. Leadership for and funding of these programs must come from the federal government, specifically the U.S. Department of Health & Human Services and the Centers for Disease Control (Atlanta). The Infectious Diseases Society of America is actively supporting a variety of tuberculosis control-related initiatives and will keep its members updated on progress in this area.(ABSTRACT TRUNCATED AT 250 WORDS)


Re-evaluation of the biocompatibility of bioinert ceramics in vivo. The affinity of bone for bioinert ceramics and stainless steel was compared using calcified bone specimens. We implanted cylinders of alumina ceramics (Al2O3), zirconia ceramics (ZrO2) and SUS-316 L stainless steel into the distal femoral epiphyses of dogs and then made observations from 4 to 96 wk post-operatively. Irregularities in the histological specimens suggested the presence of artefacts due to the insertion technique. We subsequently used screws inserted into holes tapped with a tap that had a diameter identical to the screws, and observed these implants from 4 to 96 wk after insertion. There was no detectable difference in the affinity index for all three materials from 4 to 96 wk after implantation. The affinity index was calculated as the ratio of the new bone directly adjoining the implant without any intervening fibrous membrane or bone marrow to the total length of the bone-implant interface x 100%.


Comparative biophysical study of adsorbed calf serum, fetal bovine serum and mussel adhesive protein films. Varying concentrations of different sera and adhesive agents are routinely used to increase cellular attachment to substrata. The surface-chemical effects of some of these surface-altering materials have been examined using ellipsometry, contact angle analysis and multiple-attenuated internal reflection infrared (MAIR-IR) spectroscopy. Specifically, 15% fetal bovine serum (FBS), Ham's F-12 (containing 10% FBS + 1% penicillin/streptomycin), 10% calf serum and mussel adhesive protein (MAP) were allowed to adsorb on to similar and different surfaces and then compared. Each of these preparations is capable of altering the surface-chemical properties of substrata with varying resultant surface energies. It is therefore important to characterize serum in the proper concentrations on the substrata under consideration in order to understand the interfacial effects.


Cellular reaction to the Vascugraft polyesterurethane vascular prosthesis: in vivo studies in rats. The biocompatibility of Vascugraft, a polyesterurethane vascular prosthesis manufactured by Braun-Melsungen AG, was assessed by immunofluorescence and histological studies. Discs, 1 cm2, of Vascugraft prosthesis were implanted into the peritoneal cavity of rats. Results were compared with Impra, GORE-TEX and Mitrathane prostheses and a control group. Animals were killed at 1, 2, 6, 9 and 12 wk. Total T cells, T helper cells, T suppressor cells and activated T lymphocytes expressing Interleukin-2 receptors were quantified by a cytofluorometric technique in the peripheral blood of rats. For each period of implantation, all vascular prostheses showed no significant change in the percentage of total T cells, T subsets and T cells expressing Interleukin-2 receptors when compared to the control group. Histological examination of the tissue reaction surrounding the Vascugraft revealed a mild inflammatory reaction, similar to the one observed with both polytetrafluoroethylene grafts. However, the rate and the degree of encapsulation were different between grafts. The Vascugraft prosthesis was well encapsulated 2 wk after implantation, whereas inhibition of fibroblastic proliferation into the graft wall and surrounding both polytetrafluoroethylene grafts was observed for each period of implantation. The Mitrathane prosthesis exhibited a moderate inflammatory response, characterized by a high level of activation on fibroblasts compared to other grafts.


Effect of lithotriptor treatment on the fracture toughness of acrylic bone cement. Extracorporeal shock wave lithotripsy (ESWL) has now been established as an efficacious non-invasive modality for the management of renal calculi and has shown promise for management of other types of stone, as well. Following on from these successes, ESWL has recently been proposed for use in the preliminary stages of revision of cemented total hip joint replacements as a means of breaking up the cement mantle. It is useful, therefore, to examine the effect of shock waves on pertinent mechanical properties of the cement. This study utilizes the chevron-notch short-rod specimen and a commercially available test system to obtain the values of one such property, namely fracture toughness, of Palacos Radiopaque bone cement before and after treatment with shock waves delivered from a lithotriptor. The fracture toughness drops by about 14% following the shock wave treatment, thus confirming the possibility that ESWL can be used, as indicated earlier, in revision arthroplasty.


Controlled cisplatin delivery system using poly(D,L-lactic acid). Cisplatin (CDDP)-containing poly(D,L-lactic acid) microspheres (CDDP-MS) and beads (CDDP-B) with an average molecular weight of the oligomer of 1.2 x 10(4) and 4% CDDP loading were prepared. In Tris buffer, 95% of CDDP disappeared from CDDP-MS within 3 d. In vitro and in vivo, CDDP-B released CDDP for 30-57 d, and for 21-42 d, respectively. The other CDDP-B with an average oligomer molecular weight of 9.6 x 10(3) with 5% lactic acid monomers, that contained 4% CDDP, showed a two-phase CDDP release pattern and CDDP disappeared within 41 d in vitro, and within 21 d in vivo. Histologically, tissue necrosis surrounding the CDDP-B was not severe.


Improvement of blood compatibility on cellulose dialysis membrane. 2. Blood compatibility of phospholipid polymer grafted cellulose membrane. The blood compatibility of a cellulose haemodialysis membrane whose surface was grafted with a methacrylate having a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine, was evaluated with attention to platelet adhesion to the membrane surface and complement activation induced by the membrane. When the original cellulose membrane came in contact with platelet-rich plasma for 30 min, numerous platelets adhered to the surface and aggregated. On the other hand, the membrane grafted with 2-methacryloyloxyethyl phosphorylcholine effectively suppressed platelet adhesion and activation. This effect became more pronounced with increasing surface distribution. Especially, the 2-methacryloyloxyethyl phosphorylcholine grafted membranes, whose distribution exceeded 0.27, completely inhibited platelet adhesion, even when the contact time was 180 min. Moreover, the complement activation was also reduced with increased 2-methacryloyloxyethyl phosphorylcholine distribution on the surface of the membrane.


Degradation of five polyurethane gastric bubbles following in vivo use: SEC, ATR-IR and DSC studies. Five Garren-Edwards Gastric Bubbles were characterized, following up to 4 months use in vivo, using size exclusion chromatography, differential scanning calorimetry and attenuated total reflectance infrared spectroscopy. These techniques show that the material used to construct the bubble is probably an aromatic polyester urethane and revealed a 39-55% decrease in number average molecular weight, a 9 degrees C decrease in glass transition temperature, the disappearance of soft segment crystallinity and a broadening of the hard segment melting region after exposure to highly acidic (approximately pH 1.2) gastric fluid. The results indicate that significant chemical and morphological changes have taken place in the bubble material, including loss in chemical functionality, phase separation and increased hard segment aggregation. A comparison of the decrease in glass transition temperature as a function of molecular weight suggests that glass transition temperature is a sensitive predictor of this material's stability. Additionally, evidence is provided that the broad infrared absorption at 1077-1067 cm-1 normally assigned to C-O-C hard segment may represent two types of C-O-C stretching: (1) C-O-C stretching of the free urethane carbonyl, and (2) C-O-C stretching of the hydrogen bonded urethane carbonyl.


Structure, solubility and bond strength of thin calcium phosphate coatings produced by ion beam sputter deposition. Ion beam sputter deposition was used to produce thin calcium phosphate coatings on titanium substrates. Structure, solubility and bond strength of the as-sputtered and heat treated coatings were evaluated. X-ray diffraction (XRD) analysis of the heat treated coatings revealed a hydroxyapatite-type structure. The heat treated coatings were found to have significantly lower solubility as compared to the amorphous as-sputtered coatings. Although the crystalline coatings exhibited the lowest solubility, in general, the bond strengths were lower for the heat treated coatings.


Effect of titanium implants on primary mineralization following 6 and 14 days of rat tibial healing. The effect of pure commercial titanium implants on the process of primary mineralization was studied. This was examined by insertion of titanium implants into rat tibial bone after ablation. The effects of the titanium were studied through the behaviour of extracellular matrix vesicles (MV). Methods of morphometric analysis at the TEM level were applied. The insertion of titanium implants was followed by an increase in the number of MV as well as vesicular diameter and by a decrease in vesicular distance from the calcified front when compared to normal healing. These results suggest that the process of MV maturation around titanium implants was delayed when compared to normal primary bone formation during bone healing. The delay in mineralization was compensated by an increase in vesicle production, resulting in an enhancement of primary mineralization by the titanium.


Inflammatory response to subcutaneously implanted Marlex and GORE-TEX in massively obese patients. In both vertical banded gastroplasty and in gastric banding, synthetic bands are used to reinforce the outlet from the pouch to the rest of the stomach. Two materials commonly used for these bands are polypropylene (Marlex) and polytetrafluoroethylene (GORE-TEX). As a measure of their suitability, human inflammatory response to subcutaneous implants was investigated. In a randomized series of 17 superobese patients a patch of GORE-TEX was implanted subcutaneously in one groin under local anaesthesia and Marlex mesh was implanted in the other groin. After about 2 months the implants were exstirpated and investigated in a single blind procedure by an experienced pathologist. Marlex gave a significantly greater chronic inflammatory reaction and fibrosis than GORE-TEX. The foreign body giant cell reaction was, however, significantly greater with GORE-TEX. The possible implications of these results are discussed.


Regulation of tumor cell growth at organ-specific metastases. The hallmark of malignant neoplasms is their ability to spread beyond the site of origin and produce metastases in distant organs. This nonrandom process depends on the interaction of specific tumor cells with a compatible milieu provided by a particular organ microenvironment; the molecular basis of which is under intense investigation. Recent analysis of human colon carcinoma (HCC) cells obtained from surgical specimens and implanted into athymic nude mice suggested that whereas nonmetastatic and highly metastatic cells can grow at local sites, growth per se in the secondary organ-specific site was associated only with high-metastatic HCC cells. These cells also respond in a specific manner to physiological mitogenic signals produced by damaged normal tissues. This article addresses the biological and molecular evidence supporting the hypothesis that organ-derived, perhaps, organ-specific, paracrine growth factors stimulate the growth of receptive malignant cells that possess the appropriate receptors.


Comparative aspects of the quality of life in cancer patients. Chronologically, neoplastic diseases can be divided into two categories of which the first includes the fast and aggressive disease groups which exhibit a short course after the diagnosis has been established and the second those with dormancy or a slow path of which the development extends over years, even decades. The developed treatment modalities have even expanded the time duration of both groups, and thus cancer has become a group of chronic diseases in many cases. This requires a special adaptation in regard to the life style and quality of the cancer patient. The assessment of the quality of life in the cancer patient has been evaluated through questionnaire to relatives and friends as well as through social experience with cancer patients. The diversity of the disease group is reflected in the need for a more heterogeneous improvement of life style and its quality according to the need of the patient groups. A distinction can be made between acute and chronically ill pediatric patients, the cancer patient who is able to continue his work, the outpatient not requiring hospitalization, the patient with the need for hospital care (for a shorter or longer Period), the hospice patient, the elderly patient, and the terminally ill patient as well as the patient in the last days of life. In a study of 1,227 elderly decedents in Fairfield County, Connecticut, for which 260 respondents reported cancer as the cause of death, approximately 1/5 were reported to have been in moderate or severe pain six hours before death, with little change from the previous month.(ABSTRACT TRUNCATED AT 250 WORDS)